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Sample records for experimental colorectal carcinoma

  1. Metachronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Bülow, Steffen; Svendsen, L B; Mellemgaard, A

    1990-01-01

    During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

  2. Metastatic paediatric colorectal carcinoma.

    LENUS (Irish Health Repository)

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  3. Tumor budding in colorectal carcinomas.

    Science.gov (United States)

    Sert Bektaş, Sevda; Inan Mamak, Gülsün; Cırış, Ibrahim Metin; Bozkurt, Kemal Kürşat; Kapucuoğlu, Nilgün

    2012-01-01

    In colorectal carcinomas, tumor budding has been defined as the presence of isolated single tumor cells or small cell clusters in the stroma at the invasive tumor margin. In this study, the relationship between tumor budding density at the invasive tumor margin and pathological parameters is investigated. Haematoxylin and eosin stained slides of 73 cases with colorectal carcinoma were retrospectively evaluated for the presence and intensity of tumor budding by 2 observers. After the specimens were assessed, the highest density of tumor budding area was counted in a microscopic field of x200. Cases were separated into 2 groups according to tumor budding density as low grade ( tumor invasion, histological grade, vascular invasion and lymph node involvement was investigated. Of the 73 colorectal carcinoma cases, 33 (45.2%) had low and 40 (54.8%) had high grade tumor budding density, respectively. There was a statistically significant relationship between high grade tumor budding density and histological grade (p=0.042), lymph node involvement (p=0.0001) and vascular invasion (p=0.0034). High grade tumor budding density is associated with aggressive phenotypical features in colorectal carcinoma.

  4. Preoperative hypoxyradiotherapy of colorectal carcinoma

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    Tacev, T.; Skricka, T.; Zaloudik, J.; Pacovsky, Z. [Masaryk Memorial Cancer Inst., Brno (Czech Republic)

    2002-12-01

    Aim: The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. Patients and Methods: In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplan-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A: four patients, B: 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was performed extending from the perineum to the L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). Results: Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-uper period of 6-105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of 61.5% and a local relapse

  5. Colorectal carcinoma with dome-like phenotype: an under-recognised subset of colorectal carcinoma?

    DEFF Research Database (Denmark)

    Asmussen, L; Pachler, J; Holck, S

    2008-01-01

    The term dome carcinoma has been applied to a variant of colorectal carcinoma, thought to derive from M-cells of the gut-associated lymphoid tissue. Its distinguishing morphological features include a non-polypoid plaque-like lesion composed of closely apposed cystically dilated glands lined...

  6. The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma

    NARCIS (Netherlands)

    Dove-Edwin, Isis; Boks, Dominique; Goff, Sheila; Kenter, Gemma G.; Carpenter, Robert; Vasen, Hans F. A.; Thomas, Huw J. W.

    2002-01-01

    BACKGROUND: Endometrial carcinoma is the most common extracolonic malignancy associated with hereditary nonpolyposis colorectal carcinoma syndrome (HNPCC). The risk of endometrial carcinoma in HNPCC mutation carriers is approximately ten times that of the general population, and endometrial

  7. Colorectal Carcinoma in Children and Young Adults in Ilorin, Nigeria ...

    African Journals Online (AJOL)

    Background: Colorectal carcinoma is thought to be rare among children and young adults among whom presentation is usually at a late stage with poor prognosis. Objective: To review the demography, clinical presentation, morphology, and pathological stage of cases of colorectal carcinomas diagnosed in the children and ...

  8. Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma

    OpenAIRE

    Kir, Gozde; Gurbuz, Ayse; Karateke, Ates; Kir, Mustafa

    2010-01-01

    Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the dif...

  9. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Mei-Ying Zhang

    2014-08-01

    Full Text Available Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05. According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM than adenoma and carcinoma (p < 0.05. Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05. Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05, but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM staging, differentiation or serum carcinoembryonic antigen (CEA concentration (p > 0.05. Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05. Cox’s model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05. It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

  10. Colorectal carcinoma in Port Harcourt | Adotey | Port Harcourt ...

    African Journals Online (AJOL)

    Colorectal carcinoma in Port Harcourt. ... Methodology: Patients treated for colorectal cancer at the UPTH over a 19- year period (1987-2006) and had complete information, were studied. Data were collected ... Other indices studied were treatment, postoperative complications, duration of hospital stay and outcome/mortality.

  11. p53 expression in colorectal carcinoma in relation to ...

    African Journals Online (AJOL)

    Background: It has been shown that colorectal carcinoma is increasing in incidence in African countries. This could be due to change in life style. Molecular pathogenesis of colorectal cancer commonly involves mutation in p53 gene which leads to expression of p53 protein in tumor cells. Expression of p53 protein has been ...

  12. Rectal carcinoma after radiotherapy for cervical carcinoma in patients with a family history of colorectal carcinoma: report of two cases.

    Science.gov (United States)

    Melichar, B; Ryska, A; Krepelová, A; Holecková, P

    2007-01-01

    Rectal carcinoma is a rare, but well documented late complication of pelvic irradiation. Little is known about the factors predisposing to the development of radiation-associated rectal carcinoma. We present two patients who developed rectal carcinoma 17 and 26 years after radiotherapy for carcinoma of the uterine cervix. In one patient, mutation in exon 4 of the hMLH1 gene was detected. Radiation-associated rectal carcinoma represents a rare late toxicity of radiotherapy for cervical carcinoma that may occur in patients with a family history of colorectal carcinoma, including hereditary non-polyposis colorectal cancer.

  13. Prognostic value of DNA image cytometry in colorectal carcinoma.

    Science.gov (United States)

    Sampedro, A; Urdiales, G; Martínez-Nistal, A; Riera, J; Hardisson, D

    1996-06-01

    To investigate the diagnostic sensitivity and prognosis predicting of DNA image cytometry in colorectal carcinoma. We studied the ploidy status and other DNA cytometric parameters in 68 patients with colorectal carcinoma. In addition, clinical-histologic and follow-up information was collected for at least five years. DNA histograms were available in all cases, showing a diploid DNA distribution pattern in 6 (8.8%), tetraploid in 21 (30.9%), hyperdiploid in 20 (29.4%) and hypertetraploid in 21 (30.9%). The differences in the correlation study between cytometric parameters and pathologic features were not statistically significant. Ploidy status and DNA malignancy grade were individually related to five-year survival (P < .005 and P < .05). The data show that DNA image cytometry can provide valuable prognostic information on colorectal carcinomas and may prove useful in guiding adjuvant therapy in these patients.

  14. Colorectal carcinoma in childhood: a retrospective multicenter study.

    Science.gov (United States)

    Kravarusic, Dragan; Feigin, Elad; Dlugy, Elena; Steinberg, Ran; Baazov, Arthur; Erez, Ilan; Lazar, Ludvig; Kapuller, Vadim; Grunspan, Moshe; Ash, Shifra; Freud, Enrique

    2007-02-01

    Colorectal carcinoma, a common adult malignancy, has an estimated childhood incidence of 0.3 to 1.5/million in Western countries and 0.2/million in Israel. Diagnosis is difficult because adult screening measures are unfeasible in children. The tumor is frequently associated with predisposing genetic factors, aggressive biological behavior, and poor prognosis. The aim of this multicenter study was to document the clinical profile, treatment and prognosis of colorectal carcinoma in children in Israel. The clinical, laboratory, therapeutic, and prognostic parameters of all 7 children from 4 medical centers in Israel who were diagnosed with colorectal carcinoma over a 25-y period were reviewed. Patients presented with rectal bleeding (4 of 7), abdominal pain (2 of 7), and abdominal distension (2 of 7). Average time to diagnosis was 6 months. Six patients underwent surgery (1 refused), and 5 received chemotherapy. Histopathological studies showed poorly differentiated mucinous adenocarcinoma, signet-ring type, in 4 cases, moderately differentiated adenocarcinoma in 2, and well-differentiated carcinoma in 1. Three patients died of the disease, 2 shortly after diagnosis. One patient with recurrent metastatic disease was lost to follow-up. Colorectal carcinoma in children is characterized by aggressive tumor behavior and delayed diagnosis, resulting in a worse prognosis than in adults. Heightened physician awareness of the possibility of this disease in children, with special attention to adolescents with predisposing factors and rectal bleeding, could help to improve outcome.

  15. A cost-effectiveness analysis of colorectal screening of hereditary nonpolyposis colorectal carcinoma gene carriers

    NARCIS (Netherlands)

    Vasen, HFA; van Ballegooijen, M; Buskens, E; Kleibeuker, JK; Taal, BG; Griffioen, G; Nagengast, FM; Menko, FH; Khan, PM

    1998-01-01

    BACKGROUND. It has been estimated that the prevalence of carriers of a mutated mismatch repair (MMR) gene among the general population in Western countries is between 5 and 50 per 10,000. These carriers have a risk of >85% of developing colorectal carcinoma (CRC) and therefore need careful

  16. Tumor budding in colorectal carcinoma: time to take notice.

    Science.gov (United States)

    Mitrovic, Bojana; Schaeffer, David F; Riddell, Robert H; Kirsch, Richard

    2012-10-01

    Tumor 'budding', loosely defined by the presence of individual cells and small clusters of tumor cells at the invasive front of carcinomas, has received much recent attention, particularly in the setting of colorectal carcinoma. It has been postulated to represent an epithelial-mesenchymal transition. Tumor budding is a well-established independent adverse prognostic factor in colorectal carcinoma that may allow for stratification of patients into risk categories more meaningful than those defined by TNM staging, and also potentially guide treatment decisions, especially in T1 and T3 N0 (Stage II, Dukes' B) colorectal carcinoma. Unfortunately, its universal acceptance as a reportable factor has been held back by a lack of definitional uniformity with respect to both qualitative and quantitative aspects of tumor budding. The purpose of this review is fourfold: (1) to describe the morphology of tumor budding and its relationship to other potentially important features of the invasive front; (2) to summarize current knowledge regarding the prognostic significance and potential clinical implications of this histomorphological feature; (3) to highlight the challenges posed by a lack of data to allow standardization with respect to the qualitative and quantitative criteria used to define budding; and (4) to present a practical approach to the assessment of tumor budding in everyday practice.

  17. Exosomes in colorectal carcinoma formation: ALIX under the magnifying glass.

    Science.gov (United States)

    Valcz, Gábor; Galamb, Orsolya; Krenács, Tibor; Spisák, Sándor; Kalmár, Alexandra; Patai, Árpád V; Wichmann, Barna; Dede, Kristóf; Tulassay, Zsolt; Molnár, Béla

    2016-08-01

    Exosomes are small membrane vesicles that have important roles in transporting a great variety of bioactive molecules between epithelial compartment and their microenvironment during tumor formation including colorectal adenoma-carcinoma sequence. We tested the mRNA expression of the top 25 exosome-related markers based on ExoCharta database in healthy (n=49), adenoma (n=49) and colorectal carcinoma (n=49) patients using Affymetrix HGU133 Plus2.0 microarrays. Most related genes showed significantly elevated expression including PGK1, PKM, ANXA5, ENO1, HSP90AB1 and MSN during adenoma-carcinoma sequence. Surprisingly, the expression of ALIX (ALG 2-interacting protein X), involved in multivesicular body (MVB) and exosome formation, was significantly reduced in normal vs adenoma (P=5.02 × 10(-13)) and in normal vs colorectal carcinoma comparisons (P=1.51 × 10(-10)). ALIX also showed significant reduction (PALIX protein levels were accompanied by their gradual transition from diffuse cytoplasmic expression to granular signals, which fell into the 0.6-2 μm diameter size range of MVBs. These ALIX-positive particles were seen in the tumor nests, including tumor-stroma border, which suggest their exosome function. MVB-like structures were also detected in tumor microenvironment including α-smooth muscle actin-positive stromal cells, budding off cancer cells in the tumor front as well as in cancer cells entrapped within lymphoid vessels. In conclusion, we determined the top aberrantly expressed exosome-associated markers and revealed the transition of diffuse ALIX protein signals into a MVB-like pattern during adenoma-carcinoma sequence. These tumor-associated particles seen both in the carcinoma and the surrounding microenvironment can potentially mediate epithelial-stromal interactions involved in the regulation of tumor growth, metastatic invasion and therapy response.

  18. [Surgical complications of laparoscopic colectomy in patients with colorectal carcinomas].

    Science.gov (United States)

    Skrovina, M; Czudek, S; Adamcík, L; Vanko, R

    2005-11-01

    The authors present their experience with laparoscopic resections of the large intestine in patients with colorectal carcinomas. The aim is to discuss and assess peroperative and early postoperative surgical complications. From 1st January to 30th June, the team of authors operated over 350 patients with colorectal carcinomas. In 264 patients the team completed laparoscopic resections (laparoscopy-assisted) of the colo-rectum. Patients who, following an initial laparoscopic exploration, underwent a classical procedure and patients who underwent derivation stomies, eventually by- pass procedures, were excluded from the study group. In 16 patients (out of the total 264 laparoscopic colectomies) the laparoscopic procedure was converted. The rate of peroperative complications was 3.4% and the rate of postoperative surgical complications was 14.4%. Five patients in our study group exited before the postoperative day 30. Two of these cases were directly related to surgical postoperative complications. Laparoscopic colectomy is a method of choice in patients with colorectal carcinomas. The more experienced the surgeon and the whole team, the lower the total lethality rate. The rate is similar to that of classical colectomies, however some indicators prefer the laparoscopic procedure.

  19. [A study on the mutation of P53 and K-ras gene in colorectal adenomas and colorectal carcinomas].

    Science.gov (United States)

    Xu, Wei; Cheng, Yong; Shen, Xiong-Fei

    2012-11-01

    To investigate the incidence of P53 and K-ras gene mutation in colorectal adenomas and primary colorectal carcinomas. There were 25 normal samples, 38 samples of colorectal adenoma, 78 samples of single primary colorectal cancer and 19 samples of multiple primary colorectal carcinomas (7 synchronous colorectal carcinomas and 12 metachronous colorectal carcinomas) collected in this study. With the analysis of clinico-pathologic features for each patient, exon 5-8 of P53 gene and codon 12-13 of K-ras gene of each sample were extended by real-time PCR. Multi-factor correlation analysis was carried out between the clinicopathologic features and the mutation of P53 and K-ras gene in colorectal adenoma and primary colorectal cancer. The P53 gene mutation is 0% (0/25),44.8%(17/38), 43.6% (34/78) and 42.1% (8/19) respectively in normal mucosa tissue, colorectal adenomas, single lesion and multiple lesion of primary colorectal carcinomas, while the proportion of K-ras gene mutation was 0% (0/25), 18.4%(7/38), 39.7% (31/78), 47.4% (9/19) respectively. In our investigation there were obvious statistical differences as to the proportion of mutation of the P53 and K-ras gene between normal mucosa tissue and other three groups respectively (Pras gene were found between colorectal adenomas group and single or multiple colorectal carcinoma group (Pras gene mutation in colorectal adenomas (Pras gene between the stage I , II and well-differentiated ones of primary colorectal cancers and the stageIII IV and poorly-differentiated ones. There was no relationship between the age, gender, family history and tumor locations of the patients and the mutation of the P53 and K-ras gene. The stage and grade of differentiation of cancer was not the risky factor of the mutation of the P53 and K-ras gene in primary colorectal cancers. The cancers. results of this study not only suggest that mutation of P53 suppressor gene and K-ras play a significant role in the procedure of colorectal

  20. Cryopreservation of human colorectal carcinomas prior to xenografting

    Directory of Open Access Journals (Sweden)

    Krohn Mathias

    2010-07-01

    Full Text Available Abstract Background Molecular heterogeneity of colorectal carcinoma (CRC is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Methods Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23 or after cryopreservation (N = 31; up to 643 days. Results Take rates after cryopreservation were satisfactory (71% though somewhat lower than with tumor tissues fresh from surgery (74%, but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11 was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Conclusions Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres for (preclinical studies of novel therapies or for basic research.

  1. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...... manifestations in familial adenomatous polyposis. None of the patients showed any sign of CHRPE. It is concluded that although genetic factors are presumably of importance in the development of sporadic colorectal cancer, CHRPE cannot be used as a marker for future risk of colorectal carcinoma except...

  2. TRAP1 protein signature predicts outcome in human metastatic colorectal carcinoma.

    Science.gov (United States)

    Maddalena, Francesca; Simeon, Vittorio; Vita, Giulia; Bochicchio, Annamaria; Possidente, Luciana; Sisinni, Lorenza; Lettini, Giacomo; Condelli, Valentina; Matassa, Danilo Swann; Li Bergolis, Valeria; Fersini, Alberto; Romito, Sante; Aieta, Michele; Ambrosi, Antonio; Esposito, Franca; Landriscina, Matteo

    2017-03-28

    TRAP1 is a HSP90 molecular chaperone upregulated in colorectal carcinomas and involved in control of intracellular signaling, cell cycle, apoptosis and drug resistance, stemness and bioenergetics through co-traslational regulation of a network of client proteins. Thus, the clinical significance of TRAP1 protein network was analyzed in human colorectal cancers. TRAP1 and/or its client proteins were quantified, by immunoblot analysis, in 60 surgical specimens of colorectal carcinomas at different stages and, by immunohistochemistry, in 9 colorectal adenomatous polyps, 11 in situ carcinomas and 55 metastatic colorectal tumors. TRAP1 is upregulated at the transition between low- and high-grade adenomas, in in situ carcinomas and in about 60% of human colorectal carcinomas, being downregulated only in a small cohort of tumors. The analysis of TCGA database showed that a subgroup of colorectal tumors is characterized by gain/loss of TRAP1 copy number, this correlating with its mRNA and protein expression. Interestingly, TRAP1 is co-expressed with the majority of its client proteins and hierarchical cluster analysis showed that the upregulation of TRAP1 and associated 6-protein signature (i.e., IF2α, eF1A, TBP7, MAD2, CDK1 and βCatenin) identifies a cohort of metastatic colorectal carcinomas with a significantly shorter overall survival (HR 5.4; 95% C.I. 1.1-26.6; p=0.037). Consistently, the prognostic relevance of TRAP1 was confirmed in a cohort of 55 metastatic colorectal tumors. Finally, TRAP1 positive expression and its prognostic value are more evident in left colon cancers. These data suggest that TRAP1 protein network may provide a prognostic signature in human metastatic colorectal carcinomas.

  3. Downregulation of osteoprotegerin expression in metastatic colorectal carcinoma predicts recurrent metastasis and poor prognosis.

    Science.gov (United States)

    Moon, Ahrim; Do, Sung-Im; Kim, Hyun-Soo; Kim, Youn-Wha

    2016-11-29

    We recently reported the downregulation of osteoprotegerin expression in primary colorectal carcinoma and its significant association with aggressive oncogenic behavior, which suggest that this process contributes to colorectal carcinoma development and progression. In this study, we used immunohistochemical staining to evaluate osteoprotegerin expression in 81 colorectal liver metastasis tissue samples and investigated its possible association with the clinicopathological characteristics and outcomes of patients with colorectal liver metastasis. These tissues exhibited significantly reduced expression of osteoprotegerin compared to primary colorectal carcinomas and normal colorectal mucosa. This reduced expression was significantly associated with the extent of colorectal liver metastasis, including multiplicity of metastatic tumors, involvement of the bilateral hepatic lobes, and higher histological grade. In addition, reduced osteoprotegerin expression was an independent significant predictor of recurrent liver metastasis and prognostic factor for reduced patient survival. These findings suggest that osteoprotegerin expression may be a novel predictor of recurrent liver metastasis and a prognostic biomarker in patients with colorectal liver metastasis. Patients harboring colorectal liver metastasis with reduced osteoprotegerin expression should be carefully monitored after hepatic resection for colorectal liver metastasis to enable early detection of potentially resectable metastatic recurrences.

  4. Clear cell colorectal carcinoma: Time to clarify diagnosis.

    Science.gov (United States)

    Remo, Andrea; Grillo, Federica; Mastracci, Luca; Fassan, Matteo; Sina, Sokol; Zanella, Caterina; Parcesepe, Pietro; Damiano Urso, Emanuele; Pancione, Massimo; Bortuzzo, Germana; Scarpa, Aldo; Manfrin, Erminia

    2017-05-01

    Primary clear cell colorectal carcinoma (CCC) is a very rare entity accounting for only 35 cases reported in the Literature. CCC is neither classified as a distinct entity nor is it defined as a CRC variant because its ontogeny remains unclear. Most of the reported CCC were found in the distal colon in patients with a mean age of 56 years. Histologically, clear cell change is the main morphologic feature and may present in a "pure" form, composed exclusively of clear cells, or in a "composite" form, admixed with other morphologically different components. It is possible to distinguish two biologically different types of CCC, with different clinical-pathologic features, therapeutic management and diagnostic criteria: a) Intestinal CCC consisting of an aggressive neoplasm, affecting mainly adult men, characterized by an intestinal-type immunoprofile (CK20+, CK7-, CEA+, CDX-2+) and b) Müllerian CCC consisting of an indolent carcinoma of the sigmoid-rectum, affecting young women, characterized by a different (CK7+, CK20-, CEA-, CA125 +) immunoprofile. Considerable diagnostic difficulties can arise in distinguishing CCC and primary or secondary clear cell neoplasms, such as metastases from renal carcinoma, lower urinary tract, female genital tract, adrenal gland, mesothelioma, melanoma and primary intestinal PEComa. In this paper we review the Literature with two additional cases in order to define the diagnostic criteria of CCC. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. Clinicopathological analysis of prognostic factors in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Aura Jurescu

    2016-12-01

    Full Text Available BACKGROUND Prediction of prognosis is vital for therapy options in patients with colorectal carcinoma (CRC. We aimed to identify some prognostic factors that could ensure a more adequate prediction of CRC patients’ outcome. MATERIALS AND METHODS We performed a study on a group of 253 CRC patients in the County Hospital ofTimișoara. The following variable parameters: age, gender, histological type, depth of tumor invasion (pT, histological grade (G, lymph node metastasis (LNM, lympho-vascular invasion (LVI were analyzed using Fisher’s exact test. RESULTS The incidence of CRC increased with age. Gender distribution was evidenced as follows: 159 (63% were male patients and 94 (37% were female patients. 234 (92% cases were conventional adenocarcinomas (ADK nM, 19 (8% were mucinous adenocarcinomas (ADK M. 1% of cases were pT1 stage, 9% pT2, 58% pT3 and 32% pT4 stage. 5% of the tumors were G1, 95% G2, G3, G4. In pT1&pT2 stages only 4% presented LVI, while in pT3&pT4 LVI was significantly higher, 42% of the examined cases. Only two cases from pT1&pT2 tumors showed LNM vs. 55% (127 cases of pT3&pT4 stages. CONCLUSIONS Tumor stage remains the most important prognostic predictor of clinical outcome for these patients. Pathologic assessment of various clinicopathological factors plays n essential role in patient management. Graphical abstract: Infiltrative aspects of colorectal carcinoma REFERENCES 1. Corman ML. Carcinoma of the Colon. In: Corman ML, editors. Colon and Rectal Surgery. 5-th edition. Philadelphia: Lippincott Williams nad Wilkins. 2005. p. 767-920. 2. Bresalier R. Malignant neoplasms of the large intestine. In: Feldman M, Friedman LS, Sleisenger MH (Editors. Gastrointestinal and Liver Disease (Pathology, Diagnosis, Management. Philadelphia, London,New York: Saunders. 2002. p. 2215-2263. 3. Schneider N, Langner C. Prognostic stratification of colorectal cancer patients: current perspectives. Cancer Management and Research. 2014;6:291- 300.

  6. Detection of liver metastases from colorectal carcinoma: Is there a place for routine computed tomography arteriography?

