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Sample records for advanced colorectal cancer

  1. Extended resection for locally advanced colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-ping; SONG Xin-ming

    2006-01-01

    @@ Colorectal cancer is a common cause of cancer-related mortality.1 In China, it is one of eight cancers in the cancer control blueprint, which are suggested to have comprehensive treatment.Some patients with colorectal cancer presented no symptoms when they were diagnosed, yet the tumor had already penetrated the intestinal wall and involved adjacent organs. If the tumor is localized at time of diagnosis without distant metastases, it is termed locally advanced colorectal cancer (LACC)regardless of whether there is lymph node metastasis. LACC commonly encountered in clinical practice accounts for 5%-10% of all colorectal cancers.2

  2. Colorectal cancer development and advances in screening

    OpenAIRE

    Simon K

    2016-01-01

    Karen Simon Ventura County Gastroenterology Medical Group, Inc., Camarillo, CA, USA Abstract: Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known b...

  3. Current issues in the targeted therapy of advanced colorectal cancer.

    NARCIS (Netherlands)

    Knijn, N.; Tol, J.; Punt, C.J.A.

    2010-01-01

    Currently used cytotoxic drugs in the treatment of advanced colorectal cancer (ACC) are primarily the fluoropyrimidines, irinotecan, and oxaliplatin. The introduction of targeted therapy has increased the therapeutic arsenal. Two classes of monoclonal antibodies have been approved for clinical use i

  4. Colorectal Cancer

    Science.gov (United States)

    ... rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of ... men and women. The risk of developing colorectal cancer rises after age 50. You're also more ...

  5. Clinical review: surgical management of locally advanced and recurrent colorectal cancer.

    LENUS (Irish Health Repository)

    Courtney, D

    2014-01-01

    Recurrent and locally advanced colorectal cancers frequently require en bloc resection of involved organs to achieve negative margins. The aim of this review is to evaluate the most current literature related to the surgical management of locally advanced and recurrent colorectal cancer.

  6. Recent advances in minimally invasive colorectal cancer surgery

    OpenAIRE

    Wichmann, Mathias W.; Meyer, G.; Angele, M. K.; Schildberg, Friedrich Wilhelm; Rau, H G

    2002-01-01

    Laparoscopy has improved surgical treatment of various diseases due to its limited surgical trauma and has developed as an interesting therapeutic alternative for the resection of colorectal cancer. Despite numerous clinical advantages (faster recovery, less pain, fewer wound and systemic complications, faster return to work) the laparoscopic approach to colorectal cancer therapy has also resulted in unusual complications, i.e. ureteral and bladder injury which are rarely observed with open l...

  7. Advances and perspectives of colorectal cancer stem cell vaccine.

    Science.gov (United States)

    Guo, Mei; Dou, Jun

    2015-12-01

    Colorectal cancer is essentially an environmental and genetic disease featured by uncontrolled cell growth and the capability to invade other parts of the body by forming metastases, which inconvertibly cause great damage to tissues and organs. It has become one of the leading causes of cancer-related mortality in the developed countries such as United States, and approximately 1.2 million new cases are yearly diagnosed worldwide, with the death rate of more than 600,000 annually and incidence rates are increasing in most developing countries. Apart from the generally accepted theory that pathogenesis of colorectal cancer consists of genetic mutation of a certain target cell and diversifications in tumor microenvironment, the colorectal cancer stem cells (CCSCs) theory makes a different explanation, stating that among millions of colon cancer cells there is a specific and scanty cellular population which possess the capability of self-renewal, differentiation and strong oncogenicity, and is tightly responsible for drug resistance and tumor metastasis. Based on these characteristics, CCSCs are becoming a novel target cells both in the clinical and the basic studies, especially the study of CCSCs vaccines due to induced efficient immune response against CCSCs. This review provides an overview of CCSCs and preparation technics and targeting factors related to CCSCs vaccines in detail.

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

    OpenAIRE

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

    2010-01-01

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

  9. CLINICAL-MORPHOLOGICAL CORRELATIONS IN ADVANCED COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    Gh. Bălan

    2011-11-01

    Full Text Available Background: During 2000-2007 we have selected and supervised a lot of 279 cases operated for colorectal cancer in Clinic no.1 Surgery from “St. Spiridon” Hospital. The sex repartition during the entire study period shows the preponderance of male cases (61.29% in comparison to the female cases of 38.7 %. In our study the operated colorectal carcinomas have a higher incidence at patients over 60 years old, 71.67%. There is as well a higher percent for the age group 60-70 years old and 70-80 years old which percent reaches 34.76% respectively 32.97% out of the total number of cases. When comparing the average age of the two analyzed lots there we can notice that the average age of the female patients does not differ significantly from the age of the male patients. The average age of the female patients was of 64,3±8,58 with minimum values of 51 years and maximum of 78 years and the average age of male patients was of 67,9±10,5 with minim of 44 years and maximum of 86 years. The on segments distribution of the colorectal cancer is presented as follows: rectum 108 cases (38,7%, sigmoid 96 cases (34,40%, descendent 19 cases (6,81%, hepatic angle 17 cases (6.09%, transverse 17 cases (6.09%, ascending 12 cases (4,3% % the rest of the localizations being in a smaller number. In the case of males the colorectal cancer is met most often at the level of the rectum (32.74% and the case of females at the level of the sigmoid (41.66%. Regarding the microscopic results they were: well differentiated adenocarcinoma 45.83%, moderate differentiated 43.75% and weak differentiated 10.42%. The Chi-square analysis shows that there is no association between the macroscopic aspects of the tumours and their histological aspect. Analyzing the microscopic aspect according to the location of the tumour there is observed that 86.95% of the tumours that were located at the level of the rectum have a vegetative aspect. There was not observed any link between the gender

  10. CLINICOPATHOLOGICAL CHARACTERISTICS OF ADVANCED COLORECTAL CANCER 30 mm OR SMALLER IN DIAMETER

    Institute of Scientific and Technical Information of China (English)

    Hong Zhang; Chun-sheng Chen; Jin-chun Cong; Lei Qiao; Taisuke Hasegawa; Shigeki Takashima

    2007-01-01

    Objective To investigate the clinicopathological characteristics of advanced colorectal cancer which was 30 mm or smaller in diameter.Methods Retrospective analysis documented 80 patients with small advanced colorectal cancer from May 1985 to May 2002. According to the diameter of tumors, all patients were divided into three groups; Group A (10 mm or less), Group B (11-20 mm), Group C (21-30 mm). Considering the number of patients in Group A was smaller, we combined Group A with Group B as Group D. Then various clinicopathological characteristics were compared between Group C and Group D.Results The most common site of small advanced colorectal cancer was sigmoid colon and rectum that accounted for 36. 2% and 35. 0% of all cases. The average diameter of total tumors was 23. 3 mm. Type 2 was the most common macroscopic type (63. 7% ) and the moderate differentiation was seen in 77. 5% of cases. Thirty-eight (47. 5% ) cases had lymph node metastasis. Three (3. 8% ) cases had liver metastasis and three (3. 8% ) cases had peritoneal metastasis. The frequency of lymph node metastasis was found significantly different between Group C and Group D (54. 2% vs. 28. 6% , P< 0. 05), as well as between the groups with different depth of invasion (P< 0. 05). Curability A resection was performed in 69 (86. 2% ) cases.Conclusions Tumor size and depth of invasion are related to lymph node metastasis in small advanced colorectal cancer. However, the small size of tumor may not always be a reliable parameter for estimating the risk of lymph node metastasis. Small colorectal cancers also do not always mean the early stage. Surgeons should be aware of the features of small advanced colorectal cancers to select ideal management and perform perfect resection.

  11. Inflammation-based prognostic scores and nutritional prognostic index in patients with locally-advanced unresectable colorectal cancer

    OpenAIRE

    Ikeguchi, Masahide; Urushibara, Sho-ichi; Shimoda, Ryugo; Yamamoto, Manabu; MAETA, YOSHIHIKO; Ashida, Keigo

    2014-01-01

    Background Unresectable colorectal cancer has a poor prognosis. However, some patients survive intensive chemotherapy, and complete resection of primary and metastatic tumors may even be possible. In the present study, we examined the prognostic factors associated with survival after intensive chemotherapy in patients with unresectable colorectal cancer. Methods This retrospective study enrolled 61 patients diagnosed with unresectable locally advanced colorectal cancer between January 2004 an...

  12. Genomic and oncoproteomic advances in detection and treatment of colorectal cancer.

    LENUS (Irish Health Repository)

    McHugh, Seamus M

    2009-01-01

    AIMS: We will examine the latest advances in genomic and proteomic laboratory technology. Through an extensive literature review we aim to critically appraise those studies which have utilized these latest technologies and ascertain their potential to identify clinically useful biomarkers. METHODS: An extensive review of the literature was carried out in both online medical journals and through the Royal College of Surgeons in Ireland library. RESULTS: Laboratory technology has advanced in the fields of genomics and oncoproteomics. Gene expression profiling with DNA microarray technology has allowed us to begin genetic profiling of colorectal cancer tissue. The response to chemotherapy can differ amongst individual tumors. For the first time researchers have begun to isolate and identify the genes responsible. New laboratory techniques allow us to isolate proteins preferentially expressed in colorectal cancer tissue. This could potentially lead to identification of a clinically useful protein biomarker in colorectal cancer screening and treatment. CONCLUSION: If a set of discriminating genes could be used for characterization and prediction of chemotherapeutic response, an individualized tailored therapeutic regime could become the standard of care for those undergoing systemic treatment for colorectal cancer. New laboratory techniques of protein identification may eventually allow identification of a clinically useful biomarker that could be used for screening and treatment. At present however, both expression of different gene signatures and isolation of various protein peaks has been limited by study size. Independent multi-centre correlation of results with larger sample sizes is needed to allow translation into clinical practice.

  13. Genomic and oncoproteomic advances in detection and treatment of colorectal cancer.

    LENUS (Irish Health Repository)

    McHugh, Seamus M

    2012-02-01

    AIMS: We will examine the latest advances in genomic and proteomic laboratory technology. Through an extensive literature review we aim to critically appraise those studies which have utilized these latest technologies and ascertain their potential to identify clinically useful biomarkers. METHODS: An extensive review of the literature was carried out in both online medical journals and through the Royal College of Surgeons in Ireland library. RESULTS: Laboratory technology has advanced in the fields of genomics and oncoproteomics. Gene expression profiling with DNA microarray technology has allowed us to begin genetic profiling of colorectal cancer tissue. The response to chemotherapy can differ amongst individual tumors. For the first time researchers have begun to isolate and identify the genes responsible. New laboratory techniques allow us to isolate proteins preferentially expressed in colorectal cancer tissue. This could potentially lead to identification of a clinically useful protein biomarker in colorectal cancer screening and treatment. CONCLUSION: If a set of discriminating genes could be used for characterization and prediction of chemotherapeutic response, an individualized tailored therapeutic regime could become the standard of care for those undergoing systemic treatment for colorectal cancer. New laboratory techniques of protein identification may eventually allow identification of a clinically useful biomarker that could be used for screening and treatment. At present however, both expression of different gene signatures and isolation of various protein peaks has been limited by study size. Independent multi-centre correlation of results with larger sample sizes is needed to allow translation into clinical practice.

  14. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S;

    2008-01-01

    -testis antigens. Vaccines were biweekly administered intradermally with a total of 10 vaccines per patient. CT scans were performed and responses were graded according to the RECIST criteria. Quality of life was monitored with the SF-36 questionnaire. Toxicity and adverse events were graded according...... with this DC-based cancer vaccine was safe and non-toxic. Stable disease was found in 24% (4/17) of the patients. The quality of life remained for most categories high and stable throughout the study period.......Patients with disseminated colorectal cancer have a poor prognosis. Preliminary studies have shown encouraging results from vaccines based on dendritic cells. The aim of this phase II study was to evaluate the effect of treating patients with advanced colorectal cancer with a cancer vaccine based...

  15. A clinical retrospective study of the detectable ability of the advanced colorectal cancer by plain abdominal multislice CT

    International Nuclear Information System (INIS)

    We evaluated the efficacy of plain CT for diagnosis of advanced colorectal cancer retrospectively. During 2 years between December 1999 and November 2001, 26 patients with advanced colorectal cancer underwent abdominal CT scan (Toshiba ASTEIONMULTI). The patients had received no special preparation for CT scan except for avoiding breakfast. The sensitivity of CT scan in detecting tumors was 76.9%. Moreover, cancers originated in the cecum, ascending colon and descending colon were all detectable by CT. Ninety-two percent of cancers occupying more than 2/3 of circumference of the colonic wall were detectable. These evidences may indicate that plain CT is useful for detecting colorectal cancers with little patients' burden as well as providing information about their extension and metastasis, when colorectal cancer is suspected by patients' symptom. (author)

  16. Clinical study of tegafur-gimeracil-oteracil potassium capsule (s-1) and oxaliplatin combination chemotherapy in advanced colorectal cancer

    OpenAIRE

    Huaqun Liu; Yigang Wang; Guozhong Li; Wenguang Song; Ruilin Wang

    2015-01-01

    Objective: The aim of this study was to evaluate the therapeutic efficacy and toxicity of a combination of tegafur-gimeracil-oteracil potassium capsules (S-1) with oxaliplatin for treatment of advanced or recurrent colorectal cancer. Subjects and Methods: Between October 2009 and October 2011, 70 patients at our hospital with advanced or recurrent colorectal cancer were enrolled into our study and divided randomly into two groups: A treatment group (S-1 combined with oxaliplatin) and a co...

  17. Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shigetaka Shimodaira

    2015-12-01

    Full Text Available Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1 class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT assays. WT1 expression with human leukocyte antigen (HLA-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

  18. Nursing of advanced colorectal cancer patients treated with Cetuximab combined with chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Xiaoping Zhu; Chunli Wu

    2008-01-01

    Cetuximab is a new medication that has recently been approved for the treatment of advanced colorectal cancer. To date we have had tittle experience in using this targeted agent. Eleven patients in our hospital with advanced colorectal cancer were treated with cetuximab and chemotherapy. Based on the curative effect of this combination therapy, we have concluded that the following nursing practices make an important contribution to the patients' prognosis and wellbeing: to establish a good nurse-patient relationship, to increase patient understanding of the side effects, to standardize the medications, to observe and to deal with the side effects of the medications(for example skin reaction, neutropenia, and diarrhea), and to provide continuous mental health care support and education.

  19. Clinical observation of raltitrexed/bevacizumab combined with irinotecan or oxaliplation for advanced colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jianwei Yang; Wei Gao; Jinyuan Lin; Yan Meng; Shuzhen Zhang; Tong Wang

    2014-01-01

    Objective: The aim of the study was to investigate the ef icacy and safety of raltitrexed/bevacizumab in combina-tion with irinotecan or oxaliplation for advanced colorectal cancer as the second-line and second-line above treatments. Meth-ods: Fifteen cases of advanced colorectal cancer were enrol ed to receive regimens including raltitrexed/bevacizumab com-bined with irinotecan or oxaliplation. Two cases were treated with raltitrexed + bavacizumab regimen, 9 cases with raltitrexed+ bavacizumab + irinotecan regimen, and 4 cases with raltitrexed + bevacizumab + oxaliplation regimen. The doses of the drugs were as fol ows: bevacizumab 5 mg/kg ivgtt, d1; raltitrexed 2.0 mg/m2 ivgtt 15 min, d2; irinotecan 180 mg/m2 ivgtt 1 h, d2; and oxaliplatin 85 mg/m2 ivgtt 2 h, d2. Two weeks was a cycle for each regimen. Results: The ef icacy of the 15 patients could be evaluated. Two cases were in PR ,10 cases in SD, 3 cases in PD, the response rate was 13.3%, and the disease control rate was 80.0%. The median progress-free survival was 5.1 months (95% CI: 3.404-6.813 months), and the median overal survival was 11.5 months (95% CI: 8.985-13.930 months). The adverse ef ects included anorexia, nausea/vomit-ing, fatigue, leucopenia, thrombocytopenia, etc, and the main 3-4 grades adverse ef ects were anorexia, nausea/vomiting, fatigue, and thrombocytopenia. Conclusion: Raltitrexed/bevacizumab combined with irinotecan or oxaliplatin as the second-line and second-line above treatments for advanced colorectal cancer has high disease control rates, and the adverse ef ect is wel tolerated. The combined regimen can be recommended as a phase III clinical research and second-line and second-lines above treatments for advanced colorectal cancer.

  20. Efficacy and safety of oxaliplatin, bevacizumab and oral S-1 for advanced recurrent colorectal cancer

    Science.gov (United States)

    Suzuki, Shuji; Shimazaki, Jiro; Morishita, Keiichi; Koike, Nobusada; Harada, Nobuhiko; Hayashi, Tsuneo; Suzuki, Mamoru

    2016-01-01

    The aim of this study was to evaluate the efficacy and safety of co-administration of oral S-1 and oxaliplatin (SOX) in combination with bevacizumab (bev) in patients with advanced recurrent colorectal cancer. A retrospective study of 36 patients with advanced recurrent colorectal cancer was performed, of whom 27 received first-line and 9 received second-line SOX+bev chemotherapy between 2010 and 2013 at the Hachioji Digestive Disease Hospital (Hachioji, Japan). The SOX+bev regimen consisted of administration of intravenous oxaliplatin (85 mg/m2) on days 1 and 14, bevacizumab (5 mg/kg) on day 1, and co-administration of oral S-1 twice daily on days 1–14. The drug regimen was repeated every 4 weeks. SOX+bev treatment was associated with a response rate of 45.2%, a disease control rate of 71%, and a median progression-free survival (PFS) and overall survival (OS) of 9.9 and 21.9 months, respectively. Patients who received first-line chemotherapy benefited from treatment in terms of prolonged PFS (13.8 months) and OS (28.2 months). Grade 3/4 adverse events were infrequent and included anaemia, thrombocytopenia, anorexia, diarrhea, sensory neuropathy, increased aspartate aminotransferase level and skin rash. In conclusion, SOX+bev therapy was found to be feasible and safe for patients with advanced and recurrent colorectal cancer.

  1. Five Myths about Colorectal Cancer

    Science.gov (United States)

    ... ACS » Your Local Offices Close + - Text Size Five Myths About Colorectal Cancer In many cases, colorectal cancer ... screening tests you need, when you need them. Myth: Colorectal cancer is a man’s disease. Truth: Colorectal ...

  2. Overexpression of SIRT1 is a poor prognostic factor for advanced colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jiang Kewei; Lyu Liang; Shen Zhanlong; Zhang Jizhun; Zhang Hui; Dong Jianqiang; Yan Yichao

    2014-01-01

    Background Sirtuin 1 (SIRT1) has been reported to have diverse roles in various biological processes through deacetylation of histone and nonhistone proteins.However,the correlations among SIRT1 protein expression,clinicopathological parameters,and survival of colorectal cancer patients remain unclear.Methods SIRT1 protein expression was measured by immunohistochemistry in a paraffin-embedded tissue microarray,including 120 paired colorectal cancer and normal mucosa tissues.The correlations among SIRT1 protein expression,clinicopathological features,and prognosis were analyzed.Results All samples (100%) were positive for SIRT1,with variable staining in the cytoplasm rather than in the nucleus.There was significant difference in SIRT1 overexpression between adenocarcinomas and normal mucosal tissue (P<0.01,x2 test).SIRT1 overexpression was more frequently observed in advanced-stage tumors (P=0.046,0.002,x2test).SIRT1 overexpression was significantly correlated with poor overall survival (P=0.013,log-rank test) and diseasefree survival (P=0.012,log-rank test).Conclusions SIRT1 overexpression correlated with advanced stage and poor prognosis.SIRT1 may play an important role in the progression of colorectal cancer.

  3. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... certain people. Read More "6 Common Cancers" Articles Lung Cancer / Breast Cancer / Prostate Cancer / Colorectal Cancer / Skin Cancer / Gynecologic Cancers Spring 2007 Issue: Volume 2 Number 2 Page 11 MedlinePlus | Subscribe | Magazine Information | Contact Us | Viewers & ...

  4. Get Tested for Colorectal Cancer

    Science.gov (United States)

    ... Colorectal Cancer Print This Topic En español Get Tested for Colorectal Cancer Browse Sections The Basics Overview ... cancer screening tests . Does it hurt to get tested? Some people find the tests for colorectal cancer ...

  5. Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

    Science.gov (United States)

    Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

    2016-01-01

    Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced

  6. Colorectal cancer treatment in an ageing world - Technical advances, treatment decisions and multidisciplinary care

    NARCIS (Netherlands)

    Schiphorst, A.H.W.

    2015-01-01

    The incidence of colorectal cancer has risen in recent years and currently over 50% of patients are over 70 years of age. Many questions regarding the optimal management of the growing group of elderly colorectal cancer patients are still unanswered. The research presented in this thesis focuses on

  7. The association between glyceraldehyde-derived advanced glycation end-products and colorectal cancer risk

    NARCIS (Netherlands)

    Kong, So Yeon; Takeuchi, Masayoshi; Hyogo, Hideyuki; McKeown-Eyssen, Gail; Yamagishi, Sho Ichi; Chayama, Kazuaki; O'Brien, Peter J.; Ferrari, Pietro; Overvad, Kim; Olsen, Anja; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Bastide, Nadia; Carbonnel, Franck; Kühn, Tilman; Kaaks, Rudolf; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Vasilopoulou, Effie; Masala, Giovanna; Pala, Valeria; De Magistris, Maria Santucci; Tumino, Rosario; Naccarati, Alessio; Bueno-De-Mesquita, H. B.; Peeters, Petra H.; Weiderpass, Elisabete; Quiŕos, J. Ramón; Jakszyn, Paula; ͆anchez, María Jos̈e; Dorronsoro, Miren; Gavrila, Diana; Ardanaz, Eva; Rutegård, Martin; Nyström, Hanna; Wareham, Nicholas J.; Khaw, Kay Tee; Bradbury, Kathryn E.; Romieu, Isabelle; Freisling, Heinz; Stavropoulou, Faidra; Gunter, Marc J.; Cross, Amanda J.; Riboli, Elio; Jenab, Mazda; Bruce, W. Robert

    2015-01-01

    Background: A large proportion of colorectal cancers are thought to be associated with unhealthy dietary and lifestyle exposures, particularly energy excess, obesity, hyperinsulinemia, and hyperglycemia. It has been suggested that these processes stimulate the production of toxic reactive carbonyls

  8. Consideration of therapeutic approach to advanced colorectal cancer in elderly patients

    Directory of Open Access Journals (Sweden)

    Yasuhiro Inoue

    2014-02-01

    Full Text Available Colorectal cancer (CRC is predominantly a disease of elderly and is a major cause of morbidity and mortality in the elderly population. The increased availability of treatment options for CRC has made it more difficult for clinicians to decide on the optimal therapeutic approach in elderly patients, because of the potential for poorer outcomes due to an increased burden of comorbidities, functional dependency, and limited life expectancy. It is necessary to determine which elderly patients are likely to benefit from active cancer therapy, and the establishment of treatment markers for multimodality approaches is eagerly awaited. Elderly cancer patients are at risk of exposure to various intrinsic inflammatory mediators, such as tumor-generating cytokines and surgery-induced pro-inflammatory cytokines. It is therefore important to understand the immunological changes occurring in the elderly and to adjust treatment strategies accordingly to reduce the morbidity and mortality associated with multimodality therapy for CRC that induce systemic inflammation. Several inflammation-based factors such as the Glasgow Prognostic Score (GPS may reflect the balance between tumor progression and host-related immunity, especially in elderly CRC patients. Appropriate selection criteria for multimodality therapy in elderly CRC patients may include not only tumor characteristics, but also host- and/or treatment-related factors such as comorbidities or surrogate markers using inflammation-based factors.----------------------------------------------Cite this article as: Inoue Y, Toiyama Y, Tanaka K, Mohri Y, Kusunoki M. Consideration of therapeutic approach to advanced colorectal cancer in elderly patients. Int J Cancer Ther Oncol 2014; 2(1:02014.DOI: http://dx.doi.org/10.14319/ijcto.0201.4

  9. Advances in targeted and immunobased therapies for colorectal cancer in the genomic era

    Directory of Open Access Journals (Sweden)

    Seow HF

    2016-03-01

    Full Text Available Heng Fong Seow,1 Wai Kien Yip,1 Theodora Fifis2 1Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Surgery, University of Melbourne, Melbourne, Australia Abstract: Targeted therapies require information on specific defective signaling pathways or mutations. Advances in genomic technologies and cell biology have led to identification of new therapeutic targets associated with signal-transduction pathways. Survival times of patients with colorectal cancer (CRC can be extended with combinations of conventional cytotoxic agents and targeted therapies. Targeting EGFR- and VEGFR-signaling systems has been the major focus for treatment of metastatic CRC. However, there are still limitations in their clinical application, and new and better drug combinations are needed. This review provides information on EGFR and VEGF inhibitors, new therapeutic agents in the pipeline targeting EGFR and VEGFR pathways, and those targeting other signal-transduction pathways, such as MET, IGF1R, MEK, PI3K, Wnt, Notch, Hedgehog, and death-receptor signaling pathways for treatment of metastatic CRC. Additionally, multitargeted approaches in combination therapies targeting negative-feedback loops, compensatory networks, and cross talk between pathways are highlighted. Then, immunobased strategies to enhance antitumor immunity using specific monoclonal antibodies, such as the immune-checkpoint inhibitors anti-CTLA4 and anti-PD1, as well as the challenges that need to be overcome for increased efficacy of targeted therapies, including drug resistance, predictive markers of response, tumor subtypes, and cancer stem cells, are covered. The review concludes with a brief insight into the applications of next-generation sequencing, expression profiling for tumor subtyping, and the exciting progress made in in silico predictive analysis in the development of a prescription strategy for

  10. Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Markus Moehler; Martin F Sprinzl; Murad Abdelfattah; Carl C Schimanski; Bernd Adami; Werner Godderz; Klaus Majer; Dimitri Flieger; Andreas Teufel; Juergen Siebler; Thomas Hoehler; Peter R Galle; Stephan Kanzler

    2009-01-01

    AIM: To investigate the efficacy and safety of capecitabine plus irinotecan ± bevacizumab in advanced or metastatic colorectal cancer patients.METHODS: Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer (mCRC) were recruited between 2001-2006 in a prospective open-label phase Ⅱ trial, in German community-based outpatient clinics. Patients received a standard capecitabine plus irinotecan (CAPIRI) or CAPIRI plus bevacizumab (CAPIRI-BEV) regimen every 3 wk.Dose reductions were mandatory from the first cycle in cases of > grade 2 toxicity. The treatment choice of bevacizumab was at the discretion of the physician. The primary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival.RESULTS: In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients (47%vs 24%), and more patients had colon as the primary tumor site (58.8% vs 48.2%) with fewer patients having sigmoid colon as primary tumor site (5.9% vs20.7%). Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev: 82% vs 58.6%. Partial response rates were 29.4% and 34.5%, and tumor control rates were 70.6% and 75.9%, respectively. No complete responses were observed. The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev, respectively. The median overall survival for CAPIRI was 15 mo (458 d) and for CAPIRI-Bev 24 mo (733 d). These differences were not statistically different.In the CAPIRI-Bev, group, two patients underwenta full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure.CONCLUSION: Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting. Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.

  11. Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

    International Nuclear Information System (INIS)

    Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index. Conventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods. Fascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009), but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas. Fascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with shorter survival in stage III and IV patients. Fascin may have

  12. Screening for colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans J.; Jakobsen, Karen V.; Christensen, Ib J.;

    2011-01-01

    Emerging results indicate that screening improves survival of patients with colorectal cancer. Therefore, screening programs are already implemented or are being considered for implementation in Asia, Europe and North America. At present, a great variety of screening methods are available including...... into improvements of screening for colorectal cancer includes blood-based biological markers, such as proteins, DNA and RNA in combination with various demographically and clinically parameters into a "risk assessment evaluation" (RAE) test. It is assumed that such a test may lead to higher acceptance among...... procedures for colorectal cancer. Therefore, results of present research, validating RAE tests, are awaited with interest....

  13. Colorectal cancers choosing sides

    NARCIS (Netherlands)

    Albuquerque, Cristina; Bakker, Elvira R. M.; van Veelen, Wendy; Smits, Ron

    2011-01-01

    In contrast to the majority of sporadic colorectal cancer which predominantly occur in the distal colon, most mismatch repair deficient tumours arise at the proximal side. At present, these regional preferences have not been explained properly. Recently, we have screened colorectal tumours for mutat

  14. Epidemiology of colorectal cancer

    Science.gov (United States)

    Marley, Andrew R; Nan, Hongmei

    2016-01-01

    Colorectal cancer is currently the third deadliest cancer in the United States and will claim an estimated 49,190 U.S. lives in 2016. The purpose of this review is to summarize our current understanding of this disease, based on nationally published statistics and information presented in peer-reviewed journal articles. Specifically, this review will cover the following topics: descriptive epidemiology (including time and disease trends both in the United States and abroad), risk factors (environmental, genetic, and gene-environment interactions), screening, prevention and control, and treatment. Landmark discoveries in colorectal cancer risk factor research will also be presented. Based on the information reviewed for this report, we suggest that future U.S. public health efforts aim to increase colorectal cancer screening among African American communities, and that future worldwide colorectal cancer epidemiology studies should focus on researching nutrient-gene interactions towards the goal of improving personalized treatment and prevention strategies.

  15. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context....

  16. Gallstones and colorectal cancer

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Rafaelsen, Søren Rafael

    1992-01-01

    The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1.......59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give...... substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship....

  17. Developments in Colorectal Cancer Screening

    Science.gov (United States)

    ... on. Feature: Colorectal Cancer Developments in Colorectal Cancer Screening Summer 2016 Table of Contents Dr. Asad Umar, ... know to help determine the best colon cancer screening test for them? Colonoscopy is considered the gold ...

  18. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    in the liver metastases. In addition, we prospectively compared contrast-enhanced ultrasound with CT scan in the detection of liver metastases.Results By transrectal ultrasound of polyps using the new AWS technique, a sensitivity of 96% and a specificity of 88% was found for cancer, whereas digital exploration...... to neoadjuvant chemoradiation of advanced rectal cancer.IOUS is a safe method with a significantly higher sensitivity in the detection of liver metastases than preoperative ultrasound and surgical palpation. Patients with liver metastases, which harboured power Doppler signal centrally, more often had advanced...... of rectal cancer, especially in early tumours. Screening for colorectal cancer will give rise to the detection of a number of early tumours. Contrast-enhanced liver ultrasound and intraoperative ultrasound has additional space in the detection of liver metastases from colorectal cancer....

  19. Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Yuwei Wang

    2014-01-01

    Full Text Available Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP. CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS and overall survival (OS were analyzed using Kaplan-Meier method (log-rank test and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50 of patients were characterized as CIMP positive. Univariate analysis showed stage III (P=0.049 and CIMP positive (P=0.014 patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P=0.019. In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P=0.023. Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy.

  20. Hereditary colorectal cancer diagnostics

    DEFF Research Database (Denmark)

    Klarskov, Louise; Holck, Susanne; Bernstein, Inge;

    2012-01-01

    BackgroundThe hereditary non-polyposis colorectal cancer (HNPCC) subset of tumours can broadly be divided into tumours caused by an underlying mismatch-repair gene mutation, referred to as Lynch syndrome, and those that develop in families with similar patterns of heredity but without disease......-predisposing germline mismatch repair mutations, referred to as familial colorectal cancer type X (FCCTX). Recognition of HNPCC-associated colorectal cancers is central since surveillance programmes effectively reduce morbidity and mortality. The characteristic morphological features linked to Lynch syndrome can aid...... in the identification of this subset, whereas the possibility to use morphological features as an indicator of FCCTX is uncertain.Objective and methodsTo perform a detailed morphological evaluation of HNPCC-associated colorectal cancers and demonstrate significant differences between tumours associated with FCCTX...

  1. Screening for colorectal cancer.

    Science.gov (United States)

    He, Jin; Efron, Jonathan E

    2011-01-01

    March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test. PMID:21954677

  2. Distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer.

    Science.gov (United States)

    Marchoudi, N; Amrani Hassani Joutei, H; Jouali, F; Fekkak, J; Rhaissi, H

    2013-12-01

    Targeted therapies have an increasing importance in digestive oncology. To our knowledge, we are the first to report the distribution of KRAS and BRAF mutations in Moroccan patients with advanced colorectal cancer (CRC) in order to introduce targeted therapy in the arsenal of therapeutic modalities for management of this cancer in Morocco. In this study, 92 samples obtained from patients with CRC were tested for the presence of the nine most common mutations in the KRAS gene and BRAF gene. Among the tested patients, 76.09% of patients had wt-KRAS genotype and 23.91% were KRAS mutants and the majority of mutations would result in an amino acid substitution of glycine by aspartic acid (68.2%) The predominant mutations are G>A transitions and G>T transversions. Around 5% (5.43%) of the tested patients bore the V600E mutation in BRAF gene. Only one patient showing to have the V600E mutation in BRAF was also mutated-KRAS. Summing up the results about the KRAS and the BRAF mutation carriers from our study, the portion of potentially non responsive patients for the anti-EGFR treatment is 28.26%.

  3. Clinical study of tegafur-gimeracil-oteracil potassium capsule (s-1 and oxaliplatin combination chemotherapy in advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Huaqun Liu

    2015-01-01

    Full Text Available Objective: The aim of this study was to evaluate the therapeutic efficacy and toxicity of a combination of tegafur-gimeracil-oteracil potassium capsules (S-1 with oxaliplatin for treatment of advanced or recurrent colorectal cancer. Subjects and Methods: Between October 2009 and October 2011, 70 patients at our hospital with advanced or recurrent colorectal cancer were enrolled into our study and divided randomly into two groups: A treatment group (S-1 combined with oxaliplatin and a control group (Xeloda combined with oxaliplatin. All patients received 130 mg/m 2 oxaliplatin by intravenous infusion on day 1, every three weeks. Patients in the treatment group were treated with oral administration of 30-40 mg/m 2 S-1 twice daily for 14 days. Patients in the control group were treated with oral administration of 1000 mg/m 2 Xeloda twice daily for 14 days. The efficacy and toxicity of the combination therapy were evaluated after two cycles of treatment. Results: The response rates in the treatment and control groups were 54.3% and 42.9%, respectively. The disease control rates of the two groups were 80.0% and 74.3%, respectively. The 1-year and 2-year survival rates were 73.6% and 39.1% in the treatment group, respectively, compared to 73.8% and 37.8% in the control group. No statistical difference between the two groups for any of the parameters, including toxicity, was observed (P > 0.05. Conclusion: The efficacy of the S-1 and oxaliplatin combination regimen in advanced or recurrent colorectal cancer treatment is not inferior to the combination of Xeloda and oxaliplatin and does not result in additional toxicity. Therefore, S-1 could be used to substitute Xeloda in combined chemotherapy with oxaliplatin for the treatment of advanced or recurrent colorectal cancer.

  4. Evolving management of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Jochem van der Voort van Zijp; Harald J Hoekstra; Marc D Basson

    2008-01-01

    This article reviews recent advances in surgical techniques and adjuvant therapies for colorectal cancer, including total mesorectal excision, the resection of liver and lung metastasis and advances in chemoradiation and foreshadows some interventions that may lie just beyond the frontier. In particular, little is known about the intracellular and extracellular cascades that may influence colorectal cancer cell adhesion and metastasis. Although the phosphorylation of focal adhesion kinases and focal adhesion associated proteins in response to integrin-mediated cell matrix binding ("outside in integrin signaling") is well described, the stimulation of cell adhesion by intracellular signals activated by pressure prior to adhesion represents a different signal paradigm. However, several studies have suggested that increased pressure and shear stress activate cancer cell adhesion. Further studies of the pathways that regulate integrin-driven cancer cell adhesion may identify/ways to disrupt these signals or block integrin-mediated adhesion so that adhesion and eventual metastasis can be prevented in the future.

  5. Capecitabine and bevacizumab in heavily pre-treated patients with advanced colorectal cancer

    DEFF Research Database (Denmark)

    Larsen, Finn Ole; Boisen, Mogens Karsbøl; Fromm, Anne-Lene Gunge;

    2012-01-01

    No standard treatment exists for patients with metastatic colorectal cancer who have progressed after treatment with 5-fluorouracil (5-FU), oxaliplatin, irinotecan and an anti-EGFR antibody. The efficacy and safety of bevacizumab and capecitabine in heavily pre-treated patients with metastatic...

  6. Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    I. Grivicich

    2001-09-01

    Full Text Available Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.

  7. Prophylaxis against colorectal cancer

    DEFF Research Database (Denmark)

    Bülow, Steffen; Kronborg, O

    1996-01-01

    Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing with a w...... for colorectal cancer in average-risk persons as well as high-risk groups with precursors of the disease. The present review places Danish contributions within the prophylaxis of colorectal cancer during the last decade in an international context.......Colorectal cancer is diagnosed in more than 3000 people every year in Denmark, with a population of 5 million, and 2000 die from this disease every year. The aetiology of the disease is complex, but an increasing number of cancers have been related to genetics and Denmark is contributing...... with a well-established register of familial adenomatous polyposis and a recently founded register for hereditary nonpolyposis colorectal cancer, both with major international relationships. The Danish tradition of epidemiology and clinical trials has also been demonstrated in population screening trials...

  8. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  9. Mouse models of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yunguang Tong; Wancai Yang; H. Phillip Koeffler

    2011-01-01

    Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer.

  10. Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.

    NARCIS (Netherlands)

    Koopman, M.; Antonini, N.; Douma, J.; Wals, J.; Honkoop, A.H.; Erdkamp, F.L.; Jong, R.S. de; Rodenburg, C.J.; Vreugdenhil, G.R.; Akkermans-Vogelaar, J.M.; Punt, C.J.A.

    2006-01-01

    BACKGROUND: Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with

  11. Colorectal Cancer Risk Assessment Tool

    Science.gov (United States)

    ... know before using this tool: The Colorectal Cancer Risk Assessment Tool was designed for use by doctors and other health providers with their patients. If you are not a health ... your personal risk of colorectal cancer. (Colorectal cancer is another way ...

  12. Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer – a phase II study

    Directory of Open Access Journals (Sweden)

    Savage Paul

    2002-05-01

    Full Text Available Abstract Background 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate – leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. Methods Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate – 30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV – 500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil – 600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression. Results The median age was 64 yrs (34–84 and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. Conclusions This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin are in progress and may prove encouraging.

  13. Colorectal cancer screening

    Institute of Scientific and Technical Information of China (English)

    Ramona M McLoughlin; Colm A O'Morain

    2006-01-01

    Colorectal cancer is a major public health burden worldwide.There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use.Most evidence points towards screening with fecal occult blood testing.The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests.In addition,their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can be accommodated within individual health care systems.

  14. Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.

    Science.gov (United States)

    Nio, Kenta; Higashi, Daijiro; Kumagai, Hozumi; Arita, Shuji; Shirakawa, Tsuyoshi; Nakashima, Koji; Shibata, Yoshihiro; Esaki, Motohiro; Manabe, Tatsuya; Nagai, Shuntaro; Ueki, Takashi; Nakano, Michitaka; Ariyama, Hiroshi; Kusaba, Hitoshi; Hirahashi, Minako; Oda, Yoshinao; Esaki, Taito; Mitsugi, Kenji; Futami, Kitaro; Akashi, Koichi; Baba, Eishi

    2016-06-01

    Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n=16), the left colon (n=9), or the right colon (n=4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n=6), FOLFOX+bevacizumab (n=3), and others (n=4). Adjuvant chemotherapy regimens were S-1 (n=7), oxaliplatin-based (n=4) and others (n=5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (Pchemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis.

  15. [Maintenance therapy for colorectal cancer].

    Science.gov (United States)

    Yamaguchi, Shigeo; Kato, Shunsuke

    2014-08-01

    Some trials have demonstrated the benefits of maintenance chemotherapy for advanced colorectal cancer. In chemotherapeutic strategies for advanced colorectal cancer, chemotherapy-related toxicity prevention and quality of life(QOL)maintenance are more important than the introduction of a strong regimen, especially when additional surgery is not possible. In Japan, the combination of a folinic acid/5-fluorouracil/oxaliplatin(FOLFOX)regimen and bevacizumab is a popular first-line chemotherapy regimen. However, despite its effectiveness, neuropathy or hand-foot syndrome after 5 or 6 cycles tends to lead to chemotherapy withdrawal. CAIRO3 trial reported the effectiveness of capecitabine and bevacizumab as a maintenance chemotherapy regimen. Additionally, the ML18147 trial demonstrated that bevacizumab beyond progression(BBP)prolonged overall survival(OS)and progression free survival(PFS)in patients with advanced colorectal cancer. Although those trials demonstrated the effectiveness of continuous or maintenance bevacizumab administration, no trials have compared the effectiveness of cytotoxic drugs with bevacizumab as maintenance therapies. Moreover, controversy exists regarding the selection of drugs as a maintenance therapy and the identification of patients who would benefit from maintenance therapy. PMID:25132024

  16. 晚期结直肠癌的治疗策略%Treatment strategy for advanced colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    刘德宝; 徐忠法; 范开席

    2016-01-01

    At present,the main treatment methods of the patients with advanced colorectal cancer include surgery,chemotherapy,radiotherapy,targeted therapy,physical ablation and immunotherapy,but the chemotherapy is still the main treatment.The emergence of new chemotherapy drugs and the combination of radiotherapy,chemotherapy and targeted therapy in clinical have improved curative effect for the patients with advanced colorectal cancer.In order to better improve the quality of life,reduce side effects and obtain the best effect,now the individual multidisciplinary treatment has become an inevitable trend in the treatment of advanced colorectal cancer in clinical.%目前临床上晚期结直肠癌的主要治疗方法有手术、化疗、放疗、靶向治疗、物理消融治疗以及免疫治疗,但化疗仍为主要的治疗方法.新的化疗药物的出现以及临床上放化疗与靶向治疗的结合提高了晚期结直肠癌的疗效.为更好地提高患者的生命质量,减少不良反应的发生,获得最优的疗效,目前临床上个体化的多学科综合治疗已成为晚期结直肠癌治疗的必然趋势.

  17. Colorectal Cancer Screening

    Science.gov (United States)

    ... laxatives to clear the colon, shows polyps clearly. DNA stool test This test checks DNA in stool cells for genetic changes that may be a sign of colorectal cancer. Screening clinical trials are taking place in many parts of the ... Screening tests have risks. False-negative test results can occur. ...

  18. Pharmacogenetic profiling and cetuximab outcome in patients with advanced colorectal cancer

    Directory of Open Access Journals (Sweden)

    Dahan Laetitia

    2011-11-01

    Full Text Available Abstract Background We analyzed the influence of 8 germinal polymorphisms of candidate genes potentially related to EGFR signalling (EGFR, EGF, CCND1 or antibody-directed cell cytotoxicity (FCGR2A and FCGR3A on outcome of colorectal cancer (CRC patients receiving cetuximab-based therapy. Methods Fifty-eight advanced CRC patients treated with cetuximab-irinotecan salvage therapy between 2001 and 2007 were analyzed (mean age 60; 50 PS 0-1. The following polymorphisms were analyzed on blood DNA: EGFR (CA repeats in intron 1, -216 G > T, -191C > A, R497K, EGF (A61G, CCND1 (A870G, FCGR2A (R131H, FCGR3A (F158V. Statistical analyses were conducted on the total population and on patients with wt KRas tumors. All SNPs were considered as ternary variables (wt/wt vs wt/mut vs mut/mut, with the exception of -191C > A EGFR polymorphism (AA patient merged with CA patients. Results Analysis of skin toxicity as a function of EGFR intron 1 polymorphism showed a tendency for higher toxicity in patients with a low number of CA-repeats (p = 0.058. CCND1 A870G polymorphism was significantly related to clinical response, both in the entire population and in KRas wt patients, with the G allele being associated with a lack of response. In wt KRas patients, time to progression (TTP was significantly related to EGFR -191C > A polymorphism with a longer TTP in CC patients as compared to others, and to CCND1 A870G polymorphism with the G allele being associated with a shorter TTP; a multivariate analysis including these two polymorphisms only retained CCND1 polymorphism. Overall survival was significantly related to CCND1 polymorphism with a shorter survival in patients bearing the G allele, and to FCGR3A F158V polymorphism with a shorter survival in VV patients (in the entire population and in KRas wt patients. FCGR3A F158V and CCND1 A870G polymorphisms were significant independent predictors of overall survival. Conclusions Present original data obtained in wt KRas

  19. Epigenetic changes in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yan Jia; Mingzhou Guo

    2013-01-01

    Epigenetic changes frequently occur in human colorectal cancer.Genomic global hypomethylation,gene promoter region hypermethylation,histone modifications,and alteration of miRNA patterns are major epigenetic changes in colorectal cancer.Loss of imprinting (LOI) is associated with colorectal neoplasia.Folate deficiency may cause colorectal carcinogenesis by inducing gene-specific hypermethylation and genomic global hypomethylation.HDAC inhibitors and demethylating agents have been approved by the FDA for myelodysplastic syndrome and leukemia treatment.Non-coding RNA is regarded as another kind of epigenetic marker in colorectal cancer.This review is mainly focused on DNA methylation,histone modification,and microRNA changes in colorectal cancer.

  20. Integrated analysis of overall survival in two randomised studies comparing 5-fluorouracil/leucovorin with or without trimetrexate in advanced colorectal cancer

    NARCIS (Netherlands)

    Punt, CJA; Blanke, CD; Zhang, J; Hammershaimb, L

    2002-01-01

    Background: Two randomised studies were performed with trimetrexate (TMTX) as a biochemical modulator of 5-fluorouracil (5-FU)/leucovorin (LV) in advanced colorectal cancer (ACC), one in Europe and one in the United States. Both studies were similarly designed to detect a statistically significant d

  1. TUMOR-LOCALIZATION WITH I-131-LABELED HUMAN-IGM MONOCLONAL-ANTIBODY 16.88 IN ADVANCED COLORECTAL-CANCER PATIENTS

    NARCIS (Netherlands)

    BOVEN, E; Haisma, Hidde; BRIL, H; MARTENS, HJM; VANLINGEN, A; DENHOLLANDER, W; KESSEL, MAP; DEJAGER, RL; ROOS, JC

    1991-01-01

    Human IgM monoclonal antibody 16.88 recognised an intracellular antigen strongly expressed in colorectal cancer tissue in 51% of our patients. Tumour localisation was carried out with 185 MBq I-131-16.88 (8 mg) in 20 of these patients with advanced disease. In 16 patients (80%) immunoscintigraphy wa

  2. Hedgehog Wnteraction in colorectal cancer

    OpenAIRE

    Brink, G.R. van den; Hardwick, J C H

    2006-01-01

    The Hedgehog pathway was recently shown to antagonise constitutive activity of the Wnt pathway that drives proliferation of colorectal cancer cells. Studies in this issue of Gut refine our understanding of the underlying mechanism and provide evidence for such antagonism in colorectal cancers in vivo

  3. Hedgehog Wnteraction in colorectal cancer

    NARCIS (Netherlands)

    G.R. van den Brink; J.C.H. Hardwick

    2006-01-01

    The Hedgehog pathway was recently shown to antagonise constitutive activity of the Wnt pathway that drives proliferation of colorectal cancer cells. Studies in this issue of Gut refine our understanding of the underlying mechanism and provide evidence for such antagonism in colorectal cancers in viv

  4. Colorectal Cancer Biomarkers: Where Are We Now?

    Directory of Open Access Journals (Sweden)

    Maria Gonzalez-Pons

    2015-01-01

    Full Text Available Colorectal cancer is one of the major causes of cancer-related death in the Western world. Patient survival is highly dependent on the tumor stage at the time of diagnosis. Reduced sensitivity to chemotherapy is still a major obstacle in effective treatment of advanced disease. Due to the fact that colorectal cancer is mostly asymptomatic until it progresses to advanced stages, the implementation of screening programs aimed at early detection is essential to reduce incidence and mortality rates. Current screening and diagnostic methods range from semi-invasive procedures such as colonoscopy to noninvasive stool-based tests. The combination of the absence of symptoms, the semi-invasive nature of currently used methods, and the suboptimal accuracy of fecal blood tests results in colorectal cancer diagnosis at advanced stages in a significant number of individuals. Alterations in gene expression leading to colorectal carcinogenesis are reflected in dysregulated levels of nucleic acids and proteins, which can be used for the development of novel, minimally invasive molecular biomarkers. The purpose of this review is to discuss the commercially available colorectal cancer molecular diagnostic methods as well as to highlight some of the new candidate predictive and prognostic molecular markers for tumor, stool, and blood samples.

  5. A Phase I Study of EKB-569 in Combination with Capecitabine in Patients with Advanced Colorectal Cancer

    Science.gov (United States)

    Laheru, Dan; Croghan, Gary; Bukowski, Ronald; Rudek, Michelle; Messersmith, Wells; Erlichman, Charles; Pelley, Robert; Jimeno, Antonio; Donehower, Ross; Boni, Joseph; Abbas, Richat; Martins, Patricia; Zacharchuk, Charles; Hidalgo, Manuel

    2011-01-01

    Purpose To determine the maximum tolerated dose (MTD), characterize the principal toxicities, and assess the pharmacokinetics of EKB-569, an oral selective irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with capecitabine in patients with advanced colorectal cancer. Experimental Design Patients were treated with EKB-569 daily for 21days and capecitabine twice daily for14 days of a 21-day cycle. The dose levels of EKB-569 (mg/day) and capecitabine (mg/m2 twice daily) assessed were 25/750, 50/750, 50/1,000 and 75/1,000. An expanded cohort was enrolled at the MTD to better study toxicity and efficacy. Samples of plasma were collected to characterize the pharmacokinetics of the agents. Treatment efficacy was assessed every other cycle. Results A total of 37 patients, the majority of whom had prior chemotherapy, received a total of 163 cycles of treatment. Twenty patients were treated at the MTD, 50 mg EKB-569, daily and 1,000 mg/m2 capecitabine twice daily. Dose-limiting toxicities were diarrhea and rash. No patients had complete or partial responses but 48% had stable disease. The conversion of capecitabine to 5-fluorouracil was higher for the combination of EKB-569 and capecitabine (321 ± 151 ng*h/mL) than for capecitabine alone (176 ± 62 ng*hours/mL; P = 0.0037). Conclusion In advanced colorectal cancer, 50 mg EKB-569 daily can be safely combined with 1,000 mg/m2 capecitabine twice a day. A statistically significant increase in plasma levels of 5-fluorouracil for the combination of EKB-569 and capecitabine may be due to the single-dose versus multiple-dose exposure difference, variability in exposure or a potential drug interaction. PMID:18765554

  6. Colorectal cancer and diet in Scotland

    OpenAIRE

    Theodoratou, Evropi

    2008-01-01

    Introduction Colorectal cancer is a cancer that forms in the tissues of the colon and/ or rectum and more than 95% of colorectal cancers are adenocarcinomas. It is the third most common cancer in incidence and mortality rates, accounting for 9% of all cancer cases and for 8% of all cancer related deaths (2002). The established risk factors of colorectal cancer include personal or family history of previous colorectal cancer or adenomatous polyps, chronic bowel inflammatory d...

  7. Diagnostics and Epidemiology of Colorectal Cancer.

    Science.gov (United States)

    Kolligs, Frank T

    2016-06-01

    Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality. Main risk factors include advanced age, family history, male sex, and lifestyle factors. Screening can reduce incidence and death from colorectal cancer. Therefore, prevention and early detection are crucial in order to detect and remove pre-neoplastic adenomas and to detect cancers at early stages. Colonoscopy, flexible sigmoidoscopy, and fecal occult blood tests are established tools for screening. Newer fecal immunochemical tests reveal higher sensitivities for advanced adenoma and cancer than guaiac-based hemoccult tests. Molecular stool and blood tests as well as virtual colonoscopy and colon capsule endoscopy are promising new developments so far not established as routine instruments for the prevention and early detection of colorectal cancer. Colonoscopy is the method of choice for the diagnosis of colorectal cancer and for adenoma removal. Prognosis is essentially dependent on the tumor stage at the time of the initial diagnosis. Proper staging based on imaging prior to therapy is a prerequisite. In rectal cancer, local staging is an essential requirement for the identification of appropriate candidates for neoadjuvant therapy. PMID:27493942

  8. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama

    2015-01-01

    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  9. THE NECESSITY OF ADVANCED RAS-MUTATIONS INVESTIGATION FOR COLORECTAL CANCER TREATMENT

    Directory of Open Access Journals (Sweden)

    V. A. Gorbunova

    2014-01-01

    Full Text Available Retrospective analysis of 3 randomized clinical trials of WT-KRAS metastatic colorectal cancer patients (PRIME, PEAK, FIRE-3 is presented. The PRIME study demonstrated increase in median overall survival (OS in group receiving panitumumab in addition to FOLFOX4 chemotherapy – 26.0 vs 20.2 months (р = 0.04. The РЕАК trial compared FOLFOX4 + panitumumab and FOLFOX4 + bevacizumab in the same patient group in first-line treatment, a significant increase in median PFS (13.1 vs 9.5 months, p = 0.03 and non-significant increase in median OS (41.3 vs 28.9 months, p = 0.058 was achieved. The FIRE trial demonstrated FOLFIRI + cetuximab superiority when compared to FOLFIRI + bevacizumab in median OS 33.1 vs 25.6 months (р = 0.011. All trials retrospectively analyzed additional RAS mutations, allowing to select a subgroup of patients, who benefit most from EGFR inhibition.

  10. Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.