    NARCIS (Netherlands)

    B. van Ooijen (B.); M. Oudkerk (Matthijs); P.I.M. Schmitz (Paul); T. Wiggers (Theo)

    1996-01-01

    textabstractBackground. A prospective evaluation of the liver by preoperative ultrasonography, conventional computed tomography (CT), and continuous CT angiography (CCTA) was performed in 60 patients with primary or secondary colorectal carcinoma. Methods. The standards of reference were palpation

  7. High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients

    OpenAIRE

    Fukugaiti,Márcia H.; Aline Ignacio; Miriam R. Fernandes; Ulysses Ribeiro Júnior; Viviane Nakano; Avila-Campos, Mario J.

    2015-01-01

    Abstract Colorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several microorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms in the fecal microbiota of colorectal cancer patients and healthy controls. Seventeen patients...

  8. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  9. Insight On Colorectal Carcinoma Infiltration by Studying Perilesional Extracellular Matrix.

    Science.gov (United States)

    Nebuloni, Manuela; Albarello, Luca; Andolfo, Annapaola; Magagnotti, Cinzia; Genovese, Luca; Locatelli, Irene; Tonon, Giovanni; Longhi, Erika; Zerbi, Pietro; Allevi, Raffaele; Podestà, Alessandro; Puricelli, Luca; Milani, Paolo; Soldarini, Armando; Salonia, Andrea; Alfano, Massimo

    2016-03-04

    The extracellular matrix (ECM) from perilesional and colorectal carcinoma (CRC), but not healthy colon, sustains proliferation and invasion of tumor cells. We investigated the biochemical and physical diversity of ECM in pair-wised comparisons of healthy, perilesional and CRC specimens. Progressive linearization and degree of organization of fibrils was observed from healthy to perilesional and CRC ECM, and was associated with a steady increase of stiffness and collagen crosslinking. In the perilesional ECM these modifications coincided with increased vascularization, whereas in the neoplastic ECM they were associated with altered modulation of matrisome proteins, increased content of hydroxylated lysine and lysyl oxidase. This study identifies the increased stiffness and crosslinking of the perilesional ECM predisposing an environment suitable for CRC invasion as a phenomenon associated with vascularization. The increased stiffness of colon areas may represent a new predictive marker of desmoplastic region predisposing to invasion, thus offering new potential application for monitoring adenoma with invasive potential.

  10. Scrotal metastases from colorectal carcinoma: a case report.

    LENUS (Irish Health Repository)

    McWeeney, Doireann M

    2012-01-31

    ABSTRACT: A 72-year-old man presented with a two month history of rectal bleeding. Colonoscopy demonstrated synchronous lesions at 3 cm and 40 cm with histological analysis confirming synchronous adenocarcinomata. He developed bilobar hepatic metastases while undergoing neoadjuvant chemoradiotherapy. Treatment was complicated by Fournier\\'s gangrene of the right hemiscrotum which required surgical debridement. Eight months later he re-presented with an ulcerating lesion on the right hemiscrotum. An en-bloc resection of the ulcerating scrotal lesion and underlying testis was performed. Immunohistological analysis revealed metastatic adenocarcinoma of large bowel origin. Colorectal metastasis to the urogenital tract is rare and here we report a case of rectal carcinoma metastasizing to scrotal skin.

  11. [Surgical treatment of colorectal carcinoma in the elderly].

    Science.gov (United States)

    Schuld, J; Glanemann, M

    2017-02-01

    Colorectal carcinoma is one of the most frequent tumor entities worldwide. The treatment of elderly and mostly polymorbid patients is an outstanding challenge in view of the demographic change with a continuously aging community. Due to the demographic changes the numbers of elderly (>65 years) and very old (≥80 years) patients are steadily increasing in surgical cohorts. This has resulted in higher morbidity and mortality rates in comparison to younger patients, with increased wound healing and cardiovascular complications but with comparable numbers of anastomotic insufficiency. Multivariate analysis revealed age ≥80 years, higher ASA status and emergency operations as independent risk factors for increased in-hospital mortality. With respect to the localization of colorectal cancer a shift to the right has been observed with increasing patient age. Whether minimally invasive surgical techniques can reduce postoperative morbidity and mortality rates in elderly patients requires further evaluation. Nevertheless, a reduction of both was reported without compromising the oncological result. Elderly patients require individualized treatment modalities, which take the extent of comorbidities and personal environment into consideration. So far, the cohort of octogenarians has not been adequately considered in current guidelines; therefore, geriatric expertise is recommended to be able to make a better assessment of benefit-risk ratios, as age itself has no impact on the decision for therapy.

  12. [Aspirin in primary and secondary prevention of colorectal carcinomas].

    Science.gov (United States)

    Schrör, Karsten; Rauch, Bernhard

    2013-11-01

    Observational but also some randomized trials suggest that regular long-term use of aspirin (acetylsalicylic acid) might reduce the risk of colorectal carcinomas by 15-40%. The efficacy appears to be increased with longer duration of treatment, i.e. beyond 5-10 years, but not with increasing doses. Aspirin at 75-100 mg daily appears to be sufficient in both primary as well as secondary prevention of recurrent tumors in sensitive persons, including prevention of distant metastases. The pharmacological mode of aspirin action is unclear as is the question whether only one or more sites of action exist. In any case, the mechanism(s) in charge should work at aspirin plasma levels of 10 microM or less which is the maximum concentration to be expected after antiplatelet doses. Inhibition of COX-1 and/or COX-2 is most likely involved. Follow-up reactions, such as inhibition of platelet-dependent thromboxane formation and action, release of storage products such as VEGF or sphingosine-1-phosphate and acetylation of COX-2 with subsequent generation of antioncogenic lipid mediators, such as lipoxins, are also possible. There is not much likelihood for "direct" actions of aspirin, shown in vitro at concentrations of 5 mM and more, which uncouple oxidative phosphorylation and paralyse the cell energy metabolism. benefit/risk profile, specifically regarding severe or fatal bleedings (GI-tract, cerebral). Accordingly, the actual German guideline "colorectal carcinoma" does not recommend aspirin use for prophylactic purposes. What is strongly needed are definitions of risk patients in terms of biomarkers or genetic profiling as well as data from long-term prospective randomized trials--both are underway.

  13. Mucinous and Signet Ring Cell Differentiation Affect Patterns of Metastasis in Colorectal Carcinoma and Influence Survival.

    Science.gov (United States)

    Kermanshahi, Taher Reza; Magge, Deepa; Choudry, Haroon; Ramalingam, Leksmi; Zhu, Benjamin; Pingpank, James; Ahrendt, Steven; Holtzman, Matthew; Zeh, Herbert; Bartlett, David; Zureikat, Amer; Pai, Reetesh K

    2017-04-01

    Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P metastasis was identified in patients with both synchronous and metachronous development of metastasis ( P metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement ( P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival ( P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.

  14. Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association.

    Science.gov (United States)

    Hammerling, Ulf; Bergman Laurila, Jonas; Grafström, Roland; Ilbäck, Nils-Gunnar

    2016-01-01

    Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.

  15. Urachal Carcinoma Shares Genomic Alterations with Colorectal Carcinoma and May Respond to Epidermal Growth Factor Inhibition.

    Science.gov (United States)

    Collazo-Lorduy, Ana; Castillo-Martin, Mireia; Wang, Li; Patel, Vaibhav; Iyer, Gopa; Jordan, Emmet; Al-Ahmadie, Hikmat; Leonard, Issa; Oh, William K; Zhu, Jun; McBride, Russell B; Cordon-Cardo, Carlos; Solit, David B; Sfakianos, John P; Galsky, Matthew D

    2016-11-01

    Metastatic urachal carcinoma is a rare, understudied, and aggressive malignancy with limited treatment options. Histologically, urachal carcinomas resemble enteric adenocarcinomas and anecdotally respond to systemic therapies utilized in colorectal cancer. Targeted exome sequencing of archival primary tumor tissue from a patient with metastatic urachal cancer revealed EGFR amplification and wild-type KRAS. The patient was treated with cetuximab, a monoclonal antibody directed against EGFR, as a single agent, and achieved a response lasting more than 8 mo. Subsequent whole-exome sequencing revealed no additional alterations likely to be associated with cetuximab sensitivity. Formalin-fixed, paraffin-embedded tumor specimens from nine additional urachal cancers were subjected to targeted exome sequencing. Mitogen-activated protein kinase (MAPK) pathway mutations were found in four of the nine samples, but no EGFR amplification was detected. Importantly, APC mutations were detected in two of the nine patients. To our knowledge, this is the first report of a response to single-agent cetuximab in a patient with metastatic urachal cancer and of molecular analysis to probe the basis for sensitivity. On the basis of these findings and the histologic, and now genomic, similarities with colorectal cancer, monoclonal antibodies directed at EGFR could be used in the treatment of metastatic urachal cancer. Urachal cancers are morphologically and genomically similar to colon adenocarcinomas and may respond to drugs targeting the epidermal growth factor receptor. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  16. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Inés Mármol

    2017-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%–5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%; inherited (5% and familial (25%. The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN, microsatellite instability (MSI and CpG island methylator phenotype (CIMP. Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53, and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined

  17. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer.

    Science.gov (United States)

    Mármol, Inés; Sánchez-de-Diego, Cristina; Pradilla Dieste, Alberto; Cerrada, Elena; Rodriguez Yoldi, María Jesús

    2017-01-19

    Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%-5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli . CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%); inherited (5%) and familial (25%). The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53), and mutations; in particular, genes such as c-MYC, KRAS , BRAF , PIK3CA , PTEN , SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined with

  18. Colorectal carcinogenesis: Review of human and experimental animal studies

    Directory of Open Access Journals (Sweden)

    Tanaka Takuji

    2009-01-01

    Full Text Available This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma. These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.

  19. Identification of dirty necrosis in colorectal carcinoma based on multiphoton microscopy

    Science.gov (United States)

    Li, Lianhuang; Jiang, Weizhong; Yang, Yinghong; Chen, Zhifen; Feng, Changyin; Li, Hongsheng; Guan, Guoxian; Chen, Jianxin

    2014-06-01

    Dirty necrosis within glandular lumina is often considered as a characteristic of colorectal carcinomas (CRCs) that is a diagnostically useful feature of CRCs with DNA microsatellite instability (MSI). Multiphoton microscopy (MPM), which is based on the second-harmonic generation and two-photon excited fluorescence signals, was used to identify dirty necrosis. Our results demonstrated that MPM has the ability to exhibit the microstructure of dirty necrosis and the signal intensity as well as an emission spectrum that can help to differentiate dirty necrosis from cancer cells. These findings indicate that MPM may be helpful in distinguishing MSI colorectal carcinoma via the identification of dirty necrosis.

  20. Mandibular osteomas in sporadic colorectal carcinoma. A genetic marker

    DEFF Research Database (Denmark)

    Søndergaard, J O; Rasmussen, M S; Videbaek, H

    1993-01-01

    Pantomography of the mandible was performed in 98 patients with sporadic colorectal adenocarcinoma. Twenty-eight patients (29%) had osteomas versus 5% in a control group (P osteomas are found in most patients with the premalignant dominant syndrome familial adenomatous...... polyposis. Sporadic colorectal cancer examinations of married couples have shown that diet has only a moderate influence on the development of colorectal cancer, whereas pedigree studies indicate a genetic component. On this basis we conclude that mandibular osteomas are probably genetic markers...

  1. Epidemiological, Clinico-Pathological Profile and Management of Colorectal Carcinoma in a Tertiary Referral Center of Eastern India

    OpenAIRE

    Shyamal Kumar Halder; Prosanta Kumar Bhattacharjee; Partha Bhar; Anadi Pachaury; Ranu Roy Biswas; Tapas Majhi; Pranjal Pandey

    2013-01-01

    Background: The colorectal carcinoma is a common cancer in males and in females and second most common cause of death in Europe and third commonest cause in the United States. Recent Indian study shows that there is a significant increase in incidence of colonic carcinoma but the incidence of rectal carcinoma remains steady. Aims and Objectives: This prospective study was undertaken to assess the clinico-pathological profile and management of colorectal malignanc...

  2. Olive oil, other seasoning fats, and the risk of colorectal carcinoma.

    Science.gov (United States)

    Braga, C; La Vecchia, C; Franceschi, S; Negri, E; Parpinel, M; Decarli, A; Giacosa, A; Trichopoulos, D

    1998-02-01

    An association between fats and colorectal carcinoma has been suggested, but the epidemiologic evidence by type of dietary fat is far less clear. Colorectal carcinoma rates have been relatively low in Mediterranean countries compared with most other Western countries, but the components of the Mediterranean diet responsible for this favorable pattern are unclear. The relationship between various added (seasoning) fats and colorectal carcinoma risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in six Italian areas. Cases were 1953 patients with incident, histologically confirmed colorectal carcinoma (1225 of the colon and 728 of the rectum) admitted to the major teaching and general hospitals in the study areas. Controls were 4154 subjects with no history of cancer who were admitted to hospitals in the same catchment areas for acute, nonneoplastic diseases unrelated to the the digestive tract and requiring no long term modifications of diet. Dietary habits were investigated using a validated food frequency questionnaire including 78 items. Lipid intake was estimated by taking into account the content of seasoning lipids in different dishes, the frequency of consumption and portion size of each dish, and individual fat intake patterns. The odds ratios (OR) for successive tertiles of olive oil intake, compared with the lowest one, were 0.87 (95% confidence interval [CI], 0.75-1.01) and 0.83 (95% CI, 0.70-0.99) (chi2trend = 4.49, P = 0.03) when colorectal carcinoma was analyzed as a whole, 0.82 (95% CI, 0.68-0.98) and 0.81 (95% CI, 0.66-0.99) (chi2trend = 4.05, P = 0.04) for colon carcinoma, and 0.96 (95% CI, 0.77-1.19) and 0.88 (95% CI, 0.66-1.12) for rectal carcinoma. For specific seed oils (including sunflower, maize, peanut, and soya), the OR for colorectal carcinoma was 0.91 in the highest tertile of intake, and the corresponding values were 1.01 for mixed seed oils and 0.93 for butter. None of these estimates

  3. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

    Directory of Open Access Journals (Sweden)

    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

  4. Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2014-06-01

    Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

  5. Mandibular osteomas in sporadic colorectal carcinoma. A genetic marker

    DEFF Research Database (Denmark)

    Søndergaard, J O; Rasmussen, M S; Videbaek, H

    1993-01-01

    polyposis. Sporadic colorectal cancer examinations of married couples have shown that diet has only a moderate influence on the development of colorectal cancer, whereas pedigree studies indicate a genetic component. On this basis we conclude that mandibular osteomas are probably genetic markers...

  6. Colorectal Carcinoma: An Update of Current Trends in Accra ...

    African Journals Online (AJOL)

    BACKGROUND: Clinical experience and earlier studies indicate that the number of colorectal cancer cases seen annually in the Accra metropolis is increasing. OBJECTIVE: This study was aimed at providing a current update on colorectal cancer in Accra, Ghana. METHODS: A prospective study of confirmed cases of ...

  7. Deregulation of the Replisome Factor MCMBP Prompts Oncogenesis in Colorectal Carcinomas through Chromosomal Instability

    Directory of Open Access Journals (Sweden)

    Mauricio Quimbaya

    2014-09-01

    Full Text Available Genetic instability has emerged as an important hallmark of human neoplasia. Although most types of cancers exhibit genetic instability to some extent, in colorectal cancers genetic instability is a distinctive characteristic. Recent studies have shown that deregulation of genes involved in sister chromatid cohesion can result in chromosomal instability in colorectal cancers. Here, we show that the replisome factor minichromosome maintenance complex–binding protein (MCMBP, which is directly involved in the dynamics of the minichromosome maintenance complex and contributes to maintaining sister chromatid cohesion, is transcriptionally misregulated in different types of carcinomas. Cellular studies revealed that both MCMBP knockdown and overexpression in different breast and colorectal cell lines is associated with the emergence of a subpopulation of cells with abnormal nuclear morphology that likely arise as a consequence of aberrant cohesion events. Association analysis integrating gene expression data with clinical information revealed that enhanced MCMBP transcript levels correlate with an increased probability of relapse risk in colorectal cancers and different types of carcinomas. Moreover, a detailed study of a cohort of colorectal tumors showed that the MCMBP protein accumulates to high levels in cancer cells, whereas in normal proliferating tissue its abundance is low, indicating that MCMBP could be exploited as a novel diagnostic marker for this type of carcinoma.

  8. High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients

    Directory of Open Access Journals (Sweden)

    Márcia H. Fukugaiti

    2015-01-01

    Full Text Available AbstractColorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several microorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms in the fecal microbiota of colorectal cancer patients and healthy controls. Seventeen patients (between 49 and 70 years-old visiting the Cancer Institute of the Sao Paulo State were selected, 7 of whom were diagnosed with colorectal carcinoma. Bacterial detection was performed by qRT-PCR. Although all of the tested bacteria were detected in the majority of the fecal samples, quantitative differences between the Cancer Group and healthy controls were detected only for F. nucleatum and C. difficile. The three tested oral microorganisms were frequently observed, suggesting a need for furthers studies into a potential role for these bacteria during colorectal carcinoma pathogenesis. Despite the small number of patients included in this study, we were able to detect significantly more F. nucleatumand C. difficile in the Cancer Group patients compared to healthy controls, suggesting a possible role of these bacteria in colon carcinogenesis. This finding should be considered when screening for colorectal cancer.

  9. Anti-Warburg effect of rosmarinic acid via miR-155 in colorectal carcinoma cells.

    Science.gov (United States)

    Xu, Yichun; Han, Shuai; Lei, Kesheng; Chang, Xinnan; Wang, Ke; Li, Zhou; Liu, Jianwen

    2016-11-01

    The Warburg effect, glycolytic production of ATP under aerobic conditions, is found to be a universal feature of most cancer cells. Our study was aimed to determine whether rosmarinic acid (RA) had the anti-Warburg effect activity against colorectal carcinoma. Furthermore, the mechanism for the anti-Warburg effect by RA would be investigated. In our study, we found that RA suppressed glucose consumption and lactate generation in colorectal carcinoma cells; meanwhile, RA inhibited the expression of transcription factor hypoxia-inducible factor-1α (HIF-1α) that affects the glycolytic pathway. Chronic inflammation is a key promoting factor of the Warburg effect. As we supposed, the present study also showed that RA could not only repress proinflammatory cytokines using enzyme-linked immunosorbent assay but it could also suppress microRNAs related to inflammation by real-time PCR. Therefore, we proposed that RA may inhibit the Warburg effect by suppressing the inflammatory response of colorectal carcinoma cells. Recent studies have provided evidence that miR-155 was an important mediator between inflammation and carcinogenesis. We further showed that miR-155 acted to repress the Warburg effect through the mechanism of inactivating the IL-6/STAT3 pathway. Above all, RA might be a potential therapeutic agent against colorectal carcinoma.

  10. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses

    Directory of Open Access Journals (Sweden)

    Myklebost Ola

    2007-01-01

    Full Text Available Abstract Background Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18, liver metastases (n = 4, and carcinomatoses (n = 4, relative to normal samples from the large bowel. Results Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622 mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. Conclusion By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.

  11. Loss of membranous Ep-CAM in budding colorectal carcinoma cells.

    NARCIS (Netherlands)

    Gosens, M.J.E.M.; Kempen, L.C. van; Velde, C.J. van de; Krieken, J.H.J.M. van; Nagtegaal, I.D.

    2007-01-01

    Tumor budding is a histological feature that reflects loss of adhesion of tumor cells and is associated with locoregional metastasis of colorectal carcinoma. Although nuclear localization of beta-catenin is associated with tumor budding, the molecular mechanism remains largely elusive. In this

  12. Colorectal carcinoma: nucleosomes, carcinoembryonic antigen and ca 19-9 as apoptotic markers; a comparative study

    Directory of Open Access Journals (Sweden)

    Mahgoub Samir S

    2011-07-01

    Full Text Available Abstract Background Colorectal carcinoma is a common and often fatal disease in which methods of early detection and monitoring are essential. The present study was conducted for measuring serum levels of nucleosomes, carcinoembryonic antigen (CEA and CA 19-9 in patients newly diagnosed with colorectal carcinoma and confirmed by clinicopathological study. Method Thirty subjects were included in the current study: six normal subjects as a control group with mean age (45.6 ± 7.9 and twenty four colorectal carcinoma patients with mean age (46.9 ± 15.6, which were classified pathologically according to the degree of malignant cell differentiation into well differentiated (group I, moderately differentiated (group II and poorly differentiated (group III. Fasting venous blood samples were collected preoperative. Results The results revealed a significant increase in serum level of nucleosomes in patients with poorly differentiated tumors versus patients with well differentiated tumors (p = 0.041. The levels of CEA and CA19-9 showed no significant increase (p = 0.569 and 0.450, respectively. Conclusion In conclusion, serum level of nucleosomes provides a highly sensitive and specific apoptotic marker for colorectal carcinoma.

  13. Prognostic significance of COX-2 and β-catenin in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Amani Kazem

    2014-09-01

    Conclusion: Both β-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis. This might be of therapeutic value for allocating patients with colorectal carcinoma to different treatment modalities.

  14. Cytogenetic comparisons of synchronous carcinomas and polyps in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and cytogenetically analysed: 16 non-adenomatous polyps, six adenomas, seven carcinomas, including one in polyp, and one lymph node metastasis. Clonal chromosome aberrations were found in 20 samples in 100...... found in carcinomas but not in adenomas, indicating that they might be specifically associated with carcinoma development in the large bowel mucosa. The karyotypic similarity seen between the malignant and benign tumours in the same patient, and also sometimes among non-malignant polyps in the same case...

  15. Low-Dose Paclitaxel Inhibits Tumor Cell Growth by Regulating Glutaminolysis in Colorectal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chaoxiang Lv

    2017-05-01

    Full Text Available Paclitaxel (PTX is a natural alkaloid isolated from the bark of a tree, Taxus brevifolia, and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM have rarely been illuminated. Here we report a new antitumor mechanism of low-dose PTX in colorectal carcinoma cells. We treated colorectal carcinoma HCT116 cells with PTX at 0.1 and 0.3 nM for 0, 1, 2, or 3 days, and found that low-dose PTX inhibits cell growth without altering cell morphology and cell cycle. There was a significant decrease of pH in culture media with 0.3 nM PTX for 3 days. Also, lactate production was significantly increased in a dose- and time-dependent manner. Furthermore, expression of glutaminolysis-related genes GLS, SLC7A11 and SLC1A5 were significantly decreased in the colorectal carcinoma cells treated with low-dose PTX. Meanwhile, protein expression levels of p53 and p21 increased significantly in colorectal carcinoma cells so treated. In summary, low-dose PTX down-regulated glutaminolysis-related genes and increased their lactate production, resulting in decreased pH of tumor microenvironments and inhibition of tumor cell growth. Up-regulation of p53 and p21 in colorectal carcinoma cells treated with low-dose PTX also contributed to inhibition of tumor cell growth.

  16. The TP53 tumour suppressor gene in colorectal carcinomas. I. Genetic alterations on chromosome 17.

    Science.gov (United States)

    Meling, G. I.; Lothe, R. A.; Børresen, A. L.; Graue, C.; Hauge, S.; Clausen, O. P.; Rognum, T. O.