    Science.gov (United States)

    Duffour, J; Gourgou, S; Seitz, J F; Senesse, P; Boutet, O; Castera, D; Kramar, A; Ychou, M

    2002-01-01

    This study assessed the efficacy of combined prophylactic and curative anti-diarrhoeal medication in advanced colorectal patients treated by irinotecan. Thirty-four pre-treated eligible patients were evaluated. There were 44% women, the median age was 65 and 38% of the patients had a 0 performance status. The patients received sucralfate(4g/d) and nifuroxazide(600 mg/d) prophylactic treatment on days 0-7. In the case of severe diarrhoea, preventive treatment was replaced by loperamide(12 mg/d) and diosmectite (9 g/d). Grade 3 delayed diarrhoea occurred in 18% of patients (90% CI: [9.5-28.9]) and 4.6% of cycles. No grade 4 delayed diarrhoea was observed. Twenty-nine patients (85%) received the preventive treatment at cycle 1, while 14% (90% CI: [6.2-25.7]) experienced grade 3 delayed diarrhoea in 3.7% of cycles for a median 4.5 days. The objective response rate was 8% (90% CI [1.4-23.1]) among the 25 assessable patients. Preventive combined treatment is effective in reducing the incidence of severe delayed diarrhoea, and it should be proposed to patients treated with mono-therapy Campto(r) and evaluated in poly-chemotherapy protocols. PMID:12552984

  11. Obesity and colorectal cancer risk

    International Nuclear Information System (INIS)

    Obesity is a chronic and multifactor disease characterized by presence of excess body fat harmful for health. Several studies have been conducted to assess the possible risk character of different factors for colorectal cancer including the following modifying factors: a diet rich in saturated fats, a diet low in vegetables, physical inactivity, alcohol consumption and obesity. A case-control study was conducted to include 276 adult patients (93 cases and 184 controls) consecutively seen from May, 2008 to May, 2009 in the Institute of Gastroenterology determining a possible association between obesity as risk factor and colorectal cancer. Variables measures included: sex, age, skin color, body mass index, hip-waist circumference and endoscopic location of cancer. We conclude that the colorectal cancer with predominance in female sex and in white people in both groups. Obesity according to a great relation hip-waist had an strong relation with colorectal cancer, which had predominance towards distal colon in both sexes

  12. Targeted nanoparticles for colorectal cancer

    DEFF Research Database (Denmark)

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il;

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...... take advantage of differentially expressed molecules on the surface of tumor cells, providing effective release of cytotoxic drugs. Several efforts have recently reported the use of diverse molecules as ligands on the surface of nanoparticles to interact with the tumor cells, enabling the effective...... delivery of antitumor agents. Here, we present recent advances in targeted nanoparticles against CRC and discuss the promising use of ligands and cellular targets in potential strategies for the treatment of CRCs....

  13. Serum IGF1, IGF2, and IGFBP3 and risk of advanced colorectal adenoma

    OpenAIRE

    GAO, YING; Katki, Hormuzd; Graubard, Barry; Pollak, Michael; Martin, Michael; Tao, Yuzhen; Schoen, Robert E.; Church, Timothy; Hayes, Richard B; Greene, Mark H.; Berndt, Sonja I

    2011-01-01

    The insulin-like growth factor (IGF) signaling pathway is involved in cell proliferation and differentiation. Elevated serum IGF1 levels have been associated with increased colorectal cancer risk; however, studies of this association with colorectal adenoma are inconclusive. We examined serum IGF1, IGF2, and IGFBP3 levels in relation to risk of advanced colorectal adenoma in a case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. A total of 764 advanced...

  14. Immune-modulating effects of the newest cetuximab-based chemoimmunotherapy regimen in advanced colorectal cancer patients.

    Science.gov (United States)

    Botta, Cirino; Bestoso, Elena; Apollinari, Serena; Cusi, Maria Grazia; Pastina, Pierpaolo; Abbruzzese, Alberto; Sperlongano, Pasquale; Misso, Gabriella; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Correale, Pierpaolo

    2012-06-01

    Cetuximab is a human-murine chimeric monoclonal antibody to the epidermal growth factor receptor, active for advanced colorectal cancer treatment in combination with chemotherapy. Cetuximab mainly acts by inhibiting epidermal growth factor receptor-mediated pathways in cancer cells; however, in the human host, its IgG1 backbone may offer additional antitumor activity that includes FcγRs-mediated antibody-dependent cell cytotoxicity, phagocytosis, cross priming, and tumor-specific T-cell-mediated immune response. These mechanisms are still under active investigation. At this purpose, we have performed an immunologic investigation in advanced colon cancer patients enrolled in an ongoing phase II trial aimed to test the toxicity and the biological and antitumor activity of a novel biochemotherapy regimen combining polychemotherapy with gemcitabine, irinotecan, levofolinic acid, and fluorouracil with cetuximab and with subcutaneous low-dose metronomic aldesleukin (GILFICet regimen). The peripheral blood mononuclear cells of the first 20 patients enrolled in the GILFICet trial were collected at baseline and after 6 treatment cycles and examined for immune-phenotype change by flow cytometry. Colon cancer-specific T-cell lines were also generated ex vivo from these samples and subsequently characterized for immune phenotype, functional activity, and antigen specificity. We found a treatment-related increase of circulating dendritic cells, natural killer cells, central memory T cells, and activated T cells with a T-helper 1 (Th1)-cytotoxic phenotype. In addition, the ex-vivo characterization of antigen-specific T cells derived from the treated patients revealed a significant increase in proliferating cytotoxic T-lymphocyte precursors specific for carcinoembryonic antigen and thymidylate synthase derivative epitope peptides. On these basis, we concluded that the GILFICet regimen exerts substantial immune-modulating activity that significantly affects tumor antigen

  15. Mini-invasive surgery for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Wei-Gen Zeng; Zhi-Xiang Zhou

    2014-01-01

    Laparoscopic techniques have been extensively used for the surgical management of colorectal cancer during the last two decades. Accumulating data have demonstrated that laparoscopic colectomy is associated with better short-term outcomes and equivalent oncologic outcomes when compared with open surgery. However, some controversies regarding the oncologic quality of mini-invasive surgery for rectal cancer exist. Meanwhile, some progresses in colorectal surgery, such as robotic technology, single-incision laparoscopic surgery, natural orifice specimen extraction, and natural orifice transluminal endoscopic surgery, have been made in recent years. In this article, we review the published data and mainly focus on the current status and latest advances of mini-invasive surgery for colorectal cancer.

  16. Treatment Individualization in Colorectal Cancer

    NARCIS (Netherlands)

    van Geel, Robin M J M; Beijnen, Jos H; Bernards, René; Schellens, Jan H M

    2015-01-01

    Colorectal cancer has been characterized as a genetically heterogeneous disease, with a large diversity in molecular pathogenesis resulting in differential responses to therapy. However, the currently available validated biomarkers KRAS, BRAF, and microsatellite instability do not sufficiently cover

  17. Animal Models of Colorectal Cancer

    Science.gov (United States)

    Johnson, Robert L.; Fleet, James C.

    2012-01-01

    Colorectal cancer is a heterogeneous disease that afflicts a large number of people in the United States. The use of animal models has the potential to increase our understanding of carcinogenesis, tumor biology, and the impact of specific molecular events on colon biology. In addition, animal models with features of specific human colorectal cancers can be used to test strategies for cancer prevention and treatment. In this review we provide an overview of the mechanisms driving human cancer, we discuss the approaches one can take to model colon cancer in animals, and we describe a number of specific animal models that have been developed for the study of colon cancer. We believe that there are many valuable animal models to study various aspects of human colorectal cancer. However, opportunities for improving upon these models exist. PMID:23076650

  18. Molecular genetics of colorectal cancer.

    Science.gov (United States)

    Bogaert, Julie; Prenen, Hans

    2014-01-01

    Approximately 90% of colorectal cancer cases are sporadic without family history or genetic predisposition, while in less than 10% a causative genetic event has been identified. Historically, colorectal cancer classification was only based on clinical and pathological features. Many efforts have been made to discover the genetic and molecular features of colorectal cancer, and there is more and more evidence that these features determine the prognosis and response to (targeted) treatment. Colorectal cancer is a heterogeneous disease, with three known major molecular groups. The most common is the chromosomal instable group, characterized by an accumulation of mutations in specific oncogenes and tumor suppressor genes. The second is the microsatellite instable group, caused by dysfunction of DNA mismatch repair genes leading to genetic hypermutability. The CpG Island Methylation phenotype is the third group, distinguished by hypermethylation. Colorectal cancer subtyping has also been addressed using genome-wide gene expression profiling in large patient cohorts and recently several molecular classification systems have been proposed. In this review we would like to provide an up-to-date overview of the genetic aspects of colorectal cancer. PMID:24714764

  19. Lysyl oxidase in colorectal cancer

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine T

    2013-01-01

    Colorectal cancer is the third most prevalent form of cancer worldwide and fourth-leading cause of cancer-related mortality, leading to ~600,000 deaths annually, predominantly affecting the developed world. Lysyl oxidase is a secreted, extracellular matrix-modifying enzyme previously suggested...... to act as a tumor suppressor in colorectal cancer. However, emerging evidence has rapidly implicated lysyl oxidase in promoting metastasis of solid tumors and in particular colorectal cancer at multiple stages, affecting tumor cell proliferation, invasion, and angiogenesis. This emerging research has...... stimulated significant interest in lysyl oxidase as a strong candidate for developing and deploying inhibitors as functional efficacious cancer therapeutics. In this review, we discuss the rapidly expanding body of knowledge concerning lysyl oxidase in solid tumor progression, highlighting recent...

  20. Increased topoisomerase IIalpha expression in colorectal cancer is associated with advanced disease and chemotherapeutic resistance via inhibition of apoptosis.

    LENUS (Irish Health Repository)

    Coss, Alan

    2012-02-01

    Topoisomerase IIalpha is a nuclear enzyme that regulates the tertiary structure of DNA. The influence of topoisomerase IIalpha gene (TOP2A) or protein alterations on disease progression and treatment response in colorectal cancer (CRC) is unknown. The study investigated the clinical relevance of topoisomerase IIalpha in CRC using in vivo and in vitro models. Differentially expressed genes in early and late-stage CRC were identified by array comparative genomic hybridization (CGH). Cellular location of gene amplifications was determined by fluorescence in situ hybridization (FISH). Topoisomerase IIalpha levels, proliferation index, and HER2 expression were examined in 228 colorectal tumors by immunohistochemistry. Overexpression of topoisomerase IIalpha in vitro was achieved by liposome-based transfection. Cell growth inhibition and apoptosis were quantified using the crystal violet assay and flow cytometry, respectively, in response to drug treatment. Amplification of TOP2A was identified in 3 (7.7%) tumors using array CGH and confirmed using FISH. At the protein level, topoisomerase IIalpha staining was observed in 157 (69%) tumors, and both staining and intensity levels were associated with an aggressive tumor phenotype (p values 0.04 and 0.005, respectively). Using logistic regression analysis, topoisomerase IIalpha remained significantly associated with advanced tumor stage when corrected for tumor proliferation (p=0.007) and differentiation (p=0.001). No association was identified between topoisomerase IIalpha and HER2. In vitro, overexpression of topoisomerase IIalpha was associated with resistance to irinotecan (p=0.001) and etoposide chemotherapy (p=0.03), an effect mediated by inhibition of apoptosis. Topoisomerase IIalpha overexpression is significantly associated with alterations in tumor behavior and response to drug treatment in CRC. Our results suggest that gene amplification may represent an important mechanism underlying these changes.

  1. The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer.

    OpenAIRE

    Ward, U.; Primrose, J N; Finan, P. J.; Perren, T. J.; Selby, P.; Purves, D. A.; Cooper, E H

    1993-01-01

    Tumour markers CEA, CA-195 and CA-242 were measured in 33 patients undergoing chemotherapy for advanced colorectal cancer. The aim was to determine whether they could be used to accurately monitor the course of the disease, and reduce the need for imaging. Treatment with a 5-fluorouracil based regimen resulted in a partial response in nine patients (27%), whereas the remainder either had disease stabilisation or suffered from progression. Before treatment the CEA was elevated in 85% of patien...

  2. Familial colorectal cancer type X

    DEFF Research Database (Denmark)

    Dominguez-Valentin, Mev; Therkildsen, Christina; Da Silva, Sabrina;

    2015-01-01

    Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologi...... features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.......Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic...

  3. Brain metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Vagn-Hansen, Chris Aksel; Rafaelsen, Søren Rafael

    2001-01-01

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

  4. Cost-effectiveness of colorectal cancer screening

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

    2011-01-01

    textabstractColorectal cancer is an important public health problem. Several screening methods have been shown to be effective in reducing colorectal cancer mortality. The objective of this review was to assess the cost-effectiveness of the different colorectal cancer screening methods and to determ

  5. Colorectal Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing colorectal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  6. Optimisation of colorectal cancer treatment

    NARCIS (Netherlands)

    Broek, Colette Bernadine Maria-Theresia van den

    2014-01-01

    Colorectal cancer is one of the most common cancers worldwide. Although there have been several improvements in screening, staging, and treatment in the past decades, survival differences remain. For example among certain subgroups of patients, such as elderly patients and patients with comorbiditie

  7. Immunotherapy of Colorectal Cancer.

    Science.gov (United States)

    Jäger, Dirk; Halama, Niels; Zörnig, Inka; Klug, Paula; Krauss, Jürgen; Haag, Georg-Martin

    2016-01-01

    It is known that the immune response, reflected by high T cell infiltrates in primary tumors and metastases, influences the clinical course of colorectal cancer (CRC). Therefore, immunotherapy concepts have been adapted from other tumor entities, which typically rely on the activation of T cells in the tumor microenvironment (e.g. blockade of the immune checkpoint molecules PD-1 and CTLA-4). However, most of the strategies using the approved checkpoint inhibitors and/or combination strategies have more or less failed to produce impressive results in early phase trials in CRC. Therefore, a number of novel targets for checkpoint inhibition are currently in early phase clinical testing (TIM-3, Lag-3, OX40, GITR, 4-1BB, CD40, CD70). A simple activation of infiltrating T cells will not, however, lead to a meaningful anti-tumor response without modulating the environmental factors in CRC. Thus, it is absolutely necessary to improve our understanding of the complex regulation of the tumor microenvironment in CRC to design individual combination treatments leading to effective immune control. PMID:27259331

  8. Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    LIANG Xiao-bo; HOU Sheng-huai; Li Yao-ping; WANG Li-chun; ZHANG Xin; YANG Jun

    2010-01-01

    Background To compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fiuorouracil and leucovorin as first-line therapy for advanced colorectal cancer.Methods Literature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010. Two authors drew the details of trial design, characteristics of patients, outcomes, and toxicity from the studies included. Data analysis was performed by RevMan 4.2.Results According to the screening criteria, 7 clinical studies with 2095 participants of advanced colorectal cancer were included in this meta analysis. The baseline characteristics of irinotecan group were similar to those of oxaliplatin group.The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR)=0.82, 95% confidence interval (95%CI) (0.70, 0.96), P=0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P=0.008). In the comparison of grade 3-4 toxicity between the two groups, the incidences of nausea, emesis, diarrhoea and alopecia in irinotecan group were higher than those in oxaliplatin group (RR=1.94, 95%CI(1.22, 3.09), P=0.005; 1.71, 95%CI (1.34, 2.18), P <0.001; 14.56, 95%CI (4.11,51.66), P <0.0001), respectively. However, the incidence of neurotoxicity, neutropenia and thrombocytopenia in irinotecan group were lower than those in oxaliplatin group (RR=0.06, 95%CI(0.03, 0.14), P <0.00001; 0.70, 95%CI(0.55, 0.91), P=0.006; 0.18, 95%CI(0.05, 0.61), P=0.006), respectively.Conclusions Both irinotecan and oxaliplatin combined

  9. Capecitabine in the management of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Hirsch BR

    2011-03-01

    Full Text Available Bradford R Hirsch, S Yousuf ZafarDivision of Medical Oncology, Duke University Medical Center, Durham, NC, USAAbstract: 5-Fluorouracil has been a mainstay in the treatment of colorectal cancer for nearly five decades; however, the use of oral formulations of the medication has been gaining increasing traction since capecitabine was approved for use in adjuvant settings by the US Food and Drug Administration in 2005. The use of capecitabine has since spread to a number of off-label indications, including the treatment of advanced or metastatic colorectal cancer and the neoadjuvant treatment of rectal cancer. In light of increasing utilization, it is critical that clinicians have a firm understanding of the literature supporting capecitabine across various settings as well as the attributes of the drug, such as its dosing recommendations, side-effect profile, and use in the elderly. The purpose of this review is to synthesize the literature in a fashion that can be used to help guide decisions. In a setting of increasing focus on cost, the pharmacoeconomic literature is also briefly reviewed.Keywords: colon cancer, colorectal cancer, rectal cancer, capecitabine, Xeloda

  10. Erlotinib Hydrochloride and Cetuximab in Treating Patients With Advanced Gastrointestinal Cancer, Head and Neck Cancer, Non-Small Cell Lung Cancer, or Colorectal Cancer

    Science.gov (United States)

    2015-09-28

    Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Gastrointestinal Stromal Tumor; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer

  11. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... laxatives to clear the colon, shows polyps clearly. DNA stool test This test checks DNA in stool cells for genetic changes that may be a sign of colorectal cancer. Screening clinical trials are taking place in many parts of the ... Screening tests have risks. False-negative test results can occur. ...

  12. Immunotherapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  13. Colorectal cancer and pollution

    Institute of Scientific and Technical Information of China (English)

    AM; El-Tawil

    2010-01-01

    The incidence of colorectal carcinoma is increasing in young patients, in contrast to the well established wisdom that it is exclusively diagnosed in patients older than 40 years. In this survey, we examined all possible risk factors, and we recommend a number of measures for early detection in young patients who are at risk of developing this malignant tumor.

  14. Diagnostic accuracy of 18F-FDG PET/CT for detecting synchronous advanced colorectal neoplasia in patients with gastric cancer.

    Science.gov (United States)

    Choi, Byung Wook; Kim, Hae Won; Won, Kyoung Sook; Song, Bong-Il; Cho, Kwang Bum; Bae, Sung Uk

    2016-09-01

    Preoperative screening for synchronous colorectal neoplasia (CRN) has been recommended in patients with gastric cancer because patients with gastric cancer are at increased risk for synchronous CRN. The aim of this study was to investigate the diagnostic accuracy of F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting synchronous advanced CRN in patients with gastric cancer.A total of 256 patients who underwent colonoscopy and F-FDG PET/CT for preoperative staging were enrolled in this study. The diagnosis of focal colonic F-FDG uptake on F-FDG PET/CT image was made based on histopathologic results from the colonoscopic biopsy. The F-FDG PET/CT result was considered as true positive for advanced CRN when focal F-FDG uptake matched colorectal carcinoma or adenoma with high-grade dysplasia in the same location on colonoscopy.Synchronous advanced CRN was detected in 21 of the 256 patients (4.7%). Sensitivity, specificity, and accuracy of F-FDG PET/CT were 76.2%, 96.2%, and 94.5%. The size of CRN with a true positive result was significantly larger than that with a false negative result.F-FDG PET/CT demonstrated high diagnostic accuracy for detecting synchronous advanced CRN in patients with gastric cancer. Colonoscopy is recommended as the next diagnostic step for further evaluation of a positive F-FDG PET/CT result in patients with gastric cancer. PMID:27603371

  15. DECAY ACCELERATING FACTOR AND COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    高雪芹; 鲁艳芹; 韩金祥

    2004-01-01

    Objective: To review the significance of decay accelerating factor (DAF) in the eolorectal cancer, we searched the data from PubMed and selected the related articles for review. It was found that DAF were expressed in the adenomas and adenocarcinoma of colorectal tissues. The release of DAF in the stool of the patients was also detectable. It increased more significantly in the stool of patients with colorectal cancer than other gastrointestinal cancer. Its detection by ELISA method may render a good test for the noninvasive diagnosis of colorectal cancer. It can be concluded that DAF is expressed extensively in colorectal cancer. And the detection of DAF released in the stool of colorectal cancer patients may be a good noninvasive method for the diagnosis of colorectal cancer.

  16. Whole-liver radiotherapy for end-stage colorectal cancer patients with massive liver metastases and advanced hepatic dysfunction

    Directory of Open Access Journals (Sweden)

    Kim Sun Young

    2010-10-01

    Full Text Available Abstract Background To investigate whether whole-liver radiotherapy (RT is beneficial in end-stage colorectal cancer with massive liver metastases and severe hepatic dysfunction. Methods Between June 2004 and July 2008, 10 colorectal cancer patients, who exhibited a replacement of over three quarters of their normal liver by metastatic tumors and were of Child-Pugh class B or C in liver function with progressive disease after undergoing chemotherapy, underwent whole-liver RT. RT was administered using computed tomography-based three-dimensional planning and the median dose was 21 Gy (range, 21-30 in seven fractions. Improvement in liver function tests, defined as a decrease in the levels within 1 month after RT, symptom palliation, toxicity, and overall survival were analyzed retrospectively. Results Levels of alkaline phosphatase, total bilirubin, aspartate transaminase, and alanine transaminase improved in 8, 6, 9, and all 10 patients, respectively, and the median reduction rates were 42%, 68%, 50%, and 57%, respectively. Serum carcinoembryonic antigen level decreased after RT in three of four assessable patients. For all patients, pain levels decreased and acute toxicity consisted of nausea/vomiting of grade ≤ 2. Further chemotherapy became possible in four of 10 patients. Mean survival after RT was 80 ± 80 days (range, 20-289; mean survival for four patients who received post-RT chemotherapy was 143 ± 100 days (range, 65-289, versus 38 ± 16 days (range, 20-64 for the six patients who did not receive post-RT chemotherapy (p = 0.127. Conclusions Although limited by small case number, this study demonstrated a possible role of whole-liver RT in improving hepatic dysfunction and delaying mortality from hepatic failure for end-stage colorectal cancer patients with massive liver metastases. Further studies should be followed to confirm these findings.

  17. Whole-liver radiotherapy for end-stage colorectal cancer patients with massive liver metastases and advanced hepatic dysfunction

    International Nuclear Information System (INIS)

    To investigate whether whole-liver radiotherapy (RT) is beneficial in end-stage colorectal cancer with massive liver metastases and severe hepatic dysfunction. Between June 2004 and July 2008, 10 colorectal cancer patients, who exhibited a replacement of over three quarters of their normal liver by metastatic tumors and were of Child-Pugh class B or C in liver function with progressive disease after undergoing chemotherapy, underwent whole-liver RT. RT was administered using computed tomography-based three-dimensional planning and the median dose was 21 Gy (range, 21-30) in seven fractions. Improvement in liver function tests, defined as a decrease in the levels within 1 month after RT, symptom palliation, toxicity, and overall survival were analyzed retrospectively. Levels of alkaline phosphatase, total bilirubin, aspartate transaminase, and alanine transaminase improved in 8, 6, 9, and all 10 patients, respectively, and the median reduction rates were 42%, 68%, 50%, and 57%, respectively. Serum carcinoembryonic antigen level decreased after RT in three of four assessable patients. For all patients, pain levels decreased and acute toxicity consisted of nausea/vomiting of grade ≤ 2. Further chemotherapy became possible in four of 10 patients. Mean survival after RT was 80 ± 80 days (range, 20-289); mean survival for four patients who received post-RT chemotherapy was 143 ± 100 days (range, 65-289), versus 38 ± 16 days (range, 20-64) for the six patients who did not receive post-RT chemotherapy (p = 0.127). Although limited by small case number, this study demonstrated a possible role of whole-liver RT in improving hepatic dysfunction and delaying mortality from hepatic failure for end-stage colorectal cancer patients with massive liver metastases. Further studies should be followed to confirm these findings

  18. Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver

    Directory of Open Access Journals (Sweden)

    Biffi Roberto

    2012-05-01

    Full Text Available Abstract Background An antimicrobial dressing containing ionic silver was found effective in reducing surgical-site infection in a preliminary study of colorectal cancer elective surgery. We decided to test this finding in a randomized, double-blind trial. Methods Adults undergoing elective colorectal cancer surgery at two university-affiliated hospitals were randomly assigned to have the surgical incision dressed with Aquacel® Ag Hydrofiber dressing or a common dressing. To blind the patient and the nursing and medical staff to the nature of the dressing used, scrub nurses covered Aquacel® Ag Hydrofiber with a common wound dressing in the experimental arm, whereas a double common dressing was applied to patients of control group. The primary end-point of the study was the occurrence of any surgical-site infection within 30 days of surgery. Results A total of 112 patients (58 in the experimental arm and 54 in the control group qualified for primary end-point analysis. The characteristics of the patient population and their surgical procedures were similar. The overall rate of surgical-site infection was lower in the experimental group (11.1% center 1, 17.5% center 2; overall 15.5% than in controls (14.3% center 1, 24.2% center 2, overall 20.4%, but the observed difference was not statistically significant (P = 0.451, even with respect to surgical-site infection grade 1 (superficial versus grades 2 and 3, or grade 1 and 2 versus grade 3. Conclusions This randomized trial did not confirm a statistically significant superiority of Aquacel® Ag Hydrofiber dressing in reducing surgical-site infection after elective colorectal cancer surgery. Trial registration Clinicaltrials.gov: NCT00981110

  19. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  20. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2011-05-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  1. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Fischer, Anders; Myschetzky, Peter S;

    2008-01-01

    -testis antigens. Vaccines were biweekly administered intradermally with a total of 10 vaccines per patient. CT scans were performed and responses were graded according to the RECIST criteria. Quality of life was monitored with the SF-36 questionnaire. Toxicity and adverse events were graded according...... to the National Cancer Institute's common Toxicity Criteria. Four patients were graded with stable disease. Two remained stable throughout the entire study period. Analysis of changes in the patients' quality of life revealed stability in the subgroups: 'physical function' (p=0.872), 'physical role limitation' (p...

  2. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients. PMID:27158196

  3. Dendritic cell-based cancer immunotherapy for colorectal cancer.

    Science.gov (United States)

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Saito, Keisuke; Takami, Shinichiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-01

    Colorectal cancer (CRC) is one of the most common cancers and a leading cause of cancer-related mortality worldwide. Although systemic therapy is the standard care for patients with recurrent or metastatic CRC, the prognosis is extremely poor. The optimal sequence of therapy remains unknown. Therefore, alternative strategies, such as immunotherapy, are needed for patients with advanced CRC. This review summarizes evidence from dendritic cell-based cancer immunotherapy strategies that are currently in clinical trials. In addition, we discuss the possibility of antitumor immune responses through immunoinhibitory PD-1/PD-L1 pathway blockade in CRC patients.

  4. Advances in research on microRNA-21 in colorectal cancer%MicroRNA-21在结直肠癌中的研究进展

    Institute of Scientific and Technical Information of China (English)

    梁政; 周慧芳

    2014-01-01

    结直肠癌是我国常见的消化系统恶性肿瘤之一。目前认为结直肠癌的形成是一个多因素、多步骤的过程,其具体的发病机制尚不清楚。microRNA(miRNA)是一类非编码的小分子 RNA,能在转录后水平调控基因蛋白的表达,参与肿瘤细胞增殖、分化、侵袭和转移,对结直肠癌的发生和发展具有重要的作用。miRNA-21是当前研究miRNA在结直肠癌发病机制的热点之一,本文就miR-21在结直肠癌中的研究进展作一综述。%Colorectal cancer (CRC) is one of the most common digestive system neoplasms in China. Recently, the morbidity and mortality rates of CRC continue to increase with the improvement of people's living standard and the change of the dietary structure. It was accepted that the etiology of colorectal cancer is a multi-factor and multi-step process. However, the mechanism of CRC is still unclear. MicroRNAs (miRNAs) are a class of -21 nucleotide non-coding RNAs and function as a negative regulator of gene expression after transcription, participating in tumor angiogenesis, tumor cell proliferation and invasion. MicroRNA-21 (miR-21), as an important oncogenic RNA, plays a vital role in the development and progression of CRC. This review summarizes the advances in research on miR-21 in colorectal cancer.

  5. Red meat and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Nuri Faruk Aykan

    2015-12-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer in men and the second in women worldwide. More than half of cases occur in more developed countries. The consumption of red meat (beef, pork, lamb, veal, mutton is high in developed countries and accumulated evidence until today demonstrated a convincing association between the intake of red meat and especially processed meat and CRC risk. In this review, meta-analyses of prospective epidemiological studies addressed to this association, observed link of some subtypes of red meat with CRC risk, potential carcinogenic compounds, their mechanisms and actual recommendations of international guidelines are presented.

  6. Nutrients, Foods, and Colorectal Cancer Prevention

    OpenAIRE

    Song, Mingyang; Garrett, Wendy S.; Andrew T Chan

    2015-01-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigation have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grain have been associated with a lower risk of colorectal cancer, and red meat and processed meat with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, fo...

  7. Molecular Diagnostic Applications in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Laura Huth

    2014-06-01

    Full Text Available Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer patients.  Distinction of these applications is based on the different molecular principles found in colorectal cancer (CRC. Strategies for molecular analysis of single genes (as KRAS or TP53 as well as microarray based techniques are discussed. Moreover, in addition to the fecal occult blood testing (FOBT and colonoscopy some novel assays offer approaches for early detection of colorectal cancer like the multitarget stool DNA test or the blood-based Septin 9 DNA methylation test. Liquid biopsy analysis may also exhibit great diagnostic potential in CRC for monitoring developing resistance to treatment. These new diagnostic tools and the definition of molecular biomarkers in CRC will improve early detection and targeted therapy of colorectal cancer.

  8. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder;

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...... known genes and 157 ESTs were found to be highly relevant for CRC. The alteration of known genes was confirmed in >70% of the cases by array analysis of 25 single samples. Two-way hierarchical average linkage cluster analysis clustered normal tissue together with Dukes' A, clustered Dukes' B with Dukes...

  9. Screening for Lynch syndrome in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    刘晓红

    2014-01-01

    Objective To evaluate the application of mismatch repair(MMR)genes proteins expression to screen for Lynch syndrome in colorectal cancer patients.Methods One hundred consecutive colorectal cancers cases collected from 2012 to 2013 were tested immunohistochemically for the protein expression of MLH1,MSH2,MSH6 and PMS2,and also by the ARMS method for the mutation

  10. Indeterminate Pulmonary Nodules at Colorectal Cancer Staging

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Wille-Jørgensen, Peer A; Jorgensen, Lars N;

    2013-01-01

    This study aimed to estimate the prevalence of indeterminate pulmonary nodules and specific radiological and clinical characteristics that predict malignancy of these at initial staging chest computed tomography (CT) in patients with colorectal cancer. A considerable number of indeterminate...... pulmonary nodules, which cannot readily be classified as either benign or malignant, are detected at initial staging chest CT in colorectal cancer patients....

  11. High-dose 5-fluorouracil plus low dose methotrexate plus or minus low-dose PALA in advanced colorectal cancer : a randomised phase II-III trial of the EORTC Gastrointestinal Group

    NARCIS (Netherlands)

    Wils, J; Blijham, GH; Wagener, T; De Greve, J; Jansen, RLH; Kok, TC; Nortier, JWR; Bleiberg, H; Couvreur, ML; Genicot, B; Baron, B

    2003-01-01

    The aim of this study was to investigate whether N-(phosphonacetyl)-L-aspartic acid (PALA) can enhance the activity of low-dose methotrexate (LD-MTX) modulated infusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancer. 198 patients were randomised either to (i) 5-FU 60 mg/kg as a

  12. Center for Herbal Research on Colorectal Cancer

    Data.gov (United States)

    Federal Laboratory Consortium — Research Area: Herbs Program:Centers of Excellence for Research on CAM Description:Colorectal cancer is the third most common cancer and the third leading cause of...

  13. Contemporary methods of treatment of colorectal cancer

    OpenAIRE

    Monika Kozłowska; Stanisław Głuszek

    2016-01-01

    Today, colorectal cancer (CRC) is the third most frequently diagnosed worldwide malignant cancer in males, and the second in females, with more than 1,200,000 new cases and more than 600,000 deaths, annually. Screening tests in oncology allow the detection of cancerous disease at an early, asymptomatic stage. The procedures most frequently performed in the case of colorectal cancer include: low anterior resection by the Dixon method (manual suture or staplers); abdominoperineal resection of t...

  14. New registry: National Cancer Patient Registry--Colorectal Cancer.

    Science.gov (United States)

    Wendy, L; Radzi, M

    2008-09-01

    Colorectal cancer is emerging as one of the commonest cancers in Malaysia. Data on colorectal cancer from the National Cancer Registry is very limited. Comprehensive information on all aspects of colorectal cancer, including demographic details, pathology and treatment outcome are needed as the management of colorectal cancer has evolved rapidly over the years involving several disciplines including gastroenterology, surgery, radiology, pathology and oncology. This registry will be an important source of information that can help the development of guidelines to improve colorectal cancer care relevant to this country. The database will initially recruit all colorectal cancer cases from eight hospitals. The data will be stored on a customized web-based case report form. The database has begun collecting data from 1 October 2007 and will report on its first year findings at the end of 2008.

  15. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  16. Phase II study of reintroduction of oxaliplatin for advanced colorectal cancer in patients previously treated with oxaliplatin and irinotecan: RE-OPEN study

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-06-01

    -related deaths.Conclusion: Reintroducing oxaliplatin can be both safe and effective. This may be a salvage option for patients with metastatic colorectal cancer who achieved a response or stable disease with prior oxaliplatin-based therapy followed by disease progression ≥6 months previously during prior oxaliplatin-based therapy.Keywords: reintroduction, oxaliplatin, FOLFOX, advanced colorectal cancer, salvage-line

  17. Biweekly cetuximab and irinotecan as third-line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin and 5-fluorouracil

    DEFF Research Database (Denmark)

    Pfeiffer, P.; Nielsen, Dorte; Bjerregaard, J.;

    2008-01-01

    Background: Standard weekly cetuximab and irinotecan (CetIri) is an effective regimen in heavily pretreated patients with advanced colorectal cancer (ACRC). Inspired by a pharmacokinetic study demonstrating no differences between weekly and biweekly cetuximab, we present the results of 74......-resulting in an overall treatment time of 90 min. Results: All patients had ACRC resistant to 5-fluorouracil and irinotecan and 95% to oxaliplatin. Median age was 63 years, median performance status was 0. Median duration of therapy was 4.3 months. Response rate was 25%. Median progression-free survival and overall...... survival were 5.4 months and 8.9 months, respectively, comparable to own historical controls receiving weekly CetIri. Grade 3-4 toxicity was rare (skin 7%, nail 3%, diarrhoea 10%, fatigue 3%, neutropenia 9%). One patient experienced severe allergic reaction. Conclusion: Salvage therapy with simplified...

  18. Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer.

    Science.gov (United States)

    Aung, Kyaw L; Stockley, Tracy L; Serra, Stefano; Kamel-Reid, Suzanne; Bedard, Philippe L; Siu, Lillian L

    2016-09-01

    Recent advances in molecular profiling technologies allow genetic driver events in individual tumors to be identified. The hypothesis behind this ongoing molecular profiling effort is that improvement in patients' clinical outcomes will be achieved by inhibiting these discovered genetic driver events with matched targeted drugs. This hypothesis is currently being tested in oncology clinics with variable early results. Herein, we present our experience with a case of advanced colorectal cancer (CRC) with an ERBB2 p.L755S kinase domain mutation, a BRAF p.N581S mutation, and an APC p.Q1429fs mutation, together with a brief review of the literature describing the biological and clinical significance of ERRB2 kinase domain mutations in CRC. The patient was treated with trastuzumab combined with infusional 5-fluorouracil and leucovorin based on the presence of ERBB2 p.L755S kinase mutation in the tumor and based on the available evidence at the time when standard treatment options had been exhausted. However, there was no therapeutic response illustrating the challenges we face in managing patients with potentially targetable mutations where results from functional in vitro and in vivo studies lag behind those of genomic sequencing studies. Also lagging behind are clinical utility data from oncology clinics, hampering rapid therapeutic advances. Our case also highlights the logistical barriers associated with getting the most optimal therapeutic agents to the right patient in this era of personalized therapeutics based on cancer genomics. PMID:27626067

  19. Testing ERBB2 p.L755S kinase domain mutation as a druggable target in a patient with advanced colorectal cancer

    Science.gov (United States)

    Aung, Kyaw L.; Stockley, Tracy L.; Serra, Stefano; Kamel-Reid, Suzanne; Bedard, Philippe L.; Siu, Lillian L.

    2016-01-01

    Recent advances in molecular profiling technologies allow genetic driver events in individual tumors to be identified. The hypothesis behind this ongoing molecular profiling effort is that improvement in patients’ clinical outcomes will be achieved by inhibiting these discovered genetic driver events with matched targeted drugs. This hypothesis is currently being tested in oncology clinics with variable early results. Herein, we present our experience with a case of advanced colorectal cancer (CRC) with an ERBB2 p.L755S kinase domain mutation, a BRAF p.N581S mutation, and an APC p.Q1429fs mutation, together with a brief review of the literature describing the biological and clinical significance of ERRB2 kinase domain mutations in CRC. The patient was treated with trastuzumab combined with infusional 5-fluorouracil and leucovorin based on the presence of ERBB2 p.L755S kinase mutation in the tumor and based on the available evidence at the time when standard treatment options had been exhausted. However, there was no therapeutic response illustrating the challenges we face in managing patients with potentially targetable mutations where results from functional in vitro and in vivo studies lag behind those of genomic sequencing studies. Also lagging behind are clinical utility data from oncology clinics, hampering rapid therapeutic advances. Our case also highlights the logistical barriers associated with getting the most optimal therapeutic agents to the right patient in this era of personalized therapeutics based on cancer genomics. PMID:27626067

  20. Genetic architecture of colorectal cancer.

    Science.gov (United States)

    Peters, Ulrike; Bien, Stephanie; Zubair, Niha

    2015-10-01

    Colorectal cancer (CRC) is a complex disease that develops as a consequence of both genetic and environmental risk factors. A small proportion (3-5%) of cases arise from hereditary syndromes predisposing to early onset CRC as a result of mutations in over a dozen well defined genes. In contrast, CRC is predominantly a late onset 'sporadic' disease, developing in individuals with no obvious hereditary syndrome. In recent years, genome wide association studies have discovered that over 40 genetic regions are associated with weak effects on sporadic CRC, and it has been estimated that increasingly large genome wide scans will identify many additional novel genetic regions. Subsequent experimental validations have identified the causally related variant(s) in a limited number of these genetic regions. Further biological insight could be obtained through ethnically diverse study populations, larger genetic sequencing studies and development of higher throughput functional experiments. Along with inherited variation, integration of the tumour genome may shed light on the carcinogenic processes in CRC. In addition to summarising the genetic architecture of CRC, this review discusses genetic factors that modify environmental predictors of CRC, as well as examples of how genetic insight has improved clinical surveillance, prevention and treatment strategies. In summary, substantial progress has been made in uncovering the genetic architecture of CRC, and continued research efforts are expected to identify additional genetic risk factors that further our biological understanding of this disease. Subsequently these new insights will lead to improved treatment and prevention of colorectal cancer. PMID:26187503

  1. KRASness and PIK3CAness in patients with advanced colorectal cancer: outcome after treatment with early-phase trials with targeted pathway inhibitors.

    Directory of Open Access Journals (Sweden)

    Ignacio Garrido-Laguna

    Full Text Available PURPOSE: To evaluate clinicopathologic and molecular features of patients with metastatic colorectal cancer (mCRC and their outcomes in early-phase trials using pathway-targeting agents. PATIENTS AND METHODS: We analyzed characteristics of 238 patients with mCRC referred to the phase 1 trials unit at MD Anderson Cancer Center. KRAS, PIK3CA and BRAF status were tested using PCR-based DNA sequencing. RESULTS: Fifty-one percent of patients harbored KRAS mutations; 15% had PIK3CA mutations. In the multivariate regression model for clinical characteristics KRAS mutations were associated with an increased incidence of lung and bone metastases and decreased incidence of adrenal metastases; PIK3CA mutations were marginally correlated with mucinous tumors (p = 0.05. In the univariate analysis, KRAS and PIK3CA mutations were strongly associated. Advanced Duke's stage (p<0.0001 and KRAS mutations (p = 0.01 were the only significant independent predictors of poor survival (Cox proportional hazards model. Patients with PIK3CA mutations had a trend toward shorter progression-free survival when treated with anti-EGFR therapies (p = 0.07. Eighteen of 78 assessable patients (23% treated with PI3K/Akt/mTOR axis inhibitors achieved stable disease [SD] ≥6 months or complete response/partial response (CR/PR, only one of whom were in the subgroup (N = 15 with PIK3CA mutations, perhaps because 10 of these 15 patients (67% had coexisting KRAS mutations. No SD ≥6 months/CR/PR was observed in the 10 patients treated with mitogen-activating protein kinase (MAPK pathway targeting drugs. CONCLUSIONS: KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome. Overcoming resistance may require targeting both pathways.

  2. Phase I clinical study of anti-apoptosis protein, survivin-derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer

    Directory of Open Access Journals (Sweden)

    Minamida Hidetoshi

    2004-06-01

    Full Text Available Abstract Survivin is a member of the inhibitor of apoptosis protein (IAP family containing a single baculovirus IAP repeat domain. It is expressed during fetal development but becomes undetectable in terminally differentiated normal adult tissues. We previously reported that survivin and its splicing variant survivin-2B was expressed abundantly in various types of tumor tissues as well as tumor cell lines and was suitable as a target antigen for active-specific anti-cancer immunization. Subsequently, we identified an HLA-A24-restricted antigenic peptide, survivin-2B80-88 (AYACNTSTL recognized by CD8+ cytotoxic T lymphocytes (CTLs. We, therefore, started a phase I clinical study assessing the efficacy of survivin-2B peptide vaccination in patients with advanced or recurrent colorectal cancer expressing survivin. Vaccinations with survivin-2B peptide were given subcutaneously six times at 14-day intervals. Of 15 patients who finished receiving the vaccination schedule, three suffered slight toxicities, including anemia (grade 2, general malaise (grade 1, and fever (grade 1. No severe adverse events were observed in any patient. In 6 patients, tumor marker levels (CEA and CA19-9 decreased transiently during the period of vaccination. Slight reduction of the tumor volume was observed in one patient, which was considered a minor responder. No changes were noted in three patients while the remaining eleven patients experienced tumor progression. Analysis of peripheral blood lymphocytes of one patient using HLA-A24/peptide tetramers revealed an increase in peptide-specific CTL frequency from 0.09% to 0.35% of CD8+ T cells after 4 vaccinations. This phase I clinical study indicates that survivin-2B peptide-based vaccination is safe and should be further considered for potential immune and clinical efficacy in HLA-A24-expression patients with colorectal cancer.

  3. Integrated Molecular Profiling in Advanced Cancers Trial

    Science.gov (United States)

    2016-06-21

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  4. Dosing considerations for capecitabine-irinotecan regimens in the treatment of metastatic and/or locally advanced colorectal cancer.

    Science.gov (United States)

    Cartwright, Thomas; McCollum, David; Boehm, Kristi A

    2010-06-01

    Capecitabine (Xeloda), Roche Laboratories Inc., Nutley, NJ) is an orally administered fluoropyrimidine carbamate that serves as a prodrug of 5-fluorouracil (5-FU), an integral component of chemotherapy (CT) regimens for metastatic colorectal cancer (mCRC). As the drug is orally administered, capecitabine permits greater convenience and flexibility in dosing by eliminating the need for continuous infusion and its potential complications. In phase 3 trials, capecitabine has been used as an alternative to 5-FU, both as a monotherapy and in combination with agents such as oxaliplatin (as XELOX), with good efficacy and tolerability. Combination therapy with capecitabine and irinotecan (XELIRI), however, has produced more variable results, with some dose combinations and schedules resulting in excessive and/or unexplained treatment-related toxicity. Recent initiatives using lower doses of capecitabine and irinotecan, as well as alternative dosing schedules, have resulted in more favorable outcomes (efficacy and tolerability), even in combination with targeted-agents such as bevacizumab. Dose reduction in elderly populations and in those with moderate renal impairment also appears to be important for minimizing toxicity with XELIRI regimens. Although additional phase 3 studies are needed, XELIRI may be an effective base CT regimen, allowing a greater number of treatment options for tumor control in patients with mCRC.

  5. MicroRNA Methylation in Colorectal Cancer.

    Science.gov (United States)

    Kaur, Sippy; Lotsari-Salomaa, Johanna E; Seppänen-Kaijansinkko, Riitta; Peltomäki, Päivi

    2016-01-01

    Epigenetic alterations such as DNA methylation, histone modifications and non-coding RNA (including microRNA) associated gene silencing have been identified as a major characteristic in human cancers. These alterations may occur more frequently than genetic mutations and play a key role in silencing tumor suppressor genes or activating oncogenes, thereby affecting multiple cellular processes. In recent years, studies have shown that microRNAs, that act as posttranscriptional regulators of gene expression are frequently deregulated in colorectal cancer (CRC), via aberrant DNA methylation. Over the past decade, technological advances have revolutionized the field of epigenetics and have led to the identification of numerous epigenetically dysregulated miRNAs in CRC, which are regulated by CpG island hypermethylation and DNA hypomethylation. In addition, aberrant DNA methylation of miRNA genes holds a great promise in several clinical applications such as biomarkers for early screening, prognosis, and therapeutic applications in CRC. PMID:27573897

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

    Science.gov (United States)

    ... Stay Informed Cancer Home Questions to Ask Your Doctor About Colorectal Cancer Language: English Español (Spanish) Recommend ... helps pay for colorectal cancer screening. Ask Your Doctor Do I need to get a screening test ...

  7. Metastatic colorectal cancer-past, progress and future

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  8. KRAS mutation testing in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Cong Tan; Xiang Du

    2012-01-01

    The KRAS oncogene is mutated in approximately 35%-45% of colorectal cancers,and KRAS mutational status testing has been highlighted in recent years.The most frequent mutations in this gene,point substitutions in codons 12 and 13,were validated as negative predictors of response to anti-epidermal growth factor receptor antibodies.Therefore,determining the KRAS mutational status of tumor samples has become an essential tool for managing patients with colorectal cancers.Currently,a variety of detection methods have been established to analyze the mutation status in the key regions of the KRAS gene; however,several challenges remain related to standardized and uniform testing,including the selection of tumor samples,tumor sample processing and optimal testing methods.Moreover,new testing strategies,in combination with the mutation analysis of BRAF,PIK3CA and loss of PTEN proposed by many researchers and pathologists,should be promoted.In addition,we recommend that microsatellite instability,a prognostic factor,be added to the abovementioned concomitant analysis.This review provides an overview of KRAS biology and the recent advances in KRAS mutation testing.This review also addresses other aspects of status testing for determining the appropriate treatment and offers insight into the potential drawbacks of mutational testing.

  9. Fecal Molecular Markers for Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    Rani Kanthan

    2012-01-01

    Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

  10. Colorectal cancer, one entity or three

    Institute of Scientific and Technical Information of China (English)

    Feng-ying LI; Mao-de LAI

    2009-01-01

    Understanding of the mechanism ofcolorectal carcinogenesis has been gaining momentum for some years on account of its high incidence and impact on the lives of individuals affected. Different genetic abnormalities have been found in colorectal cancers from different sites. For example, proximal colon cancer is usually related to the nucleotide instability pathway, as mi-crosatellite instability (MSI). However, distal colon cancer is usually associated with specific chromosomal instability (CIN). The development of cancer at the rectum, though similar to that at the colon, displays its own unique features. These differences might be partially attributed to different embryological development and physiological circumstances. Environmental factors such as diet and alcohol intake also differ in their role in the development of tumors in the three segments, proximal colon, distal colon, and rectum. "Proximal shift" of colon cancer has been known for some time, and survival rates of colorectal cancer are higher when rectal cancers are excluded, both of which emphasize the three different segments of colorectal cancer and their different proper-ties. Meanwhile, colonic and rectal cancers are distinctive therapeutic entities. The concept of three entities of colorectal cancer may be important in designing clinical trails or therapeutic strategies. However, the dispute about the inconsistency of data con-ceming the site-specific mechanism of colorectal carcinoma does exist, and more evidence about molecular events of carcino-genesis and targeted therapy needs to be collected to definitely confirm the conception.

  11. Diet, microbiota, and colorectal cancer.

    Science.gov (United States)

    Akin, Hakan; Tözün, Nurdan

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world causing nearly 500,000 deaths every year. In addition to genetic background, environmental factors including diet and lifestyle are accepted as major contributors to adenoma and CRC development. Lifestyle factors include high BMI, obesity, and reduced physical activity. Growing interest and accumulating data on human microbiota implicate that host-microbe interplay has an important role in the development of metabolic, neoplastic, and inflammatory diseases. Findings from recent studies suggest that colon cancer risk is determined by the interaction between diet and gut microbiota. Dietary changes affect gut microbiota and conversely microbiota mediates the generation of dietary factors triggering colon cancer. Identification of the microbial communities associated with carcinogenesis is of crucial importance. Nowadays, with the evolvement of culture-independent molecular techniques, it has become possible to identify main bacterial species in healthy individuals, inflammatory conditions, and CRC. Some recent studies have shown the differences in intestinal microbiota between colon cancer patients and healthy individuals. Animal studies have provided a better understanding of interaction between pathobionts and symbionts in the development of colon cancer. There is no single causative organism identified in CRC; however, there is strong evidence that reduction of protective bacteria, increase in some bacteria (ie, fusobacterium members; Bacteroides/Prevotella), and age-related changes in microbiota have an impact on adenoma or cancer development. Future studies will enable us to understand procarcinogenic and anticarcinogenic mechanisms and give insights to rational manipulation of the microbiota with prebiotics, probiotics, or dietary modifications. PMID:25291132

  12. Continuous quality improvement of colorectal cancer screening

    Institute of Scientific and Technical Information of China (English)

    Mariusz; Madalinski

    2013-01-01

    Quality assurance is a key issue in colorectal cancer screening, because effective screening is able to improve primary prevention of the cancer. The quality measure may be described in terms:how well the screening test tells who truly has a disease (sensitivity) and who truly does not have a disease (specificity). This paper raises concerns about identification of the optimal screening test for colorectal cancer. Colonoscopy vs flexible sigmoidoscopy in colorectal cancer screening has been a source of ongoing debate. A multicentre randomised controlled trial comparing flexible sigmoidoscopy with usual care showed that flexible sigmoidoscopy screening is able to diminish the incidence of distal and proximal colorectal cancer, and also mortality related to the distal colorectal cancer. However, colonoscopy provides a more complete examination and remains the more sensitive exam than flexible sigmoidoscopy. Moreover, colonoscopy with polypectomy significantly reduces colorectal cancer incidence and colorectal cancer-related mortality in the general population. The article considers the relative merits of both methods and stresses an ethical aspect of patient’s involvement in decision-making. Patients should be informed not only about tests tolerability and risk of endoscopy complications, but also that different screening tests for bowel cancer have different strength to exclude colonic cancer and polyps. The authorities calculate effectiveness and costs of the screening tests, but patients may not be interested in statistics regarding flexible sigmoidoscopy screening and from an ethical point of view, they have the right to chose colonoscopy, which is able to exclude a cancer and precancerous lesions in the whole large bowel.

  13. Biomarkers, Bundled Payments, and Colorectal Cancer Care

    OpenAIRE

    Ross, William; Lynch, Patrick; Raju, Gottumukkala; Rodriguez, Alma; Burke, Thomas; Hafemeister, Lisa; Hawk, Ernest; Wu, Xifeng; Raymond N. DuBois; MISHRA, LOPA

    2012-01-01

    Changes in the management of cancers such as colorectal cancer (CRC) are urgently needed, as such cancers continue to be one of the most commonly diagnosed cancers; CRC accounts for 21% of all cancers and is responsible for mortalities second only to lung cancer in the United States. A comprehensive science-driven approach towards markedly improved early detection/screening to efficacious targeted therapeutics with clear diagnostic and prognostic markers is essential. In addition, further cha...

  14. Population pharmacokinetics of oxaliplatin (85 mg/m2) in combination with 5-fluorouracil in patients with advanced colorectal cancer.

    Science.gov (United States)

    Kho, Yuhan; Jansman, Frank G A; Prins, Nicolaas H; Neef, Cees; Brouwers, Jacobus R B J

    2006-04-01

    Pharmacokinetic (PK) studies of oxaliplatin, using a dose regimen of 85 mg/m, are lacking. A PK model may be used in future studies to investigate the relationship between pharmacokinetics and dose limiting toxicity. The purpose of this study was to construct a population PK model to describe platinum (Pt) concentrations in plasma in 33 patients with colorectal cancer. The secondary objective was to determine the relationship between the amount of Pt in 24-hour urine and the amount of Pt in fractionated urine collection periods. Plasma and urine samples were collected from patients during their first oxaliplatin treatment course. Population PK analysis was performed with WinNonMix. The model that best described the Pt concentrations in plasma was a two-compartment PK model. The elimination clearance (CL) and the elimination clearance of the peripheral compartment (CL2) (median +/- SE) were 25.2 +/- 6.3 L/hr and 68 +/- 24.8 L/hr, respectively. The median volume of distribution (V1) was determined to be 41.6 +/- 9.4 L and the median volume of distribution of the peripheral compartment (V2) was 452.5 +/- 96.4 L. The relationship between the cumulative amount of Pt in urine in the first 12 hours compared with the amount of Pt in 24 hours urine was reflected by a correlation coefficient (r2) of 0.95. The cumulative Pt concentration in urine in the first 10 hours and the first 8 hours compared with 24 hours was reflected by correlation coefficients r2 = 0.93 and r2 = 0.897, respectively. This PK model could be useful in identifying predictors for PK and pharmacodynamic variability to individualize dosing. The results of this study suggest that fractionated urine samples can replace 24-hour urine collection. PMID:16628132

  15. Evaluation of Oxidative Stress in Colorectal Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    DONG CHANG; FAN WANG; YA-SHUANG ZHAO; HONG-ZHI PAN

    2008-01-01

    To evaluate the oxidative stress in patients with colorectal cancer and to investigate the relationship between oxidative stress and colorectal cancer. Methods Seventy-six subjects were divided into two groups (36 colorectal cancerpatients as the study group and 40 normal healthy individuals as the control group). Their protein oxidation, DNA damage, lipid peroxidation and antioxidants, vitamin C, vitamin E, glutathione (GSH), and antioxidative enzymes in serum were detected. Results The levels of protein carbonyl and advanced oxidation protein products (AOPP) were significantly higher in the study group than in the control group (P<0.01). Serum 8-OHdG was significantly increased in the study group compared to the control group (P<0.01). However, the mean serum level of MDA and conjugated diene was lower in the study group than in the control group (P<0.01). The activity of antioxidative enzymes was significantly decreased in the study group compared to the control group (P<0.01). Serum vitamins C and E concentrations were significantly reduced in the study group compared to the control group (P<0.01). Conclusion Colorectal cancer is associated with oxidative stress, and assessment of oxidative stress and given antioxidants is important for the treatment and prevention of colorectal cancer.