    1993-01-01

    In 231 colorectal carcinomas, allele variation at four restriction fragments length polymorphisms (RFLP) loci on chromosome 17 have been studied by Southern analysis. Heterozygous loss of the TP53 gene was found in 68% (129/189) of the carcinomas informative on both chromosome arms. In 41% (77/189) of the carcinomas the loss was found only on 17p. Two probes were used to detect alterations on 17p, pBHP53 and pYNZ22. When loss was demonstrated with pYNZ22, pBHP53 also always showed loss (n = 45), whereas when loss was demonstrated with pBHP53, only 45 of 54 (83%) showed loss with pYNZ22. Loss on 17q was found in 34% (64/189) of the carcinomas, and 6% (12/189) had loss on this chromosome arm, only. Loss on 17q was significantly associated with loss on 17p (P < 0.01). These data confirm that the TP53 gene is the target of loss on chromosome arm 17p in colorectal carcinomas, and demonstrate that loss of the TP53 gene is most frequently part of limited, subchromosomal loss. Furthermore, the results do not suggest any additional tumour suppressor gene(s) on chromosome 17 involved in colorectal carcinogenesis. Images Figure 2 PMID:8094008

  17. HRAS1 minisatellite alleles in colorectal carcinoma: relationship to microsatelite instability.

    Science.gov (United States)

    Vega, A; Barros, F; Lleonart, M E; Ramon y Cajal, S; Carracedo, A

    2001-01-01

    To further evaluate sporadic colon carcinoma risk associated with rare HRAS1 VNTR alleles, the relationship with microsatellite instability and with HRAS1 VNTR instability. The HRAS1 VNTR was genotyped in 121 tumors and normal samples from sporadic colon carcinoma patients (47 right and 74 left colon) and in 109 samples from healthy individuals. The HRAS1 alleles were identified using PCR and automatic fluorescent electrophoresis detection combined with MVR-PCR (Minisatellite Variant Repeat-Polymerase Chain Reaction). Microsatellite Instability (MI) was analysed with 10 microsatellite markers. A relative risk of 3.04 (95% CI: 1.16-4.92) associated with rare alleles was obtained. No HRAS1 minisatellite instability was present in the tumors. Samples with MI were equally distributed between the common and rare HRAS1 allele groups, while the distribution of HRAS1 alleles in samples with MI was similar in right and left colorectal carcinoma. Rare HRAS1 VNTR alleles are associated with colorectal carcinoma risk independent of the tumor location. MI is not likely to be involved in the same underlying defect that generates rare HRAS1 alleles in colorectal carcinoma.

  18. Distinct claudin expression profiles of hepatocellular carcinoma and metastatic colorectal and pancreatic carcinomas.

    Science.gov (United States)

    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

    2013-04-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1 protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis.

  19. DMBT1 expression and glycosylation during the adenoma-carcinoma sequence in colorectal cancer

    DEFF Research Database (Denmark)

    Robbe, C; Paraskeva, C; Mollenhauer, J

    2005-01-01

    The gene DMBT1 (deleted in malignant brain tumour-1) has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumour-suppressor gene. On the one hand, DMBT1 has been linked to mucosal protection, whereas, on the other, it potentially plays a role......, location and its mode of secretion during malignant transformation in colorectal cancer. Using human colorectal PC/AA cell lines and tissue sections from individual patients, we have examined the expression of DMBT1 and its glycosylation in the adenoma-carcinoma sequence leading to the adenocarcinoma...

  20. Gastric and Colorectal Metastases of Lobural Breast Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    David Buka

    2016-04-01

    Full Text Available Background: Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. Case Report: A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. Conclusions: Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

  1. Preoperative segmental localization of colorectal carcinoma: CT colonography vs. optical colonoscopy.

    Science.gov (United States)

    Offermans, T; Vogelaar, F J; Aquarius, M; Janssen-Heijnen, M L G; Simons, P C G

    2017-11-01

    Adequate preoperative segmental localization of colorectal cancer is important to indicate the right surgical treatment. Preoperative localization has become more important in the era of minimally invasive surgery. The aim of this study was to compare optical colonoscopy (OC) and CT colonography (CTC) with respect to the error rates in the segmental localization of colorectal carcinoma. A total of 420 patients with histopathologically proven colorectal carcinoma underwent CTC between December 2006 and February 2017. 284 Of these patients underwent surgical resection and had their carcinomas located on CTC report as well as OC report and surgical report. The segmental localization error rates of OC and CTC were compared using surgery as golden standard. McNemar's test was used to evaluate the differences in error rate. 284 Patients with a total of 296 colorectal carcinomas were evaluated. The segmental localization error rate of CTC (39/296, 13.2%) was found to be lower than the segmental localization error rate of OC (64/296, 21.6%) (p < 0.001). Per segment analysis showed that OC had a significantly higher error rate for carcinomas located in the descending colon (60.6% vs. 21.2% [p < 0.001] and cecum(60.0% vs. 23.3% [p = 0.001]). In 9.2% of the patients (26/284), localization based on CTC would lead to a change in surgical plan. CTC has a lower localization error rate than OC, which is most relevant for tumors located in the descending colon. If there is a doubtful localization on OC, particularly in the left-sided colon, an additional CTC should be performed to choose the best surgical treatment. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  2. miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2.

    Science.gov (United States)

    Xu, Ke; Liang, Xin; Shen, Ke; Cui, Daling; Zheng, Yuanhong; Xu, Jianhua; Fan, Zhongze; Qiu, Yanyan; Li, Qi; Ni, Lei; Liu, Jianwen

    2012-09-01

    Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2.

  3. Management of Liver Metastasis from Colo-Rectal Carcinoma with ...

    African Journals Online (AJOL)

    Review of relevant articles with literature in English language. Cross- referenced ... Conclusion: Laparoscopic liver resection was found to be a favorable alternative to open resection in metastatic colorectal cancer and is associated with low morbidity and mortality in properly selected cases in specialized centres. There is ...

  4. Hereditary non-polyposis colorectal carcinoma (HNPCC) in a ...

    African Journals Online (AJOL)

    ... of eight siblings had developed colorectal cancer, with incidence in three consecutive generations. This family satisfied Amsterdam criteria (I and II) for Lynch syndrome: three generations affected, six of them below age 50, with proximal colon tumours. Genetic testing showed loss of mismatched repair protein gene MSL2.

  5. Induction of Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma by Litchi Seed Extract

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

    Full Text Available The Litchi (Litchi chinensis fruit products possess rich amounts of flavanoids and proanthocyanidins. Its pericarp has been shown to inhibit breast and liver cancer cell growth. However, the anticolorectal cancer effect of Litchi seed extract has not yet been reported. In this study, the effects of polyphenol-rich Litchi seed ethanol extract (LCSP on the proliferation, cell cycle, and apoptosis of two colorectal cancer cell lines Colo320DM and SW480 were examined. The results demonstrated that LCSP significantly induced apoptotic cell death in a dose-dependent manner and arrested cell cycle in G2/M in colorectal carcinoma cells. LCSP also suppressed cyclins and elevated the Bax : Bcl-2 ratio and caspase 3 activity. This study provides in vitro evidence that LCSP serves as a potential chemopreventive agent for colorectal cancer.

  6. Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

    Directory of Open Access Journals (Sweden)

    Hansteen Inger-Lise

    2007-12-01

    Full Text Available Abstract Background The risk of sporadic colorectal cancer (CRC is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population. Methods We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls to test the association between dietary factors (meat versus fruit, berries and vegetables genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile105Val, EPHX1 Tyr113His and EPHX1 His139Arg, and risk of colorectal carcinomas and adenomas. Odds ratio (OR and 95% confidence interval (95% CI were estimated by binary logistic regression. Results A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. Conclusion Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma.

  7. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

    Directory of Open Access Journals (Sweden)

    Tops Carli MJ

    2009-06-01

    Full Text Available Abstract Background MUTYH-associated polyposis (MAP is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC. Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. Methods From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR of APC, p53, and SMAD4 were analyzed for somatic mutations. Results MAP CRCs frequently localized to the proximal colon (69%, 40/58, were mucinous in 21% (9/42, and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40; all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36 while 64% (23/36 had KRAS2 mutations (22/23 c.34G>T. G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. Conclusion MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development but not in P53 and SMAD4 (implicated in tumour progression might indicate a predominant MUTYH effect in early carcinogenesis.

  8. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders; Vogel, Lotte K.; Lewinsky, Rikke H

    2007-01-01

    to examine NDRG2 mRNA expression in colon cancer. By examining affected and normal tissue from individuals with colorectal adenomas and carcinomas, as well as in healthy individuals, we aim to determine whether and at which stages NDRG2 down-regulation occurs during colonic carcinogenesis. METHODS: Using......BACKGROUND: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been......-regulation is a cause or consequence of the progression of colorectal adenomas to carcinoma....

  9. Identifying and quantifying the stromal fibrosis in muscularis propria of colorectal carcinoma by multiphoton microscopy

    Science.gov (United States)

    Chen, Sijia; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2014-10-01

    The examination of stromal fibrosis within colorectal cancer is overlooked, not only because the routine pathological examinations seem to focus more on tumour staging and precise surgical margins, but also because of the lack of efficient diagnostic methods. Multiphoton microscopy (MPM) can be used to study the muscularis stroma of normal and colorectal carcinoma tissue at the molecular level. In this work, we attempt to show the feasibility of MPM for discerning the microstructure of the normal human rectal muscle layer and fibrosis colorectal carcinoma tissue practicably. Three types of muscularis propria stromal fibrosis beneath the colorectal cancer infiltration were first observed through the MPM imaging system by providing intercellular microstructural details in fresh, unstained tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen, which may further characterize the severity of fibrosis. By comparing with the pathology analysis, these results show that the MPM has potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidence, which may guide subsequent therapy procedures for patients into good prognosis.

  10. Nodular intra-abdominal panniculitis: an accompaniment of colorectal carcinoma and diverticular disease

    DEFF Research Database (Denmark)

    Bak, Martin

    1996-01-01

    Intra-abdominal panniculitis is a tumour-like inflammatory condition of adipose tissue. The aetiology and pathogenesis of the disease is unknown, but a number of associated diseases have been recorded. It has been customary to deal with only primary cases in the literature. This study was underta....... Primary diseases involved are, among others, colorectal carcinoma and diverticulosis. The aetiologic agent(s) are still unknown, but substances liberated from a damaged bowel might play a pathogenetic role....

  11. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

    Directory of Open Access Journals (Sweden)

    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  12. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lyu, Qing [School of Life Sciences, Tsinghua University, Beijing, 100084 (China); Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055 (China); Tou, Fangfang [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China); Su, Hong; Wu, Xiaoyong [First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002 (China); Chen, Xinyi [Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029 (China); Zheng, Zhi, E-mail: zheng_sheva@hotmail.com [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China)

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.

  13. Sp1 upregulates expression of TRF2 and TRF2 inhibition reduces tumorigenesis in human colorectal carcinoma cells.

    Science.gov (United States)

    Dong, Wenjie; Shen, Ruizhe; Wang, Qi; Gao, Yabo; Qi, Xiaoguang; Jiang, He; Yao, Jingjing; Lin, Xiaolin; Wu, Yunlin; Wang, Lifu

    2009-11-01

    Telomere repeat binding factor 2 (TRF2) plays a key role in the protective activity of telomere and is overexpression in several kinds of solid cancer cells. However, the role of overexpressed TRF2 in colorectal carcinoma remains unclear. The aim of this study was to determine the expression of TRF2, address the mechanism of TRF2 overexpression in human colorectal carcinoma. In present study, we examined the expression of TRF2 in colorectal cancer tissues from 39 patients, peritumoral normal tissues from 21 patients, and colon carcinoma SW480 cell line by quantitative PCR, immunohistochemistry and western blot. After siRNA silencing TRF2 expression in SW480, tumorigenesis of TRF2 was tested by cell proliferation, soft agar assay, cytofluorimetric analysis and cytogenetic analysis. To discover transcription factor that mediated TRF2 expression, Chromatin Immunoprecipitation (Chip) Assay and Electrophoretic mobility shift assays (EMSA) were employed. Overexpression of TRF2 protein was detected in SW480 cells and 19 of 39 colorectal carcinoma tissues (49%), no overexpression was observed in 21 of 21 adjacent peritumoral normal colorectal tissues. After siRNA silencing TRF2 expression, the proliferation and colony formation of SW480 cells were significantly inhibited. Defective TRF2 induced apoptosis and increased chromosomal instability in SW480 cells, in which there were more end-to-end fusions and ring chromosomes. Chip assay and EMSA showed that transcription factor Sp1 is involved in upregulation of TRF2. These results indicate that TRF2 is overexpressed in colorectal carcinoma, Sp1 upregulates TRF2 expression, TRF2 inhibition reduces tumorigenesis of colorectal cancer, which suggests that TRF2 and SP1 may become new targets for the development of anti-cancer therapy in colorectal carcinoma.

  14. Prognostic relevance of melanoma antigen D1 expression in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Zeng Zhao-lei

    2012-08-01

    Full Text Available Abstract Background Melanoma antigen D1 (MAGED1 is a member of the type II melanoma antigen (MAGE family. The down-regulation of MAGED1 expression has been shown in breast carcinoma cell lines and in glioma stem cells and may play an important role in apoptosis and anti-tumorigenesis. However, there is no report on its clinical role in colorectal cancer (CRC. Methods We examined the expression of MAGED1 by qPCR in colorectal cancer tissues and their adjacent non-tumorous tissues taken from 6 cases and performed Western blotting and IHC analyses. In addition, we analyzed MAGED1 expression in 285 clinicopathologically characterized colorectal cancer patients. Results MAGED1 expression was significantly down-regulated in colorectal cancer tissues compared with adjacent non-tumorous tissues and was associated with clinical stage (p p = 0.001, N classification (p p p = 0.002. Patients with lower MAGED1 expression had a shorter survival time than those with higher MAGED1 expression. Univariate and multivariate analyses indicated that MAGED1 expression was an independent prognostic factors (p  Conclusions MAGED1 may serve as a novel prognostic biomarker of human colorectal cancer.

  15. Prognostic and diagnostic significance of tumor budding associated with β-catenin expression in submucosal invasive colorectal carcinoma.

    Science.gov (United States)

    Umemura, Ken; Takagi, Sho; Shimada, Takenobu; Masuda, Takayuki; Shiga, Hisashi; Takahashi, Shuichiro; Takahashi, Seiichi; Kinouchi, Yoshitaka; Shibuya, Daisuke; Shimosegawa, Tooru

    2013-01-01

    Endoscopic resection has become a major curative treatment for early colorectal carcinoma without lymph node metastasis. However, lymph node metastasis, a poor prognostic factor in colorectal carcinoma, occurs in about 10% of the patients with submucosal invasive colorectal carcinoma. Therefore, it is important to identify a high-risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma. This study was designed to identify the relationship between tumor budding with β-catenin expression and lymph node metastasis in submucosal invasive colorectal carcinoma. We investigated the immunohistochemistry of tumor budding in the 142 patients who underwent surgical resection for submucosal invasive colorectal carcinomas between 1984 and 1999 and the expression pattern of β-catenin in budding tumor cells. Accordingly, all the patients were followed up for at least 10 years or until death. Among the 142 patients, lymph node metastasis was detected in 14 patients (9.9%). Univariate analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was significantly associated with lymph node metastasis (P = 0.005). In contrast, tumor budding detected by hematoxylin and eosin staining was not associated with lymph node metastasis. Multivariate logistic regression analysis showed that tumor budding with ≥ 5 tumor cells or cell clusters with expression of β-catenin in the nucleus was a significant risk factor for lymph node metastasis (odds ratio, 7.124; 95% confidence interval, 1.407-36.062). Thus, tumor budding associated with β-catenin expression is a risk factor for lymph node metastasis in submucosal invasive colorectal carcinoma.

  16. In vitro anticancer activity of ethanolic extracts of Piper nigrum against colorectal carcinoma cell lines.

    Science.gov (United States)

    Prashant, Akila; Rangaswamy, Chandini; Yadav, Anshu Kumar; Reddy, Varun; Sowmya, M N; Madhunapantula, Subbarao

    2017-01-01

    Piper nigrum (PN) is well known for its cytotoxic and pharmacological benefits. However, there is minimal documented evidence about its cytotoxic efficacy against colorectal carcinoma. We therefore sought to procure a precisely quantitative and qualitative result, pertaining the efficacy of an ethanolic extract of PN (EEPN) against colorectal carcinoma. EEPN was prepared by subjecting dried PN seeds to gradient ethanol fractionation. The total phenol content (TPC), antioxidant activity (AOA), and anti-inflammatory activity (AIA) were determined using Folin-Ciocalteu assay, ferric reducing ability of plasma and 2, 2-diphenyl-1-picrylhydrazyl methods, and human red blood cells membrane stabilizing assay, respectively. Colorectal carcinoma cell lines (HCT-116, HCT-15, and HT-29) were procured from National Centre for Cell Science, Pune, and were cultured in Dulbecco's modified eagle media supplemented with 10% fetal bovine serum and 1 mM L-glutamine. Cells were seeded into a 96-well plate, followed by treatment with increasing concentrations of EEPN. The cytotoxic efficacy was evaluated based on percentage inhibition of cells, using sulforhodamine-B assay. The IC-50 values were calculated using Prism software (Prism from GraphPad software, Inc. CA, USA). Biochemical analysis revealed that 50% EEPN exhibited higher TPC, AOA, and AIA when compared to 70% and 100% EEPN at any given concentration (P = 0.041). Cytotoxic analysis revealed a dose-dependent response with maximum cellular inhibition at TPC of 6 and 3 μg/ml, using 50% EEPN. However, 50% inhibition of cellular growth using 50% EEPN was seen with TPC of 3.2, 2.9, and 1.9 μg/ml at 24, 48, and 72 h, respectively, in HCT-15 cells. Hence, time- and dose-dependent increase in the cytotoxic efficacy of 50% EEPN against colorectal carcinoma cell lines were noted (P < 0.001). Given the significantly positive correlations exhibited between the biochemical and the cytotoxic properties evaluated in our study, we hereby

  17. Omental transposition flap in colorectal carcinoma: adjunctive use in prevention and treatment of radiation complications

    Energy Technology Data Exchange (ETDEWEB)

    Russ, J.E. (St. Joseph Hospital, Elgin, IL); Smoron, G.L.; Gagnon, J.D.

    1984-01-01

    The versatility of the omentum has led to its use as a surgical adjunct in the total oncological management of primary and recurrent colorectal carcinoma. The omentum is used as a transposition pedicle flap, broadly based on the left gastroepiploic vascular supply. Following abdominoperineal resection or low anterior resection of the rectum, the small bowel is elevated out of the pelvis by the omental bulk. The pelvic defect is reperitonealized and the risk of pelvic small bowel adhesions is diminished. With the increasing use of postoperative radiation to the pelvis for rectal carcinoma, the tolerance to therapy may be improved and the incidence of radiation enteritis and enteropathy should be reduced. Surgical complications such as leakage from low anterior anastomoses and pelvic abscesses, which may delay or contraindicate necessary postoperative radiation, are dramatically decreased. Reconstruction of the perineum with omental flap provides adequate soft tissue bulk and contour when a radical resection has been performed. The omental flap has been used in 24 patients with colorectal carcinoma; one flap was lost as a result of distal omental infarction in a patient with recurrent rectal carcinoma and radionecrosis of the perineum. The safety and ease of this procedure has allowed increased surgical innovation, especcially in the prevention and treatment of radiation complications.

  18. [Regional growth preferences in hereditary, synchronous, and metachronous colorectal carcinomas. Basics of tumor surgery Part II].

    Science.gov (United States)

    Stelzner, F

    2006-11-01

    This article discusses the therapeutic importance of the loss of self-regulation of cell division in polypoid adenomas and in the cloacogenic, cancerophilic rectal segment. Regional growth preferences can observed in familial adenomatous polyposis (FAP) and ulcerative colitis, as in other diseases featuring a cancerous disposition on the mucosa. For example, rectal carcinomas are more common than colon carcinomas if one considers the total mucosal surface area at risk. Malignant changes do not occur randomly in existing adenomas of FAP patients, and the adenomas' cell division--as in other adenomas--is governed by some degree of self-regulation. In FAP patients undergoing proctocolectomy, preferred new growth areas for carcinomas include the duodenum and ileum. In patients with synchronous colorectal cancers, the rectum is more commonly affected than other colon segments. If the rectum is resected, metachronous carcinomas are exceedingly rare in the remaining colon segments. Clinical decisions about rectal resection must be informed by understanding of the importance of this organ for anorectal continence as well as the described growth of colorectal malignancies.

  19. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

    Science.gov (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

    2017-03-01

    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Marios Giannakis

    2016-04-01

    Full Text Available Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs, memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.

  1. Soluble vascular endothelial growth factor levels in patients with primary colorectal carcinoma. The Danish RANX05 Colorectal Cancer Study Group

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Brünner, N

    2000-01-01

    INTRODUCTION: Angiogenesis is decisive in tumour progression and metastasis. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, and increased VEGF levels in patients with carcinomas may facilitate growth of both primary and secondary tumours. METHODS: Soluble (s) VEGF levels...... were determined in serum from 91 volunteer healthy blood donors and from 614 patients scheduled to undergo resection for primary colorectal cancer. None of the patients received pre- and/or post-operative chemo- and/or radiotherapy. The results of sVEGF were analysed with respect to Dukes>> stage...... disease, who had comparable values. Patients with the primary tumour localized in the colon had significantly (Pprimary tumour localized in the rectum. By classifying the patients into two groups, based on the upper limit of the 95(th)percentile of s...

  2. Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2013-08-01

    Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. MiR-4282 suppresses proliferation and mobility of human colorectal carcinoma cells by targeting semaphorin 3E.

    Science.gov (United States)

    Kang, Xing; Wang, Meng; Wang, Hao; Shen, Xiaofei; Guan, Wenxian

    2016-09-01

    MicroRNAs play an important role in cancer development. Deregulation of microRNAs can lead to tumorigenesis. Class 3 semaphorin, semaphorin 3E (Sema3E), has been shown to be implicated in tumor growth and metastasis. The role of miR-4282 in regulating colorectal carcinoma and its correlation to Sema3E remain uncertain. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the levels of miR-4282 and Sema3E in colorectal carcinoma cells and colorectal tumor tissues. Sema3E protein level in cell lines and human tissues was analyzed by western blot Transient transfections of miR-4282 inhibitor or mimics were conducted to silence or overexpress miR-4282. Sema3E siRNA was transfected to knockdown Sema3E in tumor cell lines. MTT assay was employed to measure colorectal tumor cell growth. Migration and invasion of the cells were examined by trans-well assays. Luciferase reporter assays were performed to confirm miR-4282 targeted at Sema3E. In the present study, reduced miR-4282 expression was observed in the colorectal carcinoma cell lines and human carcinoma tissues in comparison with normal human colon cells (Phuman colorectal tumor tissues (Pmobility (P<0.05). Sema3E was predicted as a target of miR-4282 in miRDB database. We found that miR-4282 overexpression significantly reduced luciferase activity of pRL-Sema3E-3'-UTR (P<0.05), but failed to alter the activity of pRL-sema3E-3'-UTR-mutation. Also, miR4282 overexpression suppressed Sema3E expression in the colorectal carcinoma cell lines. To further confirm the role of Sema3E suppression in the function of the colorectal carcinoma cells by miR-4282, HT29 and HCT116 cells were transfected with Sema3E siRNA. We found that cell growth, migration and invasion of HT29 and HCT116 cells were dramatically inhibited by Sema3E knockdown (P<0.05). Our findings suggested that miR-4282 is a tumor suppressor in colorectal carcinoma cells and exerted its inhibitory effect on the tumor cells

  4. The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma.

    Science.gov (United States)

    Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

    2016-01-01

    To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (pcitoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada. No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p<0,001 e p<0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma. Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma

  5. Glasgow Prognostic Score (GPS) can be a useful indicator to determine prognosis of patients with colorectal carcinoma.