  16. Nuclear legumain activity in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Mads H Haugen

    Full Text Available The cysteine protease legumain is involved in several biological and pathological processes, and the protease has been found over-expressed and associated with an invasive and metastatic phenotype in a number of solid tumors. Consequently, legumain has been proposed as a prognostic marker for certain cancers, and a potential therapeutic target. Nevertheless, details on how legumain advances malignant progression along with regulation of its proteolytic activity are unclear. In the present work, legumain expression was examined in colorectal cancer cell lines. Substantial differences in amounts of pro- and active legumain forms, along with distinct intracellular distribution patterns, were observed in HCT116 and SW620 cells and corresponding subcutaneous xenografts. Legumain is thought to be located and processed towards its active form primarily in the endo-lysosomes; however, the subcellular distribution remains largely unexplored. By analyzing subcellular fractions, a proteolytically active form of legumain was found in the nucleus of both cell lines, in addition to the canonical endo-lysosomal residency. In situ analyses of legumain expression and activity confirmed the endo-lysosomal and nuclear localizations in cultured cells and, importantly, also in sections from xenografts and biopsies from colorectal cancer patients. In the HCT116 and SW620 cell lines nuclear legumain was found to make up approximately 13% and 17% of the total legumain, respectively. In similarity with previous studies on nuclear variants of related cysteine proteases, legumain was shown to process histone H3.1. The discovery of nuclear localized legumain launches an entirely novel arena of legumain biology and functions in cancer.

  17. Genetics of Colorectal Cancer (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about the genetics of colorectal cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for colorectal cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary colorectal cancer syndrome are also discussed.

  18. The human epidermal growth factor receptor (EGFR gene in European patients with advanced colorectal cancer harbors infrequent mutations in its tyrosine kinase domain

    Directory of Open Access Journals (Sweden)

    Delvenne Philippe

    2011-10-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR, a member of the ErbB family of receptors, is a transmembrane tyrosine kinase (TK activated by the binding of extracellular ligands of the EGF-family and involved in triggering the MAPK signaling pathway, which leads to cell proliferation. Mutations in the EGFR tyrosine kinase domain are frequent in non-small-cell lung cancer (NSCLC. However, to date, only very few, mainly non-European, studies have reported rare EGFR mutations in colorectal cancer (CRC. Methods We screened 236 clinical tumor samples from European patients with advanced CRC by direct DNA sequencing to detect potential, as yet unknown mutations, in the EGFR gene exons 18 to 21, mainly covering the EGFR TK catalytic domain. Results EGFR sequences showed somatic missense mutations in exons 18 and 20 at a frequency of 2.1% and 0.4% respectively. Somatic SNPs were also found in exons 20 and 21 at a frequency of about 3.1% and 0.4% respectively. Of these mutations, four have not yet been described elsewhere. Conclusions These mutation frequencies are higher than in a similarly sized population characterized by Barber and colleagues, but still too low to account for a major role played by the EGFR gene in CRC.

  19. The advances of the liquid biopsy in colorectal cancer%体液检测在结直肠癌中应用的研究进展

    Institute of Scientific and Technical Information of China (English)

    邢宝才; 刘伟

    2016-01-01

    Liquid biopsy refers to the analyses of circulating tumor cells or circulating tumor DNA that mainly exist in the bloodstream and other body lfuid. Liquid biopsy is a novel kind of non-invasive technique and has a wide prospect of clinical application in the molecular pathological field. This review presents the advances of liquid biopsy and its clinical application values in the field of colorectal cancer, including prognosis assessment, early cancer screening and prediction of treatment responses.%体液检测是指以血液为主的体液标本中细胞及核酸的检测,包括了循环肿瘤细胞和循环肿瘤DNA两大类。能帮助实时动态监测肿瘤原发灶及转移复发灶基因组信息,协助早期诊断、疗效监测、预后判断,也有助于靶向治疗适应症的评估,从而推进精准医疗的实施。液态活检属于新型的无创性分子病理检测方式。在结直肠癌诊疗领域具有广阔的临床应用前景,也是推动肿瘤基础研究进展的重要助力。

  20. Colorectal Cancer - What You Need to Know

    Centers for Disease Control (CDC) Podcasts

    2011-07-05

    This podcast is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer.  Created: 7/5/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/5/2011.

  1. Measurement of serum antibodies against NY-ESO-1 by ELISA: A guide for the treatment of specific immunotherapy for patients with advanced colorectal cancer.

    Science.gov (United States)

    Long, Yan-Yan; Wang, Yu; Huang, Qian-Rong; Zheng, Guang-Shun; Jiao, Shun-Chang

    2014-10-01

    NY-ESO-1 has been identified as one of the most immunogenic antigens; thus, is a highly attractive target for cancer immunotherapy. The present study analyzed the expression of serum antibodies (Abs) against NY-ESO-1 in patients with advanced colorectal cancer (CRC), with the aim of guiding the treatment of NY-ESO-1-based specific-immunotherapy for these patients. Furthermore, the present study was the first to evaluate the kinetic expression of anti-NY-ESO-1 Abs and investigate the possible influencing factors. A total of 239 serum samples from 155 pathologically confirmed patients with advanced CRC (stages III and IV) were collected. The presence of spontaneous Abs against NY-ESO-1 was analyzed using an enzyme-linked immunosorbent assay (ELISA). The results demonstrated that 24.5% (38/155) of the investigated patients were positive for NY-ESO-1-specific Abs. No statistically significant correlations were identified between the expression of anti-NY-ESO-1 Abs and clinicopathological parameters, including age and gender, location, grading, local infiltration, lymph node status, metastatic status and K-ras mutation status (P>0.05). In 59 patients, the kinetic expression of anti-NY-ESO-1 Abs was analyzed, of which 14 patients were initially positive and 45 patients were initially negative. Notably, 16/59 (27.1%) patients changed their expression status during the study period, and the initially positive patients were more likely to change compared with the initially negative patients (85.7 vs. 8.8%; PESO-1 by ELISA is an easy and feasible method. The high expression rate of NY-ESO-1-specific Abs in CRC patients indicates that measuring the levels of serum Abs against NY-ESO-1 may guide the treatment of NY-ESO-1-based specific immunotherapy for patients with advanced CRC.

  2. Oxaliplatin-induced neuropathy in colorectal cancer

    DEFF Research Database (Denmark)

    Zedan, Ahmed; Hansen, Torben Frøstrup; Fex Svenningsen, Åsa;

    2014-01-01

    Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic...... neurotoxicity. Early identification of the neurotoxicity and alterations in dose or schedule for the medication could prevent the development of chronic symptoms, which, once established, may take many months or years to resolve or even persist throughout life with a substantial effect on quality of life....... There is no doubt that the use of pharmacogenomic methods to identify genetic bases of interindividual differences in drug response has led to what is called tailoring treatment. Yet there are some challenges regarding the application of these differences. Many efforts have been made to prevent or treat OIPN...

  3. Novel translational strategies in colorectal cancer research

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Defining translational research is still a complex task. In oncology, translational research implies using our basic knowledge learnt from in vitro and in vivo experiments to directly improve diagnostic tools and therapeutic approaches in cancer patients. Moreover, the better understanding of human cancer and its use to design more reliable tumor models and more accurate experimental systems also has to be considered a good example of translational research. The identification and characterization of new molecular markers and the discovery of novel targeted therapies are two main goals in colorectal cancer translational research. However, the straightforward translation of basic research findings, specifically into colorectal cancer treatment and vice versa is still underway. In the present paper, a summarized view of some of the new available approaches on colorectal cancer translational research is provided. Pros and cons are discussed for every approach exposed.

  4. Epigenetics and Colorectal Cancer Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  5. Molecular pathogenesis ofsporadic colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    HidetsuguYamagishi; HajimeKuroda; YasuoImai; HideyukiHiraishi

    2016-01-01

    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classiifed into three major groups according to frequently altered/mutated genes. These genes have been identiifed by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the ifrst half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a lim-ited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research ifeld and discuss its prospects.

  6. Predictive patient-specific dosimetry and individualized dosing of pretargeted radioimmunotherapy in patients with advanced colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schoffelen, Rafke; Woliner-van der Weg, Wietske; Visser, Eric P.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, PO Box 9101, Nijmegen (Netherlands); Goldenberg, David M. [Garden State Cancer Center, Morris Plains, NJ (United States); Immunomedics, Inc., Morris Plains, NJ (United States); IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Sharkey, Robert M.; McBride, William J.; Chang, Chien-Hsing [Immunomedics, Inc., Morris Plains, NJ (United States); Rossi, Edmund A. [IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Graaf, Winette T.A. van der [Radboud University Medical Center, Department of Medical Oncology, Nijmegen (Netherlands)

    2014-08-15

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an {sup 111}In-labeled pretherapy test dose for personalized dosing of {sup 177}Lu-labeled IMP288 following pretargeting with the anti-CEA x anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC). In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after {sup 111}In-IMP288 injection for individualized dosing of PRIT with {sup 177}Lu-IMP288. Different dose schedules were studied, varying the interval between the bsMAb and peptide administration (5 days vs. 1 day), increasing the bsMAb dose (75 mg vs. 150 mg), and lowering the peptide dose (100 μg vs. 25 μg). TF2 and {sup 111}In/{sup 177}Lu-IMP288 clearance was highly variable. A strong correlation was observed between peptide residence times and individual TF2 blood concentrations at the time of peptide injection (Spearman's ρ = 0.94, P < 0.0001). PRIT with 7.4 GBq {sup 177}Lu-IMP288 resulted in low radiation doses to normal tissues (BMD <0.5 Gy, kidney dose <3 Gy). Predicted {sup 177}Lu-IMP288 BMD were in good agreement with the actual measured doses (mean ± SD difference -0.0026 ± 0.028 mGy/MBq). Hematological toxicity was mild in most patients, with only two (10 %) having grade 3-4 thrombocytopenia. A correlation was found between platelet toxicity and BMD (Spearman's ρ = 0.58, P = 0.008). No nonhematological toxicity was observed. These results show that individual high activity doses in PRIT in patients with CEA-expressing CRC could be safely administered by predicting the radiation dose to red marrow and kidneys, based on dosimetric analysis of a test dose of TF2 and {sup 111}In-IMP288. (orig.)

  7. Dietary folate and APC mutations in sporadic colorectal cancer

    NARCIS (Netherlands)

    Vogel, S. de; Engeland, M. van; Lüchtenborg, M.; Bruïne, A.P. de; Roemen, G.M.J.M.; Lentjes, M.H.F.M.; Goldbohm, R.A.; Brandt, P.A. van den; Goeij, A.F.P.M. de; Weijenberg, M.P.

    2006-01-01

    Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between

  8. What's New in Colorectal Cancer Research and Treatment?

    Science.gov (United States)

    ... escape to close saved articles window. My Saved Articles » My ACS ... in colorectal cancer research? Research is always going on in the area of colorectal cancer. Scientists are looking for causes and ways to prevent ...

  9. Fecal DNA Screening in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Suzanne Richter

    2008-01-01

    Full Text Available Colorectal cancer (CRC is the third most common type of cancer diagnosed in Canada, and is the leading cause of cancer-related deaths in nonsmokers. Although CRC is considered to be 90% curable if detected early, the majority of patients present with advanced stage III or IV disease. An effective screening test may significantly decrease disease burden. The present paper examines the rationale and potential of fecal DNA testing as an alternative and adjunct to other CRC screening tests. The most efficacious fecal DNA test developed to date has a sensitivity and specificity of 87.5% and 82%, respectively. The approach has a higher positive predictive value than the currently used fecal occult blood test and offers a noninvasive option to patients. It is not reliant on the presence of bleeding, which may be intermittent or altogether absent. The test is now commercially available and is supported by a number of American insurers. Current challenges include cost reduction and demonstration of mortality benefit in a rigorous clinical trial. Despite current challenges, fecal DNA testing is worth pursuing. Both the American Gastroenterological Society and the American Cancer Society maintain that molecular testing is in its infancy but is promising. Fecal DNA testing has the potential to be an exciting addition to the current armament of CRC screening options.

  10. Cetuximab Plus Oxaliplatin May Not Be Effective Primary Treatment for Metastatic Colorectal Cancer

    Science.gov (United States)

    In a randomized phase III trial, the addition of the targeted therapy cetuximab to oxaliplatin and fluoropyrimidine chemotherapy did not prolong survival or time to disease progression of patients with advanced colorectal cancer.

  11. Efficacy and safety of oxaliplatin chemotherapy programs as adjuvant treatment in colorectal cancer after surgery

    Institute of Scientific and Technical Information of China (English)

    杨莉萍

    2013-01-01

    Objective To compare the efficacy and safety of 5-fluorouracil and calcium folinatc combined with oxaliplatin(FOLFOX) program with capecitabine regimen combined oxaliplatin(XELOX) program as adjuvant chemotherapy in advanced colorectal cancer after surgery.

  12. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  13. Ziv-aflibercept in metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Patel A

    2013-12-01

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

  14. PIK3CA in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gieri eCathomas

    2014-03-01

    Full Text Available PIK3CA, the catalytic subunit of PI3K, is mutated in many different tumours, including colorectal cancer. Mutations of PIK3CA have been reported in 10 – 20% of colorectal cancer, about 80% of mutations found in two hot spots in exon 9 and exon 20. In RAS wild-type colorectal cancers, PIK3CA mutations have been associated with a worse clinical outcome and with a negative prediction of a response to targeted therapy by anti-EGFR monoclonal antibodies. However, these findings have not been confirmed in all studies and subsequent more detailed analysis has revealed that these effects may be restricted to mutations in Exon 20. Finally, mutations in PIK3CA may be the long sought biomarker for successful adjuvant therapy with aspirin in patients with colorectal cancer. Therefore, PIK3CA mutations appear to be a promising predictive biomarker; however, further data are needed to conclusively define the impact of somatic mutations in the PIK3CA gene for the management of patients with colorectal cancer.

  15. Quality of life of patients with locally advanced rectal cancer: anterior rectal resection with colorectal anastomosis versus abdominoperineal excision

    Directory of Open Access Journals (Sweden)

    Maria-Gabriela Aniţei

    2013-09-01

    Full Text Available BACKGROUND: Despite advances in neoadjuvant treatment, rectal resection remains the gold-standard treatment for rectal cancer. AIM: The aim of this study was to assess the benefits of anal sphincter preservation and to compare the quality of life in terms of functional outcome in long term survivors who underwent low (or ultra low anterior resection with total mesorectal excision to patients with abdominoperineal excision for locally advanced rectal cancer with neoadjuvant therapy. MATERIAL AND METHODS: We retrospectively analyzed the medical records of 319 patients who underwent surgery for rectal cancer from 2006 to 2011. Quality of life in 69 eligible patients with preoperative treatment and rectal resection with total mesorectal excision was assessed using the EORTC QLQ C 30 and EORTC QLQ CR29 questionnaires. We evaluated the overall status of quality of life and functional status of these patients symptoms scale. High score for functional scores shows better function whereas high symptom score shows more problems. Results were compared for patients with anal sphincter preservation (SP, 20 patients versus abdominoperineal excision (APE, 49 patients using t-Student test for independent samples. RESULTS: The median follow up in 69 patients was 32 months (range 11-74 months, 32±2,3SD. Quality of life for our group is significantly higher than the reference EORTC population (P < 0.001. Physical functioning (P = 0.050, cognitive functioning (P = 0.039, emotional functioning (P = 0.006, physical and social functioning (P = 0.005, constipation (P = 0.018, body image (P = 0.003, abdominal pain (P = 0.004, embarrassment (P = 0.003 were significantly better for patients with SP. There was no significant differences in the general symptoms of the radiochemotherapy treatment (mouth dryness, hair loss, flavor. Most of the symptom scales like sexual interest, impotence, dyspareunia, diarrhoea did not differ. APE patients suffered more from anxiety (P = 0

  16. Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy: A pilot study

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the combination of bevacizumab with infusional 5-fluorouracil (5-FU), leucovorin (LV) and irinotecan (FOLFIRI) in patients with advanced colorectal cancer (CRC) pretreated with combination regimens including irinotecan and oxaliplatin.METHODS: Fourteen patients (median age 56 years) with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d.RESULTS: The median number of cycles of chemotherapy was six (range 3-12). The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo (95% CI 2.0-8.7),and the median overall survival was 10.9 mo (95% CI 9.6-12.1). Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever.Grade 3 hematuria and hematochezia occurred in one.Grade 2 proteinuria occurred in two patients. However,hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles.CONCLUSION: Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.

  17. 腹腔镜结直肠癌手术的应用现状与进展%Current status of and advance in laparoscopic surgery for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    郑民华

    2008-01-01

    Laparoscopic surgery for colorectal cancer has the advantages of minimal impairment of gastrointestinal and pulmonary function, less immunosuppression and shorter hospital stay, which had been appoved by evidence-based medicine. With the development of concepts and techniques of minimally invasive surgery, the combination of laparoscope and endoscope in the treatment of colorectal cancer has attracted surgeons' attention, and some conventional surgery techniques of colorectal-anal anastomosis have been adopted during laparoscopic colorectal resection, which make ultra-low anastomosis feasible. The aspects mentioned above will promote the further development of laparoscopic surgery for colorectal cancer.

  18. Cytokine-Induced Modulation of Colorectal Cancer.

    Science.gov (United States)

    Mager, Lukas F; Wasmer, Marie-Hélène; Rau, Tilman T; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

  19. Treatment of colorectal cancer - distance results

    Directory of Open Access Journals (Sweden)

    L. Vasile

    2012-01-01

    Full Text Available Significant advances about carcinogenesis and natural history of colorectal cancer (CRC,particularly the establishment of filiations polyp-cancer, are important objectives for a new approach to diagnosis of this disease. Decade 1990-2000 was the decade of CRC detection and prevention, but the decade 2000-2010 is the period of application of new diagnostic and therapeutic concepts. The aim of this study was to highlight the epidemiological,clinical,therapeutic, evolution and prognosis aspects of this cancer at five years after treatment. The research was based on examination of the computerized system of C.E.U.H. of Craiova, observation sheets, operation protocols and anatomic-pathological results, from which we identified from January 2003 until December 2005 a number of 134 patients with CRC investigated, treated and followed completely. At study end (01.07.2010 we noted that 51 of 134 resected patients (38.05% were alive. The median survival time to the entire group of 134 caseswas 44.35 + / -29.94 months. Factors that contribute to a favorable prognosis in CRC are female gender, urban environement origin, ounger than 50 years, the absence of disease or complications associated with neoplasia, colic locations, elective surgery, vegetant and papillary forms, G1 and G2 grading and the disease diagnosed in TMN stages I and II.

  20. Relationship between intestinal microbiota and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Gokhan; Cipe; Ufuk; Oguz; Idiz; Deniz; Firat; Huseyin; Bektasoglu

    2015-01-01

    The human gastrointestinal tract hosts a complexand vast microbial community with up to 1011-1012 microorganisms colonizing the colon. The gut microbiota has a serious effect on homeostasis and pathogenesis through a number of mechanisms. In recent years, the relationship between the intestinal microbiota and sporadic colorectal cancer has attracted much scientific interest. Mechanisms underlying colonic carcinogenesis include the conversion of procarcinogenic diet-related factors to carcinogens and the stimulation of procarcinogenic signaling pathways in luminal epithelial cells. Understanding each of these mechanisms will facilitate future studies, leading to the development of novel strategies for the diagnosis, treatment, and prevention of colorectal cancer. In this review, we discuss the relationship between colorectal cancer and the intestinal microbiota.

  1. MicroRNA regulation network in colorectal cancer metastasis

    Institute of Scientific and Technical Information of China (English)

    Jiao-Jiao; Zhou; Shu; Zheng; Li-Feng; Sun; Lei; Zheng

    2014-01-01

    Colorectal cancer is the third most common cancer worldwide. Metastasis is a major cause of colorectal cancer-related death. Mechanisms of metastasis remain largely obscure. MicroRNA is one of the most important epigenetic regulators by targeting mRNAs posttranscriptionally. Accumulated evidence has supported its significant role in the metastasis of colorectal cancer, including epithelial-mesenchymal transition and angiogenesis. Dissecting microRNAome potentially identifies specific microRNAs as biomarkers of colorectal cancer metastasis. Better understanding of the complex network of microRNAs in colorectal cancer metastasis provide new insights in the biological process of metastasis and in the potential targets for colorectal cancer therapies and for diagnosis of recurrent and metastatic colorectal cancer.

  2. Early diagnosis for colorectal cancer in China

    Institute of Scientific and Technical Information of China (English)

    Ya-Li Zhang; Zhen-Su Zhang; Ba-Ping Wu; Dian-Yuan Zhou

    2002-01-01

    AIM: To review the present studies on early diagnosis ofcoiorectal cancer.METHODS: The detective rate for early cancer is 1.7%-26. 1 % based on various statistical data, with much higherdetective rate in endoscopy. Since early cancer meansinvasion involved in the mucosa or submucosa, thediagnosis can only be made when the invasive depth isidentified. Pathological tissue materials from bothsurgical operation or endoscopic resection are suitable forearly cancer evaluation.RESULTS: Incidence of polyp malignancy is 1.4%~20.4%. The various constitutive proportion of polyps mayexplain the different rates. Malignant incidence is higherin adenomatous polyps, that for villous polyps can reach21 .3%-58.3%. Type Ⅱ early stage of colorectal carcinomais rarely reported in China. it is shownd that majority ofthem were not malignant, most of type lla being adenomaor hyperplasia, and llb being inflammatory and llc mightbe the isolated ulcers. The occurrence of malignancy oftype Ⅱ is far lower than that of polypoid lesion. In China,the qualitative diagnosis and classification of neoplasmgenerally adopted the WHO standard, including surgicalexcision or biopsies. There is impersonal evaluationbetween colorectal pre-malignancy and cancer. Theformer emphasizes the dysplasia of nuclei and gland,while the latter is marked with cancer invasion. Diagnosisof early stage colorectal cancer in endoscopy is made withtoo much caution which made the detective rate muchlower. Mass screening for asymptomatic subjects andfollow-up for high risk population are mainly used to findthe early stage colorectal cancer in China. Fecal occultblood test is also widely made as primary screening test,galactose oxygenase test of rectal mucus (T antigen),fecal occult albumin test are also used. The detective rateof colorectal cancer is 24-36.5 per 105 mass population.CONCLUSION: Although carcinoma associated antigen inblood or stool, microsatellite DNA instability for high riskfamilial history, molecular

  3. BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis.

    Directory of Open Access Journals (Sweden)

    Soo Kyung Nam

    Full Text Available Anti-EGFR antibody-based treatment is an important therapeutic strategy for advanced colorectal cancer (CRC; despite this, several mutations--including KRAS, BRAF, and PIK3CA mutations, and HER2 amplification--are associated with the mechanisms underlying the development of resistance to anti-EGFR therapy. The aim of our study was to investigate the frequencies and clinical implications of these genetic alterations in advanced CRC.KRAS, BRAF, and PIK3CA mutations were determined by Cobas real-time polymerase chain reaction (PCR in 191 advanced CRC patients with distant metastasis. Microsatellite instability (MSI status was determined by a fragmentation assay and HER2 amplification was assessed by silver in situ hybridization. In addition, KRAS mutations were investigated by the Sanger sequencing method in 97 of 191 CRC cases.Mutations in KRAS, BRAF, and PIK3CA were found in 104 (54.5%, 6 (3.1%, and 25 (13.1% cases of advanced CRC, respectively. MSI-high status and HER2 amplification were observed in 3 (1.6% and 16 (8.4% cases, respectively. PIK3CA mutations were more frequently found in KRAS mutant type (18.3% than KRAS wild type (6.9% (P = 0.020. In contrast, HER2 amplifications and BRAF mutations were associated with KRAS wild type with borderline significance (P = 0.052 and 0.094, respectively. In combined analyses with KRAS, BRAF and HER2 status, BRAF mutations or HER2 amplifications were associated with the worst prognosis in the wild type KRAS group (P = 0.004. When comparing the efficacy of detection methods, the results of real time PCR analysis revealed 56 of 97 (57.7% CRC cases with KRAS mutations, whereas Sanger sequencing revealed 49 cases (50.5%.KRAS mutations were found in 54.5% of advanced CRC patients. Our results support that subgrouping using PIK3CA and BRAF mutation or HER2 amplification status, in addition to KRAS mutation status, is helpful for managing advanced CRC patients.

  4. Biomarkers of Angiogenesis in Colorectal Cancer

    OpenAIRE

    Luay Mousa; Salem, Mohamed E.; Sameh Mikhail

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer worldwide and accounts for 10% of all new cancer diagnoses. Angiogenesis is a tightly regulated process that is mediated by a group of angiogenic factors such as vascular endothelial growth factor and its receptors. Given the widespread use of antiangiogenic agents in CRC, there has been considerable interest in the development of methods to identify novel markers that can predict outcome in the treatment of this disease with angiogenesi...

  5. Biomarkers in precision therapy in colorectal cancer

    OpenAIRE

    Reimers, Marlies S.; Zeestraten, Eliane C.M.; Kuppen, Peter J.K.; Liefers, Gerrit Jan; van de Velde, Cornelis J. H.

    2013-01-01

    Colorectal cancer (CRC) is the most commonly diagnosed cancer in Europe. Because CRC is also a major cause of cancer-related deaths worldwide, a lot of research has been focused on the discovery and development of biomarkers to improve the diagnostic process and to predict treatment outcomes. Up till now only a few biomarkers are recommended by expert panels. Current TNM criteria, however, cause substantial under- and overtreatment of CRC patients. Consequently, there is a growing need for ne...

  6. MicroRNAs in colorectal cancer: A new and promising early diagnostic option

    Directory of Open Access Journals (Sweden)

    Akila Prashant

    2012-01-01

    Full Text Available In spite of advances in diagnostic techniques, surgery, chemotherapy and radiotherapy, colorectal cancers remain undefeated. In the absence of screening, colorectal cancers are diagnosed in an advanced stage when regional and distant metastasis is present. Hence, the hope for control is primary prevention or early diagnosis. Western lifestyle and diet have been implicated in the causation of colon cancers. However, it is still a controversy whether this is due to excess calories, high fat content, genotoxic agents, or lack of protective agents present in vegetables and fruits. Therefore, recommending a specific cancer prevention diet can have fallacies. In this context reduction in cancer mortality can be achieved by screening population at high risk. The colorectal cancers require investigative modalities like colonoscopy, sigmoidoscopy or fecal occult blood testing (FOBT for screening. Colonoscopy is the most sensitive and specific of all the available colorectal screening tests, whereas the sensitivity and specificity for FOBT and sigmoidoscopy are much lower. Although performance of FOBT is relatively inexpensive, sigmoidoscopy and colonoscopy must be performed by trained endoscopists and are more expensive. Moreover, lack of awareness that colorectal cancer is a prevalent and serious disease, concerns about the potential discomforts of colorectal cancer procedures or of the preparations for screening appear to be potential barriers for colorectal cancer screening. MicroRNAs (miRNAs have roles in colon carcinogenesis; therefore, may be useful biomarkers for colorectal carcinoma (CRC. They are short ribonucleic acid (RNA molecules having very few nucleotides compared with other RNAs. miRNAs have been studied intensively in the field of oncological research, and emerging evidence suggests that altered miRNA regulation is involved in the pathogenesis of cancers. This review summarizes the use of miRNA in the early diagnosis of colorectal

  7. Korean Guidelines for Colorectal Cancer Screening and Polyp Detection

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Bo In [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of); Hong, Sung Pil [Yensei University College of Medicine, Seoul (Korea, Republic of); Kim, Seong Eun [Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2012-04-15

    Colorectal cancer is currently the second most common cancer among Korean males and the fourth most common among females. Since the majority of colorectal cancer case present following the prolonged transformation of adenomas into carcinomas, early detection and removal of colorectal adenomas are vital methods in its prevention. Considering the increasing incidence of colorectal cancer and polyps in Korea, it is very important to establish national guidelines for colorectal cancer screening and polyp detection. The proposed guidelines have been developed by the Korean Multi-Society Task Force using evidence-based methods. Systematic reviews and meta-analyses have been used to form the statements contained in the guidelines. This paper discusses the epidemiology of colorectal cancers and adenomas in Korea as well as optimal methods for screening of colorectal cancer and detection of adenomas including fecal occult blood tests, radiologic tests, and endoscopic examinations.

  8. Culturing intestinal stem cells: applications for colorectal cancer research

    OpenAIRE

    Fujii, Masayuki; Sato, Toshiro

    2014-01-01

    Recent advance of sequencing technology has revealed genetic alterations in colorectal cancer (CRC). The biological function of recurrently mutated genes has been intensively investigated through mouse genetic models and CRC cell lines. Although these experimental models may not fully reflect biological traits of human intestinal epithelium, they provided insights into the understanding of intestinal stem cell self-renewal, leading to the development of novel human intestinal organoid culture...

  9. Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach.

    Science.gov (United States)

    Flanagan, L; Meyer, M; Fay, J; Curry, S; Bacon, O; Duessmann, H; John, K; Boland, K C; McNamara, D A; Kay, E W; Bantel, H; Schulze-Bergkamen, H; Prehn, J H M

    2016-01-01

    Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers β-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and β-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a

  10. Gut Microbiota, Inflammation, and Colorectal Cancer.

    Science.gov (United States)

    Brennan, Caitlin A; Garrett, Wendy S

    2016-09-01

    Colorectal cancer is the second-leading cause of cancer-related deaths in the United States and fourth-leading cause of cancer-related deaths worldwide. While cancer is largely considered to be a disease of genetic and environmental factors, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping inflammatory environments and promoting tumor growth and spread. Herein, we discuss both human data from meta'omics analyses and data from mechanistic studies in cell culture and animal models that support specific bacterial agents as potentiators of tumorigenesis-including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli. Further, we consider how microbes can be used in diagnosing colorectal cancer and manipulating the tumor environment to encourage better patient outcomes in response to immunotherapy treatments. PMID:27607555

  11. Prognostic stratification of colorectal cancer patients: current perspectives

    Directory of Open Access Journals (Sweden)

    Schneider NI

    2014-07-01

    Full Text Available Nora I Schneider, Cord LangnerInstitute of Pathology, Medical University of Graz, Graz, AustriaAbstract: Tumor staging according to the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, metastasis (TNM system is currently regarded as the standard for staging of patients with colorectal cancer. This system provides the strongest prognostic information for patients with early stage disease and those with advanced disease. For patients with intermediate levels of disease, it is less able to predict disease outcome. Therefore, additional prognostic markers are needed to improve the management of affected patients. Ideal markers are readily assessable on hematoxylin and eosin-stained tumor slides, and in this way are easily applicable worldwide. This review summarizes the histological features of colorectal cancer that can be used for prognostic stratification. Specifically, we refer to the different histological variants of colorectal cancer that have been identified, each of these variants carrying distinct prognostic significance. Established markers of adverse outcomes are lymphatic and venous invasion, as well as perineural invasion, but underreporting still occurs in the routine setting. Tumor budding and tumor necrosis are recent advances that may help to identify patients at high risk for recurrence. The prognostic significance of the antitumor inflammatory response has been known for quite a long time, but a lack of standardization prevented its application in routine pathology. However, scales to assess intra- and peritumoral inflammation have recently emerged, and can be expected to strengthen the prognostic significance of the pathology report.Keywords: colorectal cancer, lymphatic invasion, blood-vessel invasion, perineural invasion, tumor budding, tumor necrosis

  12. Clinical results of carbon ion radiotherapy for pancreatic cancer and colorectal cancer

    International Nuclear Information System (INIS)

    Gastrointestinal cancer is still difficult to treat even using the particle therapy. However, because of their excellent dose distribution, cancer surrounded by gastrointestinal tract such as pancreatic cancer and local recurrence of colorectal cancer after surgery becomes to be treated by particle beam with curative intent. The usefulness of particle beam is reported in the patients with locally advanced pancreatic cancer and patents who received preoperative irradiation with resectable pancreatic cancer. In addition, the postoperative recurrence of rectal cancer is reported to achieve more than 90 percent of local control by particle beam. (author)

  13. Colorectal cancer among atomic bomb survivors

    International Nuclear Information System (INIS)

    Studies on autopsied and surgical cases of colorectal cancer in Hiroshima and Nagasaki atomic bomb (A-bomb) survivors have not shown a relationship to radiation. In a recent epidemiologic study made on a fixed population at the Radiation Effects Research Foundation (RERF), the risk of colon cancer was found to increase significantly with increasing radiation dose in both Hiroshima and Nagasaki, and also in both males and females. The dose effect for the cities and sexes combined was especially pronounced for cancer of the sigmoid colon. The effect of radiation was found to vary by age at the time of the bomb (ATB) and the effect was remarkable among those under age 20 ATB. The risk of rectal cancer was not found to increase significantly with radiation and the distribution of histological types for cancer of either the colon or rectum was unrelated to radiation dose. The effect of A-bomb exposure on the postoperative survival rate for colorectal cancer patients was studied. No difference by radiation dose could be demonstrated. In Japan, the incidence of colorectal cancer, and of colon cancer in particular, has been increasing. Therefore, close attention should be paid to changes occuring in A-bomb survivors

  14. Why I Got Tested for Colorectal Cancer

    Centers for Disease Control (CDC) Podcasts

    2016-02-29

    CDC’s Dr. Lisa Richardson explains why she got tested for colorectal cancer when she turned 50 years old. .  Created: 2/29/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 2/29/2016.

  15. Serum YKL-40 and colorectal cancer

    DEFF Research Database (Denmark)

    Cintin, C; Johansen, J S; Christensen, Ib Jarle;

    1999-01-01

    related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three...

  16. Molecular pathology of colorectal cancer predisposing syndromes

    NARCIS (Netherlands)

    Puijenbroek, Marjo van

    2008-01-01

    Each year, approximately eleven thousand new colorectal cancer (CRC) patients are registered in the Netherlands. Half of these patients will eventually die of this disease. Consequently, it is of great importance to identify individuals with an increased risk for CRC. In this thesis, we evaluate the

  17. BK polyomavirus association with colorectal cancer development.

    Science.gov (United States)

    Khabaz, M N; Nedjadi, T; Gari, M A; Al-Maghrabi, J A; Atta, H M; Basuni, A A; Elderwi, D A

    2016-01-01

    The development of human neoplasms can be provoked by exposure to one of several viruses. Burkitt lymphoma, cervical carcinoma, and hepatocellular carcinoma are associated with Epstein-Barr, human papilloma, and hepatitis B virus infections, respectively. Over the past three decades, many studies have attempted to establish an association between colorectal cancer and viruses, with debatable results. The aim of the present research was to assess the presence of BK polyomavirus (BKV) DNA and protein in colorectal cancer samples from patients in the Western Province of Saudi Arabia. DNA extracted from archival samples of colorectal cancer tissues was analyzed for BKV sequences using polymerase chain reaction (PCR)-based techniques. In addition, expression of a BKV protein was assessed using immunohistochemical staining. None of the tumor and control samples examined tested positive for BKV DNA in PCR assays. Furthermore, immunohistochemical staining failed to detect viral proteins in both cancer and control specimens. These results may indicate that BKV is not associated with the development of colorectal adenocarcinoma in patients in the Western Province of Saudi Arabia. PMID:27173319

  18. The consensus molecular subtypes of colorectal cancer

    NARCIS (Netherlands)

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-01-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data shar

  19. Familial Colorectal Cancer: Understanding the Alphabet Soup.

    Science.gov (United States)

    Giglia, Matthew D; Chu, Daniel I

    2016-09-01

    While most colorectal cancers (CRCs) originate from nonhereditary spontaneous mutations, one-third of cases are familial or hereditary. Hereditary CRCs, which account for alphabet soup of genes to provide the highest quality of care for patients and families. PMID:27582643

  20. Diagnostic interval and mortality in colorectal cancer

    DEFF Research Database (Denmark)

    Tørring, Marie Louise; Frydenberg, Morten; Hamilton, William;

    2012-01-01

    Objective To test the theory of a U-shaped association between time from the first presentation of symptoms in primary care to the diagnosis (the diagnostic interval) and mortality after diagnosis of colorectal cancer (CRC). Study Design and Setting Three population-based studies in Denmark and t...

  1. Hereditary Colorectal Cancer (CRC Program in Latvia

    Directory of Open Access Journals (Sweden)

    Irmejs Arvids

    2003-12-01

    Full Text Available Abstract Introduction The aim of the study is to evaluate the incidence and phenotype - genotype characteristics of hereditary colorectal cancer syndromes in Latvia in order to develop the basis of clinical management for patients and their relatives affected by these syndromes. Materials and methods From 02/1999-09/2002 in several hospitals in Latvia cancer family histories were collected from 865 patients with CRC. In families suspected of having a history consistent with a hereditary colorectal cancer syndrome, DNA testing for MLH1, MSH2 and MSH6 genes was performed. In addition immunohistochemical (IH examination of the normal and cancer tissue from large bowel tumors for MSH2 and MSH6 protein expression was performed prior to DNA analysis. Results From the 865 CRC cases only 3 (0.35% pedigrees fulfilled the Amsterdam II criteria of Hereditary Nonpolyposis Colorectal Cancer (HNPCC and 15 cases (1.73% were suspected of HNPCC. In 69 cases (8% with a cancer family aggregation (CFA were identified. Thus far 27 IH analyses have been performed and in 3 cancers homogenous lack of MSH2 or MSH6 protein expression was found. In one of these cases a mutation in MSH6 was identified. In 18 patients suspected of HNPCC or of matching the Amsterdam II criteria, denaturing high performance liquid chromatography (DHPLC followed by DNA sequencing of any heteroduplexes of the 35 exons comprising both MLH1 and MSH2 was performed revealing 3 mutations. For all of kindreds diagnosed definitively or with a high probability of being an HNPCC family appropriate recommendations concerning prophylactic measures, surveillance and treatment were provided in written form. Conclusions Existing pedigree/clinical data suggest that in Latvia the frequency of HNPCC is around 2% of consecutive colorectal cancer patients. It is crucial that genetic counseling is an integral part of cancer family syndrome management.

  2. Nutrients Impact the Pathogenesis and Development of Colorectal Cancer

    Science.gov (United States)

    Du, Wan; Fang, Jing-Yuan

    2016-01-01

    Background Colorectal cancer is a commonly diagnosed cancer and the cause of many cancer deaths worldwide. Nutrients might be crucial in the pathogenesis and development of colorectal cancer. Although a number of studies have demonstrated the potential effects of nutrients, many challenges still remain Summary A tremendous amount of research has emerged concerning the roles of nutrients in colorectal cancer during the past decades. Here, we review the latest research progress on nutrients, including vitamins, folic acid, calcium, selenium and dietary fiber, involved in colorectal cancer prevention Key Message Nutrients are commonly consumed in foods or dietary supplements. It is clear that nutrients could play an important role and influence colorectal cancer outcomes. The relationship between nutrients and colorectal risk is complex. Vitamins, folic acid, calcium, selenium and dietary fiber have been proposed as potential agents to prevent colorectal cancer. However, some studies found that these nutrients did not reduce the incidence of colorectal cancer Practical Implications The supplementary dose of nutrients, the length of time required to observe the effects and confounding factors during the study might influence the role of nutrients in the prevention of colorectal cancer. Therefore, more evidence from ongoing clinical trials with different population groups and longer follow-up periods is critical to determine the relationship between nutrients and colorectal cancer. PMID:27403415

  3. Research advances of the bone metastasis of the colorectal cancer%结直肠癌骨转移研究进展

    Institute of Scientific and Technical Information of China (English)

    赵亮; 苏佳灿

    2012-01-01

    As one of the most common malignant tumors, the colorectal cancer showed an increasing morbidity and mortality in recent years. Bone metastasis was the terminal manifestation of the colorectal cancer with low metastasis rate. It commonly occurred in multiple bones, leading severe pain, hypercalcemia, pathologic fracture and so on. Appropriate imaging examinations such as X-ray, CT, MRI and ECT and laboratory parameters such as CEA could provide help in the diagnose of the bone metastasis of the colorectal cancer. The mechanism of the bone metastasis of the colorectal cancer was still not clear now, however studies showed that metastasis promoting genes and metastasis suppressing genes might play important roles. The treatment of the bone metastasis included 2 aspects: the systemic treatment including radionuclide therapy, chemotherapy and bone resorption inhibitor therapy and the local treatment including operation and radiotherapy. The bone metastasis of the colorectal cancer was usually ignored in clinic and there were still a lot of problems remaining to be studied in the future.%@@ 结直肠癌是常见恶性肿瘤之一.流行病学资料刘放等[6] 分析了191例结直肠癌术后骨转移的患者,显示,2000年全世界有70万人患结直肠癌,占全部占同期治疗3454例结直肠癌的5.5%,其中结肠癌骨癌症新发病例数的9.4%;50万人死于结直肠癌,占转移率为2.9%,直肠癌转移率为7.5%,结、直肠癌癌症死亡数的7.9%[1-2] .在过去的20多年中,结直转移率差异具有显著的统计学意义.可见,结直肠肠癌的发病数和死亡数在世界大多数国家和地区都癌骨转移率虽然较低,但总体呈上升趋势,且直肠呈上升趋势.

  4. Colorectal cancer risk in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Hugh James Freeman

    2008-01-01

    There is recognized increased risk for colorectal cancer in patients with inflammatory bowel disease, particularly in long-standing and extensive ulcerative colitis. There also appears to be an increased rate of intestinal cancer in Crohn's disease, including both colon and small bowel sites. In Crohn's disease, evidence suggests that detection of colorectal cancer may be delayed with a worse progno sis. Some risk factors for cancer in Crohn's disease include the extent of inflammatory change within the colon and the presence of bypassed or excluded segments, inclu ding rectal "stump" cancer. In addition, the risk for other types of intestinal neoplasms may be increased in Crohn's disease, including lymphoma and carcinoid tumors. Earlier detection of colorectal cancer based on colonoscopy scre ening and surveillance may be achieved but, to date, this has not translated into a positive survival benefit. Moreo ver, newer staining methods and evolving micro-endos copic techniques show promise, but have not significantly altered management. Future research should focus on development of molecular or other bio-markers that might predict future dysplasia or cancer development in Crohn's disease.

  5. Microbiota disbiosis is associated with colorectal cancer

    OpenAIRE

    Gao, Zhiguang; Guo, Bomin; Gao, Renyuan; Zhu, Qingchao; Qin, Huanlong

    2015-01-01

    The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC). The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent non-cancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individual...

  6. Is more better than less? Caveats from bevacizumab and cetuximab combination in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Camillo Porta

    2011-12-01

    Full Text Available In the past few years, impressing improvements have been made in the treatment of advanced colorectal cancer. Following decades of modest achievements, in which it was just a matter of dose and schedule for 5-FU and leucovorin—the only treatment then available—first, the development of irinotecan and oxaliplatin, and then the use of the two biologicals, bevacizumab and cetuximab, have dramatically improved the life expectancy of our colorectal cancer patients...

  7. Surgery for colorectal cancer in Greece

    Institute of Scientific and Technical Information of China (English)

    Mantzoros I; Kanellos D; Pramateftakis MG; Kanellos I

    2009-01-01

    Objective The aim of this study is to analyse our experience and assess the outcome of surgery for colorectal cancer with curative intent in Greece. Methods During the last 10 years, 550 patients were treated for colorectal cancer with curative intent. 291 (52.9%) of the patients suffered from colonic cancer while 259 (47.1%) were operated for rectal cancer. Tumour site, Astler-Coller and TNM classifications and surgical procedures were recorded. Total mortality, morbidity and 5-year survival were evaluated.Results Morbidity rate was 12.0% and mortality rate was 0.68% for colonic cancer surgery, whereas the overall five year survival rate was 77.9%. Morbidity rate was 16.9% and mortality rate was of 0.38% for rectal cancer patients. The overall five year survival rate was 79.6%.Conclusion Morbidity, mortality rate and 5-year survival after colorectal surgery in our department in Greece are comparable to those published in the international literature.

  8. A transcriptome anatomy of human colorectal cancers

    International Nuclear Information System (INIS)

    Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. In this study, we clustered human colorectal normal mucosa (N), inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related expression sequence tags (EST) into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P < 0.01 Hypergeometric Test). Genes in two metabolic pathways, ribosome and glycolysis, were more enriched in the expression profiles of A and IBD than in N and T. Seven transmembrane receptor superfamily genes were typically abundant in cancers. Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers

  9. BRAF Mutation in Colorectal Cancer: An Update.

    Science.gov (United States)

    Barras, David

    2015-01-01

    Colorectal cancer (CRC) is still one of the deadliest cancer-related diseases. About 10% of CRC patients are characterized by a mutation in the B-Raf proto-oncogene serine/threonine kinase (BRAF) gene resulting in a valine-to-glutamate change at the residue 600 (V600E). This mutation is also present in more than 60% of melanoma patients. BRAF inhibitors were developed and found to improve patient survival; however, most patients at the end of the track ultimately develop resistance to these inhibitors. Melanoma patients benefit from the combination of BRAF inhibitors with mitogen/extracellular signal-regulated kinase (MEK) inhibitors, among others. Unfortunately, colorectal patients do not respond much efficiently, which suggests different resistance mechanisms between the two cancer types. This review aims at shedding light on recent discoveries that improve our understanding of the BRAF mutation biology in CRC.

  10. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, Veronica [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Gaggianesi, Miriam [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Spina, Valentina; Iovino, Flora [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Dieli, Francesco [Departement of Biopathology and Medicine Biotechnologies, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Stassi, Giorgio, E-mail: giorgio.stassi@unipa.it [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Todaro, Matilde [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy)

    2011-04-11

    Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem–like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool.

  11. Screening for colorectal cancer: the rationale and a recent advance in the detection of fecal occult blood.

    Science.gov (United States)

    Friend, W G

    1985-01-01

    For the very first time, an occult blood test has been designed to conform to convenient and natural bathroom habits. For the very first time, we therefore expect the general public to agree willingly to participate in occult blood testing. For the very first time, we expect Early Detector to successfully screen the general public, so that survival rates from colon and rectal cancer may show a significant improvement in the next decade. PMID:4034607

  12. The association between serum ferritin with colorectal cancer

    OpenAIRE

    Feng, Zhe; Chen, Ji-Wei; Feng, Jian-Hua; Shen, Fei; Cai, Wen-Song; Jie CAO; Xu, Bo

    2015-01-01

    There are conflicting reports on the correlation between serum levels of ferritin with colorectal cancer. The purpose of the present study is to clarify the association between serum ferritin with colorectal cancer using a meta-analysis approach. We searched articles indexed in Pubmed published as of July 2015 that met our predefined criteria. Six eligible articles involving 927 subjects were identified. Overall, pooled analysis indicated that subjects with colorectal cancer had lower serum l...

  13. REPRODUCTIVE FACTORS AND COLORECTAL CANCER RISK. Case - control study.

    OpenAIRE

    Adriana Ruseva; Radka Lazarova; Ilko Kosturkov; Vesselina Ianachkova; Stella Yordanova; Zhivka Boneva; Diana Nikolovska

    2015-01-01

    Colorectal cancer is one of the most common cancers worldwide. The role of the female sex hormones in the etiology of the disease is very intriguing. Reproductive factors are surrogate measure of lifetime exposition to the sex hormones. Purpose: Our aim is to investigate the association between the reproductive factors and colorectal carcinoma risk. Materials and methods: We include 234 Bulgarian women in our study – 117 cases with colorectal cancer and the same number of healthy contr...

  14. Colorectal cancer risk in hamartomatous polyposis syndromes

    Science.gov (United States)

    Campos, Fábio Guilherme; Figueiredo, Marleny Novaes; Martinez, Carlos Augusto Real

    2015-01-01

    Colorectal cancer (CRC) is a major cause of morbidity and mortality around the world, and approximately 5% of them develop in a context of inherited mutations leading to some form of familial colon cancer syndromes. Recognition and characterization of these patients have contributed to elucidate the genetic basis of CRC. Polyposis Syndromes may be categorized by the predominant histological structure found within the polyps. The aim of the present paper is to review the most important clinical features of the Hamartomatous Polyposis Syndromes, a rare group of genetic disorders formed by the peutz-Jeghers syndrome, juvenil polyposis syndrome and PTEN Hamartoma Tumor Syndrome (Bannayan-Riley-Ruvalacaba and Cowden Syndromes). A literature search was performed in order to retrieve the most recent and important papers (articles, reviews, clinical cases and clinical guidelines) regarding the studied subject. We searched for terms such as “hamartomatous polyposis syndromes”, “Peutz-Jeghers syndrome”, “juvenile polyposis syndrome”, “juvenile polyp”, and “PTEN hamartoma tumour syndrome” (Cowden syndrome, Bananyan-Riley-Ruvalcaba). The present article reports the wide spectrum of disease severity and extraintestinal manifestations, with a special focus on their potential to develop colorectal and other neoplasia. In the literature, the reported colorectal cancer risk for Juvenile Polyposis, Peutz-Jeghers and PTEN Hamartoma Tumor Syndromes are 39%-68%, 39%-57% and 18%, respectively. A review regarding cancer surveillance recommendations is also presented. PMID:25848489

  15. Treatment of colorectal cancer in the elderly

    Institute of Scientific and Technical Information of China (English)

    Monica; Millan; Sandra; Merino; Aleidis; Caro; Francesc; Feliu; Jordi; Escuder; Tani; Francesch

    2015-01-01

    Colorectal cancer has a high incidence, and approxi-mately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients(> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are underrepresented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population.

  16. A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.

    Science.gov (United States)

    Evans, W K; Nixon, D W; Daly, J M; Ellenberg, S S; Gardner, L; Wolfe, E; Shepherd, F A; Feld, R; Gralla, R; Fine, S

    1987-01-01

    One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung cancer [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific nutritional intervention during a 12-week study period when chemotherapy was administered. Those patients randomized to nutritional interventions were counselled to take oral nutrients with caloric intake equal to 1.7 to 1.95 times their basal energy expenditure, depending on their pretreatment nutritional status ("standard" group). An augmented group was counselled to have a caloric intake equivalent to that of the standard group but with 25% of calories provided as protein and additional supplements of zinc and magnesium. Counselling increased caloric intake in both tumor types but reduced weight loss in the short term only for lung cancer patients. Ninety-three NSCLC patients were evaluable for tumor response to vindesine and cisplatin. Overall, only 20.4% of the patients responded, and there were no significant differences in response rates, median time to progression, or overall duration of survival between the nutrition intervention groups and the control group. The tumor response rate to time-sequenced 5-fluorouracil (5-FU) and methotrexate in the 81 evaluable patients with colorectal cancer was only 14.8%, and no significant differences in tumor response rates were noted between the three groups. Furthermore, the median time to progression and overall duration of survival were not different for the control, standard, and augmented groups. Nutritional interventions using dietary counselling had no impact on the percent of planned chemotherapy dose administered, the degree of toxicity experienced by patients, or the frequency of treatment delays. A multivariate prognostic factor analysis demonstrated that for lung cancer, the percent of weight loss, serum albumin concentration, and presence of liver metastases were significant (P less

  17. 晚期结直肠癌血清基质金属蛋白酶-7水平变化与化疗疗效的关系%Relationship Between Serum Matrix Metalloproteinase-7 Levels and the Efficacy of Chemotherapy in Pa-tients with Advanced Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    方兰; 黎朝良; 董荣坤; 黄建朋; 韩明福

    2015-01-01

    Objective]To study the relationship between serum matrix metalloprotein-ase-7 levels and the efficacy of chemotherapy in patients with advanced colorectal cancer.[Methods]Serum MMP-7 were detected with enzyme linked im-munosorbent assay (ELISA)in 61 cases of patients with advanced colorectal cancer (chemotherapy group)and 52 cases of normal control subjects.The Serum MMP-7 levels were also compared before and after chemotherapy in 61 advanced colo-rectal cancer Patients.The therapeutic efficacy was evaluated according to WHO standards.[Results]The MMP-7 level was significantly higher in patients with advanced colorectal colorectal cancer group than the control group and the differ-ence was statistically significant (P 0.05).The serum MMP-7 level was significantly lower in the therapeutic-effective group than the therapeutic-ineffective group (P 0.05);有效组化疗后血清 MMP-7水平明显低于无效组(P <0.05)。【结论】晚期结直肠癌血清 MMP-7水平降低与化疗疗效有关,化疗后血清 MMP-7水平明显降低提示疗效较好,其血清水平的检测可能有助于评价化疗近期疗效。

  18. Contemporary methods of treatment of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Monika Kozłowska

    2016-01-01

    Full Text Available Today, colorectal cancer (CRC is the third most frequently diagnosed worldwide malignant cancer in males, and the second in females, with more than 1,200,000 new cases and more than 600,000 deaths, annually. Screening tests in oncology allow the detection of cancerous disease at an early, asymptomatic stage. The procedures most frequently performed in the case of colorectal cancer include: low anterior resection by the Dixon method (manual suture or staplers; abdominoperineal resection of the rectum by the Miles method; surgical procedure by the Hartmann method; local resection. Various techniques of preoperative radiotherapy are applied, aimed at tumour mass reduction (scheme I and/or obtaining local sterilisation (schemes I and II, which results in the reduction of local metastases (by approximately 50%, as well as an improvement with respect to long-term survival (by approximately 10%. At present, the following drugs for treatment of various forms of colorectal cancer have been registered by the Food and Drug Administration (FDA: fluorouracil capecitabine irinotecan, oxaliplatin, cetuximab, and bevacizumab. The combination of complete cytoreductive surgery (CCS, the goal of which is the removal of all visible (macroscopically cancer foci, with a simultaneous intraperitoneal chemotherapy in hyperthermia – HIPEC, destroying microscopic remains of the disease, allows the curing of some patients with peritoneal cancer. The effect of the action of monoclonal antibodies – cetuximab and panitumumab – is the inhibition of proliferation of cancer cells, intensification of their apoptosis, as well as reduction of synthesis and secretion of pro-angiogenic factors, such as interleukin 8 (IL-8 and vascular endothelial growth factor. In addition, antibodies targeted against EGFR impair the repair of DNA damage caused by chemotherapy and radiotherapy in the cells of the malignant tumour.

  19. Potential Targets for Colorectal Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ali Shamseddine

    2013-08-01

    Full Text Available The step-wise development of colorectal neoplasia from adenoma to carcinoma suggests that specific interventions could delay or prevent the development of invasive cancer. Several key factors involved in colorectal cancer pathogenesis have already been identified including cyclooxygenase 2 (COX-2, nuclear factor kappa B (NF-κB, survivin and insulin-like growth factor-I (IGF-I. Clinical trials of COX-2 inhibitors have provided the “proof of principle” that inhibition of this enzyme can prevent the formation of colonic adenomas and potentially carcinomas, however concerns regarding the potential toxicity of these drugs have limited their use as a chemopreventative strategy. Curcumin, resveratrol and quercetin are chemopreventive agents that are able to suppress multiple signaling pathways involved in carcinogenesis and hence are attractive candidates for further research.