    Science.gov (United States)

    Nozoe, Tadahiro; Matono, Rumi; Ijichi, Hideki; Ohga, Takefumi; Ezaki, Takahiro

    2014-01-01

    The Glasgow Prognostic Score (GPS), an inflammation-based score, has been used to predict the biologic behavior of malignant tumors. The aim of the current study was to elucidate a further significance of GPS in colorectal carcinoma. Correlation of GPS and modified GPS (mGPS), which are composed of combined score provided for serum elevation of C-reactive protein and hypoalbuminemia examined before surgical treatment, with clinicopathologic features was investigated in 272 patients with colorectal carcinoma. Survival of GPS 1 patients was significantly worse than that of GPS 0 patients (P= 0.009), and survival of GPS 2 patients was significantly worse than that of GPS 1 patients (P GPS (P GPS and mGPS could classify outcome of patients with a clear stratification, and could be applied as prognostic indicators in colorectal carcinoma.

  6. Applications of monoclonal antibodies and recombinant cytokines for the treatment of human colorectal and other carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Greiner, J.W.; Smalley, R.V.; Borden, E.C.; Martin, E.W.; Guadagni, F.; Roselli, M.; Schlom, J. (Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD (United States))

    1991-01-01

    Monoclonal antibodies (MAbs) which recognize a human tumor antigen, termed tumor-associated glycoprotein-72 (TAG-72), have successfully been used to localize primary as well as metastatic colorectal tumor lesions in patients. The localization of the anti-TAG-72 MAbs has also been exploited intraoperatively using a hand-held gamma probe. That procedure, termed radioimmunoguided surgery (RIGS), has identified occult tumors which were not detected using standard external imaging techniques. In another clinical trial, interferon-gamma (IFN-gamma) was administered intraperitoneally to patients diagnosed with either gastrointestinal or ovarian carcinoma with secondary ascites. Analysis of the tumor cells isolated from the malignant ascites revealed a substantial increase in TAG-72 expression on the surface of tumor cells isolated from seven of eight patients. The results provide evidence that the combination of an anti-carcinoma MAb with the administration of a cytokine, such as IFN-gamma, may be an effective approach for the detection and subsequent treatment, of colorectal carcinoma. 15 references.

  7. Treatment with capecitabine + bevacizumab following induction treatment with FOLFIRI + bevacizumab in metastatic colorectal carcinoma

    Science.gov (United States)

    Tatlı, Ali Murat; Coşkun, Hasan Şenol; Uysal, Mükremin; Arslan, Deniz; Sezgin Göksu, Sema; Güenay Gündüz, Şeyda; Çakal, Selda; Bozcuk, Hakan Şat; Savaş, Burhan

    2014-01-01

    Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, and it has been found to increase both progression-free survival and overall survival when it is combined with chemotherapeutic agents in the first-line and subsequent treatment of metastatic colorectal carcinoma. The objective of this study was to show the efficacy of maintenance treatment with capecitabine plus bevacizumab in patients with metastatic colorectal cancer who responded to treatment with FOLFIRI plus bevacizumab. The study included patients with metastatic colorectal cancer who received FOLFIRI plus bevacizumab as a first-line treatment. Patients who had objective response with FOLFIRI plus bevacizumab treatment after an average period of 6 months received a maintenance treatment with capecitabine plus bevacizumab (capecitabine 2 x 1000 mg/m2, 1 - 14 days, every 21 days, bevacizumab 7.5 mg/m2, every 21 days) until disease progression or toxicity. The time to progression on bevacizumab treatment was evaluated. A total of 29 patients (15 male, 14 female) were included. The mean age was 62 years. The mean number of cycles for maintenance treatment with capecitabine plus bevacizumab was 12. The median PFS was 16 ± 3 months, and OS was 42 ± 11 months. PFS and OS were remarkably higher in patients with a complete or near complete response to induction treatment. Fourteen patients (48%) experienced hand-foot syndrome associated with capecitabine plus bevacizumab treatment, without any severe toxicity. Inselected patients with metastatic colorectal carcinoma who had a remarkable objective response to FOLFIRI plus bevacizumab treatment, a maintenance treatment with capecitabine plus bevacizumab following FOLFIRI plus bevacizumab until disease progression may be a suitable, effective and tolerable regimen, which requires further studies. PMID:25232406

  8. The Role of Adverse Life Style Factors in the Cause of Colorectal Carcinoma in the Residents of Yazd, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Hassan Lotfi

    2016-08-01

    Full Text Available Background This study was designed to investigate the role of lifestyle factors associated with colorectal cancer risk in the population living in Yazd city. Methods This case-control study was conducted on 60 patients diagnosed with colorectal cancer and 120 subjects without any sign of colorectal cancer in the city of Yazd. Data was analyzed through SPSS16 and by using Chi-square test and Logistic regression. Results The logistic regression model showed that smoking (OR = 7.79, P = 0.04 and History of diabetes (OR = 7.31, P = 0.04 were considered as associated risk factors for colorectal cancer. Conclusions The present study showed that smoking and history of diabetes were positively associated with colorectal carcinoma.

  9. KRAS testing on colo-rectal carcinoma cytological imprints.

    Science.gov (United States)

    Malapelle, Umberto; Bellevicine, Claudio; Russo, Anna; Salatiello, Maria; Palombini, Lucio; Troncone, Giancarlo

    2011-04-01

    Anti-EGFR monoclonal antibodies, cetuximab, and panitumumab, are administrated under the condition that advanced colo-rectal cancer (CRC) carries a wild-type KRAS gene. Thus, clinicians request pathologists to genotype KRAS before treatment. In the near future routine mutation testing at the same time of the surgery may be implemented. The reliability of a rapid KRAS testing on ex vivo cytological samples obtained by direct scraping of the colon tumour tissue is here evaluated. A consecutive series of 20 surgically resected, primary CRC specimens was analysed. Fresh tissue from CRC was scraped with a scalpel blade, smeared on uncoated glass slides, air-dried and Diff-Quik stained to ensure malignant cell presence. The same tissue area was also histologically processed. Exon 2 KRAS gene mutations were evaluated on both cytological and histological specimens by dideoxy sequencing and by the DxS KRAS Mutation Test Kit (DxS, Manchester, England). Data obtained on on imprint cytology and matched histological samples showed full concordance; however, the mutation frequency was slightly higher (35%) by the DxS KRAS Mutation Test Kit than by the dideoxy sequencing (30%). Thus, colon cancer imprint cytology sample is a reliable biospecimen for both dideoxy-sequencing and DxS KRAS Mutation Test Kit analysis and it may be useful to abbreviate the KRAS assay turnaround time. Copyright © 2010 Wiley-Liss, Inc.

  10. Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome.

    Science.gov (United States)

    Mas-Moya, Jenny; Dudley, Beth; Brand, Randall E; Thull, Darcy; Bahary, Nathan; Nikiforova, Marina N; Pai, Reetesh K

    2015-11-01

    Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinomas identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathological features of colorectal and endometrial carcinomas in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified 356 (10.6%) of 3352 patients with colorectal carcinoma and 72 (33%) of 215 patients with endometrial carcinoma with deficient DNA MMR. Sixty-six patients underwent germline mutation analysis with 45 patients (68%) having evidence of a germline MMR gene mutation confirming Lynch syndrome and 21 patients (32%) having Lynch-like syndrome with no evidence of a germline mutation. Most patients with Lynch-like syndrome had carcinoma involving the right colon compared to patients with Lynch syndrome (93% versus 45%; P Lynch syndrome confirmed by germline mutation analysis. Synchronous or metachronous Lynch syndrome-associated carcinoma was more frequently identified in patients with Lynch syndrome compared to Lynch-like syndrome (38% versus 7%; P = .04). There were no significant differences in clinicopathological variables between patients with Lynch-like syndrome and Lynch syndrome with endometrial carcinoma. In summary, 32% of patients with MMR deficiency concerning Lynch syndrome will have Lynch-like syndrome. Our results demonstrate that patients with Lynch-like syndrome are more likely to have right-sided colorectal carcinoma, less likely to have synchronous or metachronous Lynch syndrome-associated carcinoma, and less likely to demonstrate isolated loss of MSH6 expression within their tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. The prognostic value of survivin expression in patients with colorectal carcinoma: a meta-analysis.

    Science.gov (United States)

    Huang, Yu-Jing; Qi, Wei-Xiang; He, Ai-Na; Sun, Yuan-Jue; Shen, Zan; Yao, Yang

    2013-10-01

    The prognostic role of survivin in colorectal carcinoma remains controversial. This meta-analysis aimed to explore the association between survivin expression and survival outcomes in patients with colorectal carcinoma. A comprehensive literature search for relevant studies published up to April 2013 was performed using PubMed, MEDLINE and ISI Web of Science. Only articles in which survivin was detected by immunohistochemical staining were included. This meta-analysis was done using STATA and Review Manager. A total of 1784 patients from 14 studies were included in the analysis. Our results showed that survivin overexpression in patients with colorectal carcinoma was significantly associated with poor overall survival (hazard ratio, 1.505; 95% confidence interval, 1.197-1.893; P = 0.000) and disease-free survival (hazard ratio, 2.323; 95% confidence interval, 1.687-3.199; P = 0.000). The results indicated that a significant relationship between survivin expression and overall survival was also exhibited in studies with an Asian country (hazard ratio, 1.684; 95% confidence interval, 1.477-1.921), patient number >100 (hazard ratio, 1.604; 95% confidence interval, 1.371-1.877), the cut-off level 50% (hazard ratio, 1.528; 95% confidence interval, 1.056-2.211) and the hazard ratio estimated (hazard ratio, 1.643; 95% confidence interval, 1.262-2.139). Moreover, upregulation of survivin was associated with stages (III/IV vs. I/II: odds ratio, 1.08; 95% confidence interval, 0.80-1.46), the depth of invasion (T3/T4 vs. T1/T2: odds ratio, 1.79; 95% confidence interval 0.67-4.74), lymph node metastasis (positive vs. negative: odds ratio, 1.49; 95% confidence interval, 0.99-2.26), distant metastasis (positive vs. negative: odds ratio, 2.37; 95% confidence interval, 0.99-5.72) and grade of differentiation (well/moderate vs. poor: odds ratio, 1.02; 95% confidence interval, 0.43-2.41), but without significance. The present meta-analysis indicated that upregulation of survivin was

  12. Colorectal carcinoma in a ten-year-old girl: A case report

    Directory of Open Access Journals (Sweden)

    Sarbani Chattopadhyay

    2012-01-01

    Full Text Available Colorectal carcinoma is very rare in childhood. In this case report, we depict a ten-year-old girl who presented with features of intestinal obstruction which turned out to be due to poorly differentiated mucin secreting adenocarcinoma of descending colon. Only increased awareness of this malignancy in this age-group and a high index of suspicion can help when a child complains of persistent pain of abdomen, altered bowel habits or rectal bleeding, and may provide diagnosis at an earlier stage, thereby improving the prognosis.

  13. High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival

    DEFF Research Database (Denmark)

    Cintin, Christina; Johansen, Julia S; Christensen, Ib Jarle

    2002-01-01

    carcinoma are associated with a significantly poorer prognosis compared to patients with normal serum YKL-40. In the current study the authors evaluated the value of serum YKL-40 in monitoring patients with colorectal carcinoma. METHODS: YKL-40 was determined by an in-house radioimmunoassay method in serum...... died. RESULTS: Serum YKL-40 was significantly decreased in the first postoperative blood sample in 62% of patients with high preoperative levels. In addition, patients with high serum YKL-40 (adjusted for age) six months after curative operation had significantly shorter survival times (P = 0...... that patients exhibiting elevated serum YKL-40 had an increased hazard for death within the following six months compared to those patients with normal serum YKL-40 level (hazard ratio [HR] = 9.6, 95% confidence interval [CI]: 6.0-15.5, P

  14. CCL5 neutralization restricts cancer growth and potentiates the targeting of PDGFRβ in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Béatrice Cambien

    Full Text Available Increased CCL5 levels are markers of an unfavourable outcome in patients with melanoma, breast, cervical, prostate, gastric or pancreatic cancer. Here, we have assessed the role played by CCL5/CCR5 interactions in the development of colon cancer. To do so, we have examined a number of human colorectal carcinoma clinical specimens and found CCL5 and its receptors over-expressed within primary as well as liver and pulmonary metastases of patients compared to healthy tissues. In vitro, CCL5 increased the growth and migratory responses of colon cancer cells from both human and mouse origins. In addition, systemic treatment of mice with CCL5-directed antibodies reduced the extent of development of subcutaneous colon tumors, of liver metastases and of peritoneal carcinosis. Consistently, we found increased numbers of CD45-immunoreactive cells within the stroma of the remaining lesions as well as at the interface with the healthy tissue. In contrast, selective targeting of CCR5 through administration of TAK-779, a CCR5 antagonist, only partially compromised colon cancer progression. Furthermore, CCL5 neutralization rendered the tumors more sensitive to a PDGFRβ-directed strategy in mice, this combination regimen offering the greatest protection against liver metastases and suppressing macroscopic peritoneal carcinosis. Collectively, our data demonstrate the involvement of CCL5 in the pathogenesis of colorectal carcinoma and point to its potential value as a therapeutic target.

  15. Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma.

    Science.gov (United States)

    Repass, John; Maherali, Nimet; Owen, Kate

    2016-02-11

    The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of key experiments from 'Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma' by Castellarin and colleagues published in Genome Research in 2012 (Castellarin et al., 2012). The experiment to be replicated is reported in Figure 2. Here, Castellarin and colleagues performed a metagenomic analysis of colorectal carcinoma (CRC) to identify potential associations between inflammatory microorganisms and gastrointestinal cancers. They conducted quantitative real-time PCR on genomic DNA isolated from tumor and matched normal biopsies from a patient cohort and found that the overall abundance of Fusobacterium was 415 times greater in CRC versus adjacent normal tissue. These results confirmed earlier studies and provide evidence for a link between tissue-associated bacteria and tumorigenesis. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.

  16. Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis.

    Science.gov (United States)

    Meling, G. I.; Lothe, R. A.; Børresen, A. L.; Hauge, S.; Graue, C.; Clausen, O. P.; Rognum, T. O.

    1991-01-01

    Alterations within the retinoblastoma (Rb) gene, as detected by the VNTR probe p68RS2.0, and flow cytometric DNA pattern have been analysed in 255 colorectal carcinomas. A total of 35.3% of the tumours had alterations within the Rb gene. Amplification of one allele was demonstrated in 29.5% of the tumours, and loss of heterozygosity was found in 11.5%. No association was found between amplification within the Rb gene and clinicopathological characteristics of the patients. The high frequency of alterations demonstrated within the Rb gene, suggests that this gene is involved in colorectal carcinogenesis with amplification as by far the most abundant genetic alteration. This may imply that the Rb gene has an oncogene-like function in colorectal carcinomas, rather than acting as a tumour suppressor gene. Sixty-three per cent of the carcinomas were DNA aneuploid, and a significant association was demonstrated between amplification within the Rb gene and DNA aneuploidy (P less than 0.01). Two other chromosome loci were analysed, on chromosome 1p (probe pYNZ2) and on chromosome 2p (probe pYNH24), respectively. On chromosome 1p, heterozygous loss was found in 22.2% of the tumours, indicating an involvement of this chromosome in a subset of colorectal carcinomas. Images Figure 1 PMID:1911187

  17. WNT1 inducible signaling pathway protein 3, WISP-3, a novel target gene in colorectal carcinomas with microsatellite instability.

    Science.gov (United States)

    Thorstensen, L; Diep, C B; Meling, G I; Aagesen, T H; Ahrens, C H; Rognum, T O; Lothe, R A

    2001-12-01

    Microsatellite instability (MSI) is the phenotype of colorectal carcinomas with defect mismatch repair. Genes with repetitive sequences within their coding regions are targets for mutations in these tumors. We have evaluated 2 novel candidate genes for potential involvement in development of MSI colorectal carcinomas and compared them with alterations in known target genes. The MSI status was determined by multiplex polymerase chain reactions (PCRs) of 5-17 markers in a Norwegian series of 275 colorectal carcinomas. All MSI tumors were analyzed for gene mutations using fluorescence PCR followed by capillary electrophoresis. Two novel candidate genes, WNT1-inducible signaling pathway protein 3 (WISP-3) and caspase-1, and 9 known target genes were analyzed. Thirteen percent of the tumors were MSI-high (H) and 12% were MSI-low (L). Thirty-three of 37 MSI-H vs. 1 of 34 MSI-L tumors showed mutations in the target genes (P WISP-3 was mutated in 31% of the MSI-H tumors. The frequencies of frameshift mutations in the known target genes were comparable with other studies. The relative high frequency of mutation, higher than those seen for other known target genes, the predicted truncation of the protein product, and the homology with WISP-1 and WISP-2, 2 proteins induced downstream of WNT1 signaling, strongly suggest WISP-3 as a novel target in development of MSI-H colorectal carcinomas.

  18. Colorectal carcinoma tumour budding and podia formation in the xenograft microenvironment.

    Science.gov (United States)

    Prall, Friedrich; Maletzki, Claudia; Hühns, Maja; Krohn, Mathias; Linnebacher, Michael

    2017-01-01

    Tumour budding and podia formation are well-appreciated in surgical pathology as an aggressive invasion phenotype of colorectal carcinoma cells that is attained in the microenvironment of the invasive margin. In this study, we addressed how tumour budding and podia formation feature in xenografts. Primary colorectal carcinomas (N = 44) of various molecular types (sporadic standard type, high-degree microsatellite-unstable, CpG island methylator phenotype) were transplanted subcutaneously into T and B cell-deficient NSG mice, making possible immunohistochemistry with routine surgical pathology antibodies. Tumor budding and podia formation were both appreciably present in the xenografts. Quantitative evaluations of cytokeratin immunostains of primaries and their corresponding xenografts showed a reduction of tumour buds in the xenografts. Furthermore, in xenografts tumour cells were completely negative by pSTAT3 immunohistochemistry, indicating absence of cytokine/chemokine signalling, but nuclear β-catenin and SMAD4 immunostainings as read-out of wnt and BMP pathway activation, respectively, were maintained. Carcinoma cells in most xenografts retained immunostaining of at least some nuclei by immunohistochemistry with antibodies against pERK1/2. K-ras/B-raf mutational status did not correlate with tumour budding or podia formation in the xenografts. Our results indicate that tumour budding and podia formation can be modelled by xenografting, and in NSG mice it can be studied with the same immunohistochemical methods as used for primaries in surgical pathology. Dysregulation of wnt and BMP signalling appears to be transferred into the xenograft microenvironment, but not cytokine/chemokine signalling.

  19. Evaluation of 1p Losses in Primary Carcinomas, Local Recurrences and Peripheral Metastases from Colorectal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Lin Thorstensen

    2000-01-01

    Full Text Available Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of ip deletions in primary carcinomas (n=28, local recurrences (n=19 and metastases (n=33 from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04. The smallest region of 1p deletion overlap (SRO defined separately for each group of lesions had the region between markers Di S2647 and D1 S2644, at 1 p35-36, in common. The genes PLA2G2A (1p35.1-36 and TP73 (1p36.3 were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18 were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%. The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences.

  20. A pathway-centric survey of somatic mutations in Chinese patients with colorectal carcinomas.

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    Chao Ling

    Full Text Available Previous genetic studies on colorectal carcinomas (CRC have identified multiple somatic mutations in four candidate pathways (TGF-β, Wnt, P53 and RTK-RAS pathways on populations of European ancestry. However, it is under-studied whether other populations harbor different sets of hot-spot somatic mutations in these pathways and other oncogenes. In this study, to evaluate the mutational spectrum of novel somatic mutations, we assessed 41 pairs of tumor-stroma tissues from Chinese patients with CRC, including 29 colon carcinomas and 12 rectal carcinomas. We designed Illumina Custom Amplicon panel to target 43 genes, including genes in the four candidate pathways, as well as several known oncogenes for other cancers. Candidate mutations were validated by Sanger sequencing, and we further used SIFT and PolyPhen-2 to assess potentially functional mutations. We discovered 3 new somatic mutations in gene APC, TCF7L2, and PIK3CA that had never been reported in the COSMIC or NCI-60 databases. Additionally, we confirmed 6 known somatic mutations in gene SMAD4, APC, FBXW7, BRAF and PTEN in Chinese CRC patients. While most were previously reported in CRC, one mutation in PTEN was reported only in malignant endometrium cancer. Our study confirmed the existence of known somatic mutations in the four candidate pathways for CRC in Chinese patients. We also discovered a number of novel somatic mutations in these pathways, which may have implications for the pathogenesis of CRC.

  1. Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas

    OpenAIRE

    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

    2013-01-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 col...

  2. Potential Biomarkers of Colorectal Adenoma–Dysplasia–Carcinoma Progression: mRNA Expression Profiling and In Situ Protein Detection on TMAs Reveal 15 Sequentially Upregulated and 2 Downregulated Genes

    Directory of Open Access Journals (Sweden)

    Orsolya Galamb

    2009-01-01

    Full Text Available Background: As most colorectal cancers (CRC develop from villous adenomas, studying alterations in gene expression profiles across the colorectal adenoma–dysplasia–carcinoma sequence may yield potential biomarkers of disease progression.

  3. Antibody-based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing

    DEFF Research Database (Denmark)

    Christensen, Mariann; Katballe, Niels; Wikman, Friedrik

    2002-01-01

    BACKGROUND: Germline mutations in the DNA mismatch repair genes, MSH2, MLH1, and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high...... carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty-five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced. RESULTS: Ninety-two percent of patients...... the three methods was found in 74 % of the tumors. CONCLUSIONS: The authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated....

  4. Circulating gastrin concentrations in patients at increased risk of developing colorectal carcinoma.

    Science.gov (United States)

    Paterson, Adrienne C; Macrae, Finlay A; Pizzey, Cathy; Baldwin, Graham S; Shulkes, Arthur

    2014-03-01

    An increase in circulating concentrations of gastrin or gastrin precursors such as progastrin and glycine-extended gastrin has been proposed to promote the development of colorectal carcinomas (CRC). The aim of this study was to investigate whether or not circulating gastrin concentrations were increased in patients with an increased risk of developing CRC. Patients were divided according to their risk into the five following groups: familial adenomatous polyposis (n = 20), hereditary non-polyposis colorectal cancer (n = 53), cluster of common colorectal cancers (n = 13), personal history and/or family history of adenomatous polyps or CRC (n = 150) and controls (n = 42). Radioimmunoassay with four region-specific gastrin antisera was used to measure progastrin, glycine-extended gastrin (gastrin-gly), amidated gastrin (gastrin-amide), and total gastrin in peripheral blood taken at the time of colonoscopy. Compared with the control group, familial adenomatous polyposis patients had significantly higher median values of total gastrin (29.8 pM vs 16.9 pM, P = 0.003) and gastrin-amide (17.1 pM vs 12.0 pM, P = 0.015). Patients with a personal or family history of adenomatous polyps or CRC also had higher circulating concentrations of total gastrin (21.8 pM) compared with controls (P gastrin, progastrin, and gastrin-amide than patients without polyps. Concentrations of gastrin precursors are increased in particular groups with an increased risk of developing CRC.

  5. Evaluation of preoperative geriatric assessment of elderly patients with colorectal carcinoma. A retrospective study.

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    Indrakusuma, R; Dunker, M S; Peetoom, J J; Schreurs, W H

    2015-01-01

    Elderly patients with colorectal carcinoma are screened with the Identification of Seniors at Risk (ISAR) questionnaire to identify frail patients. These patients are more at risk for mortality and morbidity and are referred to the geriatric specialist for assessment (Dutch acronym: DOG). The DOG assessment aims to preoperatively optimize the patient in order to improve postoperative outcomes. This study evaluates if the DOG assessment influences postoperative outcome after colorectal surgery. Retrospective cohort and match-control study. Elderly patients who underwent elective resection between 01-01-2008 and 01-08-2013 in the Medical Centre Alkmaar were included. Patients with a positive ISAR score were referred to the geriatric specialists for DOG assessment (DOG patients). DOG assessment encompassed comprehensive geriatric assessment and interventions. Mortality, delirium and length of hospital stay. postoperative complications. Cohort ISAR- (2008-2010, no ISAR questionnaire) is compared with cohort ISAR+ (2011-2013, ISAR questionnaire). Match-control comparison: DOG patients are compared with matched controls from cohort ISAR-. Compared to their matched controls, DOG patients were older and had a higher prevalence of certain risk factors for postoperative delirium. In both comparisons, no statistical significant differences were found between the groups in mortality and postoperative delirium. Length of stay was significantly shorter in cohort ISAR+. While the DOG patients were significantly more at risk for postoperative complications, the DOG patients had comparable postoperative outcomes as their matched controls. We therefore conclude that the DOG assessment has a positive influence on the postoperative outcomes after colorectal surgery. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Colorectal carcinoma evaluated by incremental dynamic CT; Comparison of CT density, histology, and tumor size

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    Furukawa, Hiroyoshi; Hara, Tsuyoshi; Taniguchi, Tetsushi (Shimizu Kosei Hospital, Shizuoka (Japan))

    1992-06-01

    Evaluation of incremental dynamic CT scan and histologic findings were compared in order to clarify the cause of the differences in colorectal carcinoma as observed on CT after administration of contrast medium. In 48 cases demonstrated on postcontrast dynamic CT scan, the CT density of the tumor was homogeneous (Type 1) in 26 (54.2%) cases and heterogeneous (Type 2) in 22 (45.8%) cases. Well differentiated adenocarcinoma was seen as Type 1 in 11 of 13 (84.6%) cases while moderately differentiated adenocarcinoma was of Type 1 in 15 of 29 (51.7%) cases. Poorly differentiated and mucinous adenocarcinoma were detected as Type 2 in all cases. A comparison of CT types and tumor size showed that as tumor size increased, the number of Type 1 cases decreased while Type 2 cases increased. Histologically, high density areas consisted mainly of well-developed tubular, branching glands of adenocarcinoma, while low density areas were composed of fibrous or mucinous stroma or necrosis. Dynamic CT scans for colorectal cancer are useful not only for preoperative staging but also for tissue characterization. (author).

  7. Cell cycle flow cytometric analysis in the diagnosis and management of colorectal carcinoma.

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    Sampedro, A; Salas-Bustamante, A; López-Artimez, M; García-Muñíz, J L; Urdiales, G

    1999-08-01

    To establish prognostic models and protocols for individualized management in colorectal carcinoma patients based on both clinical and DNA flow cytometric parameters. Prospective study of 88 colon carcinoma patients with a minimum follow-up of 12 months, operated on with the intent to cure and not treated with radiotherapy or chemotherapy. All the cases were subjected to a clinical evaluation: age, sex, tumor localization and size, histologic grade, tumor stage, disease-free interval, survival and flow cytometric study (ploidy, DNA index and S-phase fraction [SPF]). From the total of 88 neoplasms studied, 56 (63.6%) were from males and 32 (36.4%) from females; 30 (34%) were located in the right side of the colon, 7 (8%) in the transverse colon and 51 (58%) in the left side of the colon. Eleven (12.5%) were stage I, 52 (59.1%) stage II and 25 (28%) stage III. Forty-two (47.7%) were diploid and 46 (52.3%) aneuploid. The S-phase mean was 14.6% (12% for diploids and 16.9% for aneuploids). During the follow-up period, 26.1% of diploid tumors recurred, whereas aneuploid tumors recurred in 36.9% (P < .05). SPF from diploid and aneuploid tumors was analyzed separately. Regarding relapse-free interval, the behavior of diploid tumors with a high SPF was similar to that of aneuploid ones. Two kinetic profiles were established, favorable (diploid tumors with low S phase) and unfavorable (diploid with high S phase and all aneuploid tumors), that had significant prognostic value for progression and survival and that allowed identification of patients at high risk of recurrence. We formulated a prognostic index according to SPF and tumor stage that has discriminatory capacity for biologic behavior in colorectal tumors.

  8. CXCL12 chemokine expression and secretion regulates colorectal carcinoma cell anoikis through Bim-mediated intrinsic apoptosis.

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    Luke J Drury

    Full Text Available BACKGROUND: Resistance to anoikis, apoptosis triggered by a loss of cellular adhesion to the underlying extracellular matrix, is a hallmark of metastatic cancer. Previously we have shown re-establishment of CXCL12 expression in colorectal carcinoma cells inhibits metastasis by enhancing anoikis sensitivity. The objective of these studies was to define the signaling mechanisms regulating CXCL12-mediated anoikis. METHODOLOGY/PRINCIPAL FINDINGS: Adhesion, examined by crystal violet staining, immunofluorescence microscopy, and immunoblot analysis indicated decreased focal adhesion signaling corresponding with loss of adhesion in cells constitutively simulated by CXCL12. Loss of adhesion was inhibited by pertussis toxin treatment, indicating CXCL12 regulating anoikis through G(αi-protein coupled receptors. Non-adherent HCT116 and HT29 colorectal carcinoma cells expressing CXCL12 exhibited enhanced anoikis sensitivity by propidium iodide staining, caspase activity assays, and immunoblot compared to GFP control cells. CXCL12 producing carcinomas cultured on poly-HEMA displayed heightened Bim and loss of Mcl-1 and Bcl-2 preceding cytochrome c release, and caspase-9 activation. RNAi knockdown of Bim reversed anoikis sensitivity of CXCL12-expressing cells and fostered increased soft-agar foci formation and hepatic tumors in an orthotopic mouse model of metastasis. CONCLUSIONS/SIGNIFICANCE: These data indicate CXCL12 provides a barrier to metastasis by increasing anoikis via activation of a Bim-mediated intrinsic apoptotic pathway. These results underscore the importance of retaining CXCL12 expression to sensitize colorectal carcinomas to anoikis and minimize tumor progression.

  9. Reduced expression of EphA5 is associated with lymph node metastasis, advanced TNM stage, and poor prognosis in colorectal carcinoma.

    Science.gov (United States)

    Gu, Shudong; Feng, Jia; Jin, Qin; Wang, Wei; Zhang, Shu

    2017-05-01

    Colorectal carcinoma (CRC) is the third most common cancer and a major cause of morbidity and mortality throughout the world. The prognosis of patients has improved markedly over the last 15 years because of the introduction of new therapy including molecular target drugs. To comprehensively understand the molecular process of carcinogenesis of colorectal carcinoma is essential for the diagnosis, prognosis and treatment. EphA5 is a member of the Eph family and plays a critical role in carcinogenesis of lung cancer, prostate cancer, and breast cancer. The expression profile and the role of EphA5 in colorectal carcinoma have not been well investigated till now. In this study, a set of colorectal carcinoma specimens was subjected to immunohistochemical assay using an EphA5 specific antibody. The relationship between the expression of EphA5 and clinicopathological parameters was statistically analyzed. EphA5 was positively expressed in all tested normal mucosa specimens (120/120, 100%) and partly in colorectal carcinoma specimens (70/120, 58.3%). The loss of EphA5 protein was associated with depth of wall invasion (P=0.002), poor tumor differentiation (Pcarcinoma and it may be a new therapeutic target for colorectal carcinoma.

  10. PET and PET/CT imaging for the earliest detection and treatment of colorectal carcinoma

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    Kevin Carter

    2005-10-01

    Full Text Available Approximately 150,000 new cases of colorectal cancer are diagnosed each year with the life time risk of developing colon caner in developed nations being 4.6% in men and 3.2% in women. Screening patients is essential early detection of colon carcinoma to aid in complete resection. Unfortunately current screening methods carry with them poor patient compliance. PET and PET/CT may be a significant part of this screening solution. The authors reviewed and analyzed the English language articles and case reports identified on Medline during the last 10 years. PET and PET/CT results for colorectal carcinoma were tabulated and presented for the fifth Scientific Meeting of the Brazilian Society of Nuclear Biosciences. Though most studies have been retrospective analysis in using PET for staging for other malignant processes the cases that have identified additional uptake in the colon are important. The accuracy when utilizing PET and PET/CT in this screening method has a sensitivity between 65 and 90% with a specificity of 84 to 90% and a positive predictive value 71 to 78%. Early stages of malignancies and pre-cancerous polyps avidly accumulates F-18 Deoxyflouro glucose allowing us to conclude that whole body PET and PET/CT is an essential component in the work up, staging or treatment monitoring in colon carcinoma. We have to continue to accumulate data for possible introduction for whole body PET and PET/CT scanning for colon carcinoma and precancerous polyps.Aproximadamente, 150 000 novos casos de câncer coloretal são diagnosticados, anualmente, em países em desenvolvimento. Destes, 4,6% em homens e 3,2% em mulheres. A triagem de pacientes é essencial na detecção precoce do carcinoma de colon para ajudar na completa ressecção. Infelizmente, os métodos de exame atualmente disponíveis contam com uma baixa adesão dos pacientes. Parte significativa da solução desse problema pode estar no uso de PET e PET/CT. Os autores revisaram e

  11. SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells.

    Science.gov (United States)

    Dallol, Ashraf; Morton, Dion; Maher, Eamonn R; Latif, Farida

    2003-03-01

    We have shown recently that SLIT2 has tumor suppressor activity and that it is epigenetically silenced in >40% of lung and breast tumors. In this study, we have analyzed the methylation status of SLIT2 in primary colorectal cancers and matching normal colorectal mucosa. SLIT2 promoter region methylation was found in 23 (72%) of 32 primary colorectal cancers. In contrast, normal colorectal mucosa from the same patients exhibited significantly lower levels of SLIT2 promoter region hypermethylation. SLIT2 methylation was reversed and expression restored by treating colorectal tumor cell lines with the demethylating agent 5-aza-2-deoxycytidine. Loss of heterozygosity at D4S1546 marker, which maps within 100 kb of the SLIT2 gene, was observed in 39% of the methylated tumors. Furthermore, SLIT2 epigenetic silencing was independent of ROBO1/p16/RASSF1A hypermethylation. The presence of SLIT2 methylation was also independent of the presence of K-RAS mutations. Ectopic expression of SLIT2 diminished the ability to form colonies in two colorectal tumor cell lines. In addition, conditioned medium from SLIT2-transfected COS-7 cells reduced cell growth and induced apoptosis in SW48 colorectal tumor cell line. In conclusion, SLIT2 is an excellent candidate tumor suppressor gene for colorectal cancer.

  12. Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability.

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    Kim, Jung Ho; Rhee, Ye-Young; Kim, Kyung-Ju; Cho, Nam-Yun; Lee, Hye Seung; Kang, Gyeong Hoon

    2014-12-01

    Annexin A10 (ANXA10) has recently been identified as a marker of sessile serrated adenomas/polyps of the colorectum. Although the serrated neoplasia pathway is thought to be involved in the majority of microsatellite instability-high (MSI-H) sporadic colorectal carcinomas (CRCs), the clinicopathological implications of ANXA10 expression in CRC are unknown. Here, we evaluated ANXA10 expression status in 168 MSI-H CRCs by immunohistochemistry. Among 168 MSI-H CRCs, nuclear staining for ANXA10 in tumor cells revealed 28 cases (17%) with ANXA10-positive (ANXA10+) tumors. Most of the ANXA10+ tumors were located in the proximal colon (96%, p < 0.001). The ANXA10+ phenotype in MSI-H CRC was significantly associated with female gender (68%, p = 0.016), CpG island methylator phenotype-high (CIMP-H) (68%, p < 0.001), MLH1 promoter hypermethylation (61%, p < 0.001), loss of MLH1 expression (82%, p = 0.019), and wild-type KRAS status (96%, p = 0.023). Survival analysis revealed no prognostic significance of ANXA10 expression in MSI-H CRC. In conclusion, ANXA10+ MSI-H colon carcinomas are characterized by serrated pathway features, including proximal location, female predominance, and high frequencies of CIMP-H status and MLH1 methylation. © 2014 APMIS. Published by John Wiley & Sons Ltd.

  13. HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker

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    Giuseppe Sconocchia

    2014-01-01

    Full Text Available The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC tumors, its association with the clinical course of the disease, and the underlying mechanism(s. Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1α (IL-1α production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1α production by monocytes.

  14. Template reporting matters--a nationwide study on histopathology reporting on colorectal carcinoma resections.

    Science.gov (United States)

    Haugland, Hans Kristian; Casati, Bettina; Dørum, Liv Marit; Bjugn, Roger

    2011-01-01

    Complete and accurate histopathology reports are fundamental in providing quality cancer care. The Cancer Registry of Norway and the Norwegian Society of Pathology have previously developed a national electronic template for histopathology reporting on colorectal carcinoma resection specimens. The present study was undertaken to investigate (1) whether quality routines in Norwegian pathology laboratories might affect completeness of such histopathology reports and (2) whether the national electronic template improves completeness of histopathology reports compared with other modes of reporting. A questionnaire on quality routines was sent to the 21 pathology laboratories in Norway. All histopathology reports on colorectal cancer submitted to the Cancer Registry for a 3-month period in the autumn of 2007 were then evaluated on the mode of reporting and the presence of 11 key parameters. Of the 20 laboratories that handled resection specimens, 16 had written guidelines on histopathology reporting. Of these, 4 used the national electronic template, 5 used checklists, 3 used locally developed electronic templates, whereas the remaining 4 had neither obligatory checklists nor templates. Of the 650 histopathology reports submitted to the Cancer Registry in the 3-month period, the national template had been used in 170 cases (26.2%), checklists/locally developed templates in 112 cases (17.2%), and free text in 368 cases (56.6%). Quality routines in the pathology laboratories clearly governed reporting practice and the completeness of the histopathology reports. Use of the national electronic template significantly improved (P < .05) the presence of the 11 key parameters compared with reporting by checklists, locally developed electronic templates, or free text. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Cannabinoid receptor-independent cytotoxic effects of cannabinoids in human colorectal carcinoma cells: synergism with 5-fluorouracil.

    Science.gov (United States)

    Gustafsson, Sofia B; Lindgren, Theres; Jonsson, Maria; Jacobsson, Stig O P

    2009-03-01

    Cannabinoids (CBs) have been found to exert antiproliferative effects upon a variety of cancer cells, including colorectal carcinoma cells. However, little is known about the signalling mechanisms behind the antitumoural effect in these cells, whether the effects are shared by endogenous lipids related to endocannabinoids, or whether such effects are synergistic with treatment paradigms currently used in the clinic. The aim of this preclinical study was to investigate the effect of synthetic and endogenous CBs and their related fatty acids on the viability of human colorectal carcinoma Caco-2 cells, and to determine whether CB effects are synergistic with those seen with the pyrimidine antagonist 5-fluorouracil (5-FU). The synthetic CB HU 210, the endogenous CB anandamide, the endogenous structural analogue of anandamide, N-arachidonoyl glycine (NAGly), as well as the related polyunsaturated fatty acids arachidonic acid and eicosapentaenoic acid showed antiproliferative and cytotoxic effects in the Caco-2 cells, as measured by using [(3)H]-thymidine incorporation assay, the CyQUANT proliferation assay and calcein-AM fluorescence. HU 210 was the most potent compound examined, followed by anandamide, whereas NAGly showed equal potency and efficacy as the polyunsaturated fatty acids. Furthermore, HU 210 and 5-FU produced synergistic effects in the Caco-2 cells, but not in the human colorectal carcinoma cell lines HCT116 or HT29. The compounds examined produced cytotoxic, rather than antiproliferative effects, by a mechanism not involving CB receptors, since the CB receptor antagonists AM251 and AM630 did not attenuate the effects, nor did pertussis toxin. However, alpha-tocopherol and the nitric oxide synthase inhibitor L-NAME attenuated the CB toxicity, suggesting involvement of oxidative stress. It is concluded that the CB system may provide new targets for the development of drugs to treat colorectal cancer.

  16. The potential effect of biological sealants on colorectal anastomosis healing in experimental research involving severe diabetes.

    Science.gov (United States)

    Stergios, K; Kontzoglou, K; Pergialiotis, V; Korou, L M; Frountzas, M; Lalude, O; Nikiteas, N; Perrea, D N

    2017-03-01

    Colorectal anastomoses continuous to pose a significant challenge in current surgical practice. Anastomotic leakage remains one of the most frequent and dramatic complications of colorectal surgery, even in centres of high specialisation. Diabetes is a well-established independent factor which results in higher anastomotic leakage rates. Fibrin sealants have been applied in experimental and clinical studies for the prevention of anastomotic dehiscence. However, little is known regarding their impact on diabetic patients. Several fibrin sealants have been proposed as adjunct to standard surgical techniques to prevent leakage from colonic anastomoses following the reversal of temporary colostomies, approved for general haemostasis. This review summarises current advances in colorectal anastomoses and provides evidence that may strengthen the need for tissue sealants in colorectal anastomoses of diabetic patients. We searched Medline (1966-2016) and Scopus (2004-2016) for current evidence in the field. To date, there is no evidence to support the use of fibrin sealants as an adjunct in diabetic patients who undergo colorectal surgery. Experimental animal models with extreme diabetes could be of significant use in the present field and further research is needed prior to application of fibrin sealants in a clinical setting.

  17. Differential BCCIP gene expression in primary human ovarian cancer, renal cell carcinoma and colorectal cancer tissues.

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    Liu, Xiaoxia; Cao, Lingling; Ni, Jinsong; Liu, Ning; Zhao, Xiaoming; Wang, Yanfang; Zhu, Lin; Wang, Lingyao; Wang, Jin; Yue, Ying; Cai, Yong; Jin, Jingji

    2013-12-01

    Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has been implicated in many cellular processes including cell cycle regulation, DNA recombination and damage repair, telomere maintenance, embryonic development and genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in tumor suppression, has been identified in some primary cancers. Thus, we investigated the role of BCCIP expression in a large sample of clinically diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues, quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical staining (IHC) approaches were used to detect and measure gene expression. Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in 74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples, respectively. Although BCCIP expression in three different tumor tissues decreased, the relationship between BCCIP expression and clinicopathological features of each cancer was distinct. Compared to normal tissues, BCCIP expression in ovarian cancers was significantly downregulated in serous, endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues (povarian cancer and RCC tissue samples (povarian cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis of these cancers.

  18. Tumor budding in colorectal carcinoma assessed by cytokeratin immunostaining and budding areas: possible involvement of c-Met.

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    Satoh, Keisuke; Nimura, Satoshi; Aoki, Mikiko; Hamasaki, Makoto; Koga, Kaori; Iwasaki, Hiroshi; Yamashita, Yuichi; Kataoka, Hiroaki; Nabeshima, Kazuki

    2014-11-01

    Tumor budding/sprouting has been shown to be an independent adverse prognostic factor in T1 and T3N0 colorectal carcinomas, however, its assessment could be improved by more accurate identification of budding carcinoma cells and consideration of budding areas. Moreover, tumor budding mechanisms are yet to be defined. In this study, we evaluated the identification of budding tumor cells by either H&E staining alone or H&E with immunohistochemistry and developed a scoring system based on budding grades and areas. We examined whether the budding score correlated with clinicopathologic features and prognosis and the association between tumor budding/sprouting and c-Met protein expression and phosphorylation and MET gene copy numbers because c-Met is known to play an important role in colorectal carcinoma tumorigenesis. Cytokeratin immunohistochemistry could identify tumors with shorter disease-free survival (DFS) from the low-grade budding group assessed with H&E alone. High budding scores based on budding grade and area were more significantly correlated with DFS than scores obtained using the budding grade alone. In tumors with a high budding score, c-Met expression and phosphorylation levels and MET gene copy numbers were significantly increased at the invasive front compared with those in superficial tumor portions. This study showed for the first time that high levels of phospho-c-Met at the invasive front were significantly associated with a high budding score and shorter DFS. In conclusion, a budding score assessed by budding grades and budding-positive areas correlates highly with clinicopathologic aggressive features of colorectal carcinoma. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  19. Differences in endoscopic classification of early colorectal carcinoma between China and Japan: a comparative study.

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    Zhu, Ren-Min; Wang, Fang-Yu; Hirata, Ichiro; Katsu, Ken-Ichi; Xiao, Shu-Dong; Yu, Zhong-Lin; Zhang, Zhi-Hong; Xu, Zhao-Min

    2003-09-01

    To compare the differences in the endoscopic classification of early colorectal carcinoma (CRC) between Japan and China. Ten cases of early CRC were included in the study. After reviewing the color pictures of these cases, 5 Japanese endoscopists and 5 Chinese endoscopists made their classificatory diagnosis individually using the current Japanese classification, and indicated their findings on which the diagnosis was based. Some lesions diagnosed by the Japanese endoscopists as IIa or IIa plus IIc, were classified as Is or Isp by the Chinese endoscopists. For superficial lesions consisting of elevation plus central depression, IIa plus depression, IIa plus IIc or IIc plus IIa were classified according to the ratio of elevated area/depressed area. However, international as well as interobserver difference still existed in the classification of such lesions. In addition, most Chinese endoscopists overlooked slightly depressed part on the top of a protruded lesion. Laterally spreading tumor, a special type of IIa, was identified as LST by some Japanese endoscopists. Discrepancies on macroscopic classification for early CRC do exist between Japanese and Chinese endoscopists, which are found not only in terminology but also in recognition of some lesions. In order to develop a universal classification, it needs for international communication and cooperation.

  20. Increased Free Circulating DNA Integrity Index as a Serum Biomarker in Patients with Colorectal Carcinoma.

    Science.gov (United States)

    El-Gayar, Dina; El-Abd, Nevine; Hassan, Noha; Ali, Reem

    2016-01-01

    Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic non diseased cells, DNA released from necrotic cancer cells varies in size. To measure the DNA integrity index in serum and the absolute DNA concentration to assess their clinical utility as potential serum biomarkers for colorectal carcinoma (CRC) compared to CEA and CA19-9. Fifty patients with CRC, 10 with benign colonic polyps and 20 healthy sex and age matched volunteers, were investigated by real time PCR of ALU repeats (ALU q-PCR) using two sets of primers (115 and 247 bp) amplifying different lengths of DNA fragments. The DNA integrity index was calculated as the ratio of q-PCR results of ALU 247/ ALU 115bp. Serum DNA integrity was statistically significantly higher in CRC patients compared to the benign and control groups (pintegrity index is superior to the absolute DNA concentration as a potential serum biomarker for screening and diagnosis of CRC. It may also serve as an indicator for monitoring the progression of CRC patients. Combining CEA and CA19-9 with either of the genetic markers studied is better than either of them alone.

  1. Proteomic analysis reveals novel proteins associated with progression and differentiation of colorectal carcinoma

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    Yi Gan

    2014-01-01

    Full Text Available Aim: The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium. Materials and Methods: The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest. Results: Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95 th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A , glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy mutant with val b 1 replaced by met (HBB, and zinc finger protein 312 (FEZF2. Conclusions: Their functional networks were analyzed by Ingenuity systems Ingenuity Pathways Analysis and revealed the potential roles as novel biomarkers for progression in various differentiation stages of CRC.