  20. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

  1. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance......BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

  2. Capecitabine in the management of colorectal cancer

    OpenAIRE

    Hirsch BR; Zafar SY

    2011-01-01

    Bradford R Hirsch, S Yousuf ZafarDivision of Medical Oncology, Duke University Medical Center, Durham, NC, USAAbstract: 5-Fluorouracil has been a mainstay in the treatment of colorectal cancer for nearly five decades; however, the use of oral formulations of the medication has been gaining increasing traction since capecitabine was approved for use in adjuvant settings by the US Food and Drug Administration in 2005. The use of capecitabine has since spread to a number of off-label indications...

  3. Microbiota disbiosis is associated with colorectal cancer

    OpenAIRE

    Zhiguang eGao; Bomin eGuo; Renyuan eGao; Qingchao eZhu; Huanlong eQin

    2015-01-01

    The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC). The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent noncancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individuals...

  4. Colorectal Cancer Through Simulation and Experiment

    OpenAIRE

    Kershaw, S. K.; Byrne, H.M.; Gavaghan, D. J.; Osborne, J. M.

    2012-01-01

    Colorectal cancer has continued to generate a huge amount of research interest over several decades, forming a canonical example of tumourigenesis since its use in Fearon and Vogelstein’s linear model of genetic mutation. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical biology and computer-based modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the...

  5. Characterizing metabolic changes in human colorectal cancer.

    Science.gov (United States)

    Williams, Michael D; Zhang, Xing; Park, Jeong-Jin; Siems, William F; Gang, David R; Resar, Linda M S; Reeves, Raymond; Hill, Herbert H

    2015-06-01

    Colorectal cancer (CRC) remains a leading cause of cancer death worldwide, despite the fact that it is a curable disease when diagnosed early. The development of new screening methods to aid in early diagnosis or identify precursor lesions at risk for progressing to CRC will be vital to improving the survival rate of individuals predisposed to CRC. Metabolomics is an advancing area that has recently seen numerous applications to the field of cancer research. Altered metabolism has been studied for many years as a means to understand and characterize cancer. However, further work is required to establish standard procedures and improve our ability to identify distinct metabolomic profiles that can be used to diagnose CRC or predict disease progression. The present study demonstrates the use of direct infusion traveling wave ion mobility mass spectrometry to distinguish metabolic profiles from CRC samples and matched non-neoplastic epithelium as well as metastatic and primary tumors at different stages of disease (T1-T4). By directly infusing our samples, the analysis time was reduced significantly, thus increasing the speed and efficiency of this method compared to traditional metabolomics platforms. Partial least squares discriminant analysis was used to visualize differences between the metabolic profiles of sample types and to identify the specific m/z features that led to this differentiation. Identification of the distinct m/z features was made using the human metabolome database. We discovered alterations in fatty acid biosynthesis and oxidative, glycolytic, and polyamine pathways that distinguish tumors from non-malignant colonic epithelium as well as various stages of CRC. Although further studies are needed, our results indicate that colonic epithelial cells undergo metabolic reprogramming during their evolution to CRC, and the distinct metabolites could serve as diagnostic tools or potential targets in therapy or primary prevention. Graphical Abstract

  6. Immunotherapy and immunoescape in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNy in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma.

  7. DETECTION OF TUMOR MUTANT DNA IN PLASMA OF PATIENT WITH COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    李明; 万文辉; 顾晋

    2002-01-01

    Early diagnosis and prompt treatment are mandatory to prevent colorectal cancer. Detection of free circulating tumor DNA in the serum of the cancer patients provides new possibilities for cancer diagnosis. Several circulating colorectal cancer DNAs have been identified by PCR detection such as the activated K-ras oncogene, inactivated APC, p53 genes, and microsatellite instability (MSI). Circulating tumor DNA was predominantly found in patients with advanced disease and poor prognosis. It was suggested that analysis for circulating tumor DNA might be useful in early diagnosis.

  8. Serum IGF1, IGF2 and IGFBP3 and risk of advanced colorectal adenoma.

    Science.gov (United States)

    Gao, Ying; Katki, Hormuzd; Graubard, Barry; Pollak, Michael; Martin, Michael; Tao, Yuzhen; Schoen, Robert E; Church, Timothy; Hayes, Richard B; Greene, Mark H; Berndt, Sonja I

    2012-07-15

    The insulin-like growth factor (IGF) signaling pathway is involved in cell proliferation and differentiation. Elevated serum IGF1 levels have been associated with increased colorectal cancer risk; however, studies of this association with colorectal adenoma are inconclusive. We examined serum IGF1, IGF2 and IGFBP3 levels in relation to risk of advanced colorectal adenoma in a case-control study within the prostate, lung, colorectal and ovarian cancer screening trial. A total of 764 advanced, left-sided colorectal adenoma cases and 775 controls frequency-matched on gender and ethnicity, without evidence of a left-sided polyp on sigmoidoscopy were included in the current study. Serum levels of IGF1, IGF2 and IGFBP3 were measured using an enzyme linked immunosorbent assay in serum samples collected at baseline. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations adjusting for age, race, sex, year of blood draw, body mass index, smoking and education. Higher IGF1 levels were associated with increased adenoma risk: ORs = 1.58 (95% CI = 1.16-2.16), 1.42 (95% CI = 1.04-1.93), and 1.80 (95% CI = 1.30-2.47) for the second, third and fourth quartiles, respectively (p(trend) = 0.002). Elevated IGF2 levels were also associated with increased adenoma risk (OR = 1.43, 95% CI = 1.05-1.96 for the fourth vs. first quartile, p(trend) = 0.02), but the association was no longer significant after adjustment for IGF1 (p(trend) = 0.28). IGFBP3 levels were not associated with adenoma risk. Our analysis showed a significant positive association between circulating IGF1 levels and risk of advanced colorectal adenoma, suggesting that IGF1 is associated with the pivotal precursor to colorectal cancer. PMID:21932422

  9. Towards a multiscale model of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Ingeborg MM van Leeuwen; Carina M Edwards; Mohammad Ilyas; Helen M Byrne

    2007-01-01

    Colorectal cancer (CRC) is one of the best characterised cancers, with extensive data documenting the sequential gene mutations that underlie its development.Complementary datasets are also being generated describing changes in protein and RNA expression,tumour biology and clinical outcome. Both the quantity and the variety of information are inexorably increasing and there is now an accompanying need to integrate these highly disparate datasets. In this article we aim to explain why we believe that mathematical modelling represents a natural tool or language with which to integrate these data and, in so doing, to provide insight into CRC.

  10. Minimally Invasive Colorectal Cancer Surgery in Europe

    OpenAIRE

    Babaei, Masoud; Balavarca, Yesilda; Jansen, Lina; Gondos, Adam; Lemmens, Valery; Sjövall, Annika; B⊘rge Johannesen, Tom; Moreau, Michel; Gabriel, Liberale; Gonçalves, Ana Filipa; Bento, Maria José; van de Velde, Tony; Kempfer, Lana Raffaela; Becker, Nikolaus; Ulrich, Alexis

    2016-01-01

    Abstract Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse. In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared ...

  11. 结直肠癌k-ras基因检测及其靶向治疗的研究现状%Recent advances in detection of k- ras gene mutations and targeted therapy of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    王丽; 余英豪

    2011-01-01

    越来越多的研究表明,EGFR单抗对k-ras基因野生型结直肠癌患者治疗有效.k-ras基因编码的K-ras蛋白为EGFR信号通路下游区的一种小分子G蛋白,k-ras基因发生突变后,导致该信号通路异常活化,从而对EGFR单抗治疗无效.因此,检测k-ras基因状态对指导结直肠癌患者靶向治疗十分重要.本文就k-ras基因检测方法及与结直肠癌靶向治疗的研究现状进行综述.%Numerous studies have shown that anti-epidermal growth factor receptor (EGFR) monoclonal antibodies are effective in the treatment of colorectal cancer patients with the wild-type k-ras gene. The k-ras gene encodes a G-protein that functions downstream of EGFR signaling. Since k-ras mutations result in abnormal activation of the EGFR signaling pathway,anti-EGFR monoclonal antibody treatment is ineffective for patients with k-ras mutations.Therefore, k-ras mutation analysis is very important for targeted therapy of patients with colorectal cancer. This paper gives an overview of the recent advances in detection of k-ras gene mutations and targeted therapy of colorectal cancer.

  12. Decreased levels of plasma adiponectin associated with increased risk of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Sayaka; Otake; Hiroaki; Takeda; Shoichiro; Fujishima; Tadahisa; Fukui; Tomohiko; Orii; Takeshi; Sato; Yu; Sasaki; Shoichi; Nishise; Sumio; Kawata

    2010-01-01

    AIM:To investigate the association between adiponectin levels and risk of colorectal adenoma and cancer (early and advanced).METHODS: A cross-sectional study in a cohort of hospital-based patients was conducted between January 2004 and March 2006 at Yamagata University Hospital. Male subjects, who had colorectal tumors detected by endoscopic examination, were enrolled according to inclusion and exclusion criteria. Based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive c...

  13. TNIK inhibition abrogates colorectal cancer stemness

    Science.gov (United States)

    Masuda, Mari; Uno, Yuko; Ohbayashi, Naomi; Ohata, Hirokazu; Mimata, Ayako; Kukimoto-Niino, Mutsuko; Moriyama, Hideki; Kashimoto, Shigeki; Inoue, Tomoko; Goto, Naoko; Okamoto, Koji; Shirouzu, Mikako; Sawa, Masaaki; Yamada, Tesshi

    2016-01-01

    Canonical Wnt/β-catenin signalling is essential for maintaining intestinal stem cells, and its constitutive activation has been implicated in colorectal carcinogenesis. We and others have previously identified Traf2- and Nck-interacting kinase (TNIK) as an essential regulatory component of the T-cell factor-4 and β-catenin transcriptional complex. Consistent with this, Tnik-deficient mice are resistant to azoxymethane-induced colon tumorigenesis, and Tnik−/−/Apcmin/+ mutant mice develop significantly fewer intestinal tumours. Here we report the first orally available small-molecule TNIK inhibitor, NCB-0846, having anti-Wnt activity. X-ray co-crystal structure analysis reveals that NCB-0846 binds to TNIK in an inactive conformation, and this binding mode seems to be essential for Wnt inhibition. NCB-0846 suppresses Wnt-driven intestinal tumorigenesis in Apcmin/+ mice and the sphere- and tumour-forming activities of colorectal cancer cells. TNIK is required for the tumour-initiating function of colorectal cancer stem cells. Its inhibition is a promising therapeutic approach. PMID:27562646

  14. The impact of new technology on surgery for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Gregory B Makin; David J Breen; John RT Monson

    2001-01-01

    Advances in technology continue at a rapid pace and affect all aspects of life, including surgery. We have reviewed some of these advances and the impact they are having on the investigation and management of colorectal cancer. Modern endoscopes, with magnifying, variable stiffness and Iocalisation capabilities are making the primary investigation of colonic cancer easier and more acceptable for patients. Imaging investigations looking at primary, metastatic and recurrent disease are shifting to digital data sets. which can he stored, reviewed remotely, potentially fused with other modalities and reconstructed as 3 dimensional (3D) images for the purposes of advanced diagnostic interpretation and computer assisted surgery. They include virtual colonoscopy, trans-rectal ultrasound, magnetic resonance imaging, positron emission tomography and radioimmunoscintigraphy. Once a colorectal carcinoma is diagnosed, the treatment options available are expanding.Colonic stents are being used to relieve large bowel obstruction, either as a palliative measure or to improve the patient's overall condition before definitive surgery.Transenal endoscopic microsurgery and minimally invasive techniques are being used with similar outcomes and a lower mortality, morbidity and hospital stay than open trans-abdominal surgery. Transanal endoscopic microsurgery allows precise excision of both benign and early malignant lesions in the mid and upper rectum.Survival of patients with inoperable hepatic metastases following radiofrequency ablation is encouraging.Robotics and telemedicine are taking surgery well into the 21st century. Artificial neural networks are being developed to enable us to predict the outcome for individual patients. New technology has a major impact on the way we practice surgery for colorectal cancer.``

  15. Panitumumab: the evidence of its therapeutic potential in metastatic colorectal cancer care

    Directory of Open Access Journals (Sweden)

    Erika Martinelli

    2007-11-01

    Full Text Available Erika Martinelli1, Floriana Morgillo1, Teresa Troiani1, Giampaolo Tortora2, Fortunato Ciardiello11Cattedra di Oncologia Medica, Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale “F. Magrassi e A. Lanzara”, Seconda Università degli Studi di Napoli, Napoli, Italy; 2Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinina, Università di Napoli Federico II, Napoli, ItalyIntroduction: Colorectal cancer is the fourth most common malignant disease. Of newly diagnosed patients, 40% have metastatic disease at diagnosis, and approximately 25% of patients with localized disease at diagnosis will ultimately develop metastatic disease. The benefits of systemic chemotherapy in the treatment of metastatic colorectal cancer over best supportive care have been established. Panitumumab (ABX-EGF is the first fully human monoclonal antibody developed for use in colorectal cancer that targets the extracellular domains of epidermal growth factor receptor.Aims: The goal of this article is to review the published evidence for the use of panitumumab in the treatment of metastatic colorectal cancer to define its therapeutic potential.Evidence review: The major evidence of panitumumab activity in colorectal cancer has appeared in meeting report abstracts. One phase II study in monotherapy, one in combination with chemotherapy, and one phase III study have included only patients with metastatic colorectal cancer.Clinical potential: To date, in phase II clinical studies panitumumab has demonstrated antitumor activity in advanced, refractory colorectal cancer. As monotherapy it resulted in a 10% response rate with 38% of patients having stable disease, and a 36% response rate with 46% stable disease when combined with chemotherapy. A phase III study indicates a clinically significant advantage of panitumumab as third-line monotherapy over best supportive care. Panitumumab appears to have a good tolerability profile, with no maximum tolerated

  16. Colorectal Cancer Epidemiology: Incidence, Mortality, Survival, and Risk Factors

    OpenAIRE

    Haggar, Fatima A.; Boushey, Robin P.

    2009-01-01

    In this article, the incidence, mortality, and survival rates for colorectal cancer are reviewed, with attention paid to regional variations and changes over time. A concise overview of known risk factors associated with colorectal cancer is provided, including familial and hereditary factors, as well as environmental lifestyle-related risk factors such as physical inactivity, obesity, smoking, and alcohol consumption.

  17. Metabolites of tobacco smoking and colorectal cancer risk

    OpenAIRE

    Cross, Amanda J.; Boca, Simina; Freedman, Neal D.; Caporaso, Neil E.; Huang, Wen-Yi; Sinha, Rashmi; Sampson, Joshua N.; Moore, Steven C

    2014-01-01

    Epidemiologic studies report inconsistent and modest associations between smoking and colorectal cancer. Serum hydroxycotinine captures smoking behavior and metabolic variation, and is associated with a 2.7-fold increased risk of incident colorectal cancer, supporting a role for tobacco in this malignancy.

  18. Urinary nucleosides as biological markers for patients with colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yu-Fang Zheng; Jun Yang; Xin-Jie Zhao; Bo Feng; Hong-Wei Kong; Ying-Jie Chen; Shen Lv; Min-Hua Zheng; Guo-Wang Xu

    2005-01-01

    AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer.METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method.RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%).Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke's stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32)and 91% (10/11) in response group and progressive group, respectively.CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer.

  19. Correlation between expression and differentiation of endocan in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Li Zuo; Su-Mei Zhang; Ruo-Lei Hu; Hua-Qing Zhu; Qing Zhou; Shu-Yu Gui; Qiang Wu; Yuan Wang

    2008-01-01

    AIM: To investigate the expression frequency of endocan in colorectal cancer and analyze the relationship between endocan expression and clinical parameters and to study the role of endocan in colorectal carcinogenesis.METHODS: Expression of endocan in 72 tumor tissue samples of colorectal cancer as well as in 27 normal mucous membrane tissue samples was analyzed using in situ hybridization, immunohistochemistry on tissue microarray, Western blot and reverse-transcript polymerase chain reaction (RT-PCR).RESULTS: The expression of endocan was higher in normal colon and rectum tissue samples than in cancerous tissue samples (mRNA = 92.6%, protein= 36%), and was lower in colorectal cancer tissuesamples (mRNA = 70.4%, protein = 36.1%). No correlation was found between staining intensity and clinical parameters such as sex, age, tumor size and TNM stage. However, the expression of endocan was positively correlated with the tissue differentiation in colorectal cancer.CONCLUSION: The expression of endocan is down-regulated in colorectal cancer and is positively correlated with the tissue differentiation in colorectal cancer, suggesting that the expression of endocan is associated with development and differentiation of colorectal cancer.

  20. Social inequality in breast, lung and colorectal cancers

    DEFF Research Database (Denmark)

    Søndergaard, Grethe; Mortensen, Laust Hvas; Andersen, Anne-Marie Nybo;

    2013-01-01

    To examine whether family factors shared by siblings explained the association between education and risk of lung, colorectal and breast cancer.......To examine whether family factors shared by siblings explained the association between education and risk of lung, colorectal and breast cancer....

  1. Colorectal cancer screening awareness among physicians in Greece

    Directory of Open Access Journals (Sweden)

    Chatzimichalis Georgios

    2006-06-01

    Full Text Available Abstract Background Data comparison between SEER and EUROCARE database provided evidence that colorectal cancer survival in USA is higher than in European countries. Since adjustment for stage at diagnosis markedly reduces the survival differences, a screening bias was hypothesized. Considering the important role of primary care in screening activities, the purpose of the study was to investigate the colorectal cancer screening awareness among Hellenic physicians. Methods 211 primary care physicians were surveyed by mean of a self-reported prescription-habits questionnaire. Both physicians' colorectal cancer screening behaviors and colorectal cancer screening recommendations during usual check-up visits were analyzed. Results Only 50% of physicians were found to recommend screening for colorectal cancer during usual check-up visits, and only 25% prescribed cost-effective procedures. The percentage of physicians recommending stool occult blood test and sigmoidoscopy was 24% and 4% respectively. Only 48% and 23% of physicians recognized a cancer screening value for stool occult blood test and sigmoidoscopy. Colorectal screening recommendations were statistically lower among physicians aged 30 or less (p = 0.012. No differences were found when gender, level and type of specialization were analyzed, even though specialists in general practice showed a trend for better prescription (p = 0.054. Conclusion Contemporary recommendations for colorectal cancer screening are not followed by implementation in primary care setting. Education on presymptomatic control and screening practice monitoring are required if primary care is to make a major impact on colorectal cancer mortality.

  2. Epidemiology of colorectal cancer; Epidemiologie kolorektaler Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Becker, N. [Deutsches Krebsforschungszentrum Heidelberg (Germany)

    2003-02-01

    Colorectal tumors are among the most frequently encountered forms of cancer worldwide. With approximately 57,000 new cases every year, they represent the most frequent type of cancer in Germany, ranking before breast cancer (approximately 46,000) and lung cancer (approximately 37,000). Although global incidence is on the rise, in Germany it is only increasing among men, but not among women. The mortality rate (approximately 26,500 deaths annually) in Germany has declined among men for about the past 10 years and among women for about the past 20 years.The most important risk factors are familial history of colorectal and other tumors as well as lifestyle factors such as nutrition, obesity, inactivity,and smoking.Lifestyle-related risks offer a broad area for implementing primary preventive measures, which have not yet been adequately exhausted. Several proven (fecal occult blood test) and probably effective (endoscopic) methods are available for secondary prevention. Consistent encouragement of these possibilities for prevention could reduce incidence and mortality substantially and render colorectal tumors less frequent. (orig.) [German] Kolorektale Tumoren gehoeren weltweit zu den haeufigsten Krebsarten und sind mit jaehrlich ca.57000 Neuerkrankungsfaellen vor Brustkrebs (ca. 46000) und Lungenkrebs (ca. 37000) die haeufigste Krebsart in Deutschland.Waehrend die Inzidenz weltweit steigt, nimmt sie in Deutschland nur bei Maennern,nicht aber bei Frauen zu.Die Mortalitaet (jaehrlich ca.26500 Todesfaelle) geht hierzulande bei Maennern seit ca.10 Jahren, bei Frauen seit ca.20 Jahren zurueck. Die bedeutendsten Risikofaktoren sind familiaere Vorgeschichte an kolorektalen und anderen Tumoren sowie Lebensstilfaktoren wie Ernaehrung, Uebergewicht,Bewegungsmangel und Rauchen.Die lebensstilbedingten Risiken bieten breiten Raum fuer primaere Praevention, der bisher nur unzureichend ausgeschoepft ist.Auch fuer sekundaere Praevention stehen mehrere nachgewiesenermassen (Test auf

  3. Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

    OpenAIRE

    Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek; Murawa, Dawid

    2016-01-01

    Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualifi...

  4. Metastatic Colorectal Cancer Resembling Severe Preeclampsia in Pregnancy

    Directory of Open Access Journals (Sweden)

    Raminder Kaur Khangura

    2015-01-01

    Full Text Available Although colorectal cancer (CRC is the third most common cancer in women, it is a rare malignancy in pregnancy. Symptoms of CRC such as fatigue, malaise, nausea, vomiting, rectal bleeding, anemia, altered bowel habits, and abdominal mass are often considered typical symptoms of pregnancy. Many cases of CRC are diagnosed in advanced stages due to missed warning signs of CRC, which may be misinterpreted as normal symptoms related to pregnancy. This report reviews 2 cases of CRC diagnosed within a 4-month interval at our institution. Both cases were initially thought to be atypical presentations of preeclampsia. Prenatal history, hospital course, and postpartum course were reviewed for both patients. CRC is often diagnosed at advanced stages in pregnancy. Common physiological symptoms of pregnancy should be scrutinized carefully and worked up appropriately, especially if symptoms remain persistent or increase in intensity or severity.

  5. Gain of ALK gene copy number may predict lack of benefit from anti-EGFR treatment in patients with advanced colorectal cancer and RAS-RAF-PI3KCA wild-type status.

    Directory of Open Access Journals (Sweden)

    Filippo Pietrantonio

    Full Text Available Although cetuximab and panitumumab show an increased efficacy for patients with KRAS-NRAS-BRAF and PI3KCA wild-type metastatic colorectal cancer, primary resistance occurs in a relevant subset of molecularly enriched populations.We evaluated the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status (disomic vs. gain of ALK gene copy number--defined as mean of 3 to 5 fusion signals in ≥ 10% of cells. All consecutive patients received cetuximab and irinotecan or panitumumab alone for chemorefractory disease.No ALK translocations or amplifications were detected. ALK gene copy number gain was found in 25 (37% tumors. Response rate was significantly higher in patients with disomic ALK as compared to those with gain of gene copy number (70% vs. 32%; p = 0.0048. Similarly, progression-free survival was significantly different when comparing the two groups (6.7 vs. 5.3 months; p = 0.045. A trend was observed also for overall survival (18.5 vs. 15.6 months; p = 0.885.Gain of ALK gene copy number might represent a negative prognostic factor in mCRC and may have a role in resistance to anti-EGFR therapy.

  6. The Association of Cholelithiasis and Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    C Sărăcuț

    2014-02-01

    Full Text Available Background: In the literature there are a number of studies that suggest a possible correlation between cholelithiasis/cholecystectomy and colorectal cancer. The exposure of the colon mucosa to the action of bile acids that potentially have a carcinogenic effect due to the change in anatomy after cholecystectomy, seems to be the explanation of this association. The purpose of this paper was to search for such a correlation in our study group. Methods: We performed a retrospective cross-sectional study, analyzing the patients admitted to the First Surgical Clinic of the County Emergency Clinical Hospital Tîrgu Mureș, between January 1st, 2005 - December 31st, 2010. Analyzing the medical records, operation protocols and histopathological results, we paid attention to demographics, location of neoplasia, the time elapsed since the cholecystectomy to the discovery of neoplasia, histological types, trying to perform correlations between these parameters and the lithiasic factor. Results: Out of the 534 patients admitted and operated with the diagnosis of colorectal cancer, 15.6% (n = 83 showed a history of gallbladder stone affection. Most patients came from urban areas, the average age was 67.2 (range 39-88 years, females were more affected. The most common locations were: the sigmoid colon (26.5%, rectum (36.3% and the most common histological form was moderately differentiated adenocarcinoma. Conclusions: Similar to other studies, our work suggests a slight increase in the incidence of colorectal cancer in patients that underwent a cholecystectomy, without drawing a firm conclusion. We deem it necessary to see if diet changes of the Romanian population affect this relationship

  7. Focusing the Spotlight on the Zebrafish Intestine to Illuminate Mechanisms of Colorectal Cancer.

    Science.gov (United States)

    Lobert, Viola H; Mouradov, Dmitri; Heath, Joan K

    2016-01-01

    Colorectal cancer, encompassing colon and rectal cancer, arises from the epithelial lining of the large bowel. It is most prevalent in Westernised societies and is increasing in frequency as the world becomes more industrialised. Unfortunately, metastatic colorectal cancer is not cured by chemotherapy and the annual number of deaths caused by colorectal cancer, currently 700,000, is expected to rise. Our understanding of the contribution that genetic mutations make to colorectal cancer, although incomplete, is reasonably well advanced. However, it has only recently become widely appreciated that in addition to the ongoing accumulation of genetic mutations, chronic inflammation also plays a critical role in the initiation and progression of this disease. While a robust and tractable genetic model of colorectal cancer in zebrafish, suitable for pre-clinical studies, is not yet available, the identification of genes required for the rapid proliferation of zebrafish intestinal epithelial cells during development has highlighted a number of essential genes that could be targeted to disable colorectal cancer cells. Moreover, appreciation of the utility of zebrafish to study intestinal inflammation is on the rise. In particular, zebrafish provide unique opportunities to investigate the impact of genetic and environmental factors on the integrity of intestinal epithelial barrier function. With currently available tools, the interplay between epigenetic regulators, intestinal injury, microbiota composition and innate immune cell mobilisation can be analysed in exquisite detail. This provides excellent opportunities to define critical events that could potentially be targeted therapeutically. Further into the future, the use of zebrafish larvae as hosts for xenografts of human colorectal cancer tissue, while still in its infancy, holds great promise that zebrafish could one day provide a practical, preclinical personalized medicine platform for the rapid assessment of the

  8. Pulmonary nodules and metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i......% of all patients staged with a thoracic CT had IPN, however, the prevalence varied significantly between patients series. This was mainly attributed to varying/lacking definitions on IPN and variable radiological expertise in the assessment of the scans. Data were too inconsistently reported in the case...... detected in 7.5% of the patients and in 37% of these cases the metastatic spread was confined to the lungs. The prevalence of SPCM increased with the implementation of thoracic CT in CRC staging. SPCM impaired survival significantly and was associated with increasing age and rectal cancer. Resection...

  9. Targeting Notch Signaling in Colorectal Cancer.

    Science.gov (United States)

    Suman, Suman; Das, Trinath P; Ankem, Murali K; Damodaran, Chendil

    2014-12-01

    The activation of Notch signaling is implicated in tumorigenesis in the colon due to the induction of pro-survival signaling in colonic epithelial cells. Chemoresistance is a major obstacle for treatment and for the complete eradication of colorectal cancer (CRC), hence, the inhibition of Notch is an attractive target for CRC and several groups are working to identify small molecules or monoclonal antibodies that inhibit Notch or its downstream events; however, toxicity profiles in normal cells and organs often impede the clinical translation of these molecules. Dietary agents have gained momentum for targeting several pro-survival signaling cascades, and recent studies demonstrated that agents that inhibit Notch signaling result in growth inhibition in preclinical models of CRC. In this review, we focus on the importance of Notch as a preventive and therapeutic target for colon cancer and on the effect of WA on this signaling pathway in the context of colon cancer. PMID:25395896

  10. Colorectal Cancer & Molecular Mutations and Polymorphism

    Directory of Open Access Journals (Sweden)

    Aga Syed Sameer

    2013-05-01

    Full Text Available Colorectal cancer (CRC is one of the major causes of mortality and morbidity, and is the third most common cancer in men and the second most common cancer in women worldwide. The incidence of CRC shows considerable variation among racially or ethnically defined populations in multiracial/ethnic countries. The tumorigenesis of CRC is either because of the chromosomal instability (CIN or microsatellite instability (MIN or involving various proto-oncogenes, tumor suppressor genes and also epigenetic changes in the DNA. In this review I have focused on the mutations and polymorphisms of various important genes of the CIN and MIN pathways which have been implicated in the development of CRC.

  11. Expression of hippo pathway in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Kun Liang

    2014-01-01

    Full Text Available Background/Aims: Hippo pathway plays a crucial role in cell proliferation, apoptosis, and tumorigenesis. This study aimed to investigate the expression of Hippo pathway components in the progression and metastasis of colorectal cancer (CRC. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR was used to examine the mRNA expression levels of MST1, LATS2, YAP, TAZ, TEAD1, CDX2, and OCT4, and western blot (WB was used to examine the protein expression levels of MST1, YAP, TEAD1, and CDX2 in 30 specimens of human colorectal adenomas, 50 pairs of human CRC tissues, and adjacent nontumorous tissues from CRC patients. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH was used as the housekeeping gene in qRT-PCR. Results: The mRNA expression levels of MST1 and LATS2 showed an increasing tendency from CRC to adjacent nontumorous tissues (P < 0.001. Conversely, the mRNA expression levels of YAP, TAZ, TEAD, and OCT4 showed a decreasing tendency from CRC to adjacent nontumorous tissues (P < 0.001. MST1 protein was downregulated and YAP and TEAD1 proteins were upregulated in CRC (all P < 0.001. The mRNA and protein expression levels of CDX2 in CRC were significantly lower than those in colorectal adenomas and adjacent nontumorous tissues (P < 0.001, but there was no significant difference between the latter two groups (qRT-PCR, P = 0.113; WB, P = 0.151. Furthermore, statistical analysis showed that the expression levels of Hippo signal pathway components were associated with tumor differentiation, lymph node metastasis, and TNM stage. Conclusion: Hippo pathway is suppressed in the progression from colorectal adenomas to CRC and is associated with CRC progression and metastasis. This study suggests the components of Hippo pathway might be prognostic indicators for CRC patients.

  12. Hypermethylated DNA, a Biomarker for colorectal cancer

    DEFF Research Database (Denmark)

    Rasmussen, Simon Ladefoged; Krarup, Henrik Bygum; Sunesen, Kåre Gotschalck;

    2016-01-01

    AIM: In colorectal cancer (CRC), improved methods for early detection are essential for increasing survival. Hypermethylated DNA in blood or stool has been proposed as a biomarker for CRC. In recent years, biochemical methods have improved, and several hypermethylated genes that are sensitive....... In blood samples, hypermethylated P16, HLTF, TMEFF1, ALX4, VIM, and FBN2 were associated with poor prognosis, hypermethylated APC, TAC1, SEPT9, NEUROG1, RASSF1A, SDC2, and THBD were detected in early-stage CRC, and hypermethylated P16 and TFPI2 could detect CRC recurrence. In stool samples, hypermethylated...

  13. Biomechanical investigation of colorectal cancer cells

    Science.gov (United States)

    Palmieri, Valentina; Lucchetti, Donatella; Maiorana, Alessandro; Papi, Massimiliano; Maulucci, Giuseppe; Ciasca, Gabriele; Svelto, Maria; De Spirito, Marco; Sgambato, Alessandro

    2014-09-01

    The nanomechanical properties of SW480 colon cancer cells were investigated using Atomic Force Microscopy. SW480 cells are composed of two sub-populations with different shape and invasiveness. These two cells populations showed similar adhesion properties while appeared significantly different in term of cells stiffness. Since cell stiffness is related to invasiveness and growth, we suggest elasticity as a useful parameter to distinguish invasive cells inside the colorectal tumor bulk and the high-resolution mechanical mapping as a promising diagnostic tool for the identification of malignant cells.

  14. Immune cell interplay in colorectal cancer prognosis

    Institute of Scientific and Technical Information of China (English)

    Samuel; E; Norton; Kirsten; A; Ward-Hartstonge; Edward; S; Taylor; Roslyn; A; Kemp

    2015-01-01

    The immune response to colorectal cancer has proven to be a reliable measure of patient outcome in several studies. However, the complexity of the immune response in this disease is not well understood, par-ticularly the interactions between tumour-associated cells and cells of the innate and adaptive immune system. This review will discuss the relationship betweencancer associated fibroblasts and macrophages, as well as between macrophages and T cells, and demonstrate how each population may support or prevent tumour growth in a different immune environment.

  15. Development of a Federally Funded Demonstration Colorectal Cancer Screening Program

    Directory of Open Access Journals (Sweden)

    Janet Royalty, MS

    2008-04-01

    Full Text Available Colorectal cancer is the second leading cause of cancer-related mortality among U.S. adults. In 2004, treatment costs for colorectal cancer were $8.4 billion.There is substantial evidence that colorectal cancer incidence and mortality are reduced with regular screening. The natural history of this disease is also well described: most colorectal cancers develop slowly from preexisting polyps. This slow development provides an opportunity to intervene with screening tests, which can either prevent colorectal cancer through the removal of polyps or detect it at an early stage. However, much less is known about how best to implement an effective colorectal cancer screening program. Screening rates are low, and uninsured persons, low-income persons, and persons who have not visited a physician within a year are least likely to be screened.Although the Centers for Disease Control and Prevention (CDC has 15 years of experience supporting the National Breast and Cervical Cancer Early Detection Program for the underserved population, a similar national program for colorectal cancer is not in place. To explore the feasibility of implementing a national program for the underserved U.S. population and to learn which settings and which program models are most viable and cost-effective, CDC began a 3-year colorectal cancer screening demonstration program in 2005.This article describes briefly this demonstration program and the process CDC used to design it and to select program sites. The multiple-methods evaluation now under way to assess the program’s feasibility and describe key outcomes is also detailed. Evaluation results will be used to inform future activities related to organized screening for colorectal cancer.

  16. Chemopreventive drugs: Mechanisms via inhibition of cancer stem cells in colorectal cancer

    OpenAIRE

    Kim, Tae Il

    2014-01-01

    Recent epidemiological studies, basic research and clinical trials on colorectal cancer (CRC) prevention have helped identify candidates for effective chemopreventive drugs. However, because of the conflicting results of clinical trials or side effects, the effective use of chemopreventive drugs has not been generalized, except for patients with a high-risk for developing hereditary CRC. Advances in genetic and molecular technologies have highlighted the greater complexity of carcinogenesis, ...

  17. (1)H NMR Spectroscopy of Fecal Extracts Enables Detection of Advanced Colorectal Neoplasia.

    Science.gov (United States)

    Amiot, Aurelien; Dona, Anthony C; Wijeyesekera, Anisha; Tournigand, Christophe; Baumgaertner, Isabelle; Lebaleur, Yann; Sobhani, Iradj; Holmes, Elaine

    2015-09-01

    Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its etiopathogenesis and earlier diagnosis. Here, we investigated the fecal metabolic phenotype of patients with advanced colorectal neoplasia and controls using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate modeling. The fecal microbiota composition was assessed by quantitative real-time PCR as well as Wif-1 methylation levels in stools, serum, and urine and correlated to the metabolic profile of each patient. The predictivity of the model was 0.507 (Q(2)Y), and the explained variance was 0.755 (R(2)Y). Patients with advanced colorectal neoplasia demonstrated increased fecal concentrations of four short-chain fatty acids (valerate, acetate, propionate, and butyrate) and decreased signals relating to β-glucose, glutamine, and glutamate. The predictive accuracy of the multivariate (1)H NMR model was higher than that of the guaiac-fecal occult blood test and the Wif-1 methylation test for predicting advanced colorectal neoplasia. Correlation analysis between fecal metabolites and bacterial profiles revealed strong associations between Faecalibacterium prausnitzii and Clostridium leptum species with short-chain fatty acids concentration and inverse correlation between Faecalibacterium prausnitzii and glucose. These preliminary results suggest that fecal metabonomics may potentially have a future role in a noninvasive colorectal screening program and may contribute to our understanding of the role of these dysregulated molecules in the cross-talk between the host and its bacterial microbiota. PMID:26211820

  18. Colonoscopy in Colorectal Cancer Screening: Current Aspects.

    Science.gov (United States)

    Triantafillidis, John K; Vagianos, Constantine; Malgarinos, George

    2015-09-01

    Colonoscopy represents a very important diagnostic modality for screening for colorectal cancer, because it has the ability to both detect and effectively remove pro-malignant and malignant lesions. It is recommended by almost all international and national gastroenterology and cancer societies, as an initial screening modality or, following a positive fecal occult blood test, to be performed every 10 years in individuals of average risk starting from the age of 50. However, a significant problem is the so-called post-screening (interval) polyps and cancers found some years after the index colonoscopy. In order to reduce the rate of interval cancers it is extremely necessary to optimize the quality and effectiveness of colonoscopy. Bowel preparation is of paramount importance for both accurate diagnosis and subsequent treatment of lesions found on colonoscopy. The quality of bowel preparation could be significantly improved by splitting the dose regimens, a strategy that has been shown to be superior to single-dose regimen. A good endoscopic technique and optimal withdrawal time offering adequate time for inspection, would further optimize the rate of cecal intubation and the number of lesions detected. During the last years, sophisticated devices have been introduced that would further facilitate cecal intubation. The percentage of total colonoscopies is now super-passing the level of 95 % allowing the adenoma detection rate to be greater than the suggestive level of 25 % in men and 15 % in women. This review aims to provide the reader with the current knowledge concerning indications, usefulness, limitations and future perspectives of this probably most important screening technique for colorectal cancer available today. PMID:27217671

  19. Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study

    DEFF Research Database (Denmark)

    Burgdorf, S K; Fischer, A; Claesson, M H;

    2006-01-01

    Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...

  20. Expression of Obesity Hormone Leptin in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Jin-chun Cong; Xian-wei Dai; Ming-yang Shen; Jun-jiang Wang; Chun-sheng Chen; Hong Zhang; Lei Qiao

    2009-01-01

    Objective: The obesity hormone, leptin, has been found to participate in the development and proliferation of normal and malignant tissues. The aim of this study was to evaluate the role of leptin in human colorectal cancer.Methods: Serum leptin levels were measured via ABC-ELLSA in 30 colorectal cancers and 24 normal controls. Leptin concentration in colorectal cancer was analyzed in terms of selected clinicopathological features and some oncogenes.Results: The mean concentration of leptin was significantly higher for colorectal cancers(3.54±1.46 ng/ml) than normal controls(2.27±0.99 ng/ml), no gender difference was observed in this study. Leptin expression in poorly differentiated tumors was obviously lower than those in moderately and well differentiated tumors. There were no statistically significant correlations between leptin and the serum CEA and CA199 in colorectal cancers (P>0.05), and between leptin and the expressions of K-RAS, P53, APC, DCC genes in tumor tissues (P>0.05).Conclusion: Leptin is overexpressed in human colorectal cancer, which is related to the differentiation degrees of the tumor. There is no correlation between leptin expression and chages of oncogenes in colorectal cancers.

  1. RNAi technology: A Revolutionary tool for the colorectal cancer therapeutics

    Institute of Scientific and Technical Information of China (English)

    Wei Lv; Chao Zhang; Jia Hao

    2006-01-01

    With the many changes that have taken place in people's diet and lifestyle, colorectal cancer (CRC) has become a global concern. There were approximately 950000 new cases diagnosed and 500000 deaths recorded worldwide in 2000. It is the second most common type of cancer in the Western world, and it is the third most common type of digestive tumor in China. It is reported that the morbidity of CRC is 4.08/100000 for men and 3.30/100000 for women in China. Despite the rate of improvements in surgery, radiotherapy and chemotherapy, the overall five-year survival is around 50%. Therefore, novel treatment need to be developed in order to add to the therapeutic armamentarium.RNA interference (RNAi) is a sequence-specific posttranscriptional gene silencing mechanism, which is triggered by double-stranded RNA (dsRNA) and causes degradation of mRNA homologous in sequence to the dsRNA.This new approach has been successfully adopted to inhibit virus replication and tumorigenicity. Recent reports have described DNA vector-based strategies for delivery of small interfering RNA (siRNA) into mammalian cells, further expanding the utility of RNAi. With the development of the RNAi technology and deeper understanding of this field, a promising new modality of treatment appeared, which can be used in combination with the existing therapies .We reviewed the proceedings on the actualities and advancement of RNAi technology for colorectal cancer therapeutics.

  2. Personalizing medicine for metastatic colorectal cancer: Current developments

    OpenAIRE

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

    2014-01-01

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

  3. Colorectal cancer risk in hamartomatous polyposissyndromes

    Institute of Scientific and Technical Information of China (English)

    Fábio Guilherme Campos; Marleny Novaes Figueiredo; Carlos Augusto Real Martinez

    2015-01-01

    Colorectal cancer (CRC) is a major cause of morbidityand mortality around the world, and approximately 5%of them develop in a context of inherited mutationsleading to some form of familial colon cancer syndromes.Recognition and characterization of thesepatients have contributed to elucidate the genetic basisof CRC. Polyposis Syndromes may be categorized bythe predominant histological structure found within thepolyps. The aim of the present paper is to review themost important clinical features of the HamartomatousPolyposis Syndromes, a rare group of genetic disordersformed by the peutz-Jeghers syndrome, juvenil polyposissyndrome and PTEN Hamartoma Tumor Syndrome(Bannayan-Riley-Ruvalacaba and Cowden Syndromes).A literature search was performed in order to retrievethe most recent and important papers (articles,reviews, clinical cases and clinical guidelines) regardingthe studied subject. We searched for terms such as"hamartomatous polyposis syndromes", "Peutz-Jegherssyndrome", "juvenile polyposis syndrome", "juvenilepolyp", and "PTEN hamartoma tumour syndrome"(Cowden syndrome, Bananyan-Riley-Ruvalcaba). Thepresent article reports the wide spectrum of diseaseseverity and extraintestinal manifestations, with a specialfocus on their potential to develop colorectal and otherneoplasia. In the literature, the reported colorectalcancer risk for Juvenile Polyposis, Peutz-Jeghers andPTEN Hamartoma Tumor Syndromes are 39%-68%,39%-57% and 18%, respectively. A review regardingcancer surveillance recommendations is also presented.

  4. Short-term effect of Photofrin photodynamic adjuvant therapy for young people with advanced colorectal cancer%Photofrin光动力辅助治疗青年晚期结直肠癌的近期效果观察

    Institute of Scientific and Technical Information of China (English)

    何耀明

    2015-01-01

    Objective To observe the short-term efficacy and adverse drug reaction of Photofrin photodynamic adjuvant therapy for advanced colorectal cancer in young persons.Methods Selected 23 cases consecutives diagnosed as advanced colorectal cancer in young persons from September 2010 to February 2014 arriving in the Central Hospital of Jiangmen as the experiment group who were received Photofrin photodynamic therapy,and chose 30 consecutives diagnosed as advanced colorectal cancer as the control group who were received radiotherapy and chemotherapy.Using Photofrin in 2 mg/kg photosensitizer, the speed of intravenous infusion,48 hours after endoscopic into optical fiber, laser irradiation and treated with 630 nm intensity,2 days after endoscopic removal of necrotic tissue and the original lesions and new lesions were found to give according to the specific circumstances, after the removal of necrotic tissue lesions.Then compare the effects and complications.Results The total efficacy rate in experiment group was significantly more than control groupthe differences were significant (69.57% vs.40.00%, P =0.035).The in-hospital time in experiment group was significantly less((13.47±4.46) h vs.(19.72± 5.21) h, P =0.036).The adverse drug reaction rate in experiment group was significantly lower thant the control group (30.43% vs.50.00% ,P=0.021).Conclusion The Photofrin photodynamic therapy for advanced colorectal cancer in young persons may greatly improve clinical effect and decrease complication.%目的 观察Photofrin光动力辅助治疗青年晚期结直肠癌的近期效果及不良反应.方法 选择我院2010年9月至2014年2月采用半导体激光光动力辅助治疗青年晚期结直肠癌患者共23例作为试验组,选择同期行放化疗的晚期结直肠癌患者30例作为对照组.试验组患者给予光敏剂Photofrin,以2 mg/kg速度静脉滴注,48 h后经内镜导入光导纤维,并给予630 nm强度的激光照射,2d后经内镜清除坏

  5. Occurrence and survival of synchronous pulmonary metastases in colorectal cancer

    DEFF Research Database (Denmark)

    Nordholm-Carstensen, Andreas; Krarup, Peter-Martin; Jorgensen, Lars N;

    2014-01-01

    OBJECTIVE: To investigate the occurrence of synchronous colorectal cancer metastases (SCCM) confined to the lungs, risk factors for these metastases and their impact on survival. METHODS: In a nationwide cohort study of 26,200 patients data were prospectively entered into the Danish Colorectal Ca...

  6. Primary prevention of colorectal cancer: lifestyle, nutrition, exercise.

    Science.gov (United States)

    Martínez, María Elena

    2005-01-01

    The past two decades have provided a vast amount of literature related to the primary prevention of colorectal cancer. Large international variation in colorectal cancer incidence and mortality rates and the prominent increases in the incidence of colorectal cancer in groups that migrated from low- to high-incidence areas provided important evidence that lifestyle factors influence the development of this malignancy. Moreover, there is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological factor in colorectal neoplasia. Although the precise mechanisms have not been clarified, several lifestyle factors are likely to have a major impact on colorectal cancer development. Physical inactivity and to a lesser extent, excess body weight, are consistent risk factors for colon cancer. Exposure to tobacco products early in life is associated with a higher risk of developing colorectal neoplasia. Diet and nutritional factors are also clearly important. Diets high in red and processed meat increase risk. Excess alcohol consumption, probably in combination with a diet low in some micronutrients such as folate and methionine, appear to increase risk. There is also recent evidence supporting a protective effect of calcium and vitamin D in the etiology of colorectal neoplasia. The relationship between intake of dietary fiber and risk of colon cancer has been studied for three decades but the results are still inconclusive. However, some micronutrients or phytochemicals in fiber-rich foods may be important; folic acid is one such micronutrient that has been shown to protect against the development of colorectal neoplasia and is currently being studied in intervention trials of adenoma recurrence. The overwhelming evidence indicates that primary prevention of colon cancer is feasible. Continued focus on primary prevention of colorectal cancer, in combination with efforts aimed at screening and surveillance, will be vital in

  7. [Hereditary non-polyposis colorectal cancer. Report of four siblings].

    Science.gov (United States)

    Zárate, Alejandro; Alvarez, Karin; Wielandt, Ana María; Hevia, Montserrat; De la Fuente, Marjorie; Carvallo, Pilar; López-Köstner, Francisco

    2008-06-01

    Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome is an autosomic dominant syndrome involving 596-1096 of colorectal cancer patients. Mutations in MLH1 and MSH2 genes account for most cases. These two genes participate in the DNA mismatch repair pathway. Therefore mutation carriers show microsatellite instability (MSI) in tumors. This syndrome is characterized by the early development of colorectal cancer (before 50 years) and an increased incidence of cancer in other organs. We report four siblings from a family diagnosed with HNPCC. All of them were subjected to colonic surgery for colorectal cancer Moreover, one patient developed an ampulloma after her colon surgery. The molecular-genetic analysis revealed three brothers with microsatellite instability in the tumor tissue, the absence of the MLH1 protein, and the presence of a germ line mutation localized in introm 15 of the MLH1 gene. PMID:18769833

  8. Meta analysis of risk factors for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Kun Chen; Jiong-Liang Qiu; Yang Zhang; Yu-Wan Zhao

    2003-01-01

    AIM: To study the risk factors for colorectal cancer in China.METHODS: A meta-analysis of the risk factors of colorectal cancer was conducted for 14 case-control studies, and reviewed 14 reports within 13 years which included 5034cases and 5205 controls. Dersimonian and Laird random effective models were used to process the results.RESULTS: Meta analysis of the 14 studies demonstrated that proper physical activites and dietary fibers were protective factors (pooled OR<0.8), while fecal mucohemorrhage,chronic diarrhea and polyposis were highly associated with colorectal cancer (all pooled OR>4). The stratified results showed that different OR values of some factors were due to geographic factors or different resourses.CONCLUSION: Risks of colorectal cancer are significantly associated with the histories of intestinal diseases or relative symptoms, high lipid diet, emotional trauma and family history of cancers. The suitable physical activities and dietary fibers are protective factors.

  9. Colorectal cancer, diabetes and survival: epidemiological insights.

    Science.gov (United States)

    Zanders, M M J; Vissers, P A J; Haak, H R; van de Poll-Franse, L V

    2014-04-01

    Colorectal cancer (CRC) patients with pre-existing diabetes have significantly lower rates of overall survival compared with patients without diabetes. Against this backdrop, the American Diabetes Association and American Cancer Society in 2010 reviewed the scientific literature concerning diabetes and cancer. One of the key issues identified for further investigation was the need for a better understanding of whether diabetes influences cancer prognosis above and beyond the prognosis conferred by each disease state independently. Whether the worsened survival of CRC patients with diabetes could be explained by less favourable patient-, tumour- and treatment-related characteristics has also been evaluated in numerous recent studies. However, as most studies did not account for all the various potential confounders, such as cancer stage, comorbidities and body mass index (BMI) in their analyses, the current evidence for the association between diabetes and survival in CRC patients remains inconclusive. Nevertheless, based on multiple examples in the literature, the present review demonstrates that diabetes affects the presentation of CRC as well as its treatment and outcome, which may then result in lower overall rates of survival in patients with, compared to those without, diabetes. PMID:24507584

  10. Discrepancies between estimated and perceived risk of cancer among individuals with hereditary nonpolyposis colorectal cancer

    DEFF Research Database (Denmark)

    Domanska, K; Nilbert, Mef; Soller, M;

    2007-01-01

    Communicating cancer risk and recommending adequate control programs is central for genetic counseling. Individuals affected by hereditary nonpolyposis colorectal cancer (HNPCC) are at about 80% life-time risk of colorectal cancer and for female carriers 40-60% risk of endometrial cancer and 10-1...

  11. Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers.

    Science.gov (United States)

    Okugawa, Yoshinaga; Grady, William M; Goel, Ajay

    2015-10-01

    Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. One of the fundamental processes driving the initiation and progression of CRC is the accumulation of a variety of genetic and epigenetic changes in colonic epithelial cells. Over the past decade, major advances have been made in our understanding of cancer epigenetics, particularly regarding aberrant DNA methylation, microRNA (miRNA) and noncoding RNA deregulation, and alterations in histone modification states. Assessment of the colon cancer "epigenome" has revealed that virtually all CRCs have aberrantly methylated genes and altered miRNA expression. The average CRC methylome has hundreds to thousands of abnormally methylated genes and dozens of altered miRNAs. As with gene mutations in the cancer genome, a subset of these epigenetic alterations, called driver events, are presumed to have a functional role in CRC. In addition, the advances in our understanding of epigenetic alterations in CRC have led to these alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in this field suggests that these epigenetic alterations will be commonly used in the near future to direct the prevention and treatment of CRC.

  12. Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yaron Niv

    2007-01-01

    Colorectal cancer (CRC) is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through different pathways. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and most of hereditary nonpolyposis cancers. Tumors with a high frequency of microsatellite instability tend to be diploid, to possess a mucinous histology, and to have a surrounding lymphoid reaction. They are more prevalent in the proximal colon and have a fast pass from polyp to cancer. Nevertheless, they are associated with longer survival than stage-matched tumors with microsatellite stability. Resistance of colorectal cancers with a high frequency of microsatellite instability to 5-fluorouracil-based chemotherapy is well established. Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein, and prevents the normal activation of the DMA repair gene. This is an important cause for genomic instability and cell proliferation to the point of colorectal cancer formation. Better knowledge of this process will have a huge impact on colorectal cancer management, prevention, treatment and prognosis.

  13. Chemotherapy response evaluation with FDG-PET in patients with colorectal cancer.

    NARCIS (Netherlands)

    Geus-Oei, L.F. de; Laarhoven, H.W.M. van; Visser, E.P.; Hermsen, R.; Hoorn, B.A. van; Kamm, Y.J.L.; Krabbe, P.F.M.; Corstens, F.H.M.; Punt, C.J.A.; Oyen, W.J.G.

    2008-01-01

    BACKGROUND: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. METHODS: Dynamic FDG-PET was carried out before and at 2 (n = 50) and 6

  14. Hereditary non-polyposis colorectal cancer : Identification of mutation carriers and assessing pathogenicity of mutations

    NARCIS (Netherlands)

    Niessen, RC; Sijmons, RH; Berends, MJW; Ou, J; Hofstra, RNW; Kleibeuker, JH

    2004-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC), also referred to as Lynch syndrome, is an autosomal dominantly inherited disorder that is characterized by susceptibility to colorectal cancer and extracolonic malignancies, in particular endometrial cancer. HNPCC is caused by pathogenic mutations

  15. Lipid peroxidation and antioxidant status in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Elzbieta Skrzydlewska; Stanislaw Sulkowski; Mariusz Koda; Bogdan Zalewski; Luiza Kanczuga-Koda; Mariola Sulkowska

    2005-01-01

    -grade adenocarcinomas as well as clinical Ⅳ stage of colorectal cancer. We also observed a decrease of CAT activity (Adc.muc. -40±14 U/g,clinical Ⅳ stage 33±18 U/g vs84±17 U/g, P<0.001) as well as a decreased level of reduced glutathione (clinical Ⅳ stage 150±48 nmol/g vs 167±15 nmol/g, P<0.05) and vitamins C and E (vit. C-clinical Ⅳ stage 325±92 nmol/g vs 513±64 nmol/g, P<0.001; vit. E-clinical Ⅳ stage 13.3±10.3nmol/g vs37.5±5.2 nmol/g).CONCLUSION: Colorectal carcinogenesis is associated with serious oxidative stress and confirms that gradual advancement of oxidative-antioxidative disorders is followed by progression of colorectal cancer.

  16. Molecular Taxonomy and Tumourigenesis of Colorectal Cancer.

    Science.gov (United States)

    Biswas, S; Holyoake, D; Maughan, T S

    2016-02-01

    Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy.

  17. Towards the human colorectal cancer microbiome.

    Directory of Open Access Journals (Sweden)

    Julian R Marchesi

    Full Text Available Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC. To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.