  2. The peiminine stimulating autophagy in human colorectal carcinoma cells via AMPK pathway by SQSTM1

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    Zheng Zhi

    2016-01-01

    Full Text Available Autophagy is a conserved catabolic process, which functions in maintenance of cellular homeostasis in eukaryotic cells. The self-eating process engulfs cellular long-lived proteins and organelles with double-membrane vesicles, and forms a so-called autophagosome. Degradation of contents via fusion with lysosome provides recycled building blocks for synthesis of new molecules during stress, e.g. starvation. Peiminine is a steroidal alkaloid extracted from Fritillaria thunbergii which is widely used in Traditional Chinese Medicine. Previously, peiminine has been identified to induce autophagy in human colorectal carcinoma cells. In this study, we further investigated whether peiminine could induce autophagic cell death via activating autophagy-related signaling pathway AMPK-mTOR-ULK by promoting SQSTM1(P62. Xenograft tumor growth in vivo suggested that both peiminine and starvation inhibit the growth of tumor size and weight, which was prominently enhanced when peiminine and starvation combined. The therapeutical effect of peiminine in cancer treatment is to be expected.

  3. Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

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    Nusrat Bano

    2013-01-01

    Full Text Available The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (, whereas frequency and onset of peripheral neuropathy were highly significant ( in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles even at low doses (85 mg/m2, whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2 after few treatment cycles.

  4. Value of carcinoembryonic antigen monitoring in curative surgery for recurrent colorectal carcinoma.

    Science.gov (United States)

    Lucha, P A; Rosen, L; Olenwine, J A; Reed, J F; Riether, R D; Stasik, J J; Khubchandani, I T

    1997-02-01

    This study is designed to review a carcinoembryonic antigen (CEA)-driven postoperative protocol designed to identify patients suitable for curative reresection when recurrent colorectal cancer is identified. A total of 285 patients who were operated on for colon or rectal carcinoma between 1981 and 1985 were evaluated (with CEA levels) every two months for the first two years, every three months for the third year, every six months for years 4 and 5, and annually thereafter. CEA levels above 5 microg were considered abnormal and were evaluated with diagnostic imaging and/or endoscopy. Follow-up was available for 280 patients (98.2 percent). Distribution of patients by Astler-Coller was: A, 14 percent; B1, 20 percent; B2, 39 percent; C1, 5 percent; C2, 21 percent. There were 62 of 280 patients (22 percent) who developed elevated CEA levels, with 44 patients who demonstrated clinical or radiographic evidence of recurrence. Eleven patients were selected for surgery with curative intent (4 hepatic resections, 1 pulmonary wedge resection, 2 abdominoperineal resections, 2 segmental bowel resections, and 2 cranial metastasectomies). Three of 11 patients (27 percent) benefited and have disease-free survivals greater than 60 months. Of the 223 patients without elevated CEA, 22 (9.9 percent) had recurrent cancer without any survivors. Overall, 3 of 285 patients (1.1 percent) were cured as a result of CEA follow-up. CEA-driven surgery is useful in selected patients and can produce long-term survivors.

  5. Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma.

    Science.gov (United States)

    Kim, Hyun-Soo; Yoon, Gun; Do, Sung-Im; Kim, Sung-Joo; Kim, Youn-Wha

    2016-03-22

    A better understanding of tumor biology is important in the identification of molecules that are down-regulated in malignancy and in determining their role in tumor suppression. The aim of this study was to analyze osteoprotegerin (OPG) expression in colorectal carcinoma (CRC) and to investigate the underlying mechanism for changes in the expression of OPG. OPG expression was assessed in CRC tissue samples and cell lines. The methylation status of the OPG promoter region was determined, and the effects of demethylation on OPG expression were analyzed. The effects of recombinant OPG (rOPG) administration on cellular functions were also investigated. Clinical and prognostic implications of OPG protein expression in CRC patients were analyzed. The CRC tissues and cells showed significantly lower OPG expression. Pyrosequencing of OPG-silenced CRC cells revealed that the OPG gene promoter was highly methylated. Treatment with demethylating agent significantly elevated OPG mRNA and protein expression. rOPG significantly decreased cell viability and MMP-2 and VEGF-A production in CRC cells. Reduced OPG immunoreactivity was associated with aggressive oncogenic behavior in CRC. Also, OPG expression was found to be an independent predictor of recurrent hepatic metastasis and independent prognostic factor for worse survival rates. We demonstrated that OPG silencing in CRC occurs through epigenetic repression, and is involved in the development and progression of CRC. Our data suggest that OPG is a novel prognostic biomarker and a new therapeutic target for the treatment of patients with CRC.

  6. c-Myb regulates NOX1/p38 to control survival of colorectal carcinoma cells.

    Science.gov (United States)

    Pekarčíková, Lucie; Knopfová, Lucia; Beneš, Petr; Šmarda, Jan

    2016-08-01

    The c-Myb transcription factor is important for maintenance of immature cells of many tissues including colon epithelium. Overexpression of c-Myb occurring in colorectal carcinomas (CRC) as well as in other cancers often marks poor prognosis. However, the molecular mechanism explaining how c-Myb contributes to progression of CRC has not been fully elucidated. To address this point, we investigated the way how c-Myb affects sensitivity of CRC cells to anticancer drugs. Using CRC cell lines expressing exogenous c-myb we show that c-Myb protects CRC cells from the cisplatin-, oxaliplatin-, and doxorubicin-induced apoptosis, elevates reactive oxygen species via up-regulation of NOX1, and sustains the pro-survival p38 MAPK pathway. Using pharmacological inhibitors and gene silencing of p38 and NOX1 we found that these proteins are essential for the protective effect of c-Myb and that NOX1 acts upstream of p38 activation. In addition, our result suggests that transcription of NOX1 is directly controlled by c-Myb and these genes are strongly co-expressed in human tumor tissue of CRC patients. The novel c-Myb/NOX1/p38 signaling axis that protects CRC cells from chemotherapy described in this study could provide a new base for design of future therapies of CRC. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Epidemiological, Clinico-Pathological Profile and Management of Colorectal Carcinoma in a Tertiary Referral Center of Eastern India

    Directory of Open Access Journals (Sweden)

    Shyamal Kumar Halder

    2013-01-01

    Full Text Available Background: The colorectal carcinoma is a common cancer in males and in females and second most common cause of death in Europe and third commonest cause in the United States. Recent Indian study shows that there is a significant increase in incidence of colonic carcinoma but the incidence of rectal carcinoma remains steady. Aims and Objectives: This prospective study was undertaken to assess the clinico-pathological profile and management of colorectal malignancy in a tertiary referral institute of eastern India and to compare the above data with the data from the western world. Material and Methods: The patients admitted with the diagnosis of colorectal carcinoma in IPGME and R (SSKM, a tertiary hospital in eastern India, between January 2006 and December 2010, were included in this study. These patients were prospectively analyzed for age, sex, site of the lesion, clinical presentations, nature of the growth and types of surgery performed. Results: 192 patients were included in this study of which 78 patients were of younger age group (35 years. The mean age of this series was 44.1 years. The male to female ratio of younger and older group was 1.68:1 and 1.85:1 respectively. Reetal bleeding was the commenest symptom irrespective of age and sex. Pain in abdomen (39.7% and intestinal obstruction (21.8% were the predominant presenting features in the patients of younger group whereas weight loss was commonest presenting feature in the patients of older age group. Most common histological type, irrespective of age, was adenocarcinoma (93.8%. Overall, right sided colonic growth was more common in females while rectum was the commonest site of affection in males. The patients of younger age group presented in advanced stage like Duke’s C and Duke’s D. Conclusions: The younger patients are diagnosed with colorectal carcinoma. Cancer of right colon is more common than that of left. The younger patients present more often with abdominal pain and

  8. Epidemiological and Experimental Studies: The Role of Metformin on Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ratih D. Yudhani

    2016-12-01

    Full Text Available GLOBOCAN data in 2012 showed colorectal cancer was the third leading cancer worldwide. In Indonesia, based on WHO data in 2014, colorectal cancer was the second common cancer ini men and third cancer in women. Epidemiological studies showed that diabetes mellitus have a correlation with the incidence of cancer and increase colorectal cancer risk by 30%. Some of epidemiological study showed that metformin therapy in diabetes patient reduce the risk of cancer incidence. It supported by experimental study which showed that metformin inhibit the growth and proliferation of cancer cells by influence the AMPK/mTOR pathway as a main role. The method was literature review based on publication at Pubmed, Scopus, and Google Scholar with keywords “metformin, colorectal cancer”, “metformin, colon cancer”, without index factor limitation in free journal and paid journal. The aim of this review is to give a new insight of metformin activity as anti-cancer and its potential for both preventif and adjuvant cancer therapy, especially for colorectal cancer.

  9. The TP53 tumour suppressor gene in colorectal carcinomas. II. Relation to DNA ploidy pattern and clinicopathological variables.

    Science.gov (United States)

    Meling, G. I.; Lothe, R. A.; Børresen, A. L.; Graue, C.; Hauge, S.; Clausen, O. P.; Rognum, T. O.

    1993-01-01

    Heterozygous loss of the TP53 gene on chromosome arm 17p in colorectal carcinomas was strongly associated with DNA aneuploidy (P or = 1.1 and or = 1.3 had a significantly higher frequency of TP53 gene loss (85%) (P < 0.0001 and P < 0.0001, respectively). There was a significant association between loss of the TP53 gene and histological grade (P < 0.01), and there tended to be an association between loss of the TP53 gene and degree of cellular atypia (P < 0.05), with TP53 gene loss being most frequent in moderately differentiated carcinomas, and in carcinomas with severe cellular atypia, respectively. The proportion of tumours with loss of the TP53 gene increased significantly towards the distal part of the large bowel (P < 0.0001). These results indicate that different genetic mechanisms may be involved in the carcinogenesis in colon and rectum carcinomas, and in the two subsets of DNA aneuploid carcinomas. Furthermore, the data may suggest a role for the TP53 gene in the aneuploidisation process, possibly as a 'target' for a whole chromosome loss. PMID:8427784

  10. [Value of modified APACHE II score in predicting postoperative complications in patients with acute obstructing colorectal carcinoma].

    Science.gov (United States)

    Wang, Pei-ge; Li, Hui; Li, Shi-kuan; Jiang, Ying-jun; Gao, Peng; Sui, Guo-de

    2011-04-01

    To evaluate the value of modified acute physiologic and chronic health score (APACHE II score) in predicting postoperative complications in patients with acute obstructing colorectal carcinoma. Postoperative complications in 92 patients with acute obstructing colorectal carcinoma were evaluated by APACHE II score and modified APACHE II score (severe organ dysfunction and immune damage in chronic health indicators were replaced by the duration and degree of obstruction, which were considered as the severity of intestinal obstruction). The sensitivity, specificity, and Youden index were compared with regard to complication prediction. Receiver operating characteristic curves were plotted to calculate area under the curve(AUC). Twenty-five patients developed postoperative complications including 3 deaths. The APACHE-II score(13.72±4.24), modified APACHE II score (19.28±4.92), intestinal obstruction severity score (5.56±2.20) were significantly higher in patients with complications than those in patients without complications (10.58±3.44, 14.69±3.73, 4.10±1.52, all PAPACHE-II score with 20 being the optimal cut-off point, respectively, and were 0.560, 0.896, 0.804, 0.456, and 0.784 for APACHE-II (14 was the optimal cut-off point), respectively. The modified APACHE-II score system with the intestinal obstruction severity score is a better prediction method for the occurrence of postoperative complications in patients with acute obstructing colorectal carcinoma.

  11. Ex-vivo Clonally Expanded B Lymphocytes Infiltrating Colorectal Carcinoma Are of Mature Immunophenotype and Produce Functional IgG

    OpenAIRE

    Claudia Maletzki; Annika Jahnke; Christiane Ostwald; Ernst Klar; Friedrich Prall; Michael Linnebacher

    2012-01-01

    BACKGROUND: Tumor infiltrating B cells (TiBc) have not yet been investigated in detail. This may at least in part be due to technical difficulties. Here we describe a straightforward and reproducible method to isolate and culture TiBc from primary colorectal carcinomas (CRC). METHODS/RESULTS: TiBc cultures were generated by Epstein-Barr virus (EBV) immortalization. With this method, monoclonal TiBc cultures were obtained for 14/19 CRCs. As assessed by flow cytometry and ELISA, TiBc showed an ...

  12. Hyperplastic polyps of the colon and rectum - reclassification, BRAF and KRAS status in index polyps and subsequent colorectal carcinoma

    DEFF Research Database (Denmark)

    Janjua, Huma Gul Rehana; Høgdall, Estrid; Linnemann, Dorte

    2015-01-01

    (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized...... in the follow-up period (1 patient had SSL, 4 had THP, and 2 had unspecified non-neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent...... of patients with SSL subsequently developed a neoplastic lesion. Further studies are needed to clarify the cancer risk of SSL....

  13. Qualities of sessile serrated adenoma/polyp/lesion and its borderline variant in the context of synchronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Mohammadi, Mahin; Kristensen, Michael Holmsgaard; Nielsen, Hans Jørgen

    2012-01-01

    histological observations of the authors on SSA/P/L and BSSA/P/L in general are here extended to encompass attributes of these polyps in the context of synchronous colorectal carcinoma (SCRC), with a focus on the place of BSSA/P/L in the spectrum of non-dysplastic serrated polyps.......Although much data have accumulated on sessile serrated adenoma/polyp/lesion (SSA/P/L) in general, its characteristics in specified contexts are less well elucidated. This lack of knowledge is even more conspicuous concerning its borderline counterpart, referred to as BSSA/P/L. The previous...

  14. [Molecular cancer disposition diagnosis exemplified by colorectal carcinoma. What is the contribution of pathology?].

    Science.gov (United States)

    Rüschoff, J; Dietmaier, W; Bocker, T; Wallinger, S; Kullmann, F; Beham, A; Hofstädter, F

    1998-07-01

    During the last few years, the molecular basis of several cancer predisposition syndromes has been discovered which offers new tools for cancer prevention and early detection. This will be demonstrated in one of the most frequent hereditary cancer syndromes, namely the hereditary nonpolyposis colorectal cancer (HNPCC) which accounts for about 5% to 8% of CRC. Thereby, families with exclusively CRC (Lynch type I syndrome) and those with extracolonic cancers especially of endometrium, stomach, small bowel and upper urinary tract (Lynch type II syndrome) can be discriminated. At the molecular level, HNPCC is caused by germline mutations in one of the mismatch repair genes (hMSH2, hMLH1, hMSH6, hPMS2). Thus, nucleotide mispairings occurring particularly within simple repetitive genomic sequences (microsatellites) during replication are no longer be repaired properly and can be demonstrated by PCR as so-called microsatellite instability (MSI). Since more than 90% of HNPCC associated and only about 15% of sporadic CRC show MSI, this test is a useful tool for HNPCC screening. In case of a negative result HNPCC is highly unlikely. In positive cases (with > or = 2 out of 5 unstable defined microsatellite markers) the definite molecular diagnosis can only be obtained by sequencing the mismatch repair genes from the patient's blood or normal DNA. As immunohistochemistry reveals loss of hMSH2 or hMLH1 expression in most MSI positive CRC, these data provide useful information for the sequencing strategy. Molecular tumor screening by MSI test and immunohistochemistry is recommended in patients i.) with a positive family history (acc. to the Amsterdam criteria), ii.) suffering from multiple HNPCC related carcinomas, iii.) with HNPCC related cancer before 45 ys of age, and iv.) with right-sided CRC exhibiting medullary, signet-ring or mucinous differentiation. Finally, these tests as well as genetic counseling and treatment of the patient need to be done by an interdisciplinary

  15. Esophageal Squamous Cell Carcinoma Patients Have an Increased Risk of Coexisting Colorectal Neoplasms.

    Science.gov (United States)

    Baeg, Myong Ki; Choi, Myung-Gyu; Jung, Yun Duk; Ko, Sun-Hye; Lim, Chul-Hyun; Kim, Hyung Hun; Kim, Jin Su; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Kim, Sang-Woo

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) and colorectal neoplasms (CRNs) share risk factors. We aimed to investigate whether the CRN risk is increased in ESCC patients. ESCC patients who underwent a colonoscopy within 1 year of diagnosis were retrospectively analyzed. Patients were matched 13 by age, gender, and body mass index to asymptomatic controls. CRN was defined as the histological confirmation of adenoma or adenocarcinoma. Advanced CRN was defined as any of the following ≥3 adenomas, high-grade dysplasia, villous features, tumor ≥1 cm, or adenocarcinoma. The risk factors for both CRN and advanced CRN were evaluated by univariate and multivariate analyses. Sixty ESCC patients were compared with 180 controls. The ESCC group had significantly higher numbers of CRNs (odds ratio [OR], 2.311; 95% confidence interval [CI], 1.265 to 4.220; p=0.006) and advanced CRNs (OR, 2.317; 95% CI, 1.185 to 4.530; p=0.013). Significant risk factors for both CRN and advanced CRN by multivariate analysis included ESCC (OR, 2.157, 95% CI, 1.106 to 4.070, p=0.024; and OR, 2.157, 95% CI, 1.045 to 4.454, p=0.038, respectively) and older age (OR, 1.068, 95% CI, 1.032 to 1.106, p<0.001; and OR, 1.065, 95% CI, 1.024 to 1.109, p=0.002, respectively). The rates of CRN and advanced CRN are significantly increased in ESCC. Colonoscopy should be considered at ESCC diagnosis.

  16. Photoacoustic tomography of vascular therapy in a preclinical mouse model of colorectal carcinoma

    Science.gov (United States)

    Johnson, S. P.; Ogunlade, O.; Zhang, E.; Laufer, J.; Rajkumar, V.; Pedley, R. B.; Beard, P.

    2014-03-01

    Vascular therapy in oncology exploits the differences between normal blood vessels and abnormal tumour neoangiogenesis to selectively target cancer. For optimal treatment efficacy, and translation of novel compounds, the response of the tumour vasculature needs to be assessed. Photoacoustic tomography (PAT) is capable of this as it provides highly spatially resolved 3D images of vascular networks in biological tissue to cm depths. In preclinical models of cancer this is sufficient to encompass entire subcutaneous tumours, and can therefore be used to evaluate pharmacological intervention directed at the vasculature. In this study the vascular disrupting agent OXi4503 was used to treat subcutaneous tumour mouse models of two human colorectal carcinoma tumour types (SW1222, LS174T) at a range of concentrations (40mg/kg, 10mg/kg, 1mg/kg and sham dose control). The characteristic destruction of tumour vasculature caused by OXi4503 was observed by PAT and confirmed ex vivo via histology. Differences observed between the two tumour types assessed demonstrate the importance of tumour microenvironment and pathophysiology on response to therapy. Differential response to different doses of OXi4503 was observed, with outward tumour growth only seen once entire tumour viability had been re-established; this demonstrates the potential of PAT to act as a biomarker of response for the translation of novel anti-vascular compounds and also within the clinic. This study shows clearly that PAT can accurately assess the time course of drug action and relapse of pharmacodynamic effect in preclinical models of cancer and the important translational prospects for vascular targeted tumour therapies.

  17. Inhibition of Stat3 signaling pathway by nifuroxazide improves antitumor immunity and impairs colorectal carcinoma metastasis.

    Science.gov (United States)

    Ye, Ting-Hong; Yang, Fang-Fang; Zhu, Yong-Xia; Li, Ya-Li; Lei, Qian; Song, Xue-Jiao; Xia, Yong; Xiong, Ying; Zhang, Li-Dan; Wang, Ning-Yu; Zhao, Li-Feng; Gou, Hong-Feng; Xie, Yong-Mei; Yang, Sheng-Yong; Yu, Luo-Ting; Yang, Li; Wei, Yu-Quan

    2017-01-05

    Colorectal carcinoma (CRC) is the one of the most common cancers with considerable metastatic potential, explaining the need for new drug candidates that inhibit tumor metastasis. The signal transducers and activators of the transcription 3 (Stat3) signaling pathway has an important role in CRC and has been validated as a promising anticancer target for CRC therapy. In the present study, we report our findings on nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3. Our studies showed that nifuroxazide decreased the viability of three CRC cell lines and induced apoptosis of cancer cells in a concentration-dependent manner. Moreover, western blot analysis demonstrated that the occurrence of its apoptosis was correlated with the activation of Bax and cleaved caspase-3, and decreased the expression of Bcl-2. In addition, nifuroxazide markedly impaired CRC cell migration and invasion by downregulating phosphorylated-Stat3Tyr705, and also impaired the expression of matrix metalloproteinases (MMP-2 and MMP-9). Furthermore, our studies showed that nifuroxazide also significantly inhibited the tumor metastasis in lung and abdomen metastasis models of colon cancer. Meanwhile, nifuroxazide functionally reduced the proliferation index, induced tumor apoptosis and impaired metastasis. Notably, nifuroxazide reduced the number of myeloid-derived suppressor cells in the blood, spleens and tumors, accompanied by the increased infiltration of CD8+ T cells in the tumors. Importantly, a marked decrease in the number of M2-type macrophages in tumor in the abdomen metastasis model was also observed. Taken together, our results indicated that nifuroxazide could effectively inhibit tumor metastasis by mediating Stat3 pathway and it might have a therapeutic potential for the treatment of CRC.

  18. NIH-3T3 fibroblasts cultured with plasma from colorectal cancer patients generate poorly differentiated carcinomas in mice.

    Science.gov (United States)

    Serrano-Heras, Gemma; Domínguez-Berzosa, Carolina; Collantes, Elena; Guadalajara, Héctor; García-Olmo, Damián; García-Olmo, Dolores C

    2012-03-01

    The ability of cells to undergo cellular transitions, in particular, to switch between epithelial and mesenchymal states, might be highly advantageous during the progression of carcinoma. Using histological and immunohistochemical techniques, we here show that the injection into mice of spontaneously transformed NIH-3T3 cells generated fusocellular sarcomas, whereas NIH-3T3 cells that had been transformed by culturing with plasma from colorectal cancer patients gave rise to tumors that phenotypically resembled the carcinomas of the original cancer patients. Thus, plasma from cancer patients is able to transform NIH-3T3 fibroblasts into malignant epithelial-like cells, suggesting that such cells might undergo mesenchymal to epithelial transition during plasma-induced transformation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Hyperplastic polyps of the colon and rectum - reclassification, BRAF and KRAS status in index polyps and subsequent colorectal carcinoma.

    Science.gov (United States)

    Janjua, Huma Gul Rehana; Høgdall, Estrid; Linnemann, Dorte

    2015-04-01

    Hyperplastic polyps (HP) of the colon and rectum were previously considered benign. Newer studies have suggested that colorectal HP are different entities. The aim of this study was to reclassify lesions from a 5-year period previously classified as colorectal HP into traditional hyperplastic polyp (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized and correlated with the index lesion. In total, 591 HP biopsy specimens were obtained from 480 patients. The lesions were reclassified as: 358 THP, 109 SSL, 35 TA, 81 unspecified non-neoplastic lesions, four traditional serrated adenoma, and 4 SSL with cytological dysplasia. Seven patients developed CRC in the follow-up period (1 patient had SSL, 4 had THP, and 2 had unspecified non-neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent of patients with SSL subsequently developed a neoplastic lesion. Further studies are needed to clarify the cancer risk of SSL. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  20. Construction of a plasmid coding for green fluorescent protein tagged cathepsin L and data on expression in colorectal carcinoma cells

    Directory of Open Access Journals (Sweden)

    Tripti Tamhane

    2015-12-01

    Full Text Available The endo-lysosomal cysteine cathepsin L has recently been shown to have moonlighting activities in that its unexpected nuclear localization in colorectal carcinoma cells is involved in cell cycle progression (Tamhane et al., 2015 [1]. Here, we show data on the construction and sequence of a plasmid coding for human cathepsin L tagged with an enhanced green fluorescent protein (phCL-EGFP in which the fluorescent protein is covalently attached to the C-terminus of the protease. The plasmid was used for transfection of HCT116 colorectal carcinoma cells, while data from non-transfected and pEGFP-N1-transfected cells is also shown. Immunoblotting data of lysates from non-transfected controls and HCT116 cells transfected with pEGFP-N1 and phCL-EGFP, showed stable expression of cathepsin L-enhanced green fluorescent protein chimeras, while endogenous cathepsin L protein amounts exceed those of hCL-EGFP chimeras. An effect of phCL-EGFP expression on proliferation and metabolic states of HCT116 cells at 24 h post-transfection was observed.