  18. Colorectal Cancer "Methylator Phenotype": Fact or Artifact?

    Directory of Open Access Journals (Sweden)

    Charles Anacleto

    2005-04-01

    Full Text Available It has been proposed that human colorectal tumors can be classified into two groups: one in which methylation is rare, and another with methylation of several loci associated with a "CpG island methylated phenotype (CIMP," characterized by preferential proximal location in the colon, but otherwise poorly defined. There is considerable overlap between this putative methylator phenotype and the well-known mutator phenotype associated with microsatellite instability (MSI. We have examined hypermethylation of the promoter region of five genes (DAPK, MGMT, hMLH1, p16INK4a, and p14ARF in 106 primary colorectal cancers. A graph depicting the frequency of methylated loci in the series of tumors showed a continuous, monotonically decreasing distribution quite different from the previously claimed discontinuity. We observed a significant association between the presence of three or more methylated loci and the proximal location of the tumors. However, if we remove from analysis the tumors with hMLH1 methylation or those with MSI, the significance vanishes, suggesting that the association between multiple methylations and proximal location was indirect due to the correlation with MSI. Thus, our data do not support the independent existence of the so-called methylator phenotype and suggest that it rather may represent a statistical artifact caused by confounding of associations.

  19. Fecal DNA testing for colorectal cancer screening: molecular targets and perspectives

    Institute of Scientific and Technical Information of China (English)

    Amaninder; Dhaliwal; Panagiotis; J; Vlachostergios; Katerina; G; Oikonomou; Yitzchak; Moshenyat

    2015-01-01

    The early detection of colorectal cancer with effective screening is essential for reduction of cancer-specific mortality. The addition of fecal DNA testing in the armamentarium of screening methods already in clinical use launches a new era in the noninvasive part of colorectal cancer screening and emanates from a large number of previous and ongoing clinical investigations and technological advancements. In this review, we discuss the molecular rational and most important genetic alterations hallmarking the early colorectal carcinogenesis process. Also, representative DNA targets-markers and key aspects of their testing at the clinical level in comparison or/and association with other screening methods are described. Finally, a critical view of the strengths and limitations of fecal DNA tests is provided, along with anticipated barriers and suggestions for further exploitation of their use.

  20. Primary prevention of colorectal cancer: are we closer to reality?

    LENUS (Irish Health Repository)

    Qasim, Asghar

    2012-02-01

    Colorectal cancer is one of the leading causes of morbidity and mortality worldwide. An early detection of colorectal cancer determines therapeutic outcomes, while primary prevention remains a challenge. Our aim was to review the dietary, geographical and genetic factors in the causation and their possible role in the primary prevention of colorectal cancer. Data from experimental and clinical studies and population screening programmes were analysed to determine the factors responsible for causation of colorectal cancer. The role of dietary constituents, including the consumption of fat, red meat, fibre content, alcohol consumption, and other lifestyle issues, including obesity, lack of exercise and geographical variations in cancer prevalence were reviewed. The role of genetic and lifestyle factors in causation of colorectal cancer is evident from the experimental, clinical and population-based studies. Dietary factors, including the consumption of fat, fibre, red meat and alcohol, seem to have a significant influence in this regard. The role of micronutrients, vitamins, calcium may be relevant but remain largely unclear. In conclusion, there is ample evidence favouring the role of various dietary and lifestyle factors in the aetiology of colorectal cancer. Modification of these factors is an attractive option, which is likely to help in the primary prevention and reduced disease burden.

  1. Assessment of rehabilitation needs in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Wiedenbein, Liza; Kristiansen, Maria; Adamsen, Lis;

    2016-01-01

    clinical practices related to identification and documentation of rehabilitation needs among patients with colorectal cancer at Danish hospitals. Material and methods A retrospective clinical audit was conducted utilizing data from patient files randomly selected at surgical and oncology hospital...... departments treating colorectal cancer patients. Forty patients were included, 10 from each department. Semi-structured interviews were carried out among clinical nurse specialists. Audit data was analyzed using descriptive statistics, qualitative data using thematic analysis. Results Documentation...

  2. Intrahepatic therapy for liver-dominant metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Kerlijne; De; Groote; Hans; Prenen

    2015-01-01

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

  3. Colorectal Cancer Prevention Through Dietary and Lifestyle Modifications

    OpenAIRE

    Gingras, Denis; Béliveau, Richard

    2011-01-01

    Several studies indicate that Western dietary and lifestyle factors are responsible for the high incidence of colorectal cancer in industrialized countries. Diets rich in red and processed meat, refined starches, sugar, and saturated and trans-fatty acids but poor in fruits, vegetables, fiber, omega-3 fatty acids and whole grains are closely associated with an increased risk of colorectal cancer. Other main features of the western lifestyle, such as excess body mass and sedentary behaviours, ...

  4. [Overview of current modalities of colorectal cancer screening].

    Science.gov (United States)

    Kajzrlíková, Ivana Mikoviny; Vítek, Petr

    2016-04-01

    There are one-step and two-steps programs for colorectal cancer screening. The aim of all screening examinations is to detect early stage of the disease in asymptomatic patient. The aim of this article is actual review of current screening modalities such as fecal occult blood test, flexible sigmoideoscopy, colonoscopy, CT colonography, capsule endoscopy, blood-based tests and stool DNA tests. Colonoscopy still remains the gold standard for detection of colorectal neoplasias. In majority of countries worldwide programs for colorectal cancer screening are based on immunochemical fecal occult blood test followed by colonoscopy when positive.

  5. [Streamlined treatment pathway for a colorectal cancer patient].

    Science.gov (United States)

    Rantala, Arto; Ristamäki, Raija; Keränen, Ulla

    2016-01-01

    The organization of colorectal cancer patient treatment, the pathway, is an important component of the quality of care of a large patient group as nearly 3000 colorectal cancer patients are diagnosed and treated annually in Finland. By designing and describing the whole pathway, the more streamlined approach can be made and thus improve patient care. Multidisciplinary team work between colorectal surgeons, oncologists, pathologists and radiologists is flexible team work, having been proven to improve overall treatment results. This method of working together is also a good tool for the development of the pathway to a better organized treatment. PMID:27483633

  6. Screening for colorectal cancer: what fits best?

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-06-01

    Colorectal cancer (CRC) screening has been shown to be effective in reducing CRC incidence and mortality. There are currently a number of screening modalities available for implementation into a population-based CRC screening program. Each screening method offers different strengths but also possesses its own limitations as a population-based screening strategy. We review the current evidence base for accepted CRC screening tools and evaluate their merits alongside their challenges in fulfilling their role in the detection of CRC. We also aim to provide an outlook on the demands of a low-risk population-based CRC screening program with a view to providing insight as to which modality would best suit current and future needs.

  7. The consensus molecular subtypes of colorectal cancer.

    Science.gov (United States)

    Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M; Morris, Jeffrey S; Simon, Iris M; Gerster, Sarah; Fessler, Evelyn; De Sousa E Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine

    2015-11-01

    Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.

  8. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon [Korea Institute of Radiologicaland Medical Sciences, Seoul (Korea, Republic of)

    2010-11-15

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  9. Can the prognosis of colorectal cancer be improved by surgery?

    Science.gov (United States)

    Takii, Yasumasa; Maruyama, Satoshi; Nogami, Hitoshi

    2016-08-27

    Surgical resection is the only curative treatment modality for colorectal cancer limited locally. Evidence for the kind of resection procedure that is effective for improving prognosis is insufficient. Prognosis improvement is expected with the no-touch isolation technique (NTIT), making it the most important resection procedure. We are conducting a multicenter randomized controlled trial (RCT) to confirm the efficacy of NTIT in patients with colorectal cancer. The present review serves as a preface to our trial, as it focuses on basic and clinical studies that support the efficacy of NTIT. The detection ratios of circulating tumor cells (CTCs) of peripheral blood indicate the progress and prognosis of colorectal cancer. In a rabbit liver tumor model, metastases increased after surgical manipulation. Also, CTCs increased during the radical excision of colorectal cancer. However, NTIT decreased the detection of CTCs of intraoperative portal vein blood in patients with colorectal cancer. Although these aforementioned results support the use of NTIT, a previous controlled prospective trial was not able to confirm the clinical benefit of NTIT, as it had an insufficient sample size and many patients were lost to follow-up. Therefore, we initiated a large-scale high-quality RCT to confirm the efficacy of NTIT for colorectal cancer. PMID:27648161

  10. Coffee Consumption and the Incidence of Colorectal Cancer in Women

    Directory of Open Access Journals (Sweden)

    Erik J. Groessl

    2016-01-01

    Full Text Available Background. Higher coffee consumption has been associated with decreased incidence of colorectal cancer. Our objective was to examine the relationship of coffee intake to colorectal cancer incidence in a large observational cohort of postmenopausal US women. Methods. Data were collected for the Women’s Health Initiative Observational Study providing a follow-up period of 12.9 years. The mean age of our sample (N=83,778 women was 63.5 years. Daily coffee intake was grouped into 3 categories: None, moderate (>0–<4 cups, and high (4+ cups. Proportional hazards modeling was used to evaluate the relationship between coffee intake and colorectal cancer. Results. There were 1,282 (1.53% new cases of colorectal cancer during follow-up. Compared to nondrinkers, moderate and high coffee drinkers had an increased incidence of colorectal cancer in multivariate analysis (HR 1.15, 1.02–1.29; HR 1.14, 0.93–1.38. Moderate drip brew coffee intake (HR 1.20, 1.05–1.36 and high nondrip brew coffee intake (HR 1.43, 1.01–2.02 were associated with increased odds. Conclusion. Our results suggesting increased incidence of colorectal cancer associated with higher coffee consumption contradict recent meta-analyses but agree with a number of other studies showing that coffee increases risk or has no effect. Brew method results are novel and warrant further research.

  11. Hereditary nonpolyposis colorectal cancer and familial colorectal cancer in Central part of Iran, Isfahan

    Directory of Open Access Journals (Sweden)

    Amin Nemati

    2012-01-01

    Full Text Available Background: There is a lack of data on familial aggregation of colorectal cancer (CRC in Iran. We aimed to deter-mine the frequency of hereditary nonpolyposis colorectal cancer (HNPCC and familial colorectal cancer (FCC and to determine the frequency of extracolonic cancers in these families in Isfahan. Methods: We reviewed documents of all patients with a pathologically confirmed diagnosis of CRC admitted to Isfa-han referral hospitals between 1995 and 2006. We also studied our CRC registry at Poursina Hakim Research Institute from 2003 to 2008. We found HNPCC and FCC families based on the Amsterdam II criteria and interviewed them for family history of CRC and extracolonic tumors. The family history was taken at least up to the second-degree relatives. Results: During 1996 to 2008, a total of 2580 CRC cases have been diagnosed. We found 14 HNPCC and 53 FCC families. Mean age of CRC at diagnosis was 48.0 ΁ 14.6 and 49.0 ΁ 13.9 years in the HNPCC and FCC families, re-spectively (p > 0.05. The total numbers of observed extracolonic tumors were 70 (21.6%; mean age = 53.6 ΁ 11.0 years and 157 (13.8%; mean age = 54.8 ΁ 18.0 years in HNPCC and FCC families, respectively (p > 0.05. CRC was respectively found in 52 and 76 members of the HNPCC and FCC families, revealing the frequency of HNPCC and FCC as 2.0% (52/2580 and 2.9% (76/2580, respectively. Conclusions: We found a relative high frequency of HNPCC (2.0% and FCC (2.9% among CRC cases in our socie-ty and high incidence of extracolonic tumors in their families. Further studies focusing on molecular basis in this field and designing a specific screening and national cancer registry program for HNPCC and FCC families should be con-ducted.

  12. Coffee, colon function and colorectal cancer.

    Science.gov (United States)

    Vitaglione, Paola; Fogliano, Vincenzo; Pellegrini, Nicoletta

    2012-09-01

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

  13. Colorectal cancer through simulation and experiment

    KAUST Repository

    Kershaw, Sophie K.

    2013-06-01

    Colorectal cancer (CRC) has formed a canonical example of tumourigenesis ever since its use in Fearon and Vogelstein\\'s linear model of genetic mutation, and continues to generate a huge amount of research interest. Over time, the field has witnessed a transition from solely experimental work to the inclusion of mathematical and computational modelling. The fusion of these disciplines has the potential to provide valuable insights into oncologic processes, but also presents the challenge of uniting many diverse perspectives. Furthermore, the cancer cell phenotype defined by the \\'Hallmarks of Cancer\\' has been extended in recent times and provides an excellent basis for future research. The authors present a timely summary of the literature relating to CRC, addressing the traditional experimental findings, summarising the key mathematical and computational approaches, and emphasising the role of the Hallmarks in current and future developments. The authors conclude with a discussion of interdisciplinary work, outlining areas of experimental interest which would benefit from the insight that theoretical modelling can provide. © The institution of engineering and technology 2013.

  14. Microbiota disbiosis is associated with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Zhiguang eGao

    2015-02-01

    Full Text Available The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC. The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent noncancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individuals differed significantly. Firmicutes and Fusobacteria were over-represented whereas Proteobacteria was under-represented in CRC patients. In addition, Lactococcus and Fusobacterium exhibited a relatively higher abundance while Pseudomonas and Escherichia-Shigella was reduced in cancerous tissues compared to adjacent noncancerous tissues. Meanwhile, the overall microbial structures of proximal and distal colon cancerous tissues were similar; but certain potential pro-oncogenic pathogens were different. These results suggested that the mucosa-associated microbiota is dynamically associated with CRC, which may provide evidences for microbiota-associated diagnostic, prognostic, preventive and therapeutic strategies for CRC.

  15. Aspirin, cyclooxygenase inhibition and colorectal cancer.

    Science.gov (United States)

    Sostres, Carlos; Gargallo, Carla Jerusalen; Lanas, Angel

    2014-02-01

    Colorectal cancer (CRC) is the third most common type of cancer worldwide. Screening measures are far from adequate and not widely available in resource-poor settings. Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC. Increasing evidence from epidemiological studies, randomized clinical trials and basic science supports the effectiveness of aspirin, as well as other non-steroidal anti-inflammatory drugs, for chemoprevention of several types of cancer, including CRC. This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality. The detectable benefit of daily low-dose aspirin (at least 75 mg), as used to prevent cardiovascular disease events, strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy. Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase (COX)-1 in platelets (in pre-systemic circulation) while causing a limited and rapidly reversible inhibitory effect on COX-2 and/or COX-1 expressed in nucleated cells. Aspirin has a short half-life in human circulation (about 20 minutes); nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours, while platelets do not. COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  16. Aspirin, cyclooxygenase inhibition and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Carlos; Sostres; Carla; Jerusalen; Gargallo; Angel; Lanas

    2014-01-01

    Colorectal cancer(CRC)is the third most common type of cancer worldwide.Screening measures are far from adequate and not widely available in resourcepoor settings.Primary prevention strategies therefore remain necessary to reduce the risk of developing CRC.Increasing evidence from epidemiological studies,randomized clinical trials and basic science supports the effectiveness of aspirin,as well as other non-steroidal anti-inflammatory drugs,for chemoprevention of several types of cancer,including CRC.This includes the prevention of adenoma recurrence and reduction of CRC incidence and mortality.The detectable benefit of daily low-dose aspirin(at least 75 mg),as used to prevent cardiovascular disease events,strongly suggests that its antiplatelet action is central to explaining its antitumor efficacy.Daily low-dose aspirin achieves complete and persistent inhibition of cyclooxygenase(COX)-1 in platelets(in pre-systemic circulation)while causing alimited and rapidly reversible inhibitory effect on COX-2and/or COX-1 expressed in nucleated cells.Aspirin has a short half-life in human circulation(about 20 minutes);nucleated cells have the ability to resynthesize acetylated COX isozymes within a few hours,while platelets do not.COX-independent mechanisms of aspirin have been suggested to explain its chemopreventive effects but this concept remains to be demonstrated in vivo at clinical doses.

  17. Synchronous colorectal and lung cancer:Report of three cases

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The incidence of synchronous colorectal and lung cancer is relatively rare.We report three cases of patients with tumors located in the rectum,ascending colon,the lower lobe of the left lung,and the upper lobe of the right lung.Synchronous curative resection of the two lesions was performed in two patients,whereas colectomy was performed in an elderly patient with a poor lung function.Pathological examination showed the colorectal cancer was a moderately differentiated adenocarcinoma and the lung cancer was a squamous cell carcinoma.Surgical treatment and postoperative adjuvant chemotherapy for the lung cancer were different from those for colorectal cancer with pulmonary metastasis.If possible,radical resection should be performed for each cancer when synchronicity is found.

  18. Quality of Life and Mortality of Long-Term Colorectal Cancer Survivors in the Seattle Colorectal Cancer Family Registry

    OpenAIRE

    Adams, Scott V.; Rachel Ceballos; Newcomb, Polly A.

    2016-01-01

    Background and Aim Because most colorectal cancer patients survive beyond five years, understanding quality of life among these long-term survivors is essential to providing comprehensive survivor care. We sought to identify personal characteristics associated with reported quality of life in colorectal cancer survivors, and sub-groups of survivors potentially vulnerable to very low quality of life. Methods We assessed quality of life using the Veterans RAND 12-item Health Survey within a pop...

  19. New European Initiatives in Colorectal Cancer Screening : Budapest Declaration

    NARCIS (Netherlands)

    Wittmann, Tibor; Stockbrugger, Reinhold; Herszenyi, Laszlo; Jonkers, Daisy; Molnar, Bela; Saurin, Jean-Christophe; Regula, Jaroslaw; Malesci, Alberto; Laghi, Luigi; Pinter, Tamas; Teleky, Bela; Dite, Petr; Tulassay, Zsolt

    2012-01-01

    Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associa

  20. Risk of gynecologic cancers in Danish hereditary non-polyposis colorectal cancer families

    DEFF Research Database (Denmark)

    Boilesen, Astrid Elisabeth Bruun; Bisgaard, Marie Luise; Bernstein, Inge

    2008-01-01

    OBJECTIVE: Women in hereditary non-polyposis colorectal cancer (HNPCC) families have an elevated risk of endometrial and ovarian cancer. The risk in Lynch syndrome families with known mutations in mismatch repair genes (MMR genes) seems to be higher than in familial colorectal cancer (CRC) famili...

  1. Colorectal cancer: from prevention to personalized medicine.

    Science.gov (United States)

    Binefa, Gemma; Rodríguez-Moranta, Francisco; Teule, Alex; Medina-Hayas, Manuel

    2014-06-14

    Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy

  2. Improving Goals of Care Discussion in Advanced Cancer Patients

    Science.gov (United States)

    2016-06-30

    Primary Stage IV Hepatobiliary; Esophageal; Colorectal Cancer; Glioblastoma; Cancer of Stomach; Cancer of Pancreas; Melanoma; Head or Neck Cancer; Stage III; Stage IV; Lung Cancers; Pancreatic Cancers

  3. Blood donation and colorectal cancer incidence and mortality in men.

    Directory of Open Access Journals (Sweden)

    Xuehong Zhang

    Full Text Available BACKGROUND: Although blood donations may reduce body iron stores, to date, prospective data on frequent blood donation and colorectal cancer risk are limited. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether frequent blood donation is associated with a lower risk of colorectal cancer in the Health Professionals Follow-up Study. We prospectively followed 35,121 men who provide the information on lifetime number of blood donations in 1992 through 2008. Serum ferritin levels were measured in a random sample of 305 men. Cox proportional hazard regression models were used to calculate the multivariable relative risks (RRs, 95%CIs after adjusting for age and other established colorectal cancer risk factors. We documented 684 incident colorectal cancer cases and 224 deaths from colorectal cancer. The mean serum ferritin levels varied from 178 µg/L for men who did not donate blood to 98 µg/L for men who had at least 30 donations. Age-adjusted results for both incidence and mortality were essentially the same as the multivariable-adjusted results. Comparing with non-donors, the multivariable RRs (95%CIs for colorectal cancer incidence were 0.92 (0.77, 1.11 for 1-5 donation, 0.85 (0.64, 1.11 for 6-9 donations, 0.96 (0.73, 1.26 for 10-19 donations, 0.91 (0.63, 1.32 for 20-29 donations, and 0.97 (0.68, 1.38 for at least 30 donations (P(trend = 0.92. The multivariable RRs for colorectal cancer mortality were 0.99 (0.72, 1.36 for 1-5 donation, 0.93 (0.57, 1.51 for 6-9 donations, 0.85 (0.50, 1.42 for 10-19 donations, and 1.14 (0.72, 1.83 for at least 20 donations (P(trend = 0.82. The results did not vary by cancer sub-sites, intake levels of total iron, heme iron, or family history of colorectal cancer. CONCLUSIONS/SIGNIFICANCE: Frequent blood donations were not associated with colorectal cancer incidence and mortality in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis.

  4. Colorectal Cancer - What You Need to Know PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2011-07-05

    This 60 second Public Service Announcement (PSA) is based on the July, 2011 CDC Vital Signs report. Colorectal cancer kills about 50,000 men and women every year. Screening can save lives! Screening can find abnormal growths so they can be removed before turning into cancer, and can find the cancer early, when it's easiest to treat. If you're over 50, talk to your doctor about getting screened for colorectal cancer.  Created: 7/5/2011 by Centers for Disease Control and Prevention (CDC).   Date Released: 7/5/2011.

  5. The role of estrogen in the development of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    张玲; 王吉凌; 朱圣韬; 史学森

    2015-01-01

    <正>Cancer is a major public health problem in the world.With the progress of medical technology,mean 5-year survival rates of colorectal cancer(CRC)have doubled over the past 40 years[1].However,in 2013,the International Agency for Research on Cancer(IARC)released data on cancer incidence,mortality and prevalence worldwide.The IARC’s online database provides the estimates for 28 types of cancer in 184 countries worldwide.The

  6. Which endpoints should we use in evaluating the use of novel fluoropyrimidine regimens in colorectal cancer?

    OpenAIRE

    Twelves, C. J.; Cassidy, J

    2002-01-01

    Although significant advances have been made in the treatment of advanced/metastatic colorectal cancer, 5-fluorouracil (5-FU) still forms the basis of chemotherapy. Recently, new 5-FU schedules and novel fluoropyrimidines have been developed, but there are no trials directly comparing these regimens. The current review describes the mechanisms of action, pre-clinical and phase I/II studies of two oral fluoropyrimidine therapies, capecitabine and uracil with tegafur plus leucovorin. It also co...

  7. Colorectal cancer in patients with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Halfvarson, Jonas; Vogel, Ulla Birgitte

    2012-01-01

    The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC...... cholangitis were at increased risk. In this commentary, we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients. Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic...... polymorphisms involved in IBD-associated CRC. The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD. The challenge will be to translate these new findings into clinical practice and to determine appropriate...

  8. Interleukin-6 - A Key Regulator of Colorectal Cancer Development

    Directory of Open Access Journals (Sweden)

    Maximilian J. Waldner, Sebastian Foersch, Markus F. Neurath

    2012-01-01

    Full Text Available Growing evidence proposes an important role for pro-inflammatory cytokines during tumor development. Several experimental and clinical studies have linked the pleiotropic cytokine interleukin-6 (IL-6 to the pathogenesis of sporadic and inflammation-associated colorectal cancer (CRC. Increased IL-6 expression has been related to advanced stage of disease and decreased survival in CRC patients. According to experimental studies, these effects are mediated through IL-6 trans-signaling promoting tumor cell proliferation and inhibiting apoptosis through gp130 activation on tumor cells with subsequent signaling through Janus kinases (JAKs and signal transducer and activator of transcription 3 (STAT3.During recent years, several therapeutics targeting the IL-6/STAT3 pathway have been developed and pose a promising strategy for the treatment of CRC. This review discusses the molecular mechanisms and possible therapeutic targets involved in IL-6 signaling in CRC.

  9. Minimally Invasive Colorectal Cancer Surgery in Europe

    Science.gov (United States)

    Babaei, Masoud; Balavarca, Yesilda; Jansen, Lina; Gondos, Adam; Lemmens, Valery; Sjövall, Annika; B⊘rge Johannesen, Tom; Moreau, Michel; Gabriel, Liberale; Gonçalves, Ana Filipa; Bento, Maria José; van de Velde, Tony; Kempfer, Lana Raffaela; Becker, Nikolaus; Ulrich, Alexis; Ulrich, Cornelia M.; Schrotz-King, Petra; Brenner, Hermann

    2016-01-01

    Abstract Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse. In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders. The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63–0.69), Sweden (HR 0.68, 95% CI 0.60–0.76), and Norway (HR 0.73, 95% CI 0.67–0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68–0.80) and Sweden (HR 0.77, 95% CI 0.66–0.90). Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients. PMID:27258522

  10. Underpinning the repurposing of anthracyclines towards colorectal cancer

    DEFF Research Database (Denmark)

    Nygård, Sune Boris; Christensen, Ib Jarle; Smith, David Hersi;

    2013-01-01

    breast cancer. No prognostic characteristic of TOP2A was identified. Conclusion. TOP2A gene gain is present in numbers relevant to identify a subgroup of patients who may benefit from anthracycline therapy. Based on the present findings, we will initiate a prospective clinical trial designed to evaluate......Abstract Objective. We propose a repurposing strategy where anthracyclines are reintroduced to a subgroup of patients with metastatic colorectal cancer with the highest likelihood of response. In breast cancer, DNA topoisomerase II alpha gene (TOP2A) alterations predict incremental benefit of...... anthracyclines, but this association has not been investigated in colorectal cancer. Frequency analysis of TOP2A gene alterations in colorectal cancer and the association with prognosis are evaluated and the challenges of using a TOP2A/CEN-17 FISH probe combination are addressed. Material and methods. Formalin...

  11. Review: US Spelling Colorectal cancer models for novel drug discovery

    Science.gov (United States)

    Golovko, Daniel; Kedrin, Dmitriy; Yilmaz, Omer H.; Roper, Jatin

    2016-01-01

    Introduction Despite increased screening rates and advances in targeted therapy, colorectal cancer (CRC) remains the third leading cause of cancer-related mortality. CRC models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. Classic methods of modeling CRC such as human cell lines and xenograft mice, while useful for many applications, carry significant limitations. Recently developed in vitro and in vivo models overcome some of these deficiencies and thus can be utilized to better model CRC for mechanistic and translational research. Areas Covered The authors review established models of in vitro cell culture and describe advances in organoid culture for studying normal and malignant intestine. They also discuss key features of classic xenograft models and describe other approaches for in vivo CRC research, including patient-derived xenograft, carcinogen-induced, orthotopic transplantation, and transgenic mouse models. We also describe mouse models of metastatic CRC. Expert opinion No single model is optimal for drug discovery in CRC. Genetically engineered models overcome many limitations of xenograft models. Three-dimensional organoids can be efficiently derived from both normal and malignant tissue for large-scale in vitro and in vivo (transplantation) studies, and are thus a significant advance in CRC drug discovery. PMID:26295972

  12. MUC1 and colorectal cancer pathophysiology considerations

    Institute of Scientific and Technical Information of China (English)

    Yaron Niv

    2008-01-01

    Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer.A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Hukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and coinvestigators showed recently that MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through β-catenin binding,disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUCl-β-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H,which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation,differentiation or migration when ligand bound.

  13. Changes in apoptosis during the development of colorectal cancer : a systematic review of the literature

    NARCIS (Netherlands)

    Koornstra, JJ; de Jong, S; Hollema, H; de Vries, EGE; Kleibeuker, JH

    2003-01-01

    The development of colorectal cancer is characterised by an accumulation of molecular genetic alterations causing disorders in cell growth, differentiation and apoptosis. Although changes in apoptosis with colorectal cancer development have been studied extensively, a clear consensus of opinion has

  14. Association of overexpression of TIF1γ with colorectal carcinogenesis and advanced colorectal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Shilpa Jain; Fritz Francois; Zhi-Heng Pei; Peng Lee; Ru-Liang Xu; Shashideep Singhal; Franto Francis; Cristina Hajdu; Jin-Hua Wang; Arief Suriawinata; Yin-Quan Wang; Miao Zhang; Elizabeth H Weinshel

    2011-01-01

    AIM: To determine the expression and clinical significance of transcriptional intermediary factor 1 gamma (TIF1γ), Smad4 and transforming growth factor-beta (TGFβR) across a spectrum representing colorectal cancer cancer (CRC) development.METHODS: Tissue microarrays were prepared from archiival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1γ, Smad4 and TGFβRⅡ. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4). cancer (CRC) development.METHODS: Tissue microarrays were prepared from archiival paraffin embedded tissue, including 51 colorectal carcinomas, 25 tubular adenomas (TA) and 26 HPs, each with matched normal colonic epithelium. Immunohistochemistry was performed using antibodies against TIF1γ, Smad4 and TGFβRⅡ. The levels of expression were scored semi-quantitatively (score 0-3 or loss and retention for Smad4).

  15. Metabolites of tobacco smoking and colorectal cancer risk.

    Science.gov (United States)

    Cross, Amanda J; Boca, Simina; Freedman, Neal D; Caporaso, Neil E; Huang, Wen-Yi; Sinha, Rashmi; Sampson, Joshua N; Moore, Steven C

    2014-07-01

    Colorectal cancer is not strictly considered a tobacco-related malignancy, but modest associations have emerged from large meta-analyses. Most studies, however, use self-reported data, which are subject to misclassification. Biomarkers of tobacco exposure may reduce misclassification and provide insight into metabolic variability that potentially influences carcinogenesis. Our aim was to identify metabolites that represent smoking habits and individual variation in tobacco metabolism, and investigate their association with colorectal cancer. In a nested case-control study of 255 colorectal cancers and 254 matched controls identified in the Prostate, Lung, Colorectal and Ovarian cancer screening trial, baseline serum was used to identify metabolites by ultra-high-performance liquid-phase chromatography and mass spectrometry, as well as gas chromatography with tandem mass spectrometry. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Self-reported current smoking was associated with serum cotinine, O-cresol sulfate and hydroxycotinine. Self-reported current smoking of any tobacco (OR = 1.90, 95% CI: 1.02-3.54) and current cigarette smoking (OR = 1.51, 95% CI: 0.75-3.04) were associated with elevated colorectal cancer risks, although the latter was not statistically significant. Individuals with detectable levels of hydroxycotinine had an increased colorectal cancer risk compared with those with undetectable levels (OR = 2.68, 95% CI: 1.33-5.40). Although those with detectable levels of cotinine had a suggestive elevated risk of this malignancy (OR = 1.81, 95% CI: 0.98-3.33), those with detectable levels of O-cresol sulfate did not (OR = 1.16, 95% CI: 0.57-2.37). Biomarkers capturing smoking behavior and metabolic variation exhibit stronger associations with colorectal cancer than self-report, providing additional evidence for a role for tobacco in this malignancy. PMID:24648381

  16. GSTT2 promoter polymorphisms and colorectal cancer risk

    Directory of Open Access Journals (Sweden)

    Ahn Sun-A

    2007-01-01

    Full Text Available Abstract Background Glutathione S-transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs are associated with colorectal cancer risk. Methods A total of 436 colorectal cancer patients and 568 healthy controls were genotyped for three GSTT2 promoter SNPs (-537G>A, -277T>C and -158G>A, using real-time TaqMan assay and direct sequencing. An electrophoretic mobility shift assay (EMSA was performed to determine the effects of polymorphisms on protein binding to the GSTT2 promoter. Results The -537A allele (-537G/A or A/A was significantly associated with colorectal cancer risk (OR = 1.373, p = 0.025, while the -158A allele (-158G/A or A/A was involved in protection against colorectal cancer (OR = 0.539, p = 0.032. Haplotype 2 (-537A, -277T, -158G was significantly associated with colorectal cancer risk (OR = 1.386, p = 0.021, while haplotype 4 (-537G, -277C, -158A protected against colorectal cancer (OR = 0.539, p = 0.032. EMSA data revealed lower promoter binding activity in the -537A allele than its -537G counterpart. Conclusion Our results collectively suggest that SNPs and haplotypes of the GSTT2 promoter region are associated with colorectal cancer risk in the Korean population.

  17. Differences in Colorectal Cancer Outcomes by Race and Insurance.

    Science.gov (United States)

    Tawk, Rima; Abner, Adrian; Ashford, Alicestine; Brown, Clyde Perry

    2015-12-22

    Colorectal cancer (CRC) is the second most common cancer among African American women and the third most common cancer for African American men. The mortality rate from CRC is highest among African Americans compared to any other racial or ethnic group. Much of the disparity in mortality is likely due to diagnosis at later stages of the disease, which could result from unequal access to screening. The purpose of this study is to determine the impact of race and insurance status on CRC outcomes among CRC patients. Data were drawn from the Surveillance, Epidemiology, and End Results database. Logistic regressions models were used to examine the odds of receiving treatment after adjusting for insurance, race, and other variables. Cox proportional hazard models were used to measure the risk of CRC death after adjusting for sociodemographic and tumor characteristics when associating race and insurance with CRC-related death. Blacks were diagnosed at more advanced stages of disease than whites and had an increased risk of death from both colon and rectal cancers. Lacking insurance was associated with an increase in CRC related-deaths. Findings from this study could help profile and target patients with the greatest disparities in CRC health outcomes.

  18. Clinical Curative Effect Observation of Traditional Chinese and Western Medicine Combination for Treatment of Advanced Colorectal Cancer%中西医结合治疗晚期结直肠癌

    Institute of Scientific and Technical Information of China (English)

    姜国胜; 张庚; 任维聃

    2013-01-01

    目的:探讨中西医结合治疗晚期结直肠癌临床疗效.方法:选择2010年1月到2012到6月在本院治疗的63例晚期结直肠癌患者,按随机抽样的方法分为对照组31例患者和研究32例患者,对照组给予FOLFOX6化疗方治疗方案,研究组在对照组治疗的基础上,联合自拟复方中药治疗.治疗两个疗程,比较两组患者治疗效果、疼痛评分(NRS)、生活质量评分(FACT).以及治疗前后患者血清癌胚抗原(CEA),糖链抗原19-9(CA199)的变化.结果:研究组疗效(84.3%)明显高于对照组(64.5%),差异显著(P<0.05).两组治疗后,研究组疼痛评分(NRS)下降、生活质量评分(FACT)增加,与对照组比较差异显著(P<0.05).与治疗前比较,治疗后两组患者血清CEA,CA199均明显下降,差异显著(P<0.05);治疗后,与对照组患者血清CEA,CA199比较,研究组明显改善(P<0.05).结论:中西医结合治疗晚期结直肠癌术效果明显,值得临床推广.%Objective:To explore the clinical curative effect of traditional Chinese and western medicine combination for the treatment of advanced colorectal cancer.Method:Choose 63 cases of the patients with advanced colorectal cancer from January 2010 to 2012 June in our hospital.According to the random sampling method,divided into the control group witn 31 cases and research group with 32 cases.Control group given FOLFOX6 chemotherapy treatments,the rearch group on the basis of the control group treatment,combination with traditional Chinese medicine treatment,after two treatments,compared of the treatment effect of two groups,pain score numerical rating scale (NRS),the life quality score FACT,and the patients serum carcinoembryonic antigen (CEA) and sugar chain antigen 19-9 (CA199) change before and after treatment.Result:Compared with curative effect (64.5%),the team curative effect (84.3%) increased significantly (P < O.05).After the treatment of the two groups,the pain score NRS decline,the life

  19. Clinical observation of thermotherapy combined with FOLFOX6 chemotherapy for advanced colorectal cancer%热疗联合FOLFOX6方案治疗晚期结直肠癌疗效观察

    Institute of Scientific and Technical Information of China (English)

    费燕华; 王南瑶; 王琼; 袁明; 吴丹

    2012-01-01

    Objective To observe the efficacy and adverse reactions of thermotherapy combined with FOLFOX6 chemotherapy for advanced colorectal cancer. Methods 79 patients with advanced colorectal cancer were randomly divided into two groups. Treatment groups received FOLFOX6 systemic chemotherapy combined with thermotherapy; FOLFOX6 regiment was as follows; oxaliplatin 100 mg/m2 ivgtt 3h dl , leucovorin 100 mg ivgtt 2h dl , 5-fluorouracil 400mg/m2 iv dl, 5- flu-orouracil 2000 mg/m2 civ 46h. Treatment groups received thermotherapy at local tumor, twice a cycle. Control groups received only FOLFOX6 systemic chemotherapy. Results In treatment groups, 22 cases achieved PR, 8 cases achieved SD. The RR, DCR and PFS were 59. 46% , 81. 08% and 8. 2 months, respectively. While in control groups, 14 cases achieved PR, 11 cases achieved SD. And the RR, DCR and PFS were 33. 33% , 59. 52% and 5. 3 months, respeetively. So treatment group was superior to control group in the above three parameters (P < 0. 05). Conclusion Thermotherapy combined with FOLFOX6 systemic chemotherapy is safe and effective for patients with advanced colorectal cancer.%目的 观察热疗联合FOLFOX6方案治疗晚期结直肠癌的疗效和不良反应.方法 79例晚期结直肠癌患者随机分为两组,治疗组(热疗联合化疗)采用(FOLFOX6):奥沙利铂100 mg/m2静滴d1、亚叶酸钙100mg静滴2小时d1、氟尿嘧啶400 mg/m2静推d1、氟尿嘧啶2000 mg/m2持续泵入46小时,14天为一个周期.热疗针对复发转移肿瘤部位,每个化疗周期两次热疗.对照组仅采用FOLFOX6方案化疗.结果 治疗组PR 22例,SD 8例,PD7例,有效率(RR) 59.46%,疾病控制率(DCR) 81.08%,无进展生存期(PFS) 8.2个月.对照组PR 14例,SD 11例,PD 17例,有效率(RR) 33.33%,疾病控制率(DCR) 59.52%,无进展生存期(PFS) 5.3个月.治疗组在有效率、疾病无进展生存期、疾病控制率等方面优于对照组(P<0.05),且不增加毒副反应.结论 热疗联合FOLFOX6

  20. Breast Cancer Survivorship Care: Targeting a Colorectal Cancer Education Intervention

    Directory of Open Access Journals (Sweden)

    Sherri G. Homan

    2015-08-01

    Full Text Available Breast cancer survivors are at risk of developing a second primary cancer. Colorectal cancer (CRC is one of the leading second primary cancers, and it is often preventable. We developed a multi-component educational tool to inform and encourage women breast cancer survivors to engage in CRC screening. To assess the strengths and weakness of the tool and to improve the relevancy to the target audience, we convened four focus groups of women breast cancer survivors in Missouri. We also assessed the potential impact of the tool on the knowledge, attitudes, and beliefs regarding CRC and collected information on the barriers to CRC screening through pre- and post-focus groups’ questionnaires. A total of 43 women breast cancer survivors participated and provided very valuable suggestions on design and content to update the tool. Through the process and comparing pre- and post-focus group assessments, a significantly higher proportion of breast cancer survivors strongly agreed or agreed that CRC is preventable (78.6% vs. 96.9%, p = 0.02 and became aware that they were at a slightly increased risk for CRC (18.6% vs. 51.7%, p = 0.003. The most cited barrier was the complexity of preparation for colonoscopy.

  1. Role of MGMT as biomarker in colorectal cancer

    OpenAIRE

    Inno, Alessandro; Fanetti, Giuseppe; Di Bartolomeo, Maria; Gori, Stefania; Maggi, Claudia; Cirillo, Massimo; Iacovelli, Roberto; Nichetti, Federico; Martinetti, Antonia; de Braud, Filippo; Bossi, Ilaria; Pietrantonio, Filippo

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic co...

  2. Molecular Pathways: Estrogen Pathway in Colorectal Cancer

    Science.gov (United States)

    Barzi, Afsaneh; Lenz, Annika Medea; Labonte, Melissa J.; Lenz, Heinz-Josef

    2013-01-01

    Worldwide colorectal cancer (CRC) has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data supports a role for estrogen and its receptors in the initiation and progression of CRC and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of CRC. In the Women’s Health Initiative (WHI) trial use of HRT in postmenopausal women reduced the risk of colon cancer by 56% (95% CI, 0.38 to 0.81; P=0.003). A recent meta-analysis showed that in females, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03 to 0.35; P=0.026). In this review, utilizing the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of CRC. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT or soy products, exerts its effects through preventing this loss. Thus in the adenoma to carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of CRC depends on identification of susceptible CRC population(s). Thus research to better understand the estrogen pathway is fundamental for clinical delivery of these agents. PMID:23965904

  3. Risk Prediction Model for Colorectal Cancer: National Health Insurance Corporation Study, Korea

    OpenAIRE

    Aesun Shin; Jungnam Joo; Hye-Ryung Yang; Jeongin Bak; Yunjin Park; Jeongseon Kim; Jae Hwan Oh; Byung-Ho Nam

    2014-01-01

    PURPOSE: Incidence and mortality rates of colorectal cancer have been rapidly increasing in Korea during last few decades. Development of risk prediction models for colorectal cancer in Korean men and women is urgently needed to enhance its prevention and early detection. METHODS: Gender specific five-year risk prediction models were developed for overall colorectal cancer, proximal colon cancer, distal colon cancer, colon cancer and rectal cancer. The model was developed using data from a po...

  4. A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer

    DEFF Research Database (Denmark)

    Qvortrup, C; Jensen, Benny Vittrup; Fokstuen, T;

    2010-01-01

    Chronotherapy is one of the several approaches to increase efficacy and reduce toxicity of chemotherapy. In a phase II study in the second-line in patients with metastatic colorectal cancer (mCRC), we found that chronomodulated XELOX (XELOX(30Chron)) was a well-tolerated regimen with potentially ...

  5. Cardiac metastasis from colorectal cancer: A case report

    Institute of Scientific and Technical Information of China (English)

    Pyong Wha Choi; Chul Nam Kim; Sun Hee Chang; Woo Ik Chang; Chang Young Kim; Hyun Min Choi

    2009-01-01

    The heart is an unusual site of metastasis from any malignancy. We report a case of cardiac metastasis from colorectal cancer. A 70-year-old woman was referred with a presumptive diagnosis of sigmoid colon cancer with cardiac myxoma. Two-dimensional echocardiography showed a 4 cm × 4.5 cm mobile mass on the lateral right atrial wall, and computed tomography revealed a low attenuated lobulating mass in the right atrium. The patient underwent anterior resection for sigmoid colon cancer (T4N2). Thereafter, she experienced progressive shortness of breath. Therefore, a cardiac operation was performed 2 wk after the colorectal operation.Histological examination revealed adenocarcinoma,which was identical to the primary lesion. Although twodimensional echocardiography has become the diagnostic test of choice for detecting cardiac tumors, in patients with colorectal cancer showing a cardiac mass, further diagnostic evaluation such as a magnetic resonance imaging might be necessary.

  6. Multivariate Regression Analysis of Prognostic Factors in Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    YANGZuli; WANGJianping; WANGLei; DONGWenguang; HUANGYihua; QINJianzhang; ZHANWenhua

    2003-01-01

    Objective: To evaluate the relationship between clinicopathologic features and prognosis of col-orectal cancer after surgical treatment. Methods: The relationship between clinicopathological character-istics and prognosis of 941 patients with colorectal cancer after surgical treatment were investigated by univariate and multivariate analysis. Results: The overall 3- and 5-year survival rates of patients withcolorectal cancer after surgical treatment were 63.2% and 60.8% respectively with a median survival of 1841 days. Univariate analysis revealed that such factors as gross findings, degree of differentiation, depth of infiltration, nodal and distant metastasis and neoplastic intestinal obstruction were correlated with the survival rate. Dukes stages, gross tumor configuration, intramural spread and differentiation degree were shown to be available independent prognostic factors by multivariate analysis. Conclusion: Dukes stage,as the most important available independent prognostic factor for colorectal cancer (P<0.0005), can be used to assess the postoperative survival.

  7. 77 FR 11123 - Scientific Information Request on Local Therapies for Unresectable Colorectal Cancer Metastases...

    Science.gov (United States)

    2012-02-24

    ... Therapies for Unresectable Colorectal Cancer Metastases to the Liver AGENCY: Agency for Healthcare Research... unresectable colorectal cancer metastases to the liver. The EHC Program is dedicated to identifying as many... manufacturers of unresectable colorectal cancer medical devices. Scientific information is being solicited...

  8. microRNA在结直肠癌中的研究及应用进展%Advances in The Research and Utilization of MicroRNA in Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    彭伟; 杨韵; 刘韵霄; 舒晔

    2013-01-01

    Objective To summarize the relationship between microRNA and the occurrence and progression of colorectal cancer,and to investigate the application value of microRNA in the diagnosis,treatment,and prognosis evaluation of colorectal cancer.Methods Domestic and international publications involving the relationship between microRNA and colorectal cancer were retrieved and reviewed.Results MicroRNA acted as an oncogene or tumor suppressor gene to participate in cell proliferation,differentiation,apoptosis,metabolism,tumor genesis,and tumor progression.The abnormal expression of microRNA was closely related to the occurrence and progression of colorectal cancer.As specific biomarker,microRNA could be applied in early diagnosis,chemotherapy strategy-making,and prognostic evaluation of colorectal cancer.Conclusion MicroRNA is definitely related to the occurrence and progression of colorectal cancer,and it has great prospect in the basic research and clinical applications of colorectal cancer.%目的 总结微小RNA (microRNA)与结直肠癌发生和发展的关系,及其在结直肠癌诊断、治疗和预后评价中的应用价值.方法 收集国内外关于microRNA与结直肠癌关系的文献并作综述.结果 microRNA通过其类癌基因或抑癌基因的作用直接或者间接参与细胞增殖、分化、凋亡、代谢、肿瘤发生和发展等生物学过程.其异常表达与结直肠癌的发生和发展均密切相关,可作为结直肠癌早期诊断、化疗方案制定及预后评价的生物学标志物.结论 microRNA与结直肠癌的发生和发展均相关,在结直肠癌的基础研究和临床应用中具有较大前景.

  9. Relationship Between the Levels of Oxidative Stress in Mesenteric and Peripheral Serum and Clinicopathological Variables in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Sevim Purisa

    2012-06-01

    Full Text Available Objective: To explore the differences existing between the levels of oxidative stress in peripheral and mesenteric serum in patients with colorectal cancer. Material and Methods: One hundred fifty patients with colorectal cancer who underwent surgery between May 2005 and March 2010 were prospectively analyzed. The differences between oxidative stress parameters in their peripheral and mesenteric blood were measured. The associations between peripheral and mesenteric levels and the staging and clinicopathological variables were investigated.Results: Oxidative stress parameters were higher in patients with advanced tumor staging (p<0.01, lymph node invasion (p<0.01, and venous invasion (p<0.01. Differences between oxidative stress parameters in peripheral and mesenteric blood samples were also observed.Conclusions: The mesenteric levels of the oxidative stress markers were higher than the peripheral levels in these colorectal cancer patients. Higher levels of these oxidative stress markers are associated with an advanced state of cancer.

  10. Body fat and risk of colorectal cancer among postmenopausal women.

    Science.gov (United States)

    Kabat, Geoffrey C; Heo, Moonseong; Wactawski-Wende, Jean; Messina, Catherine; Thomson, Cynthia A; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

    2013-06-01

    Studies of the relationship between anthropometric indices of obesity and colorectal cancer risk in women have shown only weak and inconsistent associations. Given the limitations of such indices, we used dual-energy X-ray absorptiometry (DXA)-derived measures of body fat obtained in the Women's Health Initiative to examine the association between body fat and risk of incident colorectal cancer. We compared these risk estimates with those obtained using conventional anthropometric measurements (body mass index and waist circumference). After exclusions, the study population consisted of 11,124 postmenopausal women with DXA measurements at baseline and no history of colorectal cancer. After a median follow-up period of 12.9 years, 169 incident colorectal cancer cases were ascertained. Cox's proportional hazards models were used to estimate hazard ratios and 95 % confidence intervals for the exposures of interest. Neither DXA-derived body fat measures nor anthropometric measures showed significant associations with risk. In view of the limited number of cases, we cannot rule out the existence of weak associations of these measures with risk of colorectal cancer. PMID:23546610

  11. REPRODUCTIVE FACTORS AND COLORECTAL CANCER RISK. Case - control study.

    Directory of Open Access Journals (Sweden)

    Adriana Ruseva

    2015-02-01

    Full Text Available Colorectal cancer is one of the most common cancers worldwide. The role of the female sex hormones in the etiology of the disease is very intriguing. Reproductive factors are surrogate measure of lifetime exposition to the sex hormones. Purpose: Our aim is to investigate the association between the reproductive factors and colorectal carcinoma risk. Materials and methods: We include 234 Bulgarian women in our study – 117 cases with colorectal cancer and the same number of healthy controls. Cases are divided into three groups according to the localization of the tumor. We conduct case-control study, using questionnaires about reproductive factors. We use the following statistical methods – descriptive, variational analysis, binary logistic regression. Results: We observed that only the age at menopause is associated with colorectal cancer risk, and this factor has strongest protective effect in the proximal colon (95% CI - 0,051-0,781, OR – 0,200, p – 0,021. Conclusion: Analyzing our data we observed that among Bulgarian women the only reproductive factor that show association with the risk of colorectal cancer is the age at menopause.

  12. Analysis of colorectal cancers for human cytomegalovirus presence

    Directory of Open Access Journals (Sweden)

    Menestrina Fabio

    2009-04-01

    Full Text Available Abstract Background A possible association between human cytomegalovirus (HCMV infection and colorectal cancer progression has been inferred by the identification in tumour tissues of HCMV antigens and specific viral DNA or RNA sequences. To further investigate the relationship between HCMV and colorectal cancers we developed qualitative and quantitative PCR assay to detect HCMV DNA in 56 formalin-fixed paraffin-embedded (FFPE tissue samples from patients belonging to 4 different histological phenotypes: adenoma; poorly, moderately and well differentiated adenocarcinomas. Results Of the 56 FFPE tested tissue samples, 6 (11% were positive for HCMV nested PCR amplification, and more precisely 1 (5% of 20 cases of adenoma and 5 (21% of 24 cases of moderately differentiated adenocarcinoma. No PCR positivity was obtained in samples from well and poorly differentiated adenocarcinomas. Conclusion Our observations suggest that there is no evidence of a direct association between HCMV and colorectal cancer. Moreover, the results obtained are not supportive of a causal role of HCMV in the processes of carcinogenesis and/or progression of colorectal cancer. However, the fact that the virus may present a "hit and run" like-mechanism and HCMV can thus only be detectable at a particular stage of a processing adenocarcinoma, suggests that a significant number of colorectal cancers might have been the subject of HCMV infection that could contribute to trigger the oncogenic differentiation. Our analysis does not exclude the possibility of HCMV infection subsequent viral clearance.

  13. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte;

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic and...

  14. Anti-colorectal cancer immunity : control ‘the force’!

    NARCIS (Netherlands)

    Speetjens, Franciscus Maria

    2013-01-01

    This dissertation reports on the relation between the immune system, colorectal cancer and immunotherapy. In the first part, expression of HLA class I and expression of CXCL5 in colocectal cancer was studied. Low expression of HLA class I in rectal tumors was associated with poor survival of rectal

  15. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte;

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...

  16. Factors Influencing Colorectal Cancer Screening Participation

    Directory of Open Access Journals (Sweden)

    Antonio Z. Gimeno García

    2012-01-01

    Full Text Available Colorectal cancer (CRC is a major health problem worldwide. Although population-based CRC screening is strongly recommended in average-risk population, compliance rates are still far from the desirable rates. High levels of screening uptake are necessary for the success of any screening program. Therefore, the investigation of factors influencing participation is crucial prior to design and launches a population-based organized screening campaign. Several studies have identified screening behaviour factors related to potential participants, providers, or health care system. These influencing factors can also be classified in non-modifiable (i.e., demographic factors, education, health insurance, or income and modifiable factors (i.e., knowledge about CRC and screening, patient and provider attitudes or structural barriers for screening. Modifiable determinants are of great interest as they are plausible targets for interventions. Interventions at different levels (patient, providers or health care system have been tested across the studies with different results. This paper analyzes factors related to CRC screening behaviour and potential interventions designed to improve screening uptake.

  17. Colorectal cancer diagnosis: Pitfalls and opportunities

    Institute of Scientific and Technical Information of China (English)

    Pablo; Vega; Fátima; Valentín; Joaquín; Cubiella

    2015-01-01

    Colorectal cancer(CRC) is a major health problem in the Western world. The diagnostic process is a challenge in all health systems for many reasons: There are often no specific symptoms; lower abdominal symptoms are very common and mostly related to nonneoplastic diseases, not CRC; diagnosis of CRC is mainlybased on colonoscopy, an invasive procedure; and the resource for diagnosis is usually scarce. Furthermore, the available predictive models for CRC are based on the evaluation of symptoms, and their diagnostic accuracy is limited. Moreover, diagnosis is a complex process involving a sequence of events related to the patient, the initial consulting physician and the health system. Understanding this process is the first step in identifying avoidable factors and reducing the effects of diagnostic delay on the prognosis of CRC. In this article, we describe the predictive value of symptoms for CRC detection. We summarize the available evidence concerning the diagnostic process, as well as the factors implicated in its delay and the methods proposed to reduce it. We describe the different prioritization criteria and predictive models for CRC detection, specifically addressing the two-week wait referral guideline from the National Institute of Clinical Excellence in terms of efficacy, efficiency and diagnostic accuracy. Finally, we collected information on the usefulness of biomarkers, specifically the faecal immunochemical test, as non-invasive diagnostic tests for CRC detection in symptomatic patients.

  18. Colorectal Cancer in African Americans: An Update.

    Science.gov (United States)

    Williams, Renee; White, Pascale; Nieto, Jose; Vieira, Dorice; Francois, Fritz; Hamilton, Frank

    2016-01-01

    This review is an update to the American College of Gastroenterology (ACG) Committee on Minority Affairs and Cultural Diversity's paper on colorectal cancer (CRC) in African Americans published in 2005. Over the past 10 years, the incidence and mortality rates of CRC in the United States has steadily declined. However, reductions have been strikingly much slower among African Americans who continue to have the highest rate of mortality and lowest survival when compared with all other racial groups. The reasons for the health disparities are multifactorial and encompass physician and patient barriers. Patient factors that contribute to disparities include poor knowledge of benefits of CRC screening, limited access to health care, insurance status along with fear and anxiety. Physician factors include lack of knowledge of screening guidelines along with disparate recommendations for screening. Earlier screening has been recommended as an effective strategy to decrease observed disparities; currently the ACG and American Society of Gastrointestinal Endoscopists recommend CRC screening in African Americans to begin at age 45. Despite the decline in CRC deaths in all racial and ethnic groups, there still exists a significant burden of CRC in African Americans, thus other strategies including educational outreach for health care providers and patients and the utilization of patient navigation systems emphasizing the importance of screening are necessary. These strategies have been piloted in both local communities and Statewide resulting in notable significant decreases in observed disparities. PMID:27467183

  19. Advances in endoscopic ultrasound imaging of colorectal diseases.

    Science.gov (United States)

    Cârțână, Elena Tatiana; Gheonea, Dan Ionuț; Săftoiu, Adrian

    2016-02-01

    The development of endoscopic ultrasound (EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal (GI) and pancreatico-biliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate in-depth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn's disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and

  20. Genomic diversity of colorectal cancer: Changing landscape and emerging targets.

    Science.gov (United States)

    Ahn, Daniel H; Ciombor, Kristen K; Mikhail, Sameh; Bekaii-Saab, Tanios

    2016-07-01

    Improvements in screening and preventive measures have led to an increased detection of early stage colorectal cancers (CRC) where patients undergo treatment with a curative intent. Despite these efforts, a high proportion of patients are diagnosed with advanced stage disease that is associated with poor outcomes, as CRC remains one of the leading causes of cancer-related deaths in the world. The development of next generation sequencing and collaborative multi-institutional efforts to characterize the cancer genome has afforded us with a comprehensive assessment of the genomic makeup present in CRC. This knowledge has translated into understanding the prognostic role of various tumor somatic variants in this disease. Additionally, the awareness of the genomic alterations present in CRC has resulted in an improvement in patient outcomes, largely due to better selection of personalized therapies based on an individual's tumor genomic makeup. The benefit of various treatments is often limited, where recent studies assessing the genomic diversity in CRC have identified the development of secondary tumor somatic variants that likely contribute to acquired treatment resistance. These studies have begun to alter the landscape of treatment for CRC that include investigating novel targeted therapies, assessing the role of immunotherapy and prospective, dynamic assessment of changes in tumor genomic alterations that occur during the treatment of CRC. PMID:27433082

  1. Genomic diversity of colorectal cancer: Changing landscape and emerging targets

    Science.gov (United States)

    Ahn, Daniel H; Ciombor, Kristen K; Mikhail, Sameh; Bekaii-Saab, Tanios

    2016-01-01

    Improvements in screening and preventive measures have led to an increased detection of early stage colorectal cancers (CRC) where patients undergo treatment with a curative intent. Despite these efforts, a high proportion of patients are diagnosed with advanced stage disease that is associated with poor outcomes, as CRC remains one of the leading causes of cancer-related deaths in the world. The development of next generation sequencing and collaborative multi-institutional efforts to characterize the cancer genome has afforded us with a comprehensive assessment of the genomic makeup present in CRC. This knowledge has translated into understanding the prognostic role of various tumor somatic variants in this disease. Additionally, the awareness of the genomic alterations present in CRC has resulted in an improvement in patient outcomes, largely due to better selection of personalized therapies based on an individual’s tumor genomic makeup. The benefit of various treatments is often limited, where recent studies assessing the genomic diversity in CRC have identified the development of secondary tumor somatic variants that likely contribute to acquired treatment resistance. These studies have begun to alter the landscape of treatment for CRC that include investigating novel targeted therapies, assessing the role of immunotherapy and prospective, dynamic assessment of changes in tumor genomic alterations that occur during the treatment of CRC. PMID:27433082

  2. Genomic diversity of colorectal cancer: Changing landscape and emerging targets.

    Science.gov (United States)

    Ahn, Daniel H; Ciombor, Kristen K; Mikhail, Sameh; Bekaii-Saab, Tanios

    2016-07-01

    Improvements in screening and preventive measures have led to an increased detection of early stage colorectal cancers (CRC) where patients undergo treatment with a curative intent. Despite these efforts, a high proportion of patients are diagnosed with advanced stage disease that is associated with poor outcomes, as CRC remains one of the leading causes of cancer-related deaths in the world. The development of next generation sequencing and collaborative multi-institutional efforts to characterize the cancer genome has afforded us with a comprehensive assessment of the genomic makeup present in CRC. This knowledge has translated into understanding the prognostic role of various tumor somatic variants in this disease. Additionally, the awareness of the genomic alterations present in CRC has resulted in an improvement in patient outcomes, largely due to better selection of personalized therapies based on an individual's tumor genomic makeup. The benefit of various treatments is often limited, where recent studies assessing the genomic diversity in CRC have identified the development of secondary tumor somatic variants that likely contribute to acquired treatment resistance. These studies have begun to alter the landscape of treatment for CRC that include investigating novel targeted therapies, assessing the role of immunotherapy and prospective, dynamic assessment of changes in tumor genomic alterations that occur during the treatment of CRC.

  3. Imaging in Colorectal Cancer: Progress and Challenges for the Clinicians

    Science.gov (United States)

    Van Cutsem, Eric; Verheul, Henk M. W.; Flamen, Patrik; Rougier, Philippe; Beets-Tan, Regina; Glynne-Jones, Rob; Seufferlein, Thomas

    2016-01-01

    The use of imaging in colorectal cancer (CRC) has significantly evolved over the last twenty years, establishing important roles in surveillance, diagnosis, staging, treatment selection and follow up. The range of modalities has broadened with the development of novel tracer and contrast agents, and the fusion of technologies such as positron emission tomography (PET) and computed tomography (CT). Traditionally, the most widely used modality for assessing treatment response in metastasised colon and rectal tumours is CT, combined with use of the RECIST guidelines. However, a growing body of evidence suggests that tumour size does not always adequately correlate with clinical outcomes. Magnetic resonance imaging (MRI) is a more versatile technique and dynamic contrast-enhanced (DCE)-MRI and diffusion-weighted (DW)-MRI may be used to evaluate biological and functional effects of treatment. Integrated fluorodeoxyglucose (FDG)-PET/CT combines metabolic and anatomical imaging to improve sensitivity and specificity of tumour detection, and a number of studies have demonstrated improved diagnostic accuracy of this modality in a variety of tumour types, including CRC. These developments have enabled the progression of treatment strategies in rectal cancer and improved the detection of hepatic metastatic disease, yet are not without their limitations. These include technical, economical and logistical challenges, along with a lack of robust evidence for standardisation and formal guidance. In order to successfully apply these novel imaging techniques and utilise their benefit to provide truly personalised cancer care, advances need to be clinically realised in a routine and robust manner. PMID:27589804

  4. Risk factors for metachronous colorectal cancer following a primary colorectal cancer: A prospective cohort study.

    Science.gov (United States)

    Jayasekara, Harindra; Reece, Jeanette C; Buchanan, Daniel D; Rosty, Christophe; Dashti, S Ghazaleh; Ait Ouakrim, Driss; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Giles, Graham G; Ahnen, Dennis J; Lowery, Jan; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Parry, Susan; Jenkins, Mark A; Win, Aung Ko

    2016-09-01

    Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997-2012, except those identified as high-risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30-5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80-6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC. PMID:27098183

  5. Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer

    DEFF Research Database (Denmark)

    Kyrø, Cecilie; Olsen, Anja; Landberg, Rikard;

    2014-01-01

    . We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional...... not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). CONCLUSIONS: High concentrations of plasma...

  6. Five year colorectal cancer outcomes in a large negative CT colonography screening cohort

    Energy Technology Data Exchange (ETDEWEB)

    Kim, David H.; Pooler, B.D.; Pickhardt, Perry J. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States); Weiss, Jennifer M. [University of Wisconsin School of Medicine and Public Health, Section of Gastroenterology, Department of Internal Medicine, Madison, WI (United States)

    2012-07-15

    To assess the 5-year incidence of clinically presenting colorectal cancers following a negative CT colonography (CTC) screening examination, as few patient outcome data regarding a negative CTC screening result exist. Negative CTC screening patients (n = 1,050) in the University of Wisconsin Health system over a 14-month period were included. An electronic medical record (EMR) review was undertaken, encompassing provider, colonoscopy, imaging and histopathology reports. Incident colorectal cancers and other important GI tumours were recorded. Of the 1,050 cohort (mean [{+-}SD] age 56.9 {+-} 7.4 years), 39 (3.7%) patients were excluded owing to lack of follow-up within our system beyond the initial screening CTC. The remaining 1,011 patients were followed for an average of 4.73 {+-} 1.15 years. One incident colorectal adenocarcinoma represented a crude cancer incidence of 0.2 cancers per 1,000 patient years. EMR revealed 14 additional patients with clinically important GI tumours including: advanced adenomas (n = 11), appendiceal goblet cell carcinoid (n = 1), appendiceal mucinous adenoma (n = 1) and metastatic ileocolonic carcinoid (n = 1). All positive patients including the incident carcinoma are alive at the time of review. Clinically presenting colorectal adenocarcinoma is rare in the 5 years following negative screening CTC, suggesting that current strategies, including non-reporting of diminutive lesions, are appropriate. (orig.)

  7. Health behaviours and fear of cancer recurrence in 10 969 colorectal cancer (CRC) patients

    OpenAIRE

    Fisher, A.; Beeken, R.J.; Heinrich, M.; Williams, K.; Wardle, J.

    2016-01-01

    BACKGROUND: This study aimed to examine whether fear of cancer recurrence (FCR) was related to two important health behaviours (physical activity and smoking) in a large sample of colorectal cancer patients. METHODS: Ten thousand nine hundred sixty nine patients, diagnosed in 2010-11, and in remission in 2013, completed the 'Living with and Beyond Colorectal Cancer' survey. The survey included purpose-designed questions on fear of recurrence ('I have fear about my cancer coming back'), demogr...

  8. Time dependent ethnic convergence in colorectal cancer survival in hawaii

    Directory of Open Access Journals (Sweden)

    Hundahl Scott A

    2003-02-01

    Full Text Available Abstract Background Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. Methods Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960–2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese. The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. Results Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. Conclusion Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated.

  9. Colorectal cancer complicated by perforation. Specific features of surgical tactics

    Directory of Open Access Journals (Sweden)

    S. N. Shchaeva

    2015-01-01

    Full Text Available Objective: to assess the immediate results of surgical interventions for colorectal cancer complicated by perforation.Materials and methods. The immediate results of surgical treatment were retrospectively analyzed in 56 patients with colorectal cancer complicated by perforated colon cancer, who had been treated at Smolensk surgical hospitals in 2001 to 2013. Patients with diastatic perforation of the colon in the presence of decompensated obturation intestinal obstruction of tumor genesis were not included into this investigation.Results. The immediate results of uni- and multistage surgical interventions were analyzed in relation to the extent of peritonitis and the stage of colon cancer. More satisfactory immediate results were observed after multistage surgical treatment. Following these interventions, a fatal outcome of disseminated peritonitis in the presence of performed colorectal cancer was recorded in 8 (53.3 % cases whereas after symptomatic surgery there were 11 (67.8 % deaths. A fatal outcome was noted in 1 case (7.7 % after multistage surgery.Discussion. The results of surgical treatment in the patients with perforated colorectal cancer are directly related to the degree of peritonitis and the choice of surgical tactics.

  10. Immunotherapy in colorectal cancer: What have we learned so far?

    Science.gov (United States)

    Sanchez-Castañón, María; Er, Tze-Kiong; Bujanda, Luis; Herreros-Villanueva, Marta

    2016-09-01

    After decades of progress based on chemotherapy and targeted agents, patients with metastatic colorectal cancer still have low long-term survival, with more than 500,000 deaths occurring worldwide every year. Recent results showing clinical evidence of efficacy using immunotherapy in other types of tumors, such as melanoma and lung cancer, have also made this a viable therapy for evaluation in colorectal cancer in clinical trials. The development of cancer immunotherapies is progressing quickly, with a variety of technological approaches. This review summarizes the current status of clinical trials testing immunotherapy in colorectal cancer and discusses what has been learned based on previous results. Immunotherapy strategies, such as various models of vaccines, effector-cell therapy and checkpoint inhibitor antibodies, provide protection against progression for a limited subset of patients diagnosed with colorectal cancer. A better understanding of particular immune cell types and pathways in each patient is still needed. These findings will enable the development of novel biomarkers to select the appropriate subset of patients to be treated with a particular immunotherapy, and the tendencies determined from recent results can guide clinical practice for oncologists in this new therapeutic area and in the design of the next round of clinical trials. PMID:27350293

  11. Regulatory T cells in inflammatory bowel diseases and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Gy(o)rgyi Müzes; Béla Molnár; Ferenc Sipos

    2012-01-01

    Regulatory T cells (Tregs) are key elements in immunological self-tolerance.The number of Tregs may alter in both peripheral blood and in colonic mucosa during pathological circumstances.The local cellular,microbiological and cytokine milieu affect immunophenotype and function of Tregs.Forkhead box P3+ Tregs function shows altered properties in inflammatory bowel diseases (IBDs).This alteration of Tregs function can furthermore be observed between Crohn's disease and ulcerative colitis,which may have both clinical and therapeutical consequences.Chronic mucosal inflammation may also influence Tregs function,which together with the intestinal bacterial flora seem to have a supporting role in colitis-associated colorectal carcinogenesis.Tregs have a crucial role in the immunoevasion of cancer cells in sporadic colorectal cancer.Furthermore,their number and phenotype correlate dosely with the clinical outcome of the disease,even if their contribution to carcinogenesis has previously been controversial.Despite knowledge of the clinical relationship between IBD and colitis-associated colon cancer,and the growing number of immunological aspects encompassing sporadic colorectal carcinogenesis,the molecular and cellular links amongst Tregs,regulation of the inflammation,and cancer development are still not well understood.In this paper,we aimed to review the current data surrounding the role of Tregs in the pathogenesis of IBD,colitis-associated colon cancer and sporadic colorectal cancer.

  12. Serum YKL-40 in risk assessment for colorectal cancer

    DEFF Research Database (Denmark)

    Johansen, Julia Sidenius; Christensen, Ib Jarle; Jørgensen, Lars Nannestad;

    2015-01-01

    to endoscopy due to symptoms or other risk factors for colorectal cancer. Blood samples were collected just before large bowel endoscopy. Serum YKL-40 was determined by ELISA. Serum YKL-40 was higher (P colon cancer (median 126 μg......The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred....../L, 25%-75%: 80-206 μg/L) and rectal cancer (104, 72-204 μg/L) compared with subjects with adenoma (84, 53-154 μg/L), other nonmalignant findings (79, 49-138 μg/L), and no findings (62, 41-109 μg/L). Serum YKL-40 independently predicted colorectal cancer [OR, 1.53; 95% confidence interval (CI), 1...

  13. Predictive and Prognostic Factors in Colorectal Cancer: A Personalized Approach

    Directory of Open Access Journals (Sweden)

    Timothy A. Rockall

    2011-03-01

    Full Text Available It is an exciting time for all those engaged in the treatment of colorectal cancer. The advent of new therapies presents the opportunity for a personalized approach to the patient. This approach considers the complex genetic mechanisms involved in tumorigenesis in addition to classical clinicopathological staging. The potential predictive and prognostic biomarkers which have stemmed from the study of the genetic basis of colorectal cancer and therapeutics are discussed with a focus on mismatch repair status, KRAS, BRAF, 18qLOH, CIMP and TGF-β.

  14. Have You Been Tested for Colorectal Cancer? PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2013-11-05

    This 60 second public service announcement is based on the November 2013 CDC Vital Signs report. Colorectal cancer screening saves lives, but only if you get tested. If you’re between 50 and 75, talk with your doctor about which test is best for you. If you have inflammatory bowel disease or a family history of colorectal cancer or polyps, ask your doctor if you should start screening before age 50.  Created: 11/5/2013 by Centers for Disease Control and Prevention (CDC).   Date Released: 11/5/2013.

  15. Current trends in the chemotherapy of colorectal cancer.

    Science.gov (United States)

    Berciano-Guerrero, M A; Villa-Guzmán, J C; Acosta-Guerrero, R; Castañeda-Peñalvo, G; Rodríguez-Flores, J

    2012-01-01

    The increase in the therapeutic arsenal in the last 20 years, has given rise to changes in treating colorectal cancer (CRC) with only pyrimidines to combine several cytotoxic drugs. However, the present question is to determine the optimal sequence of this combination. This review presents an update of data on chemical and clinical features of chemotherapy used for colorectal cancer and the mechanisms of cellular resistance and potential predictive and prognostic biomarkers, which may contribute to a better selection of a therapeutic strategy. PMID:22830343

  16. Mutator gene and hereditary non-polyposis colorectal cancer

    Science.gov (United States)

    de la Chapelle, Albert; Vogelstein, Bert; Kinzler, Kenneth W.

    2008-02-05

    The human MSH2 gene, responsible for hereditary non-polyposis colorectal cancer, was identified by virtue of its homology to the MutS class of genes, which are involved in DNA mismatch repair. The sequence of cDNA clones of the human gene are provided, and the sequence of the gene can be used to demonstrate the existence of germ line mutations in hereditary non-polyposis colorectal cancer (HNPCC) kindreds, as well as in replication error.sup.+ (RER.sup.+) tumor cells.

  17. BRAF-Directed Therapy in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Korphaisarn, Krittiya; Kopetz, Scott

    2016-01-01

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

  18. Incidence and Management of Colorectal Cancer in Liver Transplant Recipients

    OpenAIRE

    Nishihori, Taiga; Strazzabosco, Mario; Saif, Muhammad Wasif

    2008-01-01

    Liver transplant recipients are at an increased risk of developing de novo malignancies because of the prolonged immunosuppression necessary to avoid acute and chronic rejections. Skin cancers and lymphoproliferative diseases are the most common malignancies, but the overall incidence of colon cancer in this patient population does differ from that of the general population. Therefore, colorectal cancer (CRC) is a major health concern in liver transplant recipients. Furthermore, there are uni...

  19. Natural Product Shows Effectiveness in Combating Colorectal Cancer | Poster

    Science.gov (United States)

    An herbal extract used for centuries to prevent heart disease has now been shown to be effective against colorectal cancer when tested in laboratory cell cultures. Scientists from NCI at Frederick found that the natural extract cryptotanshinone (CPT) stops the uncontrolled cell growth characteristic of cancer by interfering with a protein that has been implicated in several cancers, including those of the colon and rectum. The results appear in the journal Molecular and Cellular Biochemistry.

  20. Factors Influencing Selection of Treatment for Colorectal Cancer Patients

    OpenAIRE

    Cavalli-Björkman, Nina

    2012-01-01

    In Sweden and elsewhere there is evidence of poorer cancer survival for patients of low socioeconomic status (SES), and in some settings differences in treatment by SES have been shown. The aim of this thesis was to explore factors which influence cancer treatment decisions, such as knowledge reaped from clinical trials, patient-related factors, and physician-related factors. In a register study of colorectal cancer, all stages, patients were stratified for SES-factors. Differences were seen ...

  1. Identifying patients at risk of emergency admission for colorectal cancer

    OpenAIRE

    Wallace, D.; Walker, K.; Kuryba, A; Finan, P; Scott, N.; Van Der Meulen, J.

    2014-01-01

    Background: Patients whose colorectal cancer is treated after an emergency admission tend to have late-stage cancer and a poor prognosis. We identified risk factors for an emergency admission by linking data from the National Bowel Cancer Audit (NBCA) and the English Hospital Episode Statistics (HES), an administrative database of all admissions to English National Health Service hospitals, which includes data on mode of admission. Methods: We identified all adults included in the NBCA with a...

  2. Selected micronutrient intake and the risk of colorectal cancer.

    OpenAIRE

    Ferraroni, M; La Vecchia, C.; D'Avanzo, B; De Negri, E.; Franceschi, S; Decarli, A

    1994-01-01

    The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estim...

  3. Accomplishments in 2008 in the Management of Curable Metastatic Colorectal Cancer

    OpenAIRE

    Adam, René; Hoti, Emir; Folprecht, Gunnar; Benson, Al B.

    2009-01-01

    Overview of the Disease IncidencePrognosisCurrent Therapy Standards Colorectal Liver Metastases (CRLM) Resectable TumorsStrategies to Convert Nonresectable Liver Metastases to Resectable StatusSynchronous Colorectal Liver MetastasesPredictors of Survival After Resection of CRLMPeritoneal Carcinomatosis (PC) From Colorectal CancerColorectal Pulmonary Metastases (CRPM)Colorectal Liver Metastases With Extrahepatic DiseaseAccomplishments (or Lack of Accomplishments) During the Year Th...

  4. Perspectives of colorectal cancer risk and screening among Dominicans and Puerto Ricans: stigma and misperceptions.

    Science.gov (United States)

    Goldman, Roberta E; Diaz, Joseph A; Kim, Ivone

    2009-11-01

    Colorectal cancer is the second most common cancer among Latinos, but a lower percentage of Latinos are screened than Whites and Blacks. Along with recognized economic barriers, differences in knowledge and perceptions might impede colorectal screening among Latinos. We conducted 147 individual, qualitative interviews with Dominicans and Puerto Ricans in the northeastern United States to explore their explanatory models for colorectal cancer and screening barriers. Many participants had not previously heard of colorectal cancer. The most commonly mentioned cause of colorectal cancer was anal sex. Also considered risks were "bad food," digestion leading to constipation, and strained bowel movements. Screening barriers included stigma, misperceptions, embarrassment, and machismo. Progress toward increasing colorectal cancer screening requires normalization of this screening among Latinos. Higher patient familiarity, along with improved physician counseling and referral, might contribute to reducing stigma and other barriers, and to enhancing knowledge and Latino community support of colorectal cancer screening.

  5. Determining the familial risk distribution of colorectal cancer: a data mining approach.

    Science.gov (United States)

    Chau, Rowena; Jenkins, Mark A; Buchanan, Daniel D; Ait Ouakrim, Driss; Giles, Graham G; Casey, Graham; Gallinger, Steven; Haile, Robert W; Le Marchand, Loic; Newcomb, Polly A; Lindor, Noralane M; Hopper, John L; Win, Aung Ko

    2016-04-01

    This study was aimed to characterize the distribution of colorectal cancer risk using family history of cancers by data mining. Family histories for 10,066 colorectal cancer cases recruited to population cancer registries of the Colon Cancer Family Registry were analyzed using a data mining framework. A novel index was developed to quantify familial cancer aggregation. Artificial neural network was used to identify distinct categories of familial risk. Standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs) of colorectal cancer were calculated for each category. We identified five major, and 66 minor categories of familial risk for developing colorectal cancer. The distribution the major risk categories were: (1) 7% of families (SIR = 7.11; 95% CI 6.65-7.59) had a strong family history of colorectal cancer; (2) 13% of families (SIR = 2.94; 95% CI 2.78-3.10) had a moderate family history of colorectal cancer; (3) 11% of families (SIR = 1.23; 95% CI 1.12-1.36) had a strong family history of breast cancer and a weak family history of colorectal cancer; (4) 9 % of families (SIR = 1.06; 95 % CI 0.96-1.18) had strong family history of prostate cancer and weak family history of colorectal cancer; and (5) 60% of families (SIR = 0.61; 95% CI 0.57-0.65) had a weak family history of all cancers. There is a wide variation of colorectal cancer risk that can be categorized by family history of cancer, with a strong gradient of colorectal cancer risk between the highest and lowest risk categories. The risk of colorectal cancer for people with the highest risk category of family history (7% of the population) was 12-times that for people in the lowest risk category (60%) of the population. Data mining was proven an effective approach for gaining insight into the underlying cancer aggregation patterns and for categorizing familial risk of colorectal cancer.

  6. The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life

    NARCIS (Netherlands)

    Winkels, R.M.; Heine-Bröring, R.C.; Zutphen, van M.; Harten-Gerritsen, van A.S.; Kok, D.E.G.; Duijnhoven, van F.J.B.; Kampman, E.

    2014-01-01

    Background There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the “COlorectal cancer: Lon

  7. The COLON study: Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence, survival and quality of life

    NARCIS (Netherlands)

    Winkels, R.M.; Heine-Broring, R.C.; Zutphen, M. van; Harten-Gerritsen, S. van; Kok, D.E.; Duijnhoven, F.J.B. van; Kampman, E.

    2014-01-01

    BACKGROUND: There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk. However, it is not clear if those factors can affect colorectal cancer treatment, recurrence, survival and quality of life. This paper describes the background and design of the "COlorectal cancer: Lo

  8. Implications of microRNAs in Colorectal Cancer Development, Diagnosis, Prognosis and Therapeutics

    Directory of Open Access Journals (Sweden)

    Haiyan eZhai

    2011-11-01

    Full Text Available MicroRNAs (miRNAs are a class of non-coding small RNAs with critical regulatory functions as post-transcriptional regulators. Due to the fundamental importance and broad impact of miRNAs on multiple genes and pathways, dysregulated miRNAs have been associated with human diseases, including cancer. Colorectal cancer (CRC is among the most deadly diseases, and miRNAs offer a new frontier for target discovery and novel biomarkers for both diagnosis and prognosis. In this review, we summarize the recent advancement of miRNA research in CRC, in particular, the roles of miRNAs in colorectal cancer stem cells, EMT, chemoresistance, therapeutics, diagnosis and prognosis.

  9. Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III colorectal cancer: a retrospective study

    OpenAIRE

    Wang Y; Sun XR; Feng WM; Bao Y; Zheng YY

    2016-01-01

    Yao Wang,1 Xin Rong Sun,1 Wen Ming Feng,1 Ying Bao,1 Yin Yuan Zheng2 1Department of General Surgery, 2Department of Radiology, First People’s Hospital affiliated to Huzhou University Medical College, Huzhou, People’s Republic of China Background: Radical resection is the main treatment for colorectal cancer (CRC), but metastasis or recurrence is common in which liver metastasis accounted for 83% of the cases. Therefore, the prognosis of patients with advanced CRC may be improved...

  10. Postoperative prophylactic hepatic arterial infusion chemotherapy for stage III colorectal cancer: a retrospective study

    OpenAIRE

    Zheng, Yin Yuan; Wang, Yao; Sun,Xin Rong; Feng, Wen Ming; Bao, Ying

    2016-01-01

    Yao Wang,1 Xin Rong Sun,1 Wen Ming Feng,1 Ying Bao,1 Yin Yuan Zheng2 1Department of General Surgery, 2Department of Radiology, First People’s Hospital affiliated to Huzhou University Medical College, Huzhou, People’s Republic of China Background: Radical resection is the main treatment for colorectal cancer (CRC), but metastasis or recurrence is common in which liver metastasis accounted for 83% of the cases. Therefore, the prognosis of patients with advanced CRC may be ...

  11. Relationship between COX-2 expression and clinicopathological features of colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    詹俊; 刘建平; 朱兆华; 姚和瑞; 陈春燕

    2004-01-01

    Background Cyclo-oxgenase 2 (COX-2) is involved in prostaglandin synthesis in central nervous system, and it also plays a role in human carcinogenesis. Our purpose of this study is to investigate the COX-2 expression in different development stages of colorectal cancer, and to discuss the relationship between the gene expression and clinicopathological features of the cancer.Methods COX-2 expression was examined by immunohistochemical staining in 76 surgical specimens of colorectal cancer (44 of advanced stage and 32 of early stage), thirty-three adenomas and 18 normal colonic mucosal tissues taken by endoscopic biopsy. Kaplan-Meier survival curves and Cox proportional hazards regression were used to evaluate the relation of COX-2 to prognosis.Results COX-2 expression, divided into 4 grades from "-" to"+++", is respectively 83.3%, 16.7%, 0% and 0% in normal colonic mucosal tissues; 12.1%, 42.4%, 36.4% and 9.1% in adenomas; 6.3%, 28.1%, 46.9% and 18.7% in early colorectal cancers (ECCs), and 6.8%, 20.5%, 18.2% and 54.5% in advanced colorectal cancers (CRCs). The differences in COX-2 expression between advanced CRCs and early colorectal cancers (ECCs) as well as between the advanced CRCs and adenomas were statistically significant (P<0.01); but there was no significant difference between ECCs and adenomas. Kaplan-Meier survival analysis showed a significant difference in the survival curves between low high COX-2 groups (P<0.05). Cox proportional hazards regression showed that COX-2 expression was related to poorer long-term outcome with a hazard ratio of 2.665 unadjusted for other variables (P<0.05), and COX-2 expression was an independent risk factor of poor prognosis.Conclusions COX-2 expression is gradually up-regulated in the development from normal epithelium to adenomas and from ECCs to advanced CRCs. Alhough the COX-2 protein can not be regarded as a tumor marker to diagnose CRCs early, COX-2 expression can be regarded as an independent risk factor of poor

  12. DNA aptamers as molecular probes for colorectal cancer study.

    Directory of Open Access Journals (Sweden)

    Kwame Sefah

    Full Text Available BACKGROUND: Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development. METHODOLOGY AND RESULTS: Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh, nor do they recognize most other cancer cell lines tested. CONCLUSION/SIGNIFICANCE: The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers.

  13. Colorectal cancer surveillance in inflammatory bowel disease: The search continues

    Institute of Scientific and Technical Information of China (English)

    Anis Ahmadi; Steven Polyak; Peter V Draganov

    2009-01-01

    Patients with inflammatory bowel disease (IBD) are at increased risk for colorectal cancer (CRC). Risk factors for the development of CRC in the setting of IBD include disease duration, anatomic extent of disease,age at time of diagnosis, severity of inflammation,family history of colon cancer, and concomitant primary sclerosing cholangitis. The current surveillance strategy of surveillance colonoscopy with multiple random biopsies most likely reduces morbidity and mortality associated with IBD-related CRC. Unfortunately,surveillance colonoscopy also has severe limitations including high cost, sampling error at time of biopsy,and interobserver disagreement in histologically grading dysplasia. Furthermore, once dysplasia is detected there is disagreement about its management.Advances in endoscopic imaging techniques are already underway, and may potentially aid in dysplasia detection and improve overall surveillance outcomes.Management of dysplasia depends predominantly on the degree and focality of dysplasia, with the mainstay of management involving either proctocolectomy or continued colonoscopic surveillance. Lastly, continued research into additional chemopreventive agents may increase our arsenal in attempting to reduce the incidence of IBD-associated CRC.

  14. The current role of radiotherapy in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aleman, B.M.P.; Bartelink, H. [Nederlands Kanker Inst. `Antoni van Leeuwenhoekhuis`, Amsterdam (Netherlands); Gunderson, L.L. [Mayo Clinic, Rochester, MN (United States)

    1995-07-01

    During the last two decades, radiotherapy has become an integral part of the multidisciplinary approach in the treatment of patients with colorectal cancer. Currently, radiotherapy is seen mainly as an adjuvant therapy, sometimes in combination with chemotherapy, in a pre- or post-operative setting. Adjuvant radiotherapy alone leads to a significant reduction of local recurrence rates, but an impact on survival is seen only in subset analyses. Combined modality treatment can reduce local recurrence rates even further, and can also reduce the rate of distant relapses and increase survival. The acute toxicity of combined modality is considerably higher. Local radiation can also be used as a component of organ conserving local treatment for selected early lesions. Radiotherapy has been an important palliative treatment modality, diminishing symptoms in cases of inoperable primary rectal cancers or pelvic recurrences. The timing of radiation, surgery and chemotherapy has been under evaluation for years. For patients with locally advanced primary or recurrent malignancies (unresectable due to fixation), the preferred sequence is pre-operative irradiation with or without chemotherapy, followed by surgical resection. For mobile resectable lesions, sequencing issues are being tested in phase III randomised trials. (author).

  15. Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis

    Directory of Open Access Journals (Sweden)

    Kure Elin H

    2009-06-01

    Full Text Available Abstract Background Clinical trials where cancer patients were treated with protease inhibitors have suggested that the serine protease, prostasin, may act as a tumour suppressor. Prostasin is proteolytically activated by the serine protease, matriptase, which has a very high oncogenic potential. Prostasin is inhibited by protease nexin-1 (PN-1 and the two isoforms encoded by the mRNA splice variants of hepatocyte growth factor activator inhibitor-1 (HAI-1, HAI-1A, and HAI-1B. Methods Using quantitative RT-PCR, we have determined the mRNA levels for prostasin and PN-1 in colorectal cancer tissue (n = 116, severe dysplasia (n = 13, mild/moderate dysplasia (n = 93, and in normal tissue from the same individuals. In addition, corresponding tissues were examined from healthy volunteers (n = 23. A part of the cohort was further analysed for the mRNA levels of the two variants of HAI-1, here denoted HAI-1A and HAI-1B. mRNA levels were normalised to β-actin. Immunohistochemical analysis of prostasin and HAI-1 was performed on normal and cancer tissue. Results The mRNA level of prostasin was slightly but significantly decreased in both mild/moderate dysplasia (p PN-1 was more that two-fold elevated in colorectal cancer tissue as compared to healthy individuals (p HAI-1A and HAI-1B mRNAs showed the same patterns of expression. Immunohistochemistry showed that prostasin is located mainly on the apical plasma membrane in normal colorectal tissue. A large variation was found in the degree of polarization of prostasin in colorectal cancer tissue. Conclusion These results show that the mRNA level of PN-1 is significantly elevated in colorectal cancer tissue. Future studies are required to clarify whether down-regulation of prostasin activity via up regulation of PN-1 is causing the malignant progression or if it is a consequence of it.

  16. Cost-effectiveness of colorectal cancer screening - An overview

    NARCIS (Netherlands)

    I. Lansdorp-Vogelaar (Iris); A.B. Knudsen (Amy); H. Brenner (Hermann)

    2010-01-01

    textabstractThere are several modalities available for a colorectal cancer (CRC) screening program. When determining which CRC screening program to implement, the costs of such programs should be considered in comparison to the health benefits they are expected to provide. Cost-effectiveness analysi

  17. Current treatment for colorectal cancer metastatic to the liver

    NARCIS (Netherlands)

    Cromheecke, M; de Jong, KP; Hoekstra, HJ

    1999-01-01

    Surgery is currently the only available treatment option which offers the potential for cure for patients with liver metastases from colorectal cancer. Of those who undergo a potentially curative operation for their primary tumour but subsequently recur, almost 80% will develop evidence of metastati

  18. Studies on screening and surveillance for colorectal cancer

    NARCIS (Netherlands)

    S.A. Mulder (Sanna)

    2010-01-01

    textabstractColorectal cancer (CRC) is a major public health problem in the Western world. The life-time risk for developing CRC is approximately five percent and increases with age. In The Netherlands, the incidence of CRC is 67.5 per 100 000 in men and 46.7 per 100 000 in women (European Standardi

  19. Restaging of colorectal cancer and PET/CT

    Science.gov (United States)

    Çınar, Alev; Gençoğlu, Esra Arzu; Korkmaz, Meliha

    2013-01-01

    Positron Emission Tomography/Computerized Tomography (PET/CT) is an important assessment method in restaging of oncology patients. Its ability to detect the metabolic/functional changes in patients with colorectal cancer during the early stages, in which morphological changes cannot be documented, is significantly superior to other imaging modalities. PMID:25931851

  20. Haemostatic alterations in colorectal cancer: perspectives for future treatment

    DEFF Research Database (Denmark)

    Lykke, Jakob; Nielsen, Hans Jørgen

    2004-01-01

    The role of the haemostatic system in colorectal cancer (CRC) is reviewed. Correlations between the activation of the haemostatic system and overall survival have been suggested. Experimental studies indicate that the haemostatic system plays a key role in growth, invasion and dissemination of tu...

  1. Candidate driver genes in microsatellite-unstable colorectal cancer

    NARCIS (Netherlands)

    Alhopuro, Pia; Sammalkorpi, Heli; Niittymaki, Iina; Bistrom, Mia; Raitila, Anniina; Saharinen, Juha; Nousiainen, Kari; Lehtonen, Heli J.; Heliovaara, Elina; Puhakka, Jani; Tuupanen, Sari; Sousa, Sonia; Seruca, Raquel; Ferreira, Ana M.; Hofstra, Robert M. W.; Mecklin, Jukka-Pekka; Jarvinen, Heikki; Ristimaki, Ari; Orntoft, Torben F.; Hautaniemi, Sampsa; Arango, Diego; Karhu, Auli; Aaltonen, Lauri A.

    2012-01-01

    Defects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in similar to 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI

  2. Refining EGFR-monoclonal antibody treatment in colorectal cancer

    NARCIS (Netherlands)

    Krens, Lisanne Laura

    2015-01-01

    The use of the epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab is limited to colorectal cancer (CRC) patients with KRAS wild type tumors and more recently in RAS wild type only. After having become chemotherapy refractory, treatment options are limited for this substanti

  3. Special Section: Colorectal Cancer Symptoms, Diagnosis and Treatment

    Science.gov (United States)

    ... two chemopreventive agents—an anti-inflammatory and an experimental compound—are very effective at preventing the recurrence of the lesions that are often a sign of colorectal cancer. The results showed that the treatment was most effective in preventing the recurrence of ...

  4. Workload and surgeon's specialty for outcome after colorectal cancer surgery

    DEFF Research Database (Denmark)

    Archampong, David; Borowski, David; Wille-Jørgensen, Peer;

    2012-01-01

    A large body of research has focused on investigating the effects of healthcare provider volume and specialization on patient outcomes including outcomes of colorectal cancer surgery. However there is conflicting evidence about the role of such healthcare provider characteristics in the managemen...

  5. Potential role of probiotics on colorectal cancer prevention

    Directory of Open Access Journals (Sweden)

    Uccello Mario

    2012-11-01

    Full Text Available Abstract Background Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. Discussion Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention. Summary Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host’s immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.

  6. Role of chance in familial aggregaton of colorectal cancer

    DEFF Research Database (Denmark)

    Katballe, N.; Bentzen, S.M.; Christensen, M.;

    2001-01-01

    A prospective population-based study recorded family trees of 77 colorectal cancer patients younger than 50 years of age. Using mathematical modeling of population age-incidence data, we estimate that 1 (95% confidence limits 0 and 3) of these families is expected to meet the Amsterdam criteria I...

  7. Message from Terrence Howard: Screening for Colorectal Cancer PSA (:20)

    Centers for Disease Control (CDC) Podcasts

    2010-04-13

    A message from the actor/musician Terrence Howard about the importance of screening for colorectal cancer.  Created: 4/13/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/13/2010.

  8. Message from Terrence Howard: Screening for Colorectal Cancer PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    2010-04-13

    A message from the actor/musician Terrence Howard about the importance of screening for colorectal cancer.  Created: 4/13/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 4/13/2010.

  9. Colorectal cancers mimic structural organization of normal colonic crypts.

    Directory of Open Access Journals (Sweden)

    Laura Cernat

    Full Text Available Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes.

  10. Liver-first approach of colorectal cancer with synchronoushepatic metastases: A reverse strategy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Recently, there has been a change in the strategy ofhow synchronous colorectal hepatic metastases areattributed to the development of more valuable protocolsof chemotherapy and radiotherapy for neoadjuvanttreatment of colorectal neoplasms and their hepaticmetastases. There is a consensus that patients withsynchronous colorectal hepatic metastases have lowersurvival than those with metachronous colorectal hepaticmetastases. Currently, controversy remains concerningthe best approach is sequence in a patient withcolorectal cancer and synchronous hepatic metastasesresection. To obtain a better patient selection, theauthors have suggested the initial realization of systemicchemotherapy in the circumstance of patients withcolorectal tumor stage Ⅳ, since these patients have asystemic disease. The rationale behind this liver-firststrategy is initially the control of synchronous hepaticmetastases of colorectal carcinoma, which can optimizea potentially curative hepatic resection and longstandingsurvival. The liver-first strategy procedure is indicatedfor patients with colorectal hepatic metastases whorequire downstaging therapy to make a curative liverresection possible. Thus, the liver-first strategy isconsidered an option in cases of rectal carcinoma in theearly stage and with limited or advanced synchronouscolorectal hepatic metastases or in case of patientswith asymptomatic colorectal carcinoma, but withextensive liver metastases. Patients undergoing systemicchemotherapy and with progression of neoplasticdisease should not undergo hepatic resection, becauseit does not change the prognosis and may even makeit worse. To date, there have been no randomizedcontrolled trials on surgical approach of colorectalsynchronous hepatic metastases, despite the relativelyhigh number of available manuscripts on this subject.All of these published studies are observational, usuallyretrospective, and often non-comparative. The patientselection criteria for the liver-first strategy

  11. Role of cancer stem cells in age-related rise in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Pratima; Nangia-Makker; Yingjie; Yu; Adhip; PN; Majumdar

    2015-01-01

    Colorectal cancer(CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells(CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of(1) CSC;(2) epigenetic and genetic mechanisms giving rise to CSCs;(3) markers of CSC;(4) characteristics; and(5) age-related increase in CSC in the colonic crypt.

  12. Gliotoxin Inhibits Proliferation and Induces Apoptosis in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Junxiong Chen

    2015-10-01

    Full Text Available The discovery of new bioactive compounds from marine natural sources is very important in pharmacological research. Here we developed a Wnt responsive luciferase reporter assay to screen small molecule inhibitors of cancer associated constitutive Wnt signaling pathway. We identified that gliotoxin (GTX and some of its analogues, the secondary metabolites from marine fungus Neosartorya pseufofischeri, acted as inhibitors of the Wnt signaling pathway. In addition, we found that GTX downregulated the β-catenin levels in colorectal cancer cells with inactivating mutations of adenomatous polyposis coli (APC or activating mutations of β-catenin. Furthermore, we demonstrated that GTX induced growth inhibition and apoptosis in multiple colorectal cancer cell lines with mutations of the Wnt signaling pathway. Together, we illustrated a practical approach to identify small-molecule inhibitors of the Wnt signaling pathway and our study indicated that GTX has therapeutic potential for the prevention or treatment of Wnt dependent cancers and other Wnt related diseases.

  13. Risk factors for sporadic colorectal cancer in southern Chinese

    Institute of Scientific and Technical Information of China (English)

    Yi-Sheng Wei; Jia-Chun Lu; Lei Wang; Ping Lan; Hong-Jun Zhao; Zhi-Zhong Pan; Jun Huang; Jian-Ping Wang

    2009-01-01

    AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index (BMI) in sporadic colorectal cancer in southern Chinese.METHODS:A hospital-based case-control study was conducted from July 2002 to December 2008. There were 706 cases and 723 controls with their sex and age (within 5 years) matched. An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer. RESULTS:No positive association was observed between smoking status and sporadic colorectal cancer risk. Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer (CRC) (adjusted OR = 8.61 and 95% CI = 6.15-12.05; adjusted OR = 2.30, 95% CI = 1.27-4.17). Moreover, the increased risk of developing sporadic CRC was increased risk of developing sporadic CRC was significant in those with a positive family history of cancer (adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI ≥ 24.0 kg/m2 (adjusted OR = 1.39, 95% CI = 1.10-1.75). Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers (adjusted OR = 7.60 and 95% CI = 5.13-11.25; adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI ≥ 24.0 kg/m2 (adjusted OR = 1.38 and 95% CI = 1.04-1.83; adjusted OR = 1.35 and 95% CI = 1.02-1.79). The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer (adjusted OR = 2.51 and 95% CI = 1.24-5.07; adjusted OR = 1.82 and 95% CI = 1.17-2.82).CONCLUSION:Alcohol drinking, high BMI (≥ 24.0 kg/m2) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.

  14. Relationship Between Microcystin in Drinking Water and Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To investigate the association of microcystin (MC) in drinking water with the incidence of colorectal cancer. Methods The study was designed as a retrospective cohort. Eight townships or towns were randomly selected as the study sites in Haining City of Zhejiang Province, China. 408 cases of colon and rectum carcinomas diagnosed from 1977 to 1996 in the study sites were included, and a survey on types of drinking water of these patients was conducted. Samples of different water sources (well, tap, river and pond) were collected separately and microcystin concentrations were determined by indirect competitive ELISA method. Results The incidence rate of colorectal cancer was significantly higher in population who drank river and pond water than those who drank well and tap water. Compared to well water, the relative risk (RR) for colorectal cancer was 1.88 (tap), 7.94 (river) and 7.70 (pond) respectively. The positive rate (>50 pg/mL) of microcystin in samples of well, tap, river and pond water was 0, 0, 36.23% and 17.14% respectively. The concentration of microcystin in river and pond water was significantly higher than that in well and tap water (P<0.01). Spearman rank correlation analysis showed that in the study sites, the microcystin concentration of river and pond water was positively associated with the incidence of colorectal cancer (rs= 0.881, P<0.01). Conclusions The types of drinking water are positively associated with the incidence of colorectal cancer in the study sites, and this may be related to microcystin contamination of drinking water. Further biological study is needed to support the possible causative role of mycrocystin in carcinogenesis of colon and rectum.

  15. Genetic association- and linkage studies in colorectal cancer

    OpenAIRE

    Holst, Susanna von

    2014-01-01

    Colorectal cancer (CRC) is the third most common cancer type in the Western world. Over one million patients are diagnosed worldwide yearly. A family history of CRC is a major risk factor for CRC. The total genetic contribution to disease development is estimated to be 35%. High-risk syndromes caused by known genes such as familial adenomatous polyposis (FAP) and Lynch Syndrome (LS) explain less than 5% of that number. Recently, several genome-wide association studies (GWAS) ha...

  16. Analysis of mitochondrial ND1 gene in human colorectal cancer

    Directory of Open Access Journals (Sweden)

    Mansoureh Akouchekian

    2011-01-01

    Conclusions: Results showed that a high frequency of somatic alterations of mtDNA occurs during the carcinogenesis and/or the progression of colorectal cancer. Based on the mtDNA mutation pattern observed in this study and other pre-viously studies it is believed that looking for somatic mutations in mtDNA would be one of the diagnostic values in early detection of cancer.

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

    OpenAIRE

    Lynda R. Wiseman; Katherine A. Lyseng-Williamson

    2005-01-01

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

  18. Metabolic syndrome and risk of subsequent colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Raluca Pais; Horatiu Silaghi; Alina Cristina Silaghi; Mihai Lucian Rusu; Dan Lucian Dumitrascu

    2009-01-01

    The metabolic syndrome and visceral obesity have an increasing prevalence and incidence in the general population. The actual prevalence of the metabolic syndrome is 24% in US population and between 24.6% and 30.9% in Europe. As demonstrated by many clinical trials (NAHANES Ⅲ, INTERHART) the metabolic syndrome is associated with an increased risk of both diabetes and cardiovascular disease. In addition to cardiovascular disease, individual components of the metabolic syndrome have been linked to the development of cancer, particularly to colorectal cancer.Colorectal cancer is an important public health problem; in the year 2000 there was an estimated total of 944 717 incident cases of colorectal cancer diagnosed world-wide. This association is sustained by many epidemiological studies. Recent reports suggest that individuals with metabolic syndrome have a higher risk of colon or rectal cancer. Moreover, the clusters of metabolic syndrome components increase the risk of associated cancer. The physiopathological mechanism that links metabolic syndrome and colorectal cancer is mostly related to abdominal obesity and insulin resistance. Population and experimental studies demonstrated that hyperinsulinemia, elevated C-peptide, elevated body mass index, high levels of insulin growth factor-1, low levels of insulin growth factor binding protein-3, high leptin levels and low adiponectin levels are all involved in carcinogenesis. Understanding the pathological mechanism that links metabolic syndrome and its components to carcinogenesis has a major clinical significance and may have profound health benefits on a number of diseases including cancer, which represents a major cause of mortality and morbidity in our societies.

  19. Haemostatic alterations in colorectal cancer: perspectives for future treatment

    DEFF Research Database (Denmark)

    Lykke, Jakob; Nielsen, Hans Jørgen

    2004-01-01

    The role of the haemostatic system in colorectal cancer (CRC) is reviewed. Correlations between the activation of the haemostatic system and overall survival have been suggested. Experimental studies indicate that the haemostatic system plays a key role in growth, invasion and dissemination of...... tumour cells, and in tumour related angiogenesis. Additional activation by the surgical trauma and postoperative infections are discussed. Finally, anti-cancer modalities directed against regulation of the haemostatic system in CRC are considered....

  20. Reproductive factors related to the risk of colorectal cancer by subsite: a case-control analysis

    OpenAIRE

    Yoo, K-Y; Tajima, K.; M. Inoue; Takezaki, T.; Hirose, K.; Hamajima, N; Park, S.K.; Kang, D. H.; Kato, T; Hirai, T

    1999-01-01

    The authors hypothesized that reproductive factors of colorectal cancer, which are probably mediated by endogenous hormones, would differ according to colonic subsite. Information on reproductive factors was obtained from 372 female colorectal cancer cases (113 proximal colon, 126 distal colon, 133 rectum) and 31 061 cancer-free controls at the Aichi Cancer Center Hospital, Japan, between 1988 and 1995. Multiple logistic analysis showed that late age at interview, family history of colorectal...

  1. PELP1 Suppression Inhibits Colorectal Cancer through c-Src Downregulation

    OpenAIRE

    Zhifeng Ning; Youzhi Zhang; Hanwei Chen; Jiliang Wu; Tieshan Song; Qian Wu; Fuxing Liu

    2014-01-01

    Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of estrogen receptors alpha and beta, is a potential protooncogene implicated in several human cancers, including sexual hormone-responsive or sexual hormone-nonresponsive cancers. However, the functions of PELP1 in colorectal cancer remain unclear. In this study, western blot and bioinformatics revealed that PELP1 expression was higher in several colorectal cancer cell lines than in immortalized normal colorectal epi...

  2. Psychological barriers and facilitators of colorectal cancer screening: a French qualitative study

    Directory of Open Access Journals (Sweden)

    Morgiane Bridou

    2013-06-01

    Full Text Available The aim of this qualitative study was to explore the psychological barriers to and facilitators of undergoing the Hemoccult-II® colorectal cancer screening test in France. Sixty-nine French people aged 50 to 74 years were divided into seven qualitative focus groups. Three issues were discussed with participants: knowledge and beliefs about colorectal cancer screening; facilitators of colorectal cancer screening by Hemoccult-II®; barriers to colorectal cancer screening by Hemoccult-II®. All the discussions were led by two psychologists and were recorded, transcribed verbatim and analyzed using qualitative data analysis software. Correspondence factor analyses identified three dimensions for each topic. The main psychological facilitators of colorectal cancer screening were: information about colorectal cancer screening, perceived simplicity of using Hemoccult-II®, and perception of risk. Uncertainty about the reliability of Hemoccult-II®, health anxiety, and embarrassment emerged as the main barriers to colorectal cancer screening. Cross-sectional analyses identified the differences between the views expressed by women and men. Women appeared more embarrassed about Hemoccult-II® and men seemed to be more worried about colorectal cancer. This preliminary study suggests that psychological factors play an important role in colorectal cancer screening by Hemoccult-II®. This finding may help health organizations to conceive better awareness campaigns to promote colorectal cancer screening in order to reduce the related mortality rate by taking into account psychological determinants.

  3. 卡培他滨单药治疗老年晚期结直肠癌的临床观察%Clinical efficiency of capecitabine alone on advanced colorectal cancer in the elderly

    Institute of Scientific and Technical Information of China (English)

    刘宁红

    2015-01-01

    ObjectiveTo observe the short-term efficacy, side effects, impact on quality of life (QOL) of capecitabine alone in treating elderly patients with advanced colorectal cancer.Methods Thirty-nine elderly patients [aged (73.2±2.5) years, ranging from 69 to 82 years] with pathological identified advanced colorectal cancer admitted in our hospital from October 2009 to February 2014 were enrolled in this study, and they all were treated with 2500mg/(m2·d) capecitabine for 14 consecutive days and an interval of 7d (a cycle). The effectiveness and side effects were evaluated for every 2 cycles. Quality of Life Questionnaire (QLQ-C30), designed by European Organization for Research on Treatment of Cancer (EORTC), was conducted on the patients before and in 6 weeks after the therapy.Results Among the 39 patients, there were 1 case of complete remission, 11 cases of partial remission, 18 cases of stable disease, and 9 cases of progressive disease. The efficient rate was 30.76%, and tumor control rate was as high as 76.92%. The main side effects were hand-foot syndrome (61.54%), bone marrow depression (66.67%), and skin pigmentation (64.10%), and all these symptoms were mild. Their physical function, role function, social function and overall health score were increased significantly when compared with the conditions before treatment (P<0.05).Conclusion Capecitabine therapy alone is effective and only causes mild side effects for the elderly patients with advanced colorectal cancer, and it also improves their QOL.%目的:观察卡培他滨单药治疗老年晚期结直肠癌的近期疗效、毒副反应及对生存质量的影响。方法入选2009年10月至2014年2月在北京老年医院肿瘤科治疗的39例具有可测量指标的老年晚期结直肠癌患者,其中男26例,女13例,年龄69~82(73.2±2.5)岁,采用单药卡培他滨化疗,所有患者均给予卡培他滨,连服14d,休息7d(1个周期)每2个周期判定疗效及毒副反

  4. EphB2: a signature of colorectal cancer stem cells to predict relapse

    Institute of Scientific and Technical Information of China (English)

    Xiaoxue Zhang

    2011-01-01

    @@ Colorectal cancer is one of the most commonly diagnosed cancers and is the second leading cause of death from cancer.Currently, the conventional treatment in clinics is surgery combined with chemotherapy or radiation therapy.Although new drugs have been developed, relapse and metastasis occur in nearly half of colorectal cancer patients.

  5. Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions

    DEFF Research Database (Denmark)

    Wilding, Jennifer L; McGowan, Simon; Liu, Ying;

    2010-01-01

    Replication error deficient (RER+) colorectal cancers are a distinct subset of colorectal cancers, characterized by inactivation of the DNA mismatch repair system. These cancers are typically pseudodiploid, accumulate mutations in repetitive sequences as a result of their mismatch repair deficiency...

  6. New approaches in angiogenic targeting for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Colorectal carcinoma (CRC) is one of the leading causes of cancer death worldwide. In the last decade, the addition of irinotecan and oxaliplatin to standard fluorouracil-based chemotherapy regimens have set the new benchmark of survival for patients with metastatic CRC at approximately 20 mo. Despite these advances in the management of CRC, there is a strong medical need for more effective and well-tolerated therapies. The dependence of tumor growth and metastasis on blood vessels makes angiogenesis a rational target for therapy. One of the major pathways involved in this process is the vascular endothelial growth factor (VEGF) and its receptors (VEGFR). In 2004, the first agent targeting angiogenesis, bevacizumab (BV), was approved as an adjunct to first-line cytotoxic treatment of metastatic CRC. The role of BV as part of adjuvant treatment and in combination with other targeted therapies is the subject of ongoing trials. However, BV is associated with an increase in the risk of arterial thromboembolic events, hypertension and gastrointestinal perforations and its use must be cautious. Novel VEGFR TK inhibitors with different ranges of nanomolar potencies, selectivities, and pharmacokinetic properties are entering phase Ⅲ trials for the treatment of cancer. Conversely, one of these novel agents, vatalanib, has been shown not to confer survival benefit in first and second-line treatment of advanced CRC. The basis of these findings is being extensively evaluated. Ongoing and new well-designed trials will define the optimal clinical application of the actual antiangiogenic agents, and, on the other hand, intensive efforts in basic research will identify new agents with different antiangiogenic approaches for the treatment of CRC. In this review we discuss and highlight current and future approaches in angiogenic targeting for CRC.