  1. Tumor budding as a risk factor of lymph node metastasis in submucosal invasive T1 colorectal carcinoma: a retrospective study

    Directory of Open Access Journals (Sweden)

    Kye Bong-Hyeon

    2012-08-01

    Full Text Available Abstract Background This study was designed to identify risk factors for lymph node metastasis of early stage colorectal cancer, which was confirmed to a carcinoma that invaded the submucosa after radical resection. Methods In total, 55 patients revealing submucosal invasive colorectal carcinoma on pathology who underwent curative radical resection at the Department of Surgery, St. Vincent’s Hospital, The Catholic University of Korea from January 2007 to September 2010 were evaluated retrospectively. Tumor size, depth of submucosal invasion, histologic grade, lymphovascular invasion, tumor budding, and microacinar structure were reviewed by a single pathologist. Student t-test for continuous variables and Chi-square test for categorical variables were used for comparing the clinicopathological features between two groups (whether lymph node involvement existed or not. Continuous variables are expressed as the mean ± standard error while statistical significance is accepted at P  Results The mean age of 55 patients (34 males and 21 females was 61.2 ± 9.6 years (range, 43–83. Histologically, eight (14.5% patients had metastatic lymph node. In the univariate analysis, tumor budding (P = 0.047 was the only factor that was significantly associated with lymph node metastasis. Also, the tumor budding had a sensitivity of 83.3%, a specificity of 60.5%, and a negative predictive value of 0.958 for lymph node metastasis in submucosal invasive T1 colorectal cancer. Conclusions The tumor budding seems to have a high sensitivity (83.3%, acceptable specificity (60.5%, and a high negative predictive value (0.958. A close examination of pathologic finding including tumor budding should be performed in order to manage early CRC properly.

  2. [Preoperative evaluation of multi-slice spiral computed tomography angiography in laparoscopic radical operation for colorectal carcinoma].

    Science.gov (United States)

    Deng, Runshu; Mo, Linyao; He, Xihua; Chen, Jianhua; Cai, Renjun; Wang, Zaiguo; Huang, Shichuan; Lu, Huanquan; Huang, Zhaolun; Wu, Zhiming

    2016-03-01

    To investigate the clinical application of 256 multi-slice spiral computed tomography angiography (MSCTA) technique in the preoperative evaluation of mesenteric angiography in order to provide a reference to vessel anatomy and dissociation in laparoscopic radical operation for colorectal carcinoma. Clinical data of 50 patients with colorectal cancer who underwent preoperative MSCTA+FDCT and laparoscopic curative operation at our hospital from October 2013 to March 2015 were collected (MSCTA group). The evaluation item was visualization of mesenteric artery, which was compared with the findings under laparoscopic surgery. Meanwhile, another 50 colorectal cancer patients undergoing laparoscopic radical operation by the same surgeon team without preoperative MSCTA examination were used as control(control group). Clinical data were compared between the two groups. MSCTA precisely and correctly demonstrated anatomy and variations of the mesenteric artery and relative nutrient vessel in carcinoma. The angiography reconstruction images were consistent with the visual anatomy and variation from laparoscopic findings, whose diagnostic conformity rate of 100%. As compared to control group, operative time was shorter [(195.0±23.2) minutes vs.(218.0±19.6) minutes, t=8.326, P=0.015], and blood loss was less[(168.1±18.8) ml vs. (206.5±14.3) ml, t=-19.369, P=0.002] in MSCTA group. Differences of number of harvested lymph node, postoperative complication morbidity, postoperative hospital stay and hospitalization cost were not significant between two groups(all P>0.05). Preoperative MSCTA can demonstrate anatomy and variations of the mesenteric artery precisely and correctly, thus it is beneficial to shorten the operation time and to reduce blood loss.

  3. Assessment of Nutritional and Inflammatory Status to Determine the Prevalence of Malnutrition in Patients Undergoing Surgery for Colorectal Carcinoma.

    Science.gov (United States)

    Daniele, Antonella; Divella, Rosa; Abbate, Ines; Casamassima, Addolorata; Garrisi, Vito Michele; Savino, Eufemia; Casamassima, Porzia; Ruggieri, Eustachio; DE Luca, Raffaele

    2017-03-01

    Colorectal Cancer is the fourth most frequent cause of cancer death worldwide and its incidence increases from 50 years of age. It is often associated with protein-caloric malnutrition and 20% of cancer deaths occur due to this event. The aim of this study was to assess the prevalence of malnutrition and inflammatory status in 78 patients undergoing surgery for colorectal carcinoma. Nutritional Status was assessed by Mini Nutritional Assessment (MNA). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA, while albumin, C-reactive protein (CRP) and transferrin (TRF) were tested using an immunometric assay. The mean MNA score in colorectal patients was 20.4±8.4, while 23/78 patients (29.4%) were well nourished, 36/78 (46.1%) were at risk of malnutrition and 19/78 (24.3%) were malnourished, reporting in the previous six months from the date of diagnosis a significant weight loss (>10 kg), muscle mass loss and severe reduction of food intake due to loss of appetite and altered taste perception. The serum means of IL-6, TNF-α and CRP, were significantly higher in colorectal patients compared to the control group (pmalnutrition and reported an imbalance between nutritional and inflammatory status. They, therefore, require a nutritional intervention before treatment in order to have a more effective response and improve quality of life. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2002-01-01

    -plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml(-1....... The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA...

  5. [Familial non-polyposis colorectal carcinoma (Lynch syndrome) in Germany - analysis of information, advisory service and family screening].

    Science.gov (United States)

    Schneider, R; Rümmele, P; Dechant, S; Hofstädter, F; Lorenz, W; Fürst, A

    2011-01-01

    Lynch syndrome is associated with an increased incidence of colorectal carcinomas and extracolonic neoplasms. Patients fulfilling the "Revised Bethesda criteria" or the Amsterdam Citeria I or II should be screened for DNA mismatch repair deficiency. Mutation carriers and high risk individuals should undergo intensified annual screening, as recommended by the S3 guideline for colorectal carcinoma. All families of the Regensburger study group with a verified mutation were included in this study. Data acquisition was conducted by telephone interviews. We determined the number of family members who had been informed about the diagnosis and how many of them participated in the recommended screening program. Additionally, an information letter was sent to family members providing information about the opportunity of a predictive mutation analysis. 90 family members of 12 families with a total of 42 carcinomas and a mean age of tumor diagnosis of 41.3 years were included. At the beginning of the study 97.4 % of the family members were informed about the diagnosis. In the course of the study the number of family members participating in the mutation analysis increased from 29.5 % to 42.3 %. The number of index patients complying with the recommended screening program was over 90 %, in contrast to the number of family members which varied between 30 - 60 %. Relatives of index patients are not sufficiently informed about the importance of predictive testing and the re-commended surveillance guidelines. An insufficient implementation of Lynch syndrome specific aspects of the S3-guideline can be assumed. For an improved implementation barriers of physicians' adherence must be systemically analyzed. It is essential for these high-risk families to establish and enforce awareness in order to create intensified surveillance. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Combination of cetuximab and PP242 synergistically suppress the progression of wild-type KRAS colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng L

    2015-11-01

    also maximally inhibited by combination therapy, in terms of either diameter or number. More importantly, the efficacy of combination therapy was more prominent than either drug alone in established tumor xenografts. These findings supported the potential use of combination therapy of PP242 and cetuximab against wild-type KRAS colorectal carcinomas. Keywords: colorectal cancer, cancer stem-like cells, anti-EGFR treatment

  7. Foreign Body Granulomas Simulating Recurrent Tumors in Patients Following Colorectal Surgery for Carcinoma: a Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Baek, Moo Joon; Cho, Hyun Deuk [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2009-06-15

    We report here two cases of foreign body granulomas that arose from the pelvic wall and liver, respectively, and simulated recurrent colorectal carcinomas in patients with a history of surgery. On contrast-enhanced CT and MR images, a pelvic wall mass appeared as a well-enhancing mass that had invaded the distal ureter, resulting in the development of hydronephrosis. In addition, a liver mass had a hypointense rim that corresponded to the fibrous wall on a T2-weighted MR image, and showed persistent peripheral enhancement that corresponded to the granulation tissues and fibrous wall on dynamic MR images. These lesions also displayed very intense homogeneous FDG uptake on PET/CT.

  8. The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

    LENUS (Irish Health Repository)

    O'Connor, O J

    2012-02-03

    AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes\\' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes\\' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes\\'\\'D\\' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.

  9. Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study

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    Wallin Håkan

    2006-07-01

    Full Text Available Abstract Background The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. Methods We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR and 95% confidence interval (CI were estimated by binary logistic regression model adjusting for age and gender. Results The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06–1.81, which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15–2.39. The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49–1.01 and carcinomas (OR of 0.49, 95% CI 0.21–1.13 among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95–5.04 compared to all non-carriers although the estimate was not statistically significant. Conclusion We found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women.

  10. Increased expression of interleukin-21 along colorectal adenoma-carcinoma sequence and its predicating significance in patients with sporadic colorectal cancer.

    Science.gov (United States)

    Cui, Guanglin; Yuan, Aping; Zhu, Li; Florholmen, Jon; Goll, Rasmus

    2017-10-01

    The role and significance of interleukin (IL)-21 in the development of sporadic CRC have not been well defined. The aim of this study is therefore to investigate the dynamics of the IL-21 along colorectal adenoma-carcinoma sequence and to evaluate the impact of IL-21 on clinicopathological parameters and CRC prognosis. The real-time PCR results showed that the level of IL-21 in adenomas (n=50) and sporadic CRC (n=50) were significantly higher than that in normal controls (n=18), which were predominately observed in the adenoma/CRC stroma. Analysis revealed that IL-21 level was correlated with the overall survival time in CRC patients. Double immunofluorescence observations confirmed that IL-21 positive cells were mostly natural killer cells and T lymphocytes in the tumor stroma. These results indicate that significant increased IL-21 expression present within the adenoma/CRC microenvironment might have a potential predicating significance for survival time in patients with CRC. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Potentiation of 5-fluorouracil encapsulated in zeolites as drug delivery systems for in vitro models of colorectal carcinoma.

    Science.gov (United States)

    Vilaça, Natália; Amorim, Ricardo; Machado, Ana F; Parpot, Pier; Pereira, Manuel F R; Sardo, Mariana; Rocha, João; Fonseca, António M; Neves, Isabel C; Baltazar, Fátima

    2013-12-01

    The studies of potentiation of 5-fluorouracil (5-FU), a traditional drug used in the treatment of several cancers, including colorectal (CRC), were carried out with zeolites Faujasite in the sodium form, with different particle sizes (NaY, 700nm and nanoNaY, 150nm) and Linde type L in the potassium form (LTL) with a particle size of 80nm. 5-FU was loaded into zeolites by liquid-phase adsorption. Characterization by spectroscopic techniques (FTIR, (1)H NMR and (13)C and (27)Al solid-state MAS NMR), chemical analysis, thermal analysis (TGA), nitrogen adsorption isotherms and scanning electron microscopy (SEM), demonstrated the successful loading of 5-FU into the zeolite hosts. In vitro drug release studies (PBS buffer pH 7.4, 37°C) revealed the release of 80-90% of 5-FU in the first 10min. To ascertain the drug release kinetics, the release profiles were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas and Weibull kinetic models. The in vitro dissolution from the drug delivery systems (DDS) was explained by the Weibull model. The DDS efficacy was evaluated using two human colorectal carcinoma cell lines, HCT-15 and RKO. Unloaded zeolites presented no toxicity to both cancer cells, while all DDS allowed an important potentiation of the 5-FU effect on the cell viability. Immunofluorescence studies provided evidence for zeolite-cell internalization. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. pH-sensitive nanomicelles for controlled and efficient drug delivery to human colorectal carcinoma LoVo cells.

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    Shi-Ting Feng

    Full Text Available BACKGROUND: The triblock copolymers PEG-P(Asp-DIP-P(Lys-Ca (PEALCa of polyethylene glycol (PEG, poly(N-(N',N'-diisopropylaminoethyl aspartamide (P(Asp-DIP, and poly (lysine-cholic acid (P(Lys-Ca were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES, and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments. METHODOLOGY/PRINCIPAL FINDINGS: The anticancer drug Paclitaxel (PTX and hydrophilic superparamagnetic iron oxide (SPIO were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells, and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated. CONCLUSIONS/SIGNIFICANCE: These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.

  13. Tumor Budding in Colorectal Carcinoma: Confirmation of Prognostic Significance and Histologic Cutoff in a Population-based Cohort.

    Science.gov (United States)

    Graham, Rondell P; Vierkant, Robert A; Tillmans, Lori S; Wang, Alice H; Laird, Peter W; Weisenberger, Daniel J; Lynch, Charles F; French, Amy J; Slager, Susan L; Raissian, Yassaman; Garcia, Joaquin J; Kerr, Sarah E; Lee, Hee Eun; Thibodeau, Stephen N; Cerhan, James R; Limburg, Paul J; Smyrk, Thomas C

    2015-10-01

    Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporation of this parameter in clinical reports. We used an established scoring system in a population-based cohort to determine a histologic cutoff for "high" tumor budding and confirm its prognostic significance. We retrieved hematoxylin and eosin-stained sections from 553 incident colorectal carcinoma cases. Each case was previously characterized for select molecular alterations and survival data. Interobserver agreement was assessed between 2 gastrointestinal pathologists and a group of 4 general surgical pathologists. High budding (≥ 10 tumor buds in a ×20 objective field) was present in 32% of cases, low budding in 46%, and no budding in 22%. High tumor budding was associated with advanced pathologic stage (P 2 times risk of cancer-specific death (hazard ratio = 2.57 [1.27, 5.19]). After multivariate adjustment, by penalized smoothing splines, we found increasing tumor bud counts from 5 upward to be associated with an increasingly shortened cancer-specific survival. By this method, a tumor bud count of 10 corresponded to approximately 2.5 times risk of cancer-specific death. The interobserver agreement was good with weighted κ of 0.70 for 2 gastrointestinal pathologists over 121 random cases and 0.72 between all 6 pathologists for 20 random cases. Using an established method to assess budding on routine histologic stains, we have shown that a cutoff of 10 for high tumor budding is independently associated with a significantly worse prognosis. The reproducibility data provide support for the routine widespread implementation of tumor budding in clinical reports.

  14. Human Neutrophil Peptides 1-3 – Early Markers in Development of Colorectal Adenomas and Carcinomas

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    Henning Mothes

    2008-01-01

    Full Text Available Expression of Human Neutrophil Peptides (HNP 1–3 was recently found to be associated with development of colorectal cancer. Raised defensin-expression in tumours is believed to stem from increased infiltration of neutrophils into tumour environment.

  15. NDRG2 gene copy number is not altered in colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders Blomkild; Mitchelmore, Cathy

    2017-01-01

    in all three cell lines. In addition, the NDRG2 promoter was heavily methylated in these cell lines, suggesting an epigenetic regulatory mechanism. Unaltered gene copy numbers of NDRG2 were observed in the three cell lines. In the colorectal tissues, one normal and three CRC samples showed partial...

  16. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

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    Fabian Feiersinger

    Full Text Available Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01. MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01. No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01.In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

  17. X-ray diagnosis in colorectal carcinoma as practised today - present state of the art

    Energy Technology Data Exchange (ETDEWEB)

    Beyer, D.

    1988-05-01

    Long-term prognosis of this malignant and frequent disease can be improved only by early diagnosis of small polyps and of carcinomas in the early stage. It is necessary to coordinate high-quality colon contrast medium enemas (double-contrast method) and hypotension with coloscopy and endoscopic removal of polyps. If a colon carcinoma is identified, it is additionally also necessary - probably mostly by colon enema - to exclude preoperatively a metachronic second carcinoma which can be expected in about 5% of the cases. Ultrasound and computed tomography will help in visualising advanced carcinomas that have already passed the wall and are borderline cases in respect of operability, as well as in identifying lymph node and liver metastases, besides in identifying complicating local perforations. Proof, however, is only rendered by a positive finding. It will be necessary to determine at what extent magnetic resonance can be useful in this context.

  18. Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

    LENUS (Irish Health Repository)

    Canney, A

    2012-02-01

    Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

  19. High-level mRNA quantification of proliferation marker pKi-67 is correlated with favorable prognosis in colorectal carcinoma.

    Science.gov (United States)

    Ihmann, Thomas; Liu, Jian; Schwabe, Wolfgang; Häusler, Peter; Behnke, Detlev; Bruch, Hans-Peter; Broll, Rainer; Windhövel, Ute; Duchrow, Michael

    2004-12-01

    The present study retrospectively examines the expression of pKi-67 mRNA and protein in colorectal carcinoma and their correlation to the outcome of patients. Immunohistochemistry and quantitative RT-PCR were used to analyze the expression of pKi-67 in 43 archival specimens of patients with curatively resected primary colorectal carcinoma, who were not treated with neo-adjuvant therapy. We determined a median pKi-67 (MIB-1) labeling index of 31.3% (range 10.3-66.4%), and a mean mRNA level of 0.1769 (DeltaC(T): range 0.01-0.69); indices and levels did not correlate. High pKi-67 mRNA DeltaC(T) values were associated with a significantly favorable prognosis, while pKi-67 labeling indices were not correlated to prognostic outcome. A multivariate analysis of clinical and biological factors indicated that tumor stage (UICC) and pKi-67 mRNA expression level were independent prognostic factors. Quantitatively determined pKi-67 mRNA can be a good and new prognostic indicator for primary resected colorectal carcinoma.

  20. Evolving approach and clinical significance of detecting DNA mismatch repair deficiency in colorectal carcinoma.

    Science.gov (United States)

    Shia, Jinru

    2015-09-01

    The last two decades have seen significant advancement in our understanding of colorectal tumors with DNA mismatch repair (MMR) deficiency. The ever-emerging revelations of new molecular and genetic alterations in various clinical conditions have necessitated constant refinement of disease terminology and classification. Thus, a case with the clinical condition of hereditary non-polyposis colorectal cancer as defined by the Amsterdam criteria may be one of Lynch syndrome characterized by a germline defect in one of the several MMR genes, one of the yet-to-be-defined "Lynch-like syndrome" if there is evidence of MMR deficiency in the tumor but no detectable germline MMR defect or tumor MLH1 promoter methylation, or "familial colorectal cancer type X" if there is no evidence of MMR deficiency. The detection of these conditions carries significant clinical implications. The detection tools and strategies are constantly evolving. The Bethesda guidelines symbolize a selective approach that uses clinical information and tumor histology as the basis to select high-risk individuals. Such a selective approach has subsequently been found to have limited sensitivity, and is thus gradually giving way to the alternative universal approach that tests all newly diagnosed colorectal cancers. Notably, the universal approach also has its own limitations; its cost-effectiveness in real practice, in particular, remains to be determined. Meanwhile, technological advances such as the next-generation sequencing are offering the promise of direct genetic testing for MMR deficiency at an affordable cost probably in the near future. This article reviews the up-to-date molecular definitions of the various conditions related to MMR deficiency, and discusses the tools and strategies that have been used in detecting these conditions. Special emphasis will be placed on the evolving nature and the clinical importance of the disease definitions and the detection strategies. Copyright © 2015

  1. Stromal Expression of Hypoxia Regulated Proteins Is an Adverse Prognostic Factor in Colorectal Carcinomas

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    Arjen H. G. Cleven

    2007-01-01

    Full Text Available Background: Hypoxia modifies the phenotype of tumors in a way that promotes tumor aggressiveness and resistance towards chemotherapy and radiotherapy. However, the expression and influence of hypoxia-regulated proteins on tumor biology are not well characterized in colorectal tumors. We studied the role of protein expression of hypoxia-inducible factor (HIF-1α, HIF-2α, carbonic anhydrase 9 (CA9 and glucose transporter 1 (GLUT1 in patients with colorectal adenocarcinomas. Methods: Expression of HIF-1α, HIF-2α, CA9 and GLUT1 was quantified by immunohistochemistry in 133 colorectal adenocarcinomas. The expression of hypoxia markers was correlated with clinicopathological variables and overall patient survival. Results: Expression of these hypoxia markers was detected in the epithelial compartment of the tumor cells as well as in tumor-associated stromal cells. Although tumor cells frequently showed expression of one or more of the investigated hypoxia markers, no correlation among these markers or with clinical response was found. However, within the tumor stroma, positive correlations between the hypoxia markers HIF-2α, CA9 and GLUT1 were observed. Furthermore expression of HIF-2α and CA9 in tumor-associated stroma were both associated with a significantly reduced overall survival. In the Cox proportional hazard model, stromal HIF-2α expression was an independent prognostic factor for survival. Conclusion: These observations show, that expression of hypoxia regulated proteins in tumor-associated stromal cells, as opposed to their expression in epithelial tumor cells, is associated with poor outcome in colorectal cancer. This study suggests that tumor hypoxia may influence tumor-associated stromal cells in a way that ultimately contributes to patient prognosis.

  2. Targeted therapies in the management of colorectal carcinoma: role of bevacizumab

    Directory of Open Access Journals (Sweden)

    Ajithkumar Puthillath

    2008-11-01

    Full Text Available Ajithkumar Puthillath1, Anush Patel2, Marwan G Fakih11Department of Medicine at Roswell Park Cancer Institute, Buffalo, New York, USA; 2Department of Medicine at State University of Buffalo, Buffalo, New York, USAAbstract: Colorectal cancer continues to be an important public health concern, despite improvements in screening and better systemic chemotherapy. The integration of targeted therapies in the treatment of colon cancer has resulted in significant improvements in efficacy outcomes. Angiogenesis is important for tumor growth and metastasis and is an important target for new biological agents. Bevacizumab is a humanized recombinant antibody that prevents vascular endothelial growth factor (VEGF receptor binding, and inhibits angiogenesis and tumor growth. The addition of bevacizumab to fluoropyrimidine-based chemotherapy, with or without irinotecan or oxaliplatin, in both the first- and second-line treatment of metastatic colorectal cancer, significantly increased median progression-free survival and overall survival in select randomized phase III studies. Ongoing studies are evaluating the role of bevacizumab in the adjuvant treatment of colon cancer. Common toxicities associated with bevacizumab include hypertension, bleeding episodes, and thrombotic events. This review will focus on the integration of bevacizumab in the treatment paradigm of colon cancer and the management of its side effects.Keywords: colorectal cancer, metastatic, bevacizumab, fluorouracil, irinotecan, oxaliplatin

  3. CD133 mRNA expression and microsatellite instability in colorectal carcinoma.

    Science.gov (United States)

    Huh, Jung Wook; Park, Yeon Sun; Lee, Jae Hyuk; Kim, Hyeong Rok; Shin, Myung Geun; Kim, Young Jin

    2010-12-01

    The present study was performed to examine the CD133 expression in colorectal cancer and to analyze its relationship with microsatellite instability (MSI) and the clinicopathological factors, including patient survival. The CD133 mRNA levels in 61 primary colorectal adenocarcinomas were analyzed by reverse transcriptase-polymerase chain reaction, with normalization relative to GAPDH. Five microsatellite markers were analyzed to evaluate MSI. A CD133 mRNA expression was significantly associated with the depth of invasion (P = 0.017), lymph node involvement (P = 0.012), and lymphovascular invasion (P = 0.019). A CD133 expression was significantly correlated with the MSI status (P = 0.035). With a median follow-up period of 45 months, the 5-year disease-free survival rate of patients with a low CD133 mRNA expression was significantly higher than that of those patients with high levels of CD133 mRNA expression (82.9% and 59.0%, respectively; P = 0.027). However, on the multivariate analysis, a CD133 mRNA expression was not an independent predictor of disease-free survival. Elevated CD133 mRNA levels may represent more aggressive tumor biology and poorer survival in patients with colorectal cancer, correlating with a high level of MSI status. Larger prospective studies are required to confirm these findings. © 2010 Wiley-Liss, Inc.