  7. Clinical significance of detection of human telomerase reverse transcriptase in colorectal cancer and its precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    刘少平

    2014-01-01

    Objective To evaluate the expression and clinical significance of human telomerase reverse transcriptase(h TERT)in colorectal cancer and its precancerous lesion.Methods The levels of h TERT expression were detected by immunohistochemistry in colorectal cancers(n=95),colorectal adenomatous polyposis(n=30)and normal colorectal tissues(n=30).The relationship between the expression of h TERT in colorectal cancer tissues and the pathologic features and prognosis were analyzed.Results The positive rate of h TERT expression

  8. Expression of 5-Lipoxygenase in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Labile Togba Soumaoro; Satoru Iida; Hiroyuki Uetake; Megumi Ishiguro; Yoko Takagi; Tetsuro Higuchi; Masamichi Yasuno; Masayuki Enomoto; Kenichi Sugihara

    2006-01-01

    AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens in order to determine its clinicopathologic significance in human tumorigenesis.METHODS: The relative quantity of 5-Lox mRNA in paired 91 colorectal tumor and adjacent normal mucosa samples was determined by real time quantitative PCR. Additionally, the expression of 5-Lox and cyclooxygenase (Cox)-2 proteins was also examined using immunohistochemical staining methods.RESULTS: There was a marked increase in 5-Lox mRNA levels in the tumor compared with paired normal mucosa samples (P < 0.0001). Sixty six (72.5%) tumors showed high 5-Lox mRNA levels. The positivity rate of 5-Lox and Cox-2 protein expression was 68.7% and 79.1%respectively. There was a significant association between tumoral 5-Lox mRNA level and tumor size (Rho = 0.392,P = 0.0002), depth or vessel invasion.CONCLUSION: These results suggest that 5-Lox is up-regulated in colorectal cancer and that inhibition of its expression might be valuable in the prevention and treatment of colorectal cancer.

  9. Role of MGMT as biomarker in colorectal cancer

    Science.gov (United States)

    Inno, Alessandro; Fanetti, Giuseppe; Di Bartolomeo, Maria; Gori, Stefania; Maggi, Claudia; Cirillo, Massimo; Iacovelli, Roberto; Nichetti, Federico; Martinetti, Antonia; de Braud, Filippo; Bossi, Ilaria; Pietrantonio, Filippo

    2014-01-01

    O6-methylguanine DNA methyltransferase (MGMT) gene promoter methylation plays an important role in colorectal carcinogenesis, occurring in about 30%-40% of metastatic colorectal cancer. Its prognostic role has not been defined yet, but loss of expression of MGMT, which is secondary to gene promoter methylation, results in an interesting high response to alkylating agents such as dacarbazine and temozolomide. In a phase 2 study on heavily pre-treated patients with MGMT methylated metastatic colorectal cancer, temozolomide achieved about 30% of disease control rate. Activating mutations of RAS or BRAF genes as well as mismatch repair deficiency may represent mechanisms of resistance to alkylating agents, but a dose-dense schedule of temozolomide may potentially restore sensitivity in RAS-mutant patients. Further development of temozolomide in MGMT methylated colorectal cancer includes investigation of synergic combinations with other agents such as fluoropyrimidines and research for additional biomarkers, in order to better define the role of temozolomide in the treatment of individual patients. PMID:25516857

  10. Cost benefit of early diagnosis of colorectal cancer.

    Science.gov (United States)

    Bolin, T D

    1996-01-01

    In most Western countries, colorectal cancer is an important disease in terms of morbidity and mortality. As it has a premalignant asymptomatic stage in the form of benign adenomas that might be detected by screening, and as screening leads to detection of colorectal cancer at an earlier stage, there is potential for improved and better quality survival. Most cost-effective analyses rank the various screening strategies at less than an accepted benchmark value of approximately $40,000 per added year of life. Periodic colorectal screening is therefore a cost-effective intervention and the Office of Technology Assessment of the Congress of the United States has concluded that colorectal cancer screening in average-risk adults beginning at age 50 is a relatively good investment for society. Flexible sigmoidoscopy and double contrast barium enema are the most cost-effective strategies but they both require colonoscopy if a lesion is identified. Colonoscopy at 10-yearly intervals is of comparable cost to flexible sigmoidoscopy every 5 years and less costly than FSIG every 3 years. Combination strategies, using faecal occult blood testing with periodic flexible sigmoidoscopy or double contrast barium enema are as costly as colonoscopy. The choice of screening strategies needs to be tailored to the individual, and a process of community education is an essential prerequisite to the success of any programme. PMID:8898453

  11. 化疗联合射频热疗治疗晚期大肠癌的临床观察%Clinical Observation of Chemotherapy Combined with Radiofrequency Hyperthermia to Treat the Advanced Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    阮新建; 刘畅; 刘兵; 张侠; 于忠和

    2011-01-01

    Objective Discussion the curative effect and the side reaction of chemotherapy combined with radiofrequency hyperthermia to treat the advanced colorectal cancer. Methods Randomly divide the eligible patients into 2 groups, pure chemotherapy group and chemotherapy combined with radiofrequency hyperthermia groups. Basically, their chemotherapy project are similar. The group of Radiofrequency hyperthermia, meawhile, treat them with radiofrequency hyperthermia, twice a week, 60 minutes per time. Two groups do curative effect evaluation before and after treatment. Results The effective percentage of chemotherapy combined with radiofrequency hyperthermia group ( 44.11% ) is much higher than pure chemotherapy group( 35.29% ),but it fails to have the difference ( P > 0.05 ) of statistics. The side reaction of the 2 groups are still mainly related to side reaction of chemotherapy like gastrointestinal reactions, myelosuppression and peripheral nerve toxicity. To compare, it is no sense of statistics, but the clinic beifit of chemotherapy combined with radiofrequency hyperthermia groups( 58.82% )is much higher than pure chemotherapy groups( 32.35% ). Abviously, there is the big difference between the 2 groups and the meaning of statistcs( P <0.05 ). Conclusion It will have the good curative effect and? clinic benefit to do the chemotherapy combined with radiofrequency hyperthermia for the patients suffering the advanced colorectal cancer,which does not add any side effect.%目的 探讨化疗联合射频热疗治疗晚期大肠癌的近期疗效和不良反应.方法 将符合条件的患者随机分成单纯化疗组和化疗联合射频热疗组,两组化疗方案基本相同,联合射频热疗组,同时给予射频热疗,2次/周,60 min/次,两组治疗前后行疗效评定.结果 化疗联合热疗组治疗有效率(44.11%)明显高于单纯化疗组(35.29%),但无统计学差异(P>0.05),两组主要不良反应仍是与化疗相关的副反应,如消化

  12. Potential Protective Effects of Probiotics and Prebiotics Against Colorectal Cancer

    Science.gov (United States)

    Allsopp, Philip; Rowland, Ian

    Colorectal cancer (CRC) is the fourth most frequent cause of cancer related mortality in the world. Approximately 944,000 new cases were diagnosed globally in 2000 and this accounts for 9.2% of all new cancer cases (IARC, 2000). In Western societies namely Europe, North America and Australasia, it is the second most prevalent cancer after lung/breast (Boyle and Langman, 2000). About 363,000 new cases were reported in Europe in 2000 and it affects 6% of men and women by age 75, in almost equal proportion.

  13. Colorectal cancer in the young, many questions, few answers

    OpenAIRE

    Deen, Kemal I; Silva, Hiroshi; Deen, Raeed; Chandrasinghe, Pramodh C

    2016-01-01

    At a time where the incidence of colorectal cancer, a disease predominantly of developed nations, is showing a decline in those 50 years of age and older, data from the West is showing a rising incidence of this cancer in young individuals. Central to this has been the 75% increase in rectal cancer incidence in the last four decades. Furthermore, predictive data based on mathematical modelling indicates a 124 percent rise in the incidence of rectal cancer by the year 2030 - a statistic that c...

  14. Preferences and acceptance of colorectal cancer screening in Thailand.

    Science.gov (United States)

    Saengow, Udomsak; Chongsuwiwatvong, Virasakdi; Geater, Alan; Birch, Stephen

    2015-01-01

    Colorectal cancer (CRC) is now common in Thailand with an increase in incidence over time. Health authorities are planning to implement a nationwide CRC screening program using fecal immunochemical test (FIT) as a primary screening tool. This study aimed to estimate preferences and acceptance of FIT and colonoscopy, explore factors influencing the acceptance, and investigate reasons behind choosing and rejecting to screen before the program was implemented. Patients aged 50-69, visiting the primary care unit during the study period, were invited to join this study. Patients with a history of cancer or past CRC screening were excluded. Face-to-face interviews were conducted. Subjects were informed about CRC and the screening tests: FIT and colonoscopy. Then, they were asked for their opinions regarding the screening. The total number of subjects was 437 (86.7% response rate). Fifty-eight percent were females. The median age was 58 years. FIT was accepted by 74.1% of subjects compared to 55.6% for colonoscopy. The acceptance of colonoscopy was associated with perceived susceptibility to CRC and family history of cancer. No symptoms, unwilling to screen, healthy, too busy and anxious about diagnosis were reasons for refusing to screen. FIT was preferred for its simplicity and non-invasiveness compared with colonoscopy. Those rejecting FIT expressed a strong preference for colonoscopy. Subjects chose colonoscopy because of its accuracy; it was refused for the process and complications. If the screening program is implemented for the entire target population in Thailand, we estimate that 106,546 will have a positive FIT, between 8,618 and 12,749 identified with advanced adenoma and between 2,645 and 3,912 identified with CRC in the first round of the program. PMID:25824749

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

    Science.gov (United States)

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

    2016-08-01

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

  16. Oncogene Mutations in Colorectal Polyps Identified in the Norwegian Colorectal Cancer Prevention (NORCCAP) Screening Study

    Science.gov (United States)

    Lorentzen, Jon A.; Grzyb, Krzysztof; De Angelis, Paula M.; Hoff, Geir; Eide, Tor J.; Andresen, Per Arne

    2016-01-01

    Data are limited on oncogene mutation frequencies in polyps from principally asymptomatic participants of population-based colorectal cancer screening studies. In this study, DNA from 204 polyps, 5 mm or larger, were collected from 176 participants of the NORCCAP screening study and analyzed for mutations in KRAS, BRAF, and PIK3CA including the rarely studied KRAS exons 3 and 4 mutations. KRAS mutations were identified in 23.0% of the lesions and were significantly associated with tubulovillous adenomas and large size. A significantly higher frequency of KRAS mutations in females was associated with mutations in codon 12. The KRAS exon 3 and 4 mutations constituted 23.4% of the KRAS positive lesions, which is a larger proportion compared to previous observations in colorectal cancer. BRAF mutations were identified in 11.3% and were associated with serrated polyps. None of the individuals were diagnosed with de novo or recurrent colorectal cancer during the follow-up time (median 11.2 years). Revealing differences in mutation-spectra according to gender and stages in tumorigenesis might be important for optimal use of oncogenes as therapeutic targets and biomarkers. PMID:27656095

  17. New Molecular Features of Colorectal Cancer Identified - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples

  18. Seromic profiling of colorectal cancer patients with novel glycopeptide microarray

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Blixt, Ola; Bennett, Eric P;

    2011-01-01

    Cancer-associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post-translational variants of proteins are likely to induce autoantibodies, and changes in O-linked glycosylation represent one of the most important cancer-associated post...... array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer......-associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer...

  19. Clinical observation of bevacizumab plus chemotherapy for advanced colorectal cancer%贝伐单抗联合化疗治疗晚期结直肠癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    赵静; 张文; 李文桦; 朱丹

    2011-01-01

    背景与目的:贝伐单抗(bevacizumab,BV)是抗血管内皮生长因子(vascular endothelial growth factor,VEGF)的人源化单抗,与化疗药物联用于治疗复发转移性结直肠癌,可明显改善疗效和生存期,不良反应可耐受.本文旨在观察贝伐单抗联合化疗治疗晚期结直肠癌的疗效及不良反应.方法:46例经病理组织学证实的晚期结直肠癌患者均接受贝伐单抗联合化疗治疗,贝伐单抗的剂量采用美国国立综合癌症网络(NCCN)推荐的5 mg/kg,每2周重复,或7.5 mg/kg,每3周重复.每2~3个疗程后评价疗效,同时观察并记录不良反应.结果:所有患者中,PR 9例,SD 30例,PD 7例.客观有效率为20%,疾病控制率为85%.中位无进展生存期6.0个月,中位总生存期9.3个月.一线、二线、三线及以上应用贝伐单抗客观有效率分别为35%、6%和17%,疾病控制率分别为82%、88%和83%,中位无进展生存期分别为8.6、5.2和6.3个月,中位总生存期分别为12.2、8.3及8.1个月.不良反应为高血压3例,尿隐血阳性2例,蛋白尿1例,阴道出血1例,痰中带血1例,鼻衄1例,均为1~2级,对症治疗后均缓解;7例患者出现3~4级骨髓抑制,未出现粒缺性发热;2例患者因出现持续性2~4级肝功能受损未继续抗癌治疗.结论:贝伐单抗联合化疗治疗晚期结直肠癌的临床获益较肯定,且不良反应轻,患者耐受性较好,但需监测肝功能及血常规变化.%Background and purpose: Bevacizumab (BV) is a humanized monoclonal antibody for vascular endothelial growth factor (VEGF), which is used with chemotherapy for patients with recurrent and metastatic colorectal cancer, and it can significantly improve the efficacy and survival, with tolerable adverse reactions. This study aimed to evaluate the efficacy and adverse effects of bevacizumab in treating advanced colorectal cancer. Methods: Forty-six patients with advanced colorectal cancer were treated with

  20. Brief Report: Family cancer history affecting risk of colorectal cancer in a prospective cohort of Chinese women

    OpenAIRE

    Murphy, Gwen; Shu, Xiao Ou; Gao, Yu-Tang; Ji, Bu-Tian; Cook, Michael Blaise; YANG, Gong; Li, Hong-Lan; Rothman, Nathaniel; Zheng, Wei; Chow, Wong-Ho

    2009-01-01

    An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first degree relatives, mostly in Western populations. Limited data exists from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women.

  1. Combining chemotherapy and targeted therapies in metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

  2. Dietary Modulation of Inflammation-Induced Colorectal Cancer through PPARγ

    Directory of Open Access Journals (Sweden)

    Ashlee B. Carter

    2009-01-01

    Full Text Available Mounting evidence suggests that the risk of developing colorectal cancer (CRC is dramatically increased for patients with chronic inflammatory diseases. For instance, patients with Crohn's Disease (CD or Ulcerative Colitis (UC have a 12–20% increased risk for developing CRC. Preventive strategies utilizing nontoxic natural compounds that modulate immune responses could be successful in the suppression of inflammation-driven colorectal cancer in high-risk groups. The increase of peroxisome proliferator-activated receptor-γ (PPAR-γ expression and its transcriptional activity has been identified as a target for anti-inflammatory efforts, and the suppression of inflammation-driven colon cancer. PPARγ down-modulates inflammation and elicits antiproliferative and proapoptotic actions in epithelial cells. All of which may decrease the risk for inflammation-induced CRC. This review will focus on the use of orally active, naturally occurring chemopreventive approaches against inflammation-induced CRC that target PPARγ and therefore down-modulate inflammation.

  3. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor

    2016-06-29

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

  4. RHOA inactivation enhances Wnt signaling and promotes colorectal cancer

    Science.gov (United States)

    Rodrigues, Paulo; Macaya, Irati; Bazzocco, Sarah; Mazzolini, Rocco; Andretta, Elena; Dopeso, Higinio; Mateo-Lozano, Silvia; Bilić, Josipa; Cartón-García, Fernando; Nieto, Rocio; Suárez-López, Lucia; Afonso, Elsa; Landolfi, Stefania; Hernandez-Losa, Javier; Kobayashi, Kazuto; Cajal, Santiago Ramón y; Tabernero, Josep; Tebbutt, Niall C.; Mariadason, John M.; Schwartz, Simo; Arango, Diego

    2014-01-01

    Activation of the small GTPase RHOA has strong oncogenic effects in many tumor types, although its role in colorectal cancer remains unclear. Here we show that RHOA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/β-catenin signaling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of β-catenin from the membrane to the nucleus and enhanced Wnt/β-catenin signaling, resulting in increased proliferation, invasion and de-differentiation. In mice, RHOA inactivation contributes to colon cancer metastasis and reduced RHOA levels were observed at metastatic sites compared to primary human colon tumors. Therefore, we have identified a new mechanism of activation of Wnt/β-catenin signaling and characterized the role of RHOA as a novel tumor suppressor in colorectal cancer. These results constitute a shift from the current paradigm and demonstrate that RHO GTPases can suppress tumor progression and metastasis. PMID:25413277

  5. Molecular markers and targets for colorectal cancer prevention

    Institute of Scientific and Technical Information of China (English)

    Naveena B JANAKIRAM; Chinthalapally V RAO

    2008-01-01

    Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from pro-moting/developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the bio-logical and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarkerin biomolecular pathwayare elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.

  6. Colorectal cancer in geriatric patients: Endoscopic diagnosis and surgical treatment

    Institute of Scientific and Technical Information of China (English)

    Andreas Kirchgatterer; Pius Steiner; Dietmar Hubner; Eva Fritz; Gerhard Aschl; Josef Preisinger; Maximilian Hinterreiter; Bernhard Stadler; Peter Knoflach

    2005-01-01

    AIM: To investigate the prevalence of colorectal cancer in geriatric patients undergoing endoscopy and to analyze their outcome.METHODS: All consecutive patients older than 80 years who underwent lower gastrointestinal endoscopy between January 1995 and December 2002 at our institution were included.Patients with endoscopic diagnosis of colorectal cancer were evaluated with respect to indication, localization and stage of cancer, therapeutic consequences, and survival.RESULTS: Colorectal cancer was diagnosed in 88 patients (6% of all endoscopies, 55 women and 33 men, mean age 85.2 years). Frequent indications were lower gastrointestinal bleeding (25%), anemia (24%) or sonographic suspicion of tumor (10%). Localization of cancer was predominantly the sigmoid colon (27%), the rectum (26%), and the ascending colon (20%). Stage Dukes A was rare (1%), but Dukes D was diagnosed in 22% of cases. Curative surgery was performed in 54 patients (61.4%), in the remaining 34 patients (38.6%)surgical treatment was not feasible due to malnutrition and asthenia or cardiopulmonary comorbidity (15 patients), distant metastases (11 patients) or refusal of operation (8 patients).Patients undergoing surgery had a very low in-hospital mortality rate (2%). Operated patients had a one-year and three-year survival rate of 88% and 49%, and the survival rates for nonoperated patients amounted to 46% and 13% respectively.CONCLUSION: Nearly two-thirds of 88 geriatric patients with endoscopic diagnosis of colorectal cancer underwent successful surgery at a very low perioperative mortality rate, resulting in significantly higher survival rates. Hence,the clinical relevance of lower gastrointestinal endoscopy and oncologic surgery in geriatric patients is demonstrated.

  7. The Role of Chemokines in Promoting Colorectal Cancer Invasion/Metastasis

    Directory of Open Access Journals (Sweden)

    Yoshiro Itatani

    2016-04-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer-related death worldwide. Although most of the primary CRC can be removed by surgical resection, advanced tumors sometimes show recurrences in distant organs such as the liver, lung, lymph node, bone or peritoneum even after complete resection of the primary tumors. In these advanced and metastatic CRC, it is the tumor-stroma interaction in the tumor microenvironment that often promotes cancer invasion and/or metastasis through chemokine signaling. The tumor microenvironment contains numerous host cells that may suppress or promote cancer aggressiveness. Several types of host-derived myeloid cells reside in the tumor microenvironment, and the recruitment of them is under the control of chemokine signaling. In this review, we focus on the functions of chemokine signaling that may affect tumor immunity by recruiting several types of bone marrow-derived cells (BMDC to the tumor microenvironment of CRC.

  8. Primary and secondary prevention of colorectal cancer in the Czech Republic.

    Science.gov (United States)

    Azeem, Kateřina; Ševčíková, Jarmila; Kyselý, Zdeněk; Horáková, Dagmar; Vlčková, Jana; Kollárová, Helena

    2016-01-01

    Colorectal cancer is one of the most frequent malignancies in the Czech Republic and worldwide. Also, a high prevalence of overweight and obesity, a high proportion of smokers in the population, and one of the highest per capita alcohol consumption rates are typical for the Czech population. The role of general practitioners in the prevention of colorectal cancer is crucial. In primary prevention, the doctor should emphasise the importance of a healthy lifestyle - a balanced diet rich in fruits and vegetables, maintaining a normal body weight, adequate physical activity, and non-smoking. In secondary prevention, patients should be informed about the possibilities of colorectal cancer screening and the benefits of early detection of the disease. Participation rates of the target population for colorectal cancer screening are low. Steps leading to increased participation in colorectal cancer screening (including postal invitations) play an important role in influencing the mortality of colorectal cancer.

  9. Human FK506 binding protein 65 is associated with colorectal cancer

    DEFF Research Database (Denmark)

    Olesen, Sanne Harder; Christensen, Lise Lotte; Sørensen, Flemming Brandt;

    2005-01-01

    this gene hFKBP10 together with its encoded protein hFKBP65 as a novel marker associated with colorectal cancer. Analysis of 31 colorectal adenocarcinomas and 14 normal colorectal mucosa by RealTime PCR for hFKBP10 showed a significant up-regulation in tumors, when compared with normal mucosa...

  10. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

    Directory of Open Access Journals (Sweden)

    Sarah Derks

    2006-01-01

    Full Text Available Background: Colorectal cancers are characterized by genetic and epigenetic alterations. This study aimed to explore the timing of promoter methylation and relationship with mutations and chromosomal alterations in colorectal carcinogenesis. Methods: In a series of 47 nonprogressed adenomas, 41 progressed adenomas (malignant polyps, 38 colorectal carcinomas and 18 paired normal tissues, we evaluated promoter methylation status of hMLH1, O6MGMT, APC, p14ARF, p16INK4A, RASSF1A, GATA-4, GATA-5, and CHFR using methylation-specific PCR. Mutation status of TP53, APC and KRAS were studied by p53 immunohistochemistry and sequencing of the APC and KRAS mutation cluster regions. Chromosomal alterations were evaluated by comparative genomic hybridization. Results: Our data demonstrate that nonprogressed adenomas, progressed adenomas and carcinomas show similar frequencies of promoter methylation for the majority of the genes. Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16INK4A, GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1×10−5 and 0.008 respectively. P53 immunopositivity and chromosomal abnormalities occur predominantly in carcinomas (P values: 1.1×10−5 and 4.1×10−10. Conclusions: Since promoter methylation was already present in nonprogressed adenomas without chromosomal alterations, we conclude that promoter methylation can be regarded as an early event preceding TP53 mutation and chromosomal abnormalities in colorectal cancer development.

  11. Knowledge of colorectal cancer screening among young Malaysians.

    Science.gov (United States)

    Al-Naggar, Redhwan Ahmed; Bobryshev, Yuri V

    2013-01-01

    The objective of this study was to determine the knowledge and associated factors regarding colorectal cancer screening among university students in Malaysia. The questionnaire consisted of three parts: socio-demographic characteristics, lifestyle practice and knowledge of colorectal screening. A cross-sectional study was conducted among 300 students (21.3±1.4 years old). The majority of the participants were Malay with a monthly family income of less than 5,000 Ringgit Malaysia (equal to 1,700 USD) (67.0% and 76.0%, respectively). Regarding their lifestyle practices, the majority were non-smokers and had never consumed alcohol (83.7%, and 88.0%, respectively). The majority of the participants had no knowledge of digital rectal examination, colonoscopy, barium enema and fecal occult blood screening (63.3%, 60.7%, 74.0% and 62.3%, respectively). Univariate and multivariate analysis revealed that their age and the discipline which the students were studying significantly influenced their level of knowledge about colorectal screening. The present study results indicate that education campaigns about colorectal cancer should be promoted. PMID:23679301

  12. Relationship between Human Papilloma Virus and Colorectal Cancer in Northern Iran

    Directory of Open Access Journals (Sweden)

    Anahita Nosrati

    2015-10-01

    Full Text Available Background: Colorectal cancer is one of the most common malignancies worldwide with more than one million new cases. According to the Ministry of Health and Medical Education of Iran, colorectal cancer is the third most common cancer in Iran. Many risk factors are known causes of this disease. However, the molecular mechanisms associated with colorectal cancer are still under investigation. Recent studies have shown that some viruses, particularly human papilloma virus, may be associated with the pathology of colorectal cancer. Methods: This case-control study examined 95 colorectal cancer and 95 normal colon tissue paraffin blocks (control to identify the relationship between human papilloma virus and colorectal cancer by polymerase chain reaction. Results: Clinicopathological data that included sex, age, tumor grade, stage and location were recorded. All tumor and control groups (totally: 190 samples were negative in terms of the human papilloma virus genome. No relationship between clinicopathological data and human papilloma virus genome was identified. Conclusions: Regardless of other risk factors for colorectal cancer, a number of studies in different parts of the world have shown that human papilloma virus may be an important factor in the increasing incidence of colorectal cancer. However, we have found no association between human papilloma virus and colorectal cancer in this study.

  13. Clues to the pathogenesis of familial colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aaltonen, L.A.; Peltomaeki, P.; Pylkkaenen, L.; Chappelle, A. de la (Univ. of Helsinki (Finland)); Leach, F.S.; Powell, S.M.; Jen, J.; Hamilton, S.R.; Petersen, G.M.; Kinzler, K.W.; Vogelstein, B. (Johns Hopkins Univ., Baltimore, MD (United States) Johns Hopkins Hospital, Baltimore, MD (United States)); Sistonen, P. (Univ. of Helsinki (Finland) Finnish Red Cross Blood Transfusion Service, Helsinki (Finland)); Mecklin, J.P. (Jyvaeskylae Central Hospital (Finland)); Jaervinen, H. (Helsinki Univ. Central Hospital (Finland))

    1993-05-07

    A predisposition to colorectal cancer is shown to be linked to markers on chromosome 2 in some families. Molecular features of familial cancers were compared with those of sporadic colon cancers. Neither the familial nor sporadic cancers showed loss of heterozygosity for chromosome 2 markers, and the incidence of mutations in KRAS, P53, and APC was similar in the two groups of tumors. Most of the familial cancers, however, had widespread alterations in short repeated DNA sequences, suggesting that numerous replication errors had occurred during tumor development. Thirteen percent of sporadic cancers had identical abnormalities and these cancers shared biologic properties with the familial cases. These data suggest a mechanism for familial tumorigenesis different from that mediated by classic tumor suppressor genes. 22 refs., 2 figs., 2 tabs.

  14. CT colonography for synchronous colorectal lesions in patients with colorectal cancer: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    McArthur, D.R.; Karandikar, S.S. [Heart of England NHS Foundation Trust (Teaching), Department of Surgery, Birmingham (United Kingdom); Mehrzad, H.; Patel, R.; Dadds, J.; Pallan, A.; Roy-Choudhury, S. [Heart of England NHS Foundation Trust (Teaching), Department of Radiology, Birmingham (United Kingdom)

    2010-03-15

    To assess accuracy of CT colonography (CTC) in identifying synchronous lesions in patients with colorectal carcinoma. This study included 174 consecutive patients undergoing CTC as part of staging or primary investigation where a colorectal cancer was diagnosed between 2004 and 2007. Prone unenhanced and portal phase enhanced supine series with air or CO{sub 2} distension were acquired using 4- or 16-slice CT (Toshiba) and read by 2D {+-} 3D formats. Synchronous lesions were classified according to American College of Radiology's (ACR) polyp classification. Segmental gold standard was flexible sigmoidoscopy/colonoscopy within 1 year and/or histology of colonic resection supplemented by follow-up. Nine patients without gold standard were excluded. Sensitivity, specificity and accuracy were calculated on a per polyp, per patient and per segment basis and discrepancies analysed. Direct comparable data were available for 764/990 colonic segments from 165 patients. Of 41 (C2-C4) synchronous lesions on ''gold standard'', 33 were correctly identified on virtual colonoscopy (VC), overall per polyp sensitivity was 80.5%, with detection rates of 20/24 C3 (83.3%) and 3/3 C4 (100%) with per patient and per segment specificity of 95.4% and 99.2%, respectively. CTC is an accurate technique to assess for significant synchronous lesions in patients with colorectal cancer and is applicable for total pre-operative colonic visualisation. (orig.)

  15. Hydrophobic protein in colorectal cancer in relation to tumor stages and grades

    Institute of Scientific and Technical Information of China (English)

    Lay-Chin; Yeoh; Chee-Keat; Loh; Boon-Hui; Gooi; Manjit; Singh; Lay-Harn; Gam

    2010-01-01

    AIM: To identify differentially expressed hydrophobic proteins in colorectal cancer. METHODS: Eighteen pairs of colorectal cancerous tissues in addition to tissues from normal mucosa were analysed. Hydrophobic proteins were extracted from the tissues, separated using 2-D gel electrophoresis and analysed using Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS). Statistical analysis of the proteins was carried out in order to determine the significance of each protein to colorectal cancer (CRC) and als...

  16. Detection significance of serum CRP and VEGF in patients with advanced colorectal cancer and treated with chemotherapy%晚期结直肠癌患者化疗中血清C反应蛋白和VEGF检测及意义

    Institute of Scientific and Technical Information of China (English)

    陶冬梅; 黄永富

    2011-01-01

    目的 探讨血清C-反应蛋白(CRP)和血管内皮细胞生长因子(VEGF)检测在晚期结直肠癌患者化疗疗效评价、预后判断中的临床价值.方法 分别以双抗夹心酶联免疫吸附法和免疫比浊法测定并分析37例晚期结直肠癌患者化疗前和采用FOLFOX4方案化疗2个周期后血清CRP和VEGF水平.结果 晚期结直肠癌患者血清CRP及VEGF水平与患者性别、年龄及肿瘤转移、分化程度无关(P>0.05);患者化疗前后血清CRP、VEGF水平差异有统计学意义(P<0.05).结论 晚期结直肠癌患者血清CRP及VEGF水平变化与化疗疗效密切相关,动态监测血清CRP及VEGF水平可反映化疗近期疗效.%Objective To study the clinical significance of serum C reaction protein(CRP) and vascular endothelial growth factor (VEGF) in the evaluation of chemotherapeutic effect and prognosis in patients with advanced colorectal cancer. Methods Serum CRP and VEGF of 37 cases of patients with advanced colorectal cancer were measured by using double antibody sandwich enzyme linked immunosorbent assay and immunoturbidimetry, before and after 2 courses of chemotherapy of FOLFOX4 program. Results There were no correlation between serum CRP and VEGF levels of patients, with advanced colorectal cancer, with sex, age and the metastasis and differentiation level of tumor tissues(P>0.05), but there were statistical differences of serum CRP and VEGF levels when detected before and after chemotherapy. Conclusion Serum CRP and VEGF levels in patients with advanced colorectal cancer could be closely related with the chemotherapeutic effect. Dynamic monitoring of serum CRP and VEGF levels could reflect the short term effects of chemotherapy.

  17. Pulmonary nodules and metastases in colorectal cancer.

    Science.gov (United States)

    Nordholm-Carstensen, Andreas

    2016-01-01

    Patients with newly diagnosed colorectal cancer (CRC) are subjected to a preoperative thoraco-abdominal CT scan to determine the cancer stage. This staging is of relevance with regard to treatment and prognosis. About 20% of the patients have distant metastatic spread at the time of diagnosis, i.e. synchronous metastases. Most common are hepatic metastases followed by pulmonary involvement. The optimal staging modality for detecting synchronous pulmonary metastases is debated. It has been argued, that synchronous pulmonary metastases (SPCM) are rare in CRC and that the consequence of detecting SPCM is minimal. Furthermore, the current staging practice is complicated by a high number of incidental findings on the thoracic CT, so-called indeterminate pulmonary nodules (IPN). IPN can potentially represent SPCM. The purpose of this thesis was to estimate the prevalence, characteristics and clinical significance of IPN and SPCM detected at the primary staging in CRC. Study I was a systematic review of published studies on IPN in CRC focusing on the prevalence and radiological characteristics of IPN proving to be malignant. This knowledge would be of value in management strategies for IPN. On average 9% of all patients staged with a thoracic CT had IPN, however, the prevalence varied significantly between patients series. This was mainly attributed to varying/lacking definitions on IPN and variable radiological expertise in the assessment of the scans. Data were too inconsistently reported in the case series for a robust statement to be made on potential radiological characteristics suggestive of malignancy in IPN. Lymph node metastasis was the most common clinicopathological finding associated with malignancy of IPN. In conclusion, one patient of every 100 scanned patients had an IPN proving to a SPCM at follow-up, but we found no evidence that IPN should result in intensified diagnostic work-up besides routine follow-up for CRC. Study II was an analysis of the

  18. Telenovela: an innovative colorectal cancer screening health messaging tool

    Directory of Open Access Journals (Sweden)

    Melany Cueva

    2013-08-01

    Full Text Available Background. Alaska Native people have nearly twice the rate of colorectal cancer (CRC incidence and mortality as the US White population. Objective. Building upon storytelling as a culturally respectful way to share information among Alaska Native people, a 25-minute telenovela-style movie, What's the Big Deal?, was developed to increase CRC screening awareness and knowledge, role-model CRC conversations, and support wellness choices. Design. Alaska Native cultural values of family, community, storytelling, and humor were woven into seven, 3–4 minute movie vignettes. Written post-movie viewing evaluations completed by 71.3% of viewers (305/428 were collected at several venues, including the premiere of the movie in the urban city of Anchorage at a local movie theater, seven rural Alaska community movie nights, and five cancer education trainings with Community Health Workers. Paper and pencil evaluations included check box and open-ended questions to learn participants' response to a telenovela-style movie. Results. On written-post movie viewing evaluations, viewers reported an increase in CRC knowledge and comfort with talking about recommended CRC screening exams. Notably, 81.6% of respondents (249/305 wrote positive intent to change behavior. Multiple responses included: 65% talking with family and friends about colon screening (162, 24% talking with their provider about colon screening (59, 31% having a colon screening (76, and 44% increasing physical activity (110. Conclusions. Written evaluations revealed the telenovela genre to be an innovative way to communicate colorectal cancer health messages with Alaska Native, American Indian, and Caucasian people both in an urban and rural setting to empower conversations and action related to colorectal cancer screening. Telenovela is a promising health communication tool to shift community norms by generating enthusiasm and conversations about the importance of having recommended colorectal

  19. Quality of life and its determinants among colorectal cancer survivors

    Directory of Open Access Journals (Sweden)

    Hossein Ali Nikbakht

    2015-05-01

    Full Text Available Background: Colorectal cancer has a significant impact on physical, mental and social discomfort of patients. The aim of this study was to assess different aspects of health-related quality of life and its association with demographic characteristics and some clinical features in colorectal cancer survivors in the city of Babol. Methods: This cross-sectional study was conducted in 2013 among 120 colorectal cancer survivors identified in the cancer registry from 2007 to 2012. A questionnaire containing demographic data, disease characteristics and health-related quality of life (EORTC-QLQ-C30 standard questionnaire was completed via face to face interview at patients’ homes. Results: The mean total score of performance scale was significantly higher in men (69/24± 16/71 than in women (57/67 ± 17/87 (P=0.001. Men obtained higher scores in all 5 performance scales which was statistically significant in the domains of physical, emotional and cognitive performance. Among the demographic variables, comorbidities, education and employment were identified as the independent predictors of quality of life. Conclusion: The patients had an average quality of life which was associated with employment, education and comorbidities. Therefore, , empowering the health staff , increasing the awareness of patients and their families as well as better management of comorbidities can help the patients to return to an active life.

  20. Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Adam Elzagheid; Abdelbaset Buhmeida; Eija Korkeila; Yrj(o) Collan; Karl Syrj(a)nen; Seppo Pyrh(o)nen

    2008-01-01

    AIM: To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC).METHODS.Archival tumor samples were analyzed for β-catenin using immunohistochemisry (IHC) in 95 patients with advanced CRC.RESULTS: Membranous β-catenin expression was found in the normal colorectal epithelium.Almost 100% of CRCcases showed membranous and cytoplasmic expression,and 55 (58%) cases showed nuclear expression.In univariate (Kaplan-Meier)survival analysis,only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P=0.023; n = 35),with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045,ANOVA).The other indices were not significant predictors of DFS,and none of the three tested indices (for membranous,cytoplasmic,or nuclear expression) predicted diseasespecific survival (DSS).However,when dichotomized as positive or negative nuclear expression,the former was a significant predictor of more favorable DFS (P =0.041) and DSS (P = 0.046).CONCLUSION: Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.

  1. Differential expression of a novel colorectal cancer differentiation-related gene in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Xing-Guo Li; Jin-Dan Song; Yun-Qing Wang

    2001-01-01

    AIM To investigate SBA2 expression in CRC cell lines snd surgical specimens of CRC and sutologous healthy mucosa. METHODS Reverse transcription-polymerase chain reaction (RT-PCR) was used for relative quantification of SBA2 mRNA levels in 4 human CRC cell lines with different grades of differentiation and 30 clinical samples.Normalization of the results was achieved by simultaneous amplification of β-actin as an internal control. RESULTS In the exponential range of amplification, fairly good linearity demonstrated identical amplification efficiency for SBA2 and β-actin (82%). Markedly lower levels of SBA2 mRNA were detectable in tumors, as compared with the coupled normal counterparts ( P < 0.01 ). SBA2 expression was significantly (0.01 < P <0.05) correlated with the grade of differentiation in CRC,with relatively higher levels in well-differentiated samples and lower in poorly-differentiated cases. Of the 9 cases with lymph nodes affected, 78% (7/9) had reduced SBA2 mRNA expression in contrast to 24% (5/21) in nonmetastasis samples (0.01 < P < 0.05 ). CONCLUSION SBA2 gene might be a promising novel biomarker of cell differentiation in colorectal cancer and its biological features need further studies.

  2. The impact of organisational external peer review on colorectal cancer treatment and survival in the Netherlands

    NARCIS (Netherlands)

    Kilsdonk, M. J.; van Dijk, B. A. C.; Otter, R.; Siesling, S.; van Harten, W. H.

    2014-01-01

    Background: Organisational external peer review was introduced in 1994 in the Netherlands to improve multidisciplinary cancer care. We examined the clinical impact of this programme on colorectal cancer care. Methods: Patients with primary colorectal cancer were included from 23 participating hospit

  3. Prognostic significance of detection of microscopic peritoneal disease in colorectal cancer: a systematic review.

    LENUS (Irish Health Repository)

    Mohan, Helen M

    2013-06-01

    Free intraperitoneal tumour cells are an independent indicator of poor prognosis, and are encorporated in current staging systems in upper gastrointestinal cancers, but not colorectal cancer. This systematic review aimed to evaluate the role and prognostic significance of positive peritoneal lavage in colorectal cancer.

  4. Determinants of participation in colorectal cancer screening with faecal occult blood testing

    DEFF Research Database (Denmark)

    von Euler-Chelpin, My; Brasso, Klaus; Lynge, Elsebeth

    2009-01-01

    BACKGROUND: Colorectal cancer is one of the most common cancers in men and women. Participation rates in faecal occult blood testing (FOBT) screening activities are, however, relatively low. In terms of lowering the colorectal cancer mortality, high participation rates are essential, and therefor...

  5. Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

    Energy Technology Data Exchange (ETDEWEB)

    Al-Ebraheem, A. [Department of Radiography, City Community and Health Sciences, City University, London, EC1V 0HB (United Kingdom); Mersov, A. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St. West. Hamilton, Ontario, L8S 4L8 (Canada); Gurusamy, K. [HPB and Liver Transplant Surgery, Royal Free and University College School of Medicine, UCL and Royal Free NHS trust, London (United Kingdom); Farquharson, M.J., E-mail: farquhm@mcmaster.c [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St. West. Hamilton, Ontario, L8S 4L8 (Canada)

    2010-07-21

    A microbeam synchrotron X-ray fluorescence ({mu}SRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 {mu}m thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe (P=0.009) from independent T test.

  6. Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers.

    Science.gov (United States)

    Tovar-Camargo, Oscar A; Toden, Shusuke; Goel, Ajay

    2016-05-01

    Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called 'exosomes', which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches. PMID:26892862

  7. Chemoresistive Gas Sensors for the Detection of Colorectal Cancer Biomarkers

    Directory of Open Access Journals (Sweden)

    Cesare Malagù

    2014-10-01

    Full Text Available Numerous medical studies show that tumor growth is accompanied by protein changes that may lead to the peroxidation of the cell membrane with consequent emission of volatile organic compounds (VOCs by breath or intestinal gases that should be seen as biomarkers for colorectal cancer (CRC. The analysis of VOCs represents a non-invasive and potentially inexpensive preliminary screening technique. An array of chemoresistive gas sensors based on screen-printed metal oxide semiconducting films has been selected to discriminate gases of oncological interest, e.g., 1-iodononane and benzene, widely assumed to be biomarkers of colorectal cancer, from those of interference in the gut, such as methane and nitric oxide.

  8. Epidermal growth factor receptor analyses in colorectal cancer

    DEFF Research Database (Denmark)

    Spindler, Karen-Lise Garm; Lindebjerg, Jan; Nielsen, Jens Nederby;

    2006-01-01

    equivalent EGFR status (28/34). There was a tendency to higher median protein level (by ELISA) in IHC positive patients compared to IHC negative patients (p=0.086). The median EGFR gene expression level was significantly lower in tumours than in the normal colon with no difference according to IHC status......EGFR immunohistochemistry (IHC) status is not a reliable predictive marker for response to EGFR-targeted therapies. The present study compares the EGFR status at DNA, RNA and protein level. Blood samples, corresponding normal colon and colorectal cancer tissue were collected from 199 colorectal...... cancer (CRC) patients. EGFR status was evaluated by FISH analysis, real-time RT-PCR, ELISA and IHC. A polymorphism in the EGFR promoter was evaluated by PCR analysis. The EGFR levels by different methods were mutually compared. Seventy-eight percent of primary tumours and corresponding lymph nodes had...

  9. Heterogenous mismatch-repair status in colorectal cancer

    DEFF Research Database (Denmark)

    Joost, Patrick; Veurink, Nynke; Holck, Susanne;

    2014-01-01

    BACKGROUND: Immunohistochemical staining for mismatch repair proteins is efficient and widely used to identify mismatch repair defective tumors. The tumors typically show uniform and widespread loss of MMR protein staining. We identified and characterized colorectal cancers with alternative......, heterogenous mismatch repair protein staining in order to delineate expression patterns and underlying mechanisms. METHODS: Heterogenous staining patterns that affected at least one of the mismatch repair proteins MLH1, PMS2, MSH2 and MSH6 were identified in 14 colorectal cancers. Based on alternative...... expression patterns macro-dissected and micro-dissected tumor areas were separately analyzed for microsatellite instability and MLH1 promoter methylation. RESULTS: Heterogenous retained/lost mismatch repair protein expression could be classified as intraglandular (within or in-between glandular formations...

  10. EFFECT OF BODY MASS INDEX ON COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    张霁; 苏向前; 郑俊全; 顾晋; 宗祥龙; 王怡; 季加孚

    2003-01-01

    Objective: To evaluate the association between obesity and the risk of colorectal cancer. Methods: 331 patients with rectal cancer and 175 with colon cancer who accepted surgical operation at Beijing Cancer Hospital during 1995 and 2002 were enrolled. Data were collected by reviewing the pathology materials and hospital records. 258 healthy people who accepted health examination at Beijing Cancer Hospital during 2000 and 2002 were also enrolled as control. Data of height, weight and gender at the time of examination were also collected. Obesity was estimated by body mass index (BMI), computed as weight in kilograms divided by height in meters squared (kg/m2). The degree of obesity was compared between the two groups using BMI(18.5, 24-27.9 and (28 (kg/m2) as the cut-off points for underweight, overweight and obesity. Associations with obesity were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). All ORs were adjusted for age and sex. Results: Obesity was significantly prevalent in female patients with rectal cancer. All the patients with colon cancer showed lower level of BMI than control subjects. The ORs for rectal cancer rose with increasing BMI in women. Meanwhile, the ORs for colon cancer dropped with increasing BMI in both men and women. Obesity was an independent risk factor for rectal cancer, but not an independent risk factor for colon cancer. Conclusion: Rectal cancer and colon cancer may have different biological behavior. Obese women have relatively high risk for rectal cancer.

  11. Lymphatic drainage of the liver and its implications in the management of colorectal cancer liver metastases.

    Science.gov (United States)

    Lupinacci, Renato Micelli; Paye, François; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Herman, Paulo

    2014-12-01

    The liver is the most common site of distant metastases in patients with colorectal cancer. Surgery represents the mainstream for curative treatment of colorectal cancer liver metastases (CRCLM) with long-term survival up to 58 and 36 % at 5 and 10 years, respectively. Despite advances on diagnosis, staging and surgical strategies, 60-70 % of patients will develop recurrence of the disease even after R0 resection of CRCLM. Tumor staging, prognosis, and therapeutic approaches for cancer are most often based on the extent of involvement of regional lymph nodes (LNs) and, to a lesser extent, on the invasion of regional lymphatic vessels draining the primary tumor. For CRCLM, the presence of intra hepatic lymphatic and blood vascular dissemination has been associated with an increased risk of intra hepatic recurrence, poorer disease-free and overall survival after liver resection. Also, several studies have reviewed the role of surgery in the patient with concomitant CRCLM and liver pedicle LN metastasis. Although pedicle LN involvement is related to worst survival rates, it does not differentiate patients that will relapse from those that will not. This review aims to briefly describe the anatomy of the liver's lymphatic drainage, the incidence of intrahepatic lymphatic invasion and hilar lymph node involvement, as well as their clinical impact in CRCLM. A better understanding of the role of liver lymphatic metastasis might, in the near future, impact the strategy of systemic therapies after liver resection as for primary colorectal tumors.

  12. Clinical Experience on Colorectal Cancer%大肠癌临证心悟

    Institute of Scientific and Technical Information of China (English)

    程剑华

    2014-01-01

    This article would summarize the author's experience in treating colorectal cancer from aspects of the main points of colorectal cancer's syndrome differentiation, using the principle of syndrome differentiation to guide individualized treatment, make full use of the drugs' attributive channel theory and use classical prescriptions and paired herbs, advanced colorectal cancer patients should focus on conditioning and improving symptoms, develop route of administration to play advantages of Chinese medicine, pay attention to life care and match with diet therapy, psychother-apy and medication, in order to provide some references to clinical treatment.%本文将从大肠癌的辨证要点、运用辨证论治原则指导个体化治疗、充分利用药物归经理论,运用经方,使用对药、晚期肠癌患者重在调理和改善症状、拓展给药途径,发挥中医优势、重视生活调养,食疗、心理治疗与药物治疗相配合等方面对笔者治疗大肠癌的心得体会进行总结,以供临床参考。

  13. Colorectal cancer and dysplasia in inflammatory bowel disease.

    Science.gov (United States)

    Zisman, Timothy L; Rubin, David T

    2008-05-01

    Both ulcerative colitis and Crohn's disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis, greater extent and duration of disease, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis. Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication. Nonetheless heightened vigilance and a careful, comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients. Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia-carcinoma sequence. A thorough understanding of the definition and natural history of dysplasia in IBD, as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention, and understanding the limitations of the current approach to prevention. This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD, as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia. PMID:18461651

  14. Colorectal cancer and dysplasia in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Timothy L Zisman; David T Rubin

    2008-01-01

    Both ulcerative colitis and Crohn's disease carry an increased risk of developing colorectal cancer.Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis,greater extent and duration of disease,increased severity of inflammation,family history of colorectal cancer and coexisting primary sclerosing cholangitis.Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication.Nonetheless heightened vigilance and a careful,comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients.Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia-carcinoma sequence.A thorough understanding of the definition and natural history of dysplasia in IBD,as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention,and understanding the limitations of the current approach to prevention.This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD,as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia.

  15. Serum amino acid profiles and their alterations in colorectal cancer.

    Science.gov (United States)

    Leichtle, Alexander Benedikt; Nuoffer, Jean-Marc; Ceglarek, Uta; Kase, Julia; Conrad, Tim; Witzigmann, Helmut; Thiery, Joachim; Fiedler, Georg Martin

    2012-08-01

    Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.

  16. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer.

    Science.gov (United States)

    Liu, Can; Dai, Longhai; Liu, Yueping; Rong, Long; Dou, Dequan; Sun, Yuanxia; Ma, Lanqing

    2016-06-13

    Colorectal cancer and throat cancer are the world's most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9) and phosphorylated extracellular signal-regulated kinases (ERK)1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

  17. Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer

    Directory of Open Access Journals (Sweden)

    Can Liu

    2016-06-01

    Full Text Available Colorectal cancer and throat cancer are the world’s most prevalent neoplastic diseases, and a serious threat to human health. Plant triterpene glycosides have demonstrated antitumor activity. In this study, we investigated potential anticancer effects of mogroside IVe, a triterpenoid glycoside from monk fruit, using in vitro and in vivo models of colorectal and laryngeal cancer. The effects of mogroside IVe on the proliferation of colorectal cancer HT29 cells and throat cancer Hep-2 cells were determined by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, and the expression levels of p53, phosphorylated ERK1/2, and MMP-9 were analyzed by western blotting and immunohistochemistry. The results indicated that mogroside IVe inhibited, in a dose-dependent manner, the proliferation of HT29 and Hep-2 cells in culture and in xenografted mice, which was accompanied by the upregulation of tumor suppressor p53, and downregulation of matrix metallopeptidase 9 (MMP-9 and phosphorylated extracellular signal-regulated kinases (ERK1/2. This study revealed the suppressive activity of mogroside IVe towards colorectal and throat cancers and identified the underlying mechanisms, suggesting that mogroside IVe may be potentially used as a biologically-active phytochemical supplement for treating colorectal and throat cancers.

  18. Socioeconomic position and participation in colorectal cancer screening

    DEFF Research Database (Denmark)

    Frederiksen, B L; Jørgensen, Torben; Brasso, K;

    2010-01-01

    Colorectal cancer (CRC) screening with faecal occult blood test (FOBT) has the potential to reduce the incidence and mortality of CRC. Screening uptake is known to be inferior in people with low socioeconomic position (SEP) when compared with those with high position; however, the results of most...... information on education, employment, and income to encompass different but related aspects of socioeconomic stratification. Also, the impact of ethnicity and cohabiting status was analysed....

  19. Mitotic Origins of Chromosomal Instability in Colorectal Cancer

    OpenAIRE

    Dalton, W. Brian; Yang, Vincent W.

    2007-01-01

    Mitosis is a crucial part of the cell cycle. A successful mitosis requires the proper execution of many complex cellular behaviors. Thus, there are many points at which mitosis may be disrupted. In cancer cells, chronic disruption of mitosis can lead to unequal segregation of chromosomes, a phenomenon known as chromosomal instability. A majority of colorectal tumors suffer from this instability, and recent studies have begun to reveal the specific ways in which mitotic defects promote chromos...

  20. Multi-class texture analysis in colorectal cancer histology

    OpenAIRE

    Jakob Nikolas Kather; Cleo-Aron Weis; Francesco Bianconi; Melchers, Susanne M; Schad, Lothar R; Timo Gaiser; Alexander Marx; Frank Gerrit Zöllner

    2016-01-01

    Automatic recognition of different tissue types in histological images is an essential part in the digital pathology toolbox. Texture analysis is commonly used to address this problem; mainly in the context of estimating the tumour/stroma ratio on histological samples. However, although histological images typically contain more than two tissue types, only few studies have addressed the multi-class problem. For colorectal cancer, one of the most prevalent tumour types, there are in fact no pu...

  1. Glycosylation of plasma IgG in colorectal cancer prognosis

    OpenAIRE

    Evropi Theodoratou; Kujtim Thaçi; Felix Agakov; Timofeeva, Maria N.; Jerko Štambuk; Maja Pučić-Baković; Frano Vučković; Peter Orchard; Anna Agakova; DIN, FARHAT V. N.; Ewan Brown; Rudd, Pauline M; Susan M. Farrington; Dunlop, Malcolm G; Harry Campbell

    2016-01-01

    In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glyca...

  2. Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer

    OpenAIRE

    Victoria Gonzalo; Juan José Lozano; Jenifer Muñoz; Francesc Balaguer; Maria Pellisé; Cristina Rodríguez de Miguel; Montserrat Andreu; Rodrigo Jover; Xavier Llor; M Dolores Giráldez; Teresa Ocaña; Anna Serradesanferm; Virginia Alonso-Espinaco; Mireya Jimeno; Miriam Cuatrecasas

    2010-01-01

    BACKGROUND: Colorectal cancer (CRC) multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-...

  3. High level of ezrin expression in colorectal cancer tissues is closely related to tumor malignancy

    Institute of Scientific and Technical Information of China (English)

    Hong-Jian Wang; Jin-Shui Zhu; Qiang Zhang; Qun Sun; Hua Guo

    2009-01-01

    AIM: To investigate the ezrin expression in normal colorectal mucosa and colorectal cancer tissues,and study the correlation between ezrin expression in colorectal cancer tissues and tumor invasion and metastasis.METHODS: Eighty paraffin-embedded cancer tissue samples were selected from primary colorectal adenocarcinoma. Twenty-eight patients had welldifferentiated,22 had moderately differentiated and 30had poorly differentiated adenocarcinoma. Forty-five patients and 35 patients had lymph node metastasis.Forty-five patients were of Dukes A to B stage, and 35were of C to D stage. Another 22 paraffin-embedded tissue blocks of normal colorectal epithelium (> 5 cm away from the edge of the tumor) were selected as the control group. All patients with colorectal cancer were treated surgically and diagnosed histologically, without preoperative chemotherapy or radiotherapy. The immunohistochemistry was used to detect the ezrin expression in paraffin-embedded normal colorectal mucosa tissues and colorectal cancer tissue samples.RESULTS: Ezrin expression in colorectal cancer was significantly higher than in normal colorectal mucosa (75.00% vs 9.09%, P < 0.01), and there was a close relationship between ezrin expression and the degree of tumor differentiation, lymph node metastasis and Dukes stage (88.46% vs 50.00%, P < 0.01; 94.28%vs 51.11%, P < 0.01; 94.28% vs 51.11%, P < 0.01).

  4. DEK over expression as an independent biomarker for poor prognosis in colorectal cancer

    International Nuclear Information System (INIS)

    The DEK protein is related to chromatin reconstruction and gene transcription, and plays an important role in cell apoptosis. High expression levels of the human DEK gene have been correlated with numerous human malignancies. This study explores the roles of DEK in tumor progression and as a prognostic determinant of colorectal cancer. Colorectal cancer specimens from 109 patients with strict follow-up, and colorectal adenomas from 52 patients were selected for analysis of DEK protein by immunohistochemistry. The correlations between DEK over expression and the clinicopathological features of colorectal cancers were evaluated by Chi-square test and Fisher’s exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. DEK protein showed a nuclear immunohistochemical staining pattern in colorectal cancers. The strongly positive rate of DEK protein was 48.62% (53/109) in colorectal cancers, which was significantly higher than that in either adjacent normal colon mucosa (9.17%, 10/109) or colorectal adenomas (13.46%, 7/52). DEK over expression in colorectal cancers was positively correlated with tumor size, grade, lymph node metastasis, serosal invasion, late stage, and disease-free survival- and 5-year survival rates. Further analysis showed that patients with late stage colorectal cancer and high DEK expression had worse survival rates than those with low DEK expression. Moreover, multivariate analysis showed high DEK expression, serosal invasion, and late stage are significant independent risk factors for mortality in colorectal cancer. DEK plays an important role in the progression of colorectal cancers and it is an independent poor prognostic factor of colorectal cancers

  5. Prognostic Values of microRNAs in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Yaguang Xi

    2006-01-01

    Full Text Available The functions of non-coding microRNAs (miRNAs in tumorigenesis are just beginning to emerge. Previous studies from our laboratory have identifi ed a number of miRNAs that were deregulated in colon cancer cell lines due to the deletion of the p53 tumor suppressor gene. In this study, the in vivo signifi cance of some of these miRNAs was further evaluated using colorectal clinical samples. Ten miRNAs (hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b, hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR-30c were evaluated for their potential prognostic value in colorectal cancer patients. Forty eight snap frozen clinical colorectal samples (24 colorectal cancer and 24 paired normal patient samples with detailed clinical follow-up information were selected . The expression levels of 10 miRNAs were quantified via qRT-PCR analysis. The statistical signifi cance of these markers for disease prognosis was evaluated using a two tailed paired Wilcoxon test. A Kaplan-Meier survival curve was generated followed by performing a Logrank test. Among the ten miRNAs, hsa-miR-15b (p = 0.0278, hsa-miR-181b (p = 0.0002, hsa-miR-191 (p = 0.0264 and hsa-miR-200c (p = 0.0017 were signifi cantly over-expressed in tumors compared to normal colorectal samples. Kaplan-Meier survival analysis indicated that hsa-miR-200c was signifi cantly associated with patient survival (p = 0.0122. The patients (n = 15 with higher hsa-miR-200c expression had a shorter survival time (median survival = 26 months compared to patients (n = 9 with lower expression (median survival = 38 months. Sequencing analysis revealed that hsa-miR-181b (p = 0.0098 and hsa-miR-200c (p = 0.0322 expression were strongly associated with the mutation status of the p53 tumor suppressor gene. Some of these miRNAs may function as oncogenes due to their over-expression in tumors. hsa-miR-200c may be a potential novel prognostic factor in colorectal cancer.

  6. Two cases of colorectal cancer complicating radiation enterocolitis

    Energy Technology Data Exchange (ETDEWEB)

    Honma, Kaneatsu; Muto, Yoshihiro; Kusano, Toshiomi; Tokumine, Akio; Okushima, Norihiko; Tamashiro, Tetsuo (University of the Ryukyus, Okinawa (Japan). Faculty of Medicine)

    1993-09-01

    A 74-year-old woman presented with bowel movement disorder. She had received radiation therapy with 60 Gy for uterine cervical cancer approximately 20 years before. Barium enema and colonofiberscopy revealed radiation enterocolitis. Thereafter, the patient was admitted to the hospital due to stricture of the sigmoid colon and an increased CEA and was diagnosed as having Borrmann II type colorectal well differentiated adenocarcinoma. Histological examination revealed stage I with no associated lymph node metastases. She is alive 3 years and 10 month after surgery. The other patient was a 65 year-old woman with a history of cervical cancer. Twenty-one years after combined hysterectomy and postoperative external irradiation of 45 Gy, the patient presented with melena. Detailed examination revealed colorectal adenocarcinoma. Simultaneously, barium enema revealed radiation enterocolitis. At surgery, intrapelvic area was found to be frozen due to irradiation. She has no evidence of metastasis 2 years after surgery. As can be shown in the two patients, patients developing radiation enterocolitis should be followed up periodically for the early detection of coexistent colorectal cancer. (N.K.).

  7. Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer

    DEFF Research Database (Denmark)

    Havelund, Birgitte Mayland; Spindler, Karen-Lise Garm; Sørensen, Flemming Brandt;

    to a standardized scheme. 2. The prognostic value of HIF-1α is investigated by SNP analysis and HIF-1α expression in tissue from 300 patients operated for colorectal cancer and the results is validated in a prospectively population of 200 patients. 3. The predictive value of HIF-1α will be investigated in patients......Clinical Aspects of Hypoxia-inducible Factors in Colorectal Cancer   Birgitte Mayland Havelund1,4 MD, Karen-Lise Garm Spindler1,4 MD, PhD, Flemming Brandt Sørensen2,4 MD, DMSc, Ivan Brandslund3 MD, DMSc, Anders Jakobsen1,4 MD, DMSc. 1Department of Oncology, 2Pathology and 3Biochemistry, Vejle...... Hospital, Vejle, Denmark 4Institute of Regional Health Services Research, University of Southern Denmark, Odense Denmark Background Prognostic and predictive markers are needed for individualizing the treatment of colorectal cancer. Hypoxia-inducible factor 1α (HIF-1α) is a transcription-inducing factor...

  8. Problems in screening colorectal cancer in the elderly

    Institute of Scientific and Technical Information of China (English)

    Davidovic M. Mladen; Milosevic P. Dragoslav; Zdravkovic Sanja; Bojic Bozidar; Djurica Snezana

    2003-01-01

    AIM: To explore the problems in the screening of colorectal carcinoma in the elderly.METHODS: Three models of colorectal cancer prevention were examined: standard screening, active check-up of suspected cases and summons to have endoscopic checkup for previously diagnosed colorectal polyps. The study was performed among three groups of elderly individuals:Group 1 (167 cases), hospitalized asymptomatic individuals without symptoms in large intestines. Group 2 (612 cases):old individuals at home for the aged, out of which 32 showed symptoms of colon disorders; Group 3 (44 cases): elderly people with diagnosed polyps. As a result of 1788rectosigmoidoscopies, we identified 61 individuals with polyps, out of which 44 patients were over 65 years old.However, only 9 of these 44 individuals agreed to have the endoscopy performed again.RESULTS: One cancer and 13 polyps were detected in Group 1, and two polyps in Group 2. However, it should be noted that only eleven individuals from Group 2 agreed to have the endoscopy. In Group 3, there were no relapses of the polyps among the nine individuals who came back for the endoscopy.CONCLUSION: Poor understanding of the screening procedures is one of the greatest problems in early detection of the cancer in the aged. Paradoxically, the cooperation is better with hospitalized patients, than with "successfully old"persons.

  9. Geographic and Demographic Disparities in Late-stage Breast and Colorectal Cancer Diagnoses Across the US

    Directory of Open Access Journals (Sweden)

    Lee R Mobley

    2015-08-01

    Full Text Available Problem: In 2009, breast cancer was the most common cancer in women, and colorectal cancer was the third most common cancer in both men and women. Currently, the majority of colorectal and almost 1/3 of breast cancers are diagnosed at an advanced stage in the US, which results in higher morbidity and mortality than would obtain with earlier detection. The incidence of late-stage cancer diagnoses varies considerably across the US, and few analyses have examined the entire US.Purpose: Using the newly available US Cancer Statistics database representing 98% of the US population, we perform multilevel analysis of the incidence of late-stage cancer diagnoses and translate the findings via bivariate mapping, answering questions related to both Why and Where demographic and geographic disparities in these diagnoses are observed.Methods: To answer questions related to Why disparities are observed, we utilize a three-level, random-intercepts model including person-, local area-, and region- specific levels of influence. To answer questions related to Where disparities are observed, we generate county level robust predictions of late-stage cancer diagnosis rates and map them, contrasting counties ranked in the upper and lower quantiles of all county predicted rates. Bivariate maps are used to spatially translate the geographic variation among US counties in the distribution of both BC and CRC late-stage diagnoses.Conclusions: Empirical modeling results show demographic disparities, while the spatial translation of empirical results shows geographic disparities that may be quite useful for state cancer control planning. Late stage BC and CRC diagnosis rates are not spatially random, manifesting as place-specific patterns that compare counties in individual states to counties across all states. Providing a relative comparison that enables assessment of how results in one state compare with others, this paper is to be disseminated to all state cancer control

  10. Psychological distress following fecal occult blood test in colorectal cancer screening--a population-based study

    DEFF Research Database (Denmark)

    Brasso, Klaus; Ladelund, Steen; Frederiksen, Birgitte Lidegaard;

    2010-01-01

    To evaluate the possible psychological side-effect of participating in a colorectal cancer (CRC)-screening program.......To evaluate the possible psychological side-effect of participating in a colorectal cancer (CRC)-screening program....

  11. Long-term risk of colorectal cancer in patients with sessile serrated adenomas, traditional serrated adenomas, and hyperplastic polyps

    DEFF Research Database (Denmark)

    Baron, John A; Erichsen, Rune; Hamilton-Dutoit, Stephen Jacques;

    Long-term risk of colorectal cancer in patients with sessile serrated adenomas, traditional serrated adenomas, and hyperplastic polyps......Long-term risk of colorectal cancer in patients with sessile serrated adenomas, traditional serrated adenomas, and hyperplastic polyps...

  12. Pelvic exenteration for colorectal cancer: oncologic outcome in 59 patients at a single institution

    International Nuclear Information System (INIS)

    Pelvic exenteration (PE) continues to be the only curative option in selected patients with advanced or recurrent pelvic neoplasms. A current debate exists concerning the appropriate selection of patients for PE, with the most important factor being the absence of extrapelvic disease. To evaluate the outcome of patients submitted to exenterative surgery. A review of the clinical charts of patients with colorectal cancer who underwent PE between January 1994 and June 2010 at the Institute National of Cancerología in Mexico City was performed. We selected 59 patients, 53 of whom were females (90%), and six of whom were males (10%). Mean age at the time of diagnosis was 50 years (range, 21–77 years). A total of 51 patients underwent posterior PE (86%), and eight patients underwent total PE (14%). Operative mortality occurred in two cases (3%), and 29 patients developed complications (49%). Overall, 11 patients (19%) experienced local failure with mean disease-free survival time of 10.2 months. After a mean follow-up of 28.3 months, nine patients are still alive without evidence of the disease (15%). PE should be considered in advanced colorectal cancer without extrapelvic metastatic disease. PE is accompanied by considerable morbidity (49%) and mortality (3%), but local control is desirable. Overall survival justifies the use of this procedure in patients with primary or recurrent locally advanced rectal cancer

  13. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    International Nuclear Information System (INIS)

    It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does

  14. Advances in study of miR-106b-25 duster in colorectal cancer%microRNA-106b-25簇在结直肠癌中的作用研究进展

    Institute of Scientific and Technical Information of China (English)

    李利发; 周彤; 刘佳嘉; 石国露

    2015-01-01

    结直肠癌是全世界癌症死亡的主要原因之一,迫切需要寻找一种高特异性和灵敏性的肿瘤标记物,实现结直肠癌的早期诊断和预后评估。近年来研究发现,多种 microRNA 与结直肠癌密切相关。其中以microRNA-106b-25簇为典型代表,microRNA-106b-25簇包括microRNA-106b、microRNA-93和microRNA-25,这些microRNA不但能通过p21、p57及Bim来促进结直肠癌细胞增殖,抑制细胞凋亡,还能通过与抑癌基因RB和PTEN相互作用参与结肠癌的起源和发展。此外在转化生长因子β(TGF-β)信号通路中,microRNA-106b-25簇的高表达能使肿瘤细胞逃避 TGF-β诱导的生长抑制作用。因而深入研究microRNA-106b-25簇在结直肠癌发生发展中的作用,有望在其诊断、治疗以及预后评估方面提供新的思路。%Colorectal cancer (CRC) is a major cause of cancer mortality worldwide. In order to achieve early diagnosis and prognosis evaluation of colorectal cancer, there is an urgent need to find tumor markers with high specificity and sensitivity. In recent years, some studies have found that a variety of microRNAs are closely related with colorectal cancer. Among microRNA-106b-25 cluster which include the microRNA-106b, microRNA-93 and microRNA-25 is a typical representative. Over-expressions of these microRNAs not only promote the growth of tumor cells by negatively regulating p21 and p57, and suppress the apoptosis of tumor cells through inhibition of Bim, but also involve in the origin and development of colorectal cancer by inhibiting tumor suppressor gene of RB and PTEN. Furthermore, high expression of microRNA-106b-25 cluster might endue tumor cells with resistance to inhibitory effect of cell growth induced by TGF-β signaling path. Further research on the molecular mechanism of microRNA-106b-25 cluster in colorectal genesis and progression will provide new clue in cancer diagnosis, anticancer therapy and prognosis.

  15. Quality of Life and Mortality of Long-Term Colorectal Cancer Survivors in the Seattle Colorectal Cancer Family Registry.

    Directory of Open Access Journals (Sweden)

    Scott V Adams

    Full Text Available Because most colorectal cancer patients survive beyond five years, understanding quality of life among these long-term survivors is essential to providing comprehensive survivor care. We sought to identify personal characteristics associated with reported quality of life in colorectal cancer survivors, and sub-groups of survivors potentially vulnerable to very low quality of life.We assessed quality of life using the Veterans RAND 12-item Health Survey within a population-based sample of 1,021 colorectal cancer survivors in the Seattle Colorectal Cancer Family Registry, approximately 5 years post-diagnosis. In this case-only study, mean physical component summary scores and mental component summary scores were examined with linear regression. To identify survivors with substantially reduced ability to complete daily tasks, logistic regression was used to estimate odds ratios for "very low" summary scores, defined as a score in the lowest decile of the reference US population. All cases were followed for vital status following QoL assessment, and mortality was analyzed with Cox proportional hazards regression.Lower mean physical component summary score was associated with older age, female sex, obesity, smoking, and diabetes or other co-morbidity; lower mean mental component summary score was associated with younger age and female sex. Higher odds of very low physical component summary score was associated with older age, obesity, less education, smoking, co-morbidities, and later stage at diagnosis; smoking was associated with higher odds of very low mental component summary score. A very low physical component score was associated with higher risk of mortality (hazard ratio (95% confidence interval: 3.97 (2.95-5.34.Our results suggest that identifiable sub-groups of survivors are vulnerable to very low physical components of quality of life, decrements that may represent meaningful impairment in completing everyday tasks and are associated with

  16. Motexafin Gadolinium and Doxorubicin in Treating Patients With Advanced Cancer

    Science.gov (United States)

    2015-09-30

    Breast Cancer; Chronic Myeloproliferative Disorders; Colorectal Cancer; Head and Neck Cancer; Leukemia; Lung Cancer; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic/Myeloproliferative Diseases; Prostate Cancer; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific

  17. TGF β1 expression and angiogenesis in colorectal cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Bin Xiong; Ling-Ling Gong; Feng Zhang; Ming-Bo Hu; Hong-Yin Yuan

    2002-01-01

    AIM: Transforming growth factor(TGF)β1 is involved in avariety of important cellular functions, including cell growthand differentiation, angiogenesis, immune function andextracellular matrix formation. However, the role of TGF β1as an angiogenic factor in colorectal cancer is still unclear.We investigate the relationship between transforming growthfactor β1 and angiogenesis by analyzing the expression oftransforming growth factor(TGF) β1 in colorectal cancer, aswell as its association with VEGF and MVDMETHODS: The expression of TGF β1 、VEGF, as well as MVDwere detected in 98 colorectal cancer by immunohistochemicalstaining. The relationship between the TGF β1 expression andVEGF expression、MVD was evaluated. To evaluate the effect ofTGF β1 on the angiogenesis of colorectal cancers.RESULTS: Among 98 cases of colorectal cancer, 37 werepositive for TGF β1 (37. 8 %),36 for VEGF(36. 7 %),respectively. The microvessel counts ranged from 19 to 139.8, with a mean of 48.7 (standard deviation, 21. 8). Theexpression of TGF β1 was correlated significantly with thedepth of invasion, stage of disease, lymph nodemetastasis, VEGF expression and MVD. Patients in T3-T4,stage Ⅲ-Ⅳ and with lymph node metastasis had muchhigher expression of TGF β1 than patients in T1-T2, stage Ⅰ -Ⅱ and without lymph node metastasis ( P < 0.05).Thepositive expression rate of VEGF (58.3 %) in the TGF-β1positive group is higher than that in the TGF-β1 negativegroup(41.7 %, P< 0.05). Also, the microvessel count (54+ 18) in TGF-β1 positive group is significantly highar thanthat in TGF-β1 negative group (46 + 15, P < 0.05 ). Themicrovessel count in tumors with both TGF-β1 and VEGFpositive were the highest (58 + 20, 36-140, P < 0. 05 ).Whereas that in tumors with both TGF-β1 and VEGF negativewere the lowest (38+ 16, 19-60, P<0.05).CONCLUSION: TGF β1 might be associated with tumorprogression by madulating the angiogenesis in colorectalcancer and TGF β1 may be used as a

  18. c-src activating mutation analysis in Chinese patients with colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Ye-Xiong Tan; Han-Tao Wang; Peng Zhang; Zhong-Hua Yan; Guan-Long Dai; Meng-Chao Wu; Hong-Yang Wang

    2005-01-01

    AIM: To investigate the occurrence of cellular src (c-src)activating mutation at codon 531 in colorectal cancer patients from Chinese mainland.METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay followed by sequencing and single-strand conformation polymorphism analysis were carried out to screen 110 samples of primary colorectal cancer and 20 colorectal liver metastases.RESULTS: Only one sample showed PCR-RFLP-positive results and carried somatic codon 531 mutations. No additional mutation of c-src exon 12 was found.CONCLUSION: c-src codon 531 mutation in colorectal cancer is not the cause of c-src activation.

  19. Apoptotic Versus Angiogenic Factors in Gastric and Colorectal Cancers

    Directory of Open Access Journals (Sweden)

    Enas A Hamed

    2012-04-01

    Conclusions. Gastric-colon malignancy patients exhibited decreased apoptosis, as evident by an increase in antiapoptotic indices, i.e. sFas and bcl-2, and increased angiogenic activity, as evident by enhanced proteolytic activity of cathepsin-D and calpain I and II. These parameters were higher in gastric than colorectal cancers reflecting aggressive behavior of the earlier. Thus, decreased apoptosis and enhanced angiogenesis give growth priority in gastric-colon cancers, and the angiogenic factors and #8217; blockage may delay the tumor and #8217;s spread. [Arch Clin Exp Surg 2012; 1(2.000: 71-84

  20. Frequent occurrence of uniparental disomy in colorectal cancer

    DEFF Research Database (Denmark)

    Andersen, Claus Lindbjerg; Wiuf, Carsten; Kruhøffer, Mogens;

    2007-01-01

      We used SNP arrays to identify and characterize genomic alterations associated with colorectal cancer (CRC). Laser microdissected cancer cells from 15 adenocarinomas were investigated by Affymetrix Mapping 10K SNP arrays. Analysis of the data extracted from the SNP arrays revealed multiple......p). The analysis also showed that genes in regions with increased copy number (including 7p and 20q) were predominantly upregulated. Further analyses of the SNP data revealed a subset of the identified alterations to be specifically associated with TP53 inactivation (including 8q gain and 17p loss...

  1. Evaluation of complement proteins as screening markers for colorectal cancer

    DEFF Research Database (Denmark)

    Storm, Line; Christensen, Ib J; Jensenius, Jens C;

    2015-01-01

    BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Lack of symptoms results in late detection and increased mortality. Inflammation, including complement activation, plays an important role in tumorigenesis. EXPERIMENTAL DESIGN: The concentrations of nine proteins...... of the lectin pathway of the complement system were determined using time-resolved immunofluorometric assays. The first cohort investigated comprised a matched case-control study of 95 patients with CRC, 48 patients with adenomas and 48 individuals without neoplastic findings. Based on the results, Collectin...

  2. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.

    Science.gov (United States)

    zur Hausen, Harald

    2012-06-01

    An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. PMID:22212999

  3. Linkage Analysis in Familial Non-Lynch Syndrome Colorectal Cancer Families from Sweden

    OpenAIRE

    Vinaykumar Kontham; Susanna von Holst; Annika Lindblom

    2013-01-01

    Family history is a major risk factor for colorectal cancer and many families segregate the disease as a seemingly monogenic trait. A minority of familial colorectal cancer could be explained by known monogenic genes and genetic loci. Familial polyposis and Lynch syndrome are two syndromes where the predisposing genes are known but numerous families have been tested without finding the predisposing gene. We performed a genome wide linkage analysis in 121 colorectal families with an increased ...

  4. Pre-Diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women

    OpenAIRE

    Hongmei Nan; Giovannucci, Edward L; Kana Wu; Jacob Selhub; Ligi Paul; Bernard Rosner; Fuchs, Charles S; Eunyoung Cho

    2013-01-01

    BACKGROUND: Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia. METHODS: We evaluated the association between pre-diagnostic leukocyte genomic DNA methylation level and the risk of colorectal cancer in a nested case-control study of 358 colorectal cancer cases and 661 matched controls within the all-female cohort of the Nurses' Health Study (NHS). Among control subjects, we further ...

  5. Effective interventions to facilitate the uptake of breast, cervical and colorectal cancer screening: an implementation guideline

    Science.gov (United States)

    2011-01-01

    implementation guideline to advise on interventions to increase the rate of breast, cervical and colorectal cancer screening. While advancements have been made in these areas of implementation science, more investigations are warranted. PMID:21958602

  6. Effective interventions to facilitate the uptake of breast, cervical and colorectal cancer screening: an implementation guideline

    Directory of Open Access Journals (Sweden)

    Brouwers Melissa C

    2011-09-01

    frameworks, we developed an implementation guideline to advise on interventions to increase the rate of breast, cervical and colorectal cancer screening. While advancements have been made in these areas of implementation science, more investigations are warranted.

  7. Extended pelvic resections for the treatment of locally advanced and recurrent anal canal and colorectal cancer: technical aspects and morbimortality predictors aftet 24 consecutive cases

    Directory of Open Access Journals (Sweden)

    José Wilson Benevides de Mesquita Neto

    2016-04-01

    Full Text Available ABSTRACT Objective: to evaluate the profile of morbidity and mortality and its predictors related to extensive pelvic resections, including pelvic exenteration, to optimize the selection of patients and achieve better surgical results. Methods: we performed 24 major resections for anorectal pelvic malignancy from 2008 to 2015 in the Instituto do Câncer do Ceará. The factors analyzed included age, weight loss, resected organs, total versus posterior exenteration, angiolymphatic and perineural invasion, lymph node metastasis and overall and disease-free survival. Results: the median age was 57 years and the mean follow-up was ten months. Overall morbidity was 45.8%, with five (20.8% serious complications. There were no deaths in the first 30 postoperative days. The median overall survival was 39.5 months, and disease-free survival, 30.7 months. Concomitant resection of the bladder was an isolated prognostic factor for higher risk of complications (87.5% vs. 26.7%, p = 0.009. Angiolymphatic invasion and lymph node metastasis did not reach significance with respect to disease-free survival. Conclusion: treatment of advanced anorectal tumors is challenging, often requiring combined resections, such as cystectomy and sacrectomy, and complex reconstructions. The magnitude of the operation still carries a high morbidity rate, but is a procedure considered safe and feasible, with a low mortality and adequate locoregional tumor control when performed in referral centers.

  8. Clinicoepidemiologic characterization and endoscopy in patients with colorectal cancer

    International Nuclear Information System (INIS)

    Colorectal carcinoma is recognized as the second death cause from cancer in most of developed countries; the increasing exposure to risk factor such as smoking, changes in diet, in lifestyles, as well as environmental and infectious factors is conductive to its morbidity and mortality increase. A prospective and descriptive study was conducted in 65 patients older than 18 years seen from April, 2007 to April, 2008 in the Endoscopy Service of the National Institute of Gastroenterology, diagnosed with colorectal carcinoma by colonoscopy and histology. In collection form were registered: sex, age, personal backgrounds of colon cancer, polyps, intestinal inflammatory disease and cholecystectomy; family backgrounds of colon cancer or another location; toxic habits: smoking and alcoholism; diet as regards: vegetal fiber ingestion and animal fat; anatomic location of cancer and histology. We conclude that there was predominance of female sex, the more frequent diagnosis age was between 60 and 70 years. The personal background of colon polyp and the family background of colon cancer were the more frequent. There was also predominance of smokers and heavy drinkers with or without effect. There was a great ingestion of animal fat and few ingestion of vegetal fiber. The more frequent anatomical location was the rectosygmoid, where the histological colon adenocarcinoma had the greater frequency

  9. Prognostic factors in 165 elderly colorectal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun Nan; Hai-Xia Qin; Guang Yang

    2003-01-01

    AIM: To analyse the prognostic factors in 165 colorectal patients aged ≥70.METHODS: One hundred and sixty-five elderly patients with colorectal cancer diagnosed by histology were entered into the retrospective study between 1994 and 2001. Patients were given optimal operation alone, chemotherapy after operation, or chemotherapy alone according to tumor stage,histology, physical strength, and co-morbid problems.Survival rate was calculated by Kaplan-Meier method, and compared with meaningful variances by Log-rank method.Prognostic factors were analyzed by Cox regression.RESULTS: The 1,2,3,4,5 year survival rate (all-cause rnortality)was 87.76%, 65.96%, 52.05%, 42.77%, 40.51%,respectively. The mean survival time was 41.89±2.33 months (95% CI: 37.33-46.45 months), and the median survival time was 37 months. Univariate analysis showed that factors such as age, nodal metastasis, treatment method, Duke's stage, gross findings, kind of histology, and degree of differentiation had influences on the survival rate. Multivariate analysis showed that factors such as treatment method,Duke's stage, kind of histology and degree of differentiation were independent prognostic factors.CONCLUSION: This study suggests that the prognosis of elderly colorectal cancer patients is influenced by several factors. Most of elderly patients can endure surgery and/or chemotherapy, and have a long-time survival and good quality of life.

  10. [Robotic surgery for colorectal cancer in elderly patients].

    Science.gov (United States)

    Xu, Pingping; Wei, Ye; Xu, Jianmin

    2016-05-25

    The outstanding advantages of robotic surgery include the stable and three-dimension image and the convenience of surgery manipulation. The disadvantages include the lack of factile feedback, high cost and prolonged surgery time. It was reported that robotic surgery was associated with less trauma stress and faster recovery in elderly patients(≥75 years old) when compared with open surgery. Elderly people have a higher incidence of carcinogenesis and also have more comorbidities and reduced functional reserve. Clinical data of patients over 75 years old treated by robotic surgery in Zhongshan Hospital affiliated to Fudan University from March 2011 to October 2014 were analyzed retrospectively. A total of 24 consecutive patients were included with a median age of 77.8 years old. There were 18 male and 6 female patients. Among them, 14 patients were diagnosed with descending and sigmoid colon cancers while 10 with rectal cancers; 19 had tumor size larger than 5 cm; 16 were diagnosed with ulcerative adenocarcinoma. Fourteen patients were complicated with hypertension, 6 with cardiopulmonary diseases, 4 with diabetes mellitus and 3 with cerebrovascular diseases. Twenty-two patients underwent low anterior resection and 2 abdominoperineal resection. The estimated blood loss was 85 ml; the median operation time was (123.1±45.2) min; the median number of retrieved lymph node was 12.4. Postoperative pathologic results showed that 3 patients were stageI(, 10 stageII(, and 11 stageIII(. Postoperative complication was observed in 3 patients: urinary infection in 1 case, intraperitoneal infection in 1 case and atria fibrillation in 1 case, respectively. Median time to first postoperative flatus was 2.8 days. Our results indicated that robotic surgery is safe and feasible in the elderly patients. The next generation of robotic system may make up for these deficiencies through new technologies. With the advantage of more advanced surgical simulator, robotic surgery will play a

  11. Serum 25-hydroxyvitamin D, vitamin D binding protein and risk of colorectal cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Weinstein, Stephanie J; Purdue, Mark P; Smith-Warner, Stephanie A; Mondul, Alison M; Black, Amanda; Ahn, Jiyoung; Huang, Wen-Yi; Horst, Ronald L; Kopp, William; Rager, Helen; Ziegler, Regina G; Albanes, Demetrius

    2015-03-15

    The potential role of vitamin D in cancer prevention has generated substantial interest, and laboratory experiments indicate several anti-cancer properties for vitamin D compounds. Prospective studies of circulating 25-hydroxyvitamin D [25(OH)D], the accepted biomarker of vitamin D status, suggest an inverse association with colorectal cancer risk, but with some inconsistencies. Furthermore, the direct or indirect impact of the key transport protein, vitamin D binding protein (DBP), has not been examined. We conducted a prospective study of serum 25(OH)D and DBP concentrations and colorectal cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, based on 476 colorectal cancer cases and 476 controls, matched on age, sex, race and date of serum collection. All subjects underwent sigmoidoscopic screening at baseline and once during follow-up. Conditional logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Circulating 25(OH)D was inversely associated with colorectal cancer (OR = 0.60, 95% CI 0.38-0.94 for highest versus lowest quintile, p trend 0.01). Adjusting for recognized colorectal cancer risk factors and accounting for seasonal vitamin D variation did not alter the findings. Neither circulating DBP nor the 25(OH)D:DBP molar ratio, a proxy for free circulating 25(OH)D, was associated with risk (OR = 0.82, 95% CI 0.54-1.26, and OR = 0.79, 95% CI 0.52-1.21, respectively), and DBP did not modify the 25(OH)D association. The current study eliminated confounding by colorectal cancer screening behavior, and supports an association between higher vitamin D status and substantially lower colorectal cancer risk, but does not indicate a direct or modifying role for DBP. PMID:25156182

  12. Role of APC and DNA mismatch repair genes in the development of colorectal cancers

    Directory of Open Access Journals (Sweden)

    Roy Deodutta

    2003-12-01

    Full Text Available Abstract Colorectal cancer is the third most common cause of cancer-related death in both men and women in the western hemisphere. According to the American Cancer Society, an estimated 105,500 new cases of colon cancer with 57,100 deaths will occur in the U.S. in 2003, accounting for about 10% of cancer deaths. Among the colon cancer patients, hereditary risk contributes approximately 20%. The main inherited colorectal cancers are the familial adenomatous polyposis (FAP and the hereditary nonpolyposis colorectal cancers (HNPCC. The FAP and HNPCC are caused due to mutations in the adenomatous polyposis coli (APC and DNA mismatch repair (MMR genes. The focus of this review is to summarize the functions of APC and MMR gene products in the development of colorectal cancers.

  13. Nanoscale/Molecular analysis of Fecal Colonocytes for Colorectal Cancer Screening | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Existing guidelines recommend colorectal cancer (CRC) screening for all patients over age 50. However, CRC remains the second leading cause of cancer death among Americans largely because colonoscopic screening of all the >100 million Americans over age 50 is unfeasible for both patient-related (non-compliance) and societal (inadequate endoscopic capacity and funding) reasons. |

  14. Manipulation of DNA Repair Proficiency in Mouse Models of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Michael A. Mcilhatton

    2016-01-01

    Full Text Available Technical and biological innovations have enabled the development of more sophisticated and focused murine models that increasingly recapitulate the complex pathologies of human diseases, in particular cancer. Mouse models provide excellent in vivo systems for deciphering the intricacies of cancer biology within the context of precise experimental settings. They present biologically relevant, adaptable platforms that are amenable to continual improvement and refinement. We discuss how recent advances in our understanding of tumorigenesis and the underlying deficiencies of DNA repair mechanisms that drive it have been informed by using genetically engineered mice to create defined, well-characterized models of human colorectal cancer. In particular, we focus on how mechanisms of DNA repair can be manipulated precisely to create in vivo models whereby the underlying processes of tumorigenesis are accelerated or attenuated, dependent on the composite alleles carried by the mouse model. Such models have evolved to the stage where they now reflect the initiation and progression of sporadic cancers. The review is focused on mouse models of colorectal cancer and how insights from these models have been instrumental in shaping our understanding of the processes and potential therapies for this disease.

  15. Manipulation of DNA Repair Proficiency in Mouse Models of Colorectal Cancer.

    Science.gov (United States)

    Mcilhatton, Michael A; Boivin, Gregory P; Groden, Joanna

    2016-01-01

    Technical and biological innovations have enabled the development of more sophisticated and focused murine models that increasingly recapitulate the complex pathologies of human diseases, in particular cancer. Mouse models provide excellent in vivo systems for deciphering the intricacies of cancer biology within the context of precise experimental settings. They present biologically relevant, adaptable platforms that are amenable to continual improvement and refinement. We discuss how recent advances in our understanding of tumorigenesis and the underlying deficiencies of DNA repair mechanisms that drive it have been informed by using genetically engineered mice to create defined, well-characterized models of human colorectal cancer. In particular, we focus on how mechanisms of DNA repair can be manipulated precisely to create in vivo models whereby the underlying processes of tumorigenesis are accelerated or attenuated, dependent on the composite alleles carried by the mouse model. Such models have evolved to the stage where they now reflect the initiation and progression of sporadic cancers. The review is focused on mouse models of colorectal cancer and how insights from these models have been instrumental in shaping our understanding of the processes and potential therapies for this disease. PMID:27413734

  16. KRAS mutational status as a predictor of epidermal growth factor receptor inhibitor efficacy in colorectal cancer.

    Science.gov (United States)

    Baynes, Roy D; Gansert, Jennifer

    2009-01-01

    Inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated promising potential in the treatment of advanced colorectal cancer. However, a proportion of patients do not respond to therapy with EGFR inhibitors, and therefore, there has been interest in identifying those patients most likely to benefit from therapy with these agents. KRAS, a member of the RAS family of signaling proteins, plays an important role in EGFR-mediated regulation of cellular proliferation and survival. Although there is still some debate regarding the prognostic importance of KRAS mutations in patients with metastatic colorectal cancer, several recent phase 2 and 3 studies have identified the presence of mutations at codons 12 and 13 of KRAS as predictors of poor response to the anti-EGFR monoclonal antibodies panitumumab and cetuximab. Patients with wild-type KRAS were found to have significantly better progression-free survival, overall survival, and/or objective response rate compared with patients harboring KRAS mutations. As a result, there has been growing interest in the development of KRAS mutational status as a biomarker for predicting patient response to EGFR-targeted therapy. Screening colorectal tumors for the absence of KRAS mutations may help identify patients most likely to benefit from anti-EGFR therapies.

  17. Referral patterns of patients with liver metastases due to colorectal cancer for resection.

    LENUS (Irish Health Repository)

    Al-Sahaf, O

    2012-02-01

    INTRODUCTION: Colorectal carcinoma accounts for 10% of cancer deaths in the Western World, with the liver being the most common site of distant metastases. Resection of liver metastases is the treatment of choice, with a 5-year survival rate of 35%. However, only 5-10% of patients are suitable for resection at presentation. AIMS: To examine the referral pattern of patients with liver metastases to a specialist hepatic unit for resection. METHODOLOGY: Retrospective review of patient\\'s charts diagnosed with colorectal liver metastases over a 10-year period. RESULTS: One hundred nine (38 women, 71 men) patients with liver metastases were included, mean age 61 years; 79 and 30 patients had synchronous and metachronus metastases, respectively. Ten criteria for referral were identified; the referral rate was 8.25%, with a resection rate of 0.9%. Forty two percent of the patients had palliative chemotherapy; 42% had symptomatic treatment. CONCLUSION: This study highlights the advanced stage of colorectal cancer at presentation; in light of modern evidence-based, centre-oriented therapy of liver metastasis, we conclude that criteria of referral for resection should be based on the availability of treatment modalities.

  18. Loss of heterozygosity: An independent prognostic factor of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Shih-Ching Chang; Jen-Kou Lin; Tzu-Chen Lin; Wen-Yih Liang

    2005-01-01

    AIM: Colorectal cancers result from the accumulation of several distinct genetic alterations. This study was to investigate the frequency and prognostic value of loss of heterozygosity (LOH) and microsatellite instability (MSI) at 14 genetic loci located near or within regions containing important genes implicated in colorectal tumorigenesis.METHODS: We studied colorectal cancers with corresponding normal mucosae in 207 patients (139 males and 68 females,mean age at the time of tumor resection 66.2±12.4 years,range 22-88 years). There were 37 right-sided colonic tumors, 85 left-sided colonic tumors and 85 rectal tumors.The distribution of tumor staging was stage Ⅰ in 25, stage Ⅱ in 73, stage Ⅲ in 68, and stage Ⅳ in 41. We analyzed the LOH and MSI of HPC1, hMSH2, hMLH1, APC, MET,P53, NH23-H1, DCC, BAT25, BAT26, D17S250, MYCL1 and D8S254 with fluorescent polymerase chain reaction and denatured gel electrophoresis. High-frequency LOH was determined to be greater than three, or more than 50%of the informative marker with LOH. High-frequency MSI (MSI-H) was determined as more than four markers with instability (>30%). Correlations of LOH and MSI with clinical outcomes and pathological features were analyzed and compared.RESULTS: The occurrence of MSI-H was 7.25%, located predominantly in the right colons (7/15) and had a higher frequency of poor differentiation (6/15) and mucin production (7/15). LOH in at least one genetic locus occurred in 78.7% of the tumors and was significantly associated with disease progression. Of the 166 potentially cured patients, 45 developed tumor recurrence within 36 mo of follow-up. Clinicopathological factors affecting 3-year disease-free survival (DFS) were TNM staging, grade of differentiation, preoperative CEA level, and high LOH status. Patients with high LOH tumors had a significantly lower DFS (50%) compared with patients with low LOH tumors (84%). Of the patients developing subsequent tumor recurrence, the number and

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  20. Public Awareness of Colorectal Cancer Screening: Knowledge, Attitudes, and Interventions for Increasing Screening Uptake

    Science.gov (United States)

    Gimeno Garcia, Antonio Z.; Hernandez Alvarez Buylla, Noemi; Nicolas-Perez, David; Quintero, Enrique

    2014-01-01

    Colorectal cancer ranks as one of the most incidental and death malignancies worldwide. Colorectal cancer screening has proven its benefit in terms of incidence and mortality reduction in randomized controlled trials. In fact, it has been recommended by medical organizations either in average-risk or family-risk populations. Success of a screening campaign highly depends on how compliant the target population is. Several factors influence colorectal cancer screening uptake including sociodemographics, provider and healthcare system factors, and psychosocial factors. Awareness of the target population of colorectal cancer and screening is crucial in order to increase screening participation rates. Knowledge about this disease and its prevention has been used across studies as a measurement of public awareness. Some studies found a positive relationship between knowledge about colorectal cancer, risk perception, and attitudes (perceived benefits and barriers against screening) and willingness to participate in a colorectal cancer screening campaign. The mentioned factors are modifiable and therefore susceptible of intervention. In fact, interventional studies focused on average-risk population have tried to increase colorectal cancer screening uptake by improving public knowledge and modifying attitudes. In the present paper, we reviewed the factors impacting adherence to colorectal cancer screening and interventions targeting participants for increasing screening uptake. PMID:24729896

  1. Dietary fiber intake and risk of colorectal cancer: A pooled analysis of prospective cohort studies

    NARCIS (Netherlands)

    Park, Y.; Hunter, D.J.; Spiegelman, D.; Bergkvist, L.; Berrino, F.; Brandt, P.A. van den; Buring, J.E.; Colditz, G.A.; Freudenheim, J.L.; Fuchs, C.S.; Giovannucci, E.; Goldbohm, R.A.; Graham, S.; Harnack, L.; Hartman, A.M.; Jacobs, D.R.; Kato, I.; Krogh, V.; Leitzmann, M.F.; McCullough, M.L.; Miller, A.B.; Pietinen, P.; Rohan, T.E.; Schatzkin, A.; Willett, W.C.; Wolk, A.; Zeleniuch-Jacquotte, A.; Zhang, S.M.; Smith-Warner, S.A.

    2005-01-01

    Context: Inconsistent findings from observational studies have continued the controversy over the effects of dietary fiber on colorectal cancer. Objective: To evaluate the association between dietary fiber intake and risk of colorectal cancer. Design, Setting, and Participants: From 13 prospective c

  2. Public stated preferences and predicted uptake for genome-based colorectal cancer screening

    NARCIS (Netherlands)

    Groothuis-Oudshoorn, Catharina G.M.; Fermont, Jilles M.; Til, van Janine A.; IJzerman, Maarten J.

    2014-01-01

    Background Emerging developments in nanomedicine allow the development of genome-based technologies for non-invasive and individualised screening for diseases such as colorectal cancer. The main objective of this study was to measure user preferences for colorectal cancer screening using a nanopill.

  3. Colorectal cancer risk and dyslipidemia: a case-cohort study nested in an Italian multicentre cohort

    NARCIS (Netherlands)

    Agnoli, C.; Grioni, S.; Sieri, S.; Sacerdote, C.; Vineis, P.; Tumino, R.; Giurdanella, M.C.; Pala, V.; Mattiello, A.; Chiodini, P.; Iacoviello, L.; Curtis, de A.; Cattaneo, L.; Duijnhoven, van F.J.B.

    2014-01-01

    Background: Dyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers. Methods: We conducted a

  4. Plasma Fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer

    DEFF Research Database (Denmark)

    Nimptsch, Katharina; Aleksandrova, Krasimira; Boeing, Heiner;

    2015-01-01

    Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the associ...

  5. Colorectal cancers detected through screening are associated with lower stages and improved survival

    DEFF Research Database (Denmark)

    Lindebjerg, Jan; Osler, Merete; Bisgaard, Claus

    2014-01-01

    INTRODUCTION: Population screening for colorectal cancer (CRC) using faecal occult blood test (FOBT) will be introduced in Denmark in 2014. Prior to the implementation of the screening programme, a feasibility study was performed in 2005-2006. In this paper, occurrences of colorectal cancer...

  6. Fluid intake and colorectal cancer risk in the Netherlands cohort study

    NARCIS (Netherlands)

    Simons, C.C.J.M.; Leurs, L.J.; Weijenberg, M.P.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2010-01-01

    Total fluid intake, specifically water intake, has been suggested to protect against colorectal cancer. We examined the association of total fluid intake with colorectal cancer endpoints and possible effect modification by fiber intake within the Netherlands Cohort Study (N = 120,852). We also inves

  7. The Association of Perceived Provider-Patient Communication and Relationship Quality with Colorectal Cancer Screening

    Science.gov (United States)

    Underhill, Meghan L.; Kiviniemi, Marc T.

    2012-01-01

    Background: Two-thirds of adults aged 50 years and older are adherent to recommendations for colorectal cancer screening. Provider-patient communication and characteristics of the patient-provider relationship may relate to screening behavior. Methods: The association of provider communication quality, relationship, and colorectal cancer screening…

  8. Urine Metabolite Profiling of Human Colorectal Cancer by Capillary Electrophoresis Mass Spectrometry Based on MRB

    Directory of Open Access Journals (Sweden)

    Jin-Lian Chen

    2012-01-01

    (P<0.05. Conclusion. The technique of capillary electrophoresis mass spectrometry based on MRB could reveal the significant metabolic alterations during progression of colorectal cancer, and the method is feasible and may be useful for the early diagnosis of colorectal cancer.

  9. Dairy foods, calcium, and colorectal cancer: A pooled analysis of 10 cohort studies

    NARCIS (Netherlands)

    Cho, E.; Smith-Warner, S.A.; Spiegelman, D.; Beeson, W.L.; Brandt, P.A. van den; Colditz, G.A.; Folsom, A.R.; Fraser, G.E.; Freudenheim, J.L.; Giovannucci, E.; Goldbohm, R.A.; Graham, S.; Miller, A.B.; Pietinen, P.; Potter, J.D.; Rohan, T.E.; Terry, P.; Toniolo, P.; Virtanen, M.J.; Willet, W.C.; Wolk, A.; Wu, K.; Yaun, S.-S.; Zeleniuch-Jacquotte, A.; Hunter, D.J.

    2004-01-01

    Background: Studies in animals have suggested that calcium may reduce the risk of colorectal cancer. However, results from epidemiologic studies of intake of calcium or dairy foods and colorectal cancer risk have been inconclusive. Methods: We pooled the primary data from 10 cohort studies in five c

  10. Prediagnostic plasma vitamin B6 (pyridoxal 50-phosphate) and survival in patients with colorectal cancer

    Science.gov (United States)

    Higher plasma pyridoxal 5'-phosphate (PLP) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma PLP on survival of patients with colorectal cancer is unknown. We prospectively examined whether prediagnostic plasma PLP levels are associated with mortality...

  11. Diverging trends in colorectal cancer morbidity and mortality. Earlier diagnosis comes at a price

    NARCIS (Netherlands)

    L.G.A. Bonneux (Luc); J.J.M. Barendregt (Jan); C.W.N. Looman (Caspar); P.J. van der Maas (Paul)

    1995-01-01

    textabstractIn developed countries, time trends in the incidence of colorectal cancer differ markedly from trends in mortality. This study sought to explain simultaneously changes in both colorectal cancer incidence and mortality. Data on first admissions, interventions and outcome from the national

  12. The CHEK2 1100delC variant in Swedish colorectal cancer

    DEFF Research Database (Denmark)

    Djureinovic, Tatjana; Lindblom, Annika; Dalén, Johan;

    2007-01-01

    BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. PATIENTS AND METHODS: To evaluate the role o...

  13. Mendelian Randomization Study of Body Mass Index and Colorectal Cancer Risk

    DEFF Research Database (Denmark)

    Thrift, Aaron P.; Gong, Jian; Peters, Ulrike;

    2015-01-01

    the causal association between BMI and colorectal cancer. Methods: We used data from 10,226 colorectal cancer cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study–identified variants associated...

  14. Differential CARM1 expression in prostate and colorectal cancers

    Directory of Open Access Journals (Sweden)

    Nguyen Nguyen

    2010-05-01

    Full Text Available Abstract Background Coactivator-associated arginine methyltransferase 1 (CARM1 functions as a transcriptional coactivator of androgen receptor (AR-mediated signaling. Correspondingly, overexpression of CARM1 has been associated with the development of prostate cancer (PCa and its progression to androgen-independent PCa. In our preliminary study, however, the promoting effects of CARM1, with regard to androgen-stimulated AR target gene expression were minimal. These results suggested that the AR target gene expression associated with CARM1 may result primarily from non-hormone dependent activity. The goal of this study was to confirm the pattern of expression of CARM1 in human tumors and determine the mechanism of action in CARM1 overexpressed tumors. Methods Tissue microarray was used to determine the pattern of expression of CARM1 in human cancers by immunohistochemistry. CARM1 expression was also evaluated in prostate and colorectal surgical specimens and the clinical records of all cases were reviewed. In addition, a reporter transcription assay using the prostate-specific antigen (PSA promoter was used to identify the signaling pathways involved in non-hormone-mediated signal activation associated with CARM1. Results The tissue microarray showed that CARM1 was particularly overexpressed in the colorectal cancers while CARM1 expression was not prevalent in the prostate and breast cancers. Further studies using surgical specimens demonstrated that CARM1 was highly overexpressed in 75% of colorectal cancers (49 out of 65 but not in the androgen-independent PCa. In addition, CARM1's coactivating effect on the entire PSA promoter was very limited in both androgen-dependent and androgen-independent PCa cells. These results suggest that there are other factors associated with CARM1 expression in PSA regulation. Indeed, CARM1 significantly regulated both p53 and NF-κB target gene transcription. Conclusions The results of this study suggest that, in

  15. Patients’ perspectives on palliative chemotherapy of colorectal and non - colorectal cancer: a prospective study in a chemotherapy- experienced population

    International Nuclear Information System (INIS)

    A better understanding of patients’ views on the benefit and burden obtained from palliative chemotherapy would facilitate shared decision making. We evaluated palliative cancer patients’ reported outcomes (PROs) for toxicity and investigated the survival threshold for which they would repeat chemotherapy (CTx). Patients who had received a minimum of three months of palliative CTx for advanced colorectal (CRC) or non-colorectal (non-CRC: upper gastrointestinal, lung and head-and-neck) cancer were assessed by questionnaire. Patients were questioned about PROs for toxicity, subjective burden from side effects, and were asked for the survival threshold necessary for them to repeat CTx. Expected survival (sum of indicated survival threshold and median survival time with best supportive care) was compared to the patients’ actual survival. One hundred and thirty-four patients (CRC: 58; non-CRC: 76) were surveyed. The most frequent PRO- grade 3/4 toxicities were acne (12.8%), fatigue (9.0%), and diarrhea (8.5%). The symptom causing the highest subjective burden was fatigue and was worse than expected in 29.9% of the patients. The median survival threshold for which patients would repeat CTx was significantly longer in CRC than in non-CRC patients (p=0.01). Median expected survival was significantly longer than actual median survival (CRC: 44.0 months [22.0-65.9] compared with 30.0 months of actual survival [20.9-39.1]; non-CRC: 22.0 months [15.3-28.6] compared with 19.0 months of actual survival [15.1-22.9], p=0.03). Fatigue deserves more attention when toxicity of treatment and symptoms of disease are explained to patients. Patients’ survival expectations from palliative chemotherapy are higher than previously described, exceed the median survival time known from phase III trials, and are significantly longer than their actual survival

  16. Clinical and biological characteristics of colorectal cancer with familial predisposition

    Institute of Scientific and Technical Information of China (English)

    WU Bao-ping; ZHANG Ya-li; ZHOU Dian-yuan; GAO Chun-fang; LAI Zhuo-sheng

    2001-01-01

    To evaluate the microsatellite instability (MSI), expression of mismatch repair (MMR) gene (hMLH1, hMSH2) and proliferation kinetics in colorectal cancer (CRC) with familial predisposition. Method:Forty-six cases of CRC were studied using silver staining polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, streptavidin-peroxidase (SP) immunohistochemical method and flow cytometry. Results: In CRC patients with familial predisposition, the MSI-positive rate was higher than in sporadic CRC (P<0.05). Familial predisposition and positive MSI were strongly related to early age of cancer onset, the proclivity for proximal colonic cancer, poor differentiated and extracolorectaln malignancies (P<0.01, P<0.05). The incidence of negative expression ofhMLH1 in tumor tissue and hMLH1, hMSH2 in normal colorectal tissues was significantly higher (P<0.05). The negative expression of hMLH1 together with hMSH2 was related with positive MSI (P<0.05).In MSI-positive CRC cells, the proliferation cell nucleus antigen (PCNA) expression, proliferation index and S-phase cells decreased obviously (P<0.01, P<0.05). Conclusion: In CRC with familial predisposition, MSI might be an important contributor. The rate ofhMLH1 and hMSH2 mutation increased in tumor and normal tissue, and the proliferation activity of their cancer cell was lower.

  17. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    Science.gov (United States)

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  18. Effect of onion flavonoids on colorectal cancer with hyperlipidemia: an in vivo study

    Directory of Open Access Journals (Sweden)

    He Y

    2014-01-01

    Full Text Available Yongshan He,1,* Heiying Jin,1,* Wei Gong,2,* Chunxia Zhang,1 Acheng Zhou1 1National Center of Colorectal Surgery, Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, People's Republic of China; 2Department of Surgery, Jiangyin Hospital of Traditional Chinese Medicine, Jiangyin, People's Republic of China *These authors contributed equally to this work Objectives: This study aims to find the effect of onion's extraction on the colorectal cancer with hyperlipidemia. Method: We established a hyperlipidemia-subcutaneously heterotopic colorectal cancer orthotopic transplant model and fed mice a high fat diet and performing transplantation. Animal models were treated with capecitabine and/or simvastatin and low-, middle-, high- dose of onion's extraction and both tumor growth rate and blood lipid levels were monitored. Results: We found that colorectal cancer in onion's extraction groups was significantly inhibited, and the effect of high dose of onion's extraction was equivalent to capecitabine. Onion's extraction effectively decreased levels of apoB and TC. Conclusion: Our study established a hyperlipidemia colon tumor model involving subcutaneous colon translocation and orthotopic transplantation, this model was an ideal research model for mutual influence of hyperlipidemia and colorectal cancer. Onion's extraction could inhibit the proliferation of colorectal cancer; the function of the high-dose of onion's extraction was fairly to capecitabine, which provided a new direction in protecting and treating colorectal cancer. Keywords: colorectal cancer, hyperlipidemia, onion flavonoids, capecitabine, simvastatin

  19. Colorectal cancer in Denmark 1943-1997

    DEFF Research Database (Denmark)

    Thygesen, Lau C; Grønbaek, Morten; Johansen, Christoffer

    2004-01-01

    PURPOSE: This article reports the incidence rates of colon and rectal cancer in Denmark during 55 years of data registration and estimates the number of cases identified attributable to four modifiable risk factors and potentially preventable. METHODS: On the basis of reports in the nationwide...... rate of rectal cancer was observed for both genders, but the incidence rate among males was higher than that among females. The proportion of cases that could have been prevented if the Danish population had not been exposed to the four known risk factors varied from 0 to 15 percent for each...... of the four risk factors. CONCLUSIONS: This study shows that the incidence rate of colon cancer has increased, whereas that of rectal cancer has decreased in Denmark during 55 years of observation. The potentially preventable proportions of incident cases are substantial but not as high as might have been...

  20. Engaging Health Systems to Increase Colorectal Cancer Screening: Community–Clinical Outreach in Underserved Areas of Wisconsin

    OpenAIRE

    LoConte, Noelle K.; Weeth-Feinstein, Lauren; Conlon, Amy; Scott, Sheryl

    2013-01-01

    Background Colorectal cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer-related death in Wisconsin. Incidence and mortality rates for colorectal cancer vary by age, race/ethnicity, geography, and socioeconomic status. From 2010 through 2012, the Wisconsin Comprehensive Cancer Control Program awarded grants to 5 regional health systems for the purpose of planning and implementing events to increase colorectal cancer screening rates in underserved commun...