  4. Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations

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    Hussain Azhar R

    2010-07-01

    Full Text Available Abstract Background Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4 and TRAIL receptor 2 (DR5. Expression of TRAIL receptors is higher in colorectal carcinoma (CRC as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells. Methods We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological features including key molecular alterations and overall survival. Results CRC subset with TRAIL-R1 expression was associated with a less aggressive phenotype characterized by early stage (p = 0.0251 and a histology subtype of adenocarcinomas (p = 0.0355. Similarly CRC subset with TRAIL-R2 expression was associated with a well-differentiated tumors (p KIP1 and KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2 expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p = 0.0011. Interestingly, TRAIL-R2 expression was associated with a microsatellite stable (MS--S/L phenotype (p = 0.0003 and with absence of KRAS mutations (p = 0.0481. Conclusion TRAIL-R1 expression was an independent prognostic marker for better survival in all CRC samples and even in the CRC group that received adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement of chemosensitivity towards standard chemotherapeutic agents and the effect of endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive therapeutic target.

  5. Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the Ca(2+-binding proteins S100A6 and S100A11.

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    Christian Melle

    Full Text Available BACKGROUND: It is unknown, on the proteomic level, whether the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known. METHODOLOGY/PRINCIPAL FINDINGS: In this study, tissue from colon-derived liver metastases (n = 17 were classified, laser-microdissected, and analysed by ProteinChip arrays (SELDI. The resulting spectra were compared with data for primary colorectal (CRC and hepatocellular carcinomas (HCC from our former studies. Of 49 signals differentially expressed in primary HCC, primary CRC, and liver metastases, two were identified by immunodepletion as S100A6 and S100A11. Both proteins were precisely localized immunohistochemically in cells. S100A6 and S100A11 can discriminate significantly between the two primary tumor entities, CRC and HCC, whereas S100A6 allows the discrimination of metastases and HCC. CONCLUSIONS: Both identified proteins can be used to discriminate different tumor entities. Specific markers or proteomic patterns for the metastases of different primary cancers will allow us to determine the biological characteristics of metastasis in general. It is unknown how the protein patterns of tumors change during metastasis or whether markers are present that allow metastases to be allocated to a specific tumor entity. The latter is of clinical interest if the primary tumor is not known.

  6. Anaesthesia in colorectal carcinoma surgery at the Clinic for Digestive Surgery from 1997 to 2007.

    Science.gov (United States)

    Palibrk, I; Ranković, V; Masirević, V; Marcetić, Lj; Matić, M; Milenković, M; Palibrk, V Pantić

    2009-01-01

    Colorectal cancers are one of the most present neoplasms in human population. This pathology is one of the most frequent ones at the Clinic for Digestive Surgery in Belgrade. To investigate if there were any changes in both number and structure of patients with colorectal cancers (age, gender, co-morbidity) as well as in both type and duration of surgical procedures and in providing and maintaining anaesthesia in patients with this disease. This is a retrospective study. Research materials were anaesthesiological cards written for patients undergoing surgery in order to treat colorectal cancers at the Clinic for Digestive surgery in both 1997 and 2007. Demographics, co-morbidity, ASA score were the parameters we followed in our survey as well as the type of the resection and duration of these surgical interventions. Besides that providing and maintaining anaesthesia and balance of circulatory volume were considered too. The number of the colorectal surgical interventions has been increased up to 489 (13.1% of all) in 2007 comparing to the number of 379 (13.55% of all) in 1997. The percentage has remained the same because the number of all surgical procedures has been increased. The percentage of the rectal resections is increased highly significante in 2007 (50.1% in 1997; 62.6% in 2007). During the same year the duration of the operations was shortened (mean value 176.31 minutes in 1997, 157.5 minutes in 2007). In 2007 highly statistically significant is bigger amount of colloid and crystalloid infusions that were given for supplementation of circulatory volume (mean value 3294.89 ml in 2007; 2552.22 ml in 1997). On the other hand lower amount of blood was given in 2007 than in 1997 (mean value 102.76 opposite to 488.07) what is statisticly significant. The number of the patients with co-morbidities is not statisticly importantly changed in these two followed years. Anaesthesiology technique has been changed and is monitored by higher use of inhalation anesthetics

  7. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC

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    Annegret Müller

    2004-01-01

    Full Text Available Genomic instability at simple repeated sequences, termed microsatellite instability (MSI, plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.

  8. Physical and Nutritional Prehabilitation in Older Patients With Colorectal Carcinoma: A Systematic Review.

    Science.gov (United States)

    Looijaard, Stéphanie M L M; Slee-Valentijn, Monique S; Otten, René H J; Maier, Andrea B

    2017-03-01

    Sarcopenia and malnourishment are highly prevalent in older patients with colorectal cancer (CRC), who form a growing group of patients at risk of adverse outcome after surgery. Intervention on physical function and/or nutritional status may decrease the risk of postoperative complications. However, the overall effect of preoperative physical and nutritional interventions (better known as prehabilitation) in older patients with CRC remains unknown. The objective was to review the literature on physical and nutritional prehabilitation performed as observational cohort studies or randomized controlled trials in patients 60 years and older undergoing elective CRC surgery. We searched PubMed, Embase.com, CINAHL, and the Cochrane Library from inception to July 16, 2015, for relevant literature. Search terms included colorectal cancer, aged, pre- and perioperative period, surgery, physical activity, and nutrition. A total of 6 studies were included: 1 study applied a physical intervention, 3 studies applied a nutritional intervention, and 2 studies applied a combination of both interventions. None of the preoperative interventions significantly reduced length of stay, mortality, or readmission rates. Physical and nutritional prehabilitation in older patients with CRC has not shown a significant reduction in postoperative complications or length of stay. One study that examined the effect of a perioperative nutritional supplement reported a reduction in postoperative complications. Future research should explore targeted combined interventions, taking into account physical and nutritional patient requirements.

  9. Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.

    Science.gov (United States)

    Mármol, Inés; Virumbrales-Muñoz, María; Quero, Javier; Sánchez-de-Diego, Cristina; Fernández, Luis; Ochoa, Ignacio; Cerrada, Elena; Yoldi, Mª Jesús Rodríguez

    2017-11-01

    Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC 5 H 4 )(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NC 5 H 4 )(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NC 5 H 4 )(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance. Copyright © 2017. Published by Elsevier Inc.

  10. Negative Correlation between miR-200c and Decorin Plays an Important Role in the Pathogenesis of Colorectal Carcinoma

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    Ren-Yi Tang

    2017-01-01

    Full Text Available Aim. To demonstrate the regulatory role of miRNA in colorectal carcinoma (CRC and reveal the transcript markers that may be associated with CRC clinical outcomes. Method. Herein, we analyzed both mRNA and miRNA gene expression profiles of 255 CRC tumor samples from The Cancer Genome Atlas project to reveal the regulatory association between miRNA and mRNA. Also, the potential role of gene coexpression network in CRC has been explored. Results. The negative correlation between miR-200c and DCN (Decorin was calculated in CRC, indicating that DCN could be a potential target of miR-200c. Clinical features indicated that colon polyp history and overall survival were significantly related to the expression level of miR-200c. Three coexpression networks have been constructed, and genes involved in the networks are related to cell cycle, NOTCH, and mTOR signaling pathways. Conclusion. Our result provides a new insight into cancer related mRNA coexpression network in CRC research.

  11. Ex-vivo clonally expanded B lymphocytes infiltrating colorectal carcinoma are of mature immunophenotype and produce functional IgG.

    Science.gov (United States)

    Maletzki, Claudia; Jahnke, Annika; Ostwald, Christiane; Klar, Ernst; Prall, Friedrich; Linnebacher, Michael

    2012-01-01

    Tumor infiltrating B cells (TiBc) have not yet been investigated in detail. This may at least in part be due to technical difficulties. Here we describe a straightforward and reproducible method to isolate and culture TiBc from primary colorectal carcinomas (CRC). TiBc cultures were generated by Epstein-Barr virus (EBV) immortalization. With this method, monoclonal TiBc cultures were obtained for 14/19 CRCs. As assessed by flow cytometry and ELISA, TiBc showed an activated immunophenotype (CD23(+), CD80(+)) and produced immunoglobulin (Ig; IgG secretion in 55% of the cultures). In functional in vitro analysis, most of the IgGs specifically bound to allogeneic CRC target cells. These data suggest that TiBc are antigen-experienced and thus may exhibit functionality in situ. Additionally, mini-cultures generated from 12 further CRCs revealed TiBc outgrowth exclusively in the presence of EBV. In summary, this simple method provides a cellular tool and our data set the stage for analysing the bivalent role of TiBc; being antigen-presenting cells on the one hand and tumor-specific antibody producers on the other. Additionally, the generation of long-term TiBc cultures and their monoclonal Ig may serve to identify novel tumor-specific antigens.

  12. Anticancer Activity of Marine Sponge Hyrtios sp. Extract in Human Colorectal Carcinoma RKO Cells with Different p53 Status

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    Hyun Kyung Lim

    2014-01-01

    Full Text Available Drug development using marine bioresources is limited even though the ocean occupies about 70% of the earth and contains a large number of biological materials. From the screening test of the marine sponge extracts, we found Hyrtios sp. sponge collected from Chuuk island, Micronesia. In this study, the Hyrtios sp. extract was examined for anticancer activity against human colorectal carcinoma RKO cells that are wildtype for p53 and RKO-E6 that are p53 defective. The Hyrtios sp. extract dose-dependently inhibited viability in both cell lines. Multinucleation as an indication of mitotic catastrophe was also observed. Cytotoxicity tests gave significantly different results for RKO and RKO-E6 cells after 48 h exposure to Hyrtios sp. extract. In RKO cells treated with Hyrtios sp. extract, cell death occurred by induction of p53 and p21 proteins. In p53-defective RKO-E6 cells, Hyrtios sp. extract decreased expression of JNK protein and increased p21 protein. These results indicate that Hyrtios sp. extract induced apoptosis via different pathways depending on p53 status and could be a good natural product for developing new anticancer drugs.

  13. Ex-vivo clonally expanded B lymphocytes infiltrating colorectal carcinoma are of mature immunophenotype and produce functional IgG.

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    Claudia Maletzki

    Full Text Available BACKGROUND: Tumor infiltrating B cells (TiBc have not yet been investigated in detail. This may at least in part be due to technical difficulties. Here we describe a straightforward and reproducible method to isolate and culture TiBc from primary colorectal carcinomas (CRC. METHODS/RESULTS: TiBc cultures were generated by Epstein-Barr virus (EBV immortalization. With this method, monoclonal TiBc cultures were obtained for 14/19 CRCs. As assessed by flow cytometry and ELISA, TiBc showed an activated immunophenotype (CD23(+, CD80(+ and produced immunoglobulin (Ig; IgG secretion in 55% of the cultures. In functional in vitro analysis, most of the IgGs specifically bound to allogeneic CRC target cells. These data suggest that TiBc are antigen-experienced and thus may exhibit functionality in situ. Additionally, mini-cultures generated from 12 further CRCs revealed TiBc outgrowth exclusively in the presence of EBV. CONCLUSION: In summary, this simple method provides a cellular tool and our data set the stage for analysing the bivalent role of TiBc; being antigen-presenting cells on the one hand and tumor-specific antibody producers on the other. Additionally, the generation of long-term TiBc cultures and their monoclonal Ig may serve to identify novel tumor-specific antigens.

  14. Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo

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    Wang Haibo

    2010-09-01

    Full Text Available Abstract Background RhoA and RhoC have been proved to be over-expressed in many solid cancers, including colorectal cancer. The reduction of RhoA and RhoC expression by RNA interference (RNAi resulted growth inhibition of cancer cells. The present study was to evaluate the effect of silencing of RhoA and RhoC expression by RNAi on growth of human colorectal carcinoma (CRC in tumor-bearing nude mice in vivo. Methods To establish HCT116 cell transplantable model, the nude mice were subcutaneously inoculated with 1.0 × 107 HCT116 cells and kept growing till the tumor xenografts reached 5-7 mm in diameter. Then the mice were randomly assigned to three groups(seven mice in each group: (1 normal saline(NS group, (2replication-defective recombinant adenovirus carrying the negative control shRNA (Ad-HK group and (3replication-defective recombinant adenovirus carrying the 4-tandem linked RhoA and RhoC shRNAs (Ad-RhoA-RhoC group. Ad-HK (4 × 108 pfu, 30 ul/mouse, Ad-RhoA-RhoC (4 × 108 pfu, 30 ul/mouse or PBS (30 ul/mouse was injected intratumorally four times once every other day. The weight and volumes of tumor xenografts were recorded. The levels of RhoA and RhoC mRNA transcripts and proteins in tumor xenografts were detected by reverse quantitative transcription polymerase chain reaction (QRT-PCR and immunohistochemical staining respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay was used to detect the death of cells. Results The xenografts in mice could be seen at 5th day from the implantation of HCT116 cells and all had reached 5-7 mm in size at 9th day. After injection intratumorally, the growth speed of tumor xenografts in Ad-RhoA-RhoC group was significantly delayed compared with those in NS and Ad-HK group(P RhoA and RhoC reduced more in Ad-RhoA-RhoC group than those in NS and Ad-HK group. The relative RhoA and RhoC mRNA transcripts were decreased to 48% and 43% respectively (P RhoA and Rho

  15. High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival

    DEFF Research Database (Denmark)

    Cintin, Christina; Johansen, Julia S; Christensen, Ib Jarle

    2002-01-01

    obtained pre- and postoperatively from 324 patients who underwent curative resection (Dukes Stage A: 47; B: 148; C: 119; and D: 10). The patients were followed with serum YKL-40 levels every 6 months postoperatively, and the median followup time was 82 months (range, 68-95). In that period 146 patients...... died. RESULTS: Serum YKL-40 was significantly decreased in the first postoperative blood sample in 62% of patients with high preoperative levels. In addition, patients with high serum YKL-40 (adjusted for age) six months after curative operation had significantly shorter survival times (P = 0......BACKGROUND: YKL-40 is a member of family 18 glycosyl hydrolases. YKL-40 is a growth factor and may stimulate migration of endothelial cells. YKL-40 may also play a role in inflammation and degradation of connective tissue. Elevated preoperative serum YKL-40 levels in patients with colorectal...

  16. Prevalence of adenomas and hyperplastic polyps in mismatch repair mutation carriers among CAPP2 participants: report by the colorectal adenoma/carcinoma prevention programme 2

    DEFF Research Database (Denmark)

    Liljegren, Annelie; Barker, Gail; Elliott, Faye

    2008-01-01

    PURPOSE: To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously....... CONCLUSION: Adenoma prevalence increases with age among MMR mutation carriers, whereas hyperplastic polyp prevalence is consistent. No sex differences were observed for either type of lesion....... in smaller studies, and the results have been found to be variable. PATIENTS AND METHODS: Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before...

  17. COLD-PCR enhanced melting curve analysis improves diagnostic accuracy for KRAS mutations in colorectal carcinoma.

    Science.gov (United States)

    Pritchard, Colin C; Akagi, Laura; Reddy, Poluru L; Joseph, Loren; Tait, Jonathan F

    2010-11-26

    KRAS mutational analysis is the standard of care prior to initiation of treatments targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer. Sensitive methods are required to reliably detect KRAS mutations in tumor samples due to admixture with non-mutated cells. Many laboratories have implemented sensitive tests for KRAS mutations, but the methods often require expensive instrumentation and reagents, parallel reactions, multiple steps, or opening PCR tubes. We developed a highly sensitive, single-reaction, closed-tube strategy to detect all clinically significant mutations in KRAS codons 12 and 13 using the Roche LightCycler® instrument. The assay detects mutations via PCR-melting curve analysis with a Cy5.5-labeled sensor probe that straddles codons 12 and 13. Incorporating a fast COLD-PCR cycling program with a critical denaturation temperature (Tc) of 81°C increased the sensitivity of the assay >10-fold for the majority of KRAS mutations. We compared the COLD-PCR enhanced melting curve method to melting curve analysis without COLD-PCR and to traditional Sanger sequencing. In a cohort of 61 formalin-fixed paraffin-embedded colorectal cancer specimens, 29/61 were classified as mutant and 28/61 as wild type across all methods. Importantly, 4/61 (6%) were re-classified from wild type to mutant by the more sensitive COLD-PCR melting curve method. These 4 samples were confirmed to harbor clinically-significant KRAS mutations by COLD-PCR DNA sequencing. Five independent mixing studies using mutation-discordant pairs of cell lines and patient specimens demonstrated that the COLD-PCR enhanced melting curve assay could consistently detect down to 1% mutant DNA in a wild type background. We have developed and validated an inexpensive, rapid, and highly sensitive clinical assay for KRAS mutations that is the first report of COLD-PCR combined with probe-based melting curve analysis. This assay significantly improved diagnostic

  18. COLD-PCR enhanced melting curve analysis improves diagnostic accuracy for KRAS mutations in colorectal carcinoma

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    Joseph Loren

    2010-11-01

    Full Text Available Abstract Background KRAS mutational analysis is the standard of care prior to initiation of treatments targeting the epidermal growth factor receptor (EGFR in patients with metastatic colorectal cancer. Sensitive methods are required to reliably detect KRAS mutations in tumor samples due to admixture with non-mutated cells. Many laboratories have implemented sensitive tests for KRAS mutations, but the methods often require expensive instrumentation and reagents, parallel reactions, multiple steps, or opening PCR tubes. Methods We developed a highly sensitive, single-reaction, closed-tube strategy to detect all clinically significant mutations in KRAS codons 12 and 13 using the Roche LightCycler® instrument. The assay detects mutations via PCR-melting curve analysis with a Cy5.5-labeled sensor probe that straddles codons 12 and 13. Incorporating a fast COLD-PCR cycling program with a critical denaturation temperature (Tc of 81°C increased the sensitivity of the assay >10-fold for the majority of KRAS mutations. Results We compared the COLD-PCR enhanced melting curve method to melting curve analysis without COLD-PCR and to traditional Sanger sequencing. In a cohort of 61 formalin-fixed paraffin-embedded colorectal cancer specimens, 29/61 were classified as mutant and 28/61 as wild type across all methods. Importantly, 4/61 (6% were re-classified from wild type to mutant by the more sensitive COLD-PCR melting curve method. These 4 samples were confirmed to harbor clinically-significant KRAS mutations by COLD-PCR DNA sequencing. Five independent mixing studies using mutation-discordant pairs of cell lines and patient specimens demonstrated that the COLD-PCR enhanced melting curve assay could consistently detect down to 1% mutant DNA in a wild type background. Conclusions We have developed and validated an inexpensive, rapid, and highly sensitive clinical assay for KRAS mutations that is the first report of COLD-PCR combined with probe

  19. Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; Mohamed, Mie Ali

    2015-10-01

    c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Investigation of Metastasis-Related Genes: A Rat Model Mimicking Liver Metastasis of Colorectal Carcinoma

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    Hassan Adwan

    2017-07-01

    Full Text Available Liver is the main target of colorectal cancer (CRC metastasis. Currently, the number of reports is small, which describe changes in gene expression supporting liver metastasis. Here, a rat model was used for analyzing mRNA modulations during liver colonization and compared with available literature. In the model, CC531 rat CRC cells were injected via a mesenteric vein into isogenic WAG/Rij rats and re-isolated at early, intermediate, advanced, and terminal stages of liver colonization. These cells were used for RNA isolation. Microarrays were used for analyzing mRNA profiles of expression. The number of deregulated genes is comparatively large and only part of it has been studied so far. As reported to date, claudins and insulin-like growth factor-binding proteins (IGFBPs were found to be deregulated. The fact that the chosen method is efficient is confirmed by the study of claudins and IGFBPs, which show altered expression in the initial stages of liver colonization and then return to normalcy. In addition, cadherin was described to be downregulated in epithelial–mesenchymal transition models. It can, therefore, be concluded that the models used are helpful in finding genes, which are instrumental for metastatic liver colonization.

  1. Driver Gene Mutations in Stools of Colorectal Carcinoma Patients Detected by Targeted Next-Generation Sequencing.

    Science.gov (United States)

    Armengol, Gemma; Sarhadi, Virinder K; Ghanbari, Reza; Doghaei-Moghaddam, Masoud; Ansari, Reza; Sotoudeh, Masoud; Puolakkainen, Pauli; Kokkola, Arto; Malekzadeh, Reza; Knuutila, Sakari

    2016-07-01

    Detection of driver gene mutations in stool DNA represents a promising noninvasive approach for screening colorectal cancer (CRC). Amplicon-based next-generation sequencing (NGS) is a good option to study mutations in many cancer genes simultaneously and from a low amount of DNA. Our aim was to assess the feasibility of identifying mutations in 22 cancer driver genes with Ion Torrent technology in stool DNA from a series of 65 CRC patients. The assay was successful in 80% of stool DNA samples. NGS results showed 83 mutations in cancer driver genes, 29 hotspot and 54 novel mutations. One to five genes were mutated in 75% of cases. TP53, KRAS, FBXW7, and SMAD4 were the top mutated genes, consistent with previous studies. Of samples with mutations, 54% presented concomitant mutations in different genes. Phosphatidylinositol 3-kinase/mitogen-activated protein kinase pathway genes were mutated in 70% of samples, with 58% having alterations in KRAS, NRAS, or BRAF. Because mutations in these genes can compromise the efficacy of epidermal growth factor receptor blockade in CRC patients, identifying mutations that confer resistance to some targeted treatments may be useful to guide therapeutic decisions. In conclusion, the data presented herein show that NGS procedures on stool DNA represent a promising tool to detect genetic mutations that could be used in the future for diagnosis, monitoring, or treating CRC. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  2. Overexpression of c-Myb is associated with suppression of distant metastases in colorectal carcinoma.

    Science.gov (United States)

    Tichý, Michal; Knopfová, Lucia; Jarkovský, Jiří; Pekarčíková, Lucie; Veverková, Lenka; Vlček, Petr; Katolická, Jana; Čapov, Ivan; Hermanová, Markéta; Šmarda, Jan; Beneš, Petr

    2016-08-01

    The MYB gene codes for the c-Myb transcription factor maintaining proliferation of colon epithelial progenitors, thus controlling colon development and homeostasis. This gene is overexpressed in early phases of colorectal cancer (CRC) tumorigenesis. The aim of this study was to examine the expression of c-Myb in CRC tissue samples both at the messenger RNA (mRNA) and protein levels and to evaluate their associations with clinicopathological characteristics in a group of 108 CRC patients. Statistically significant negative association was found between the frequency of the c-Myb-positive tumor cells assessed by immunohistochemistry and the presence of distant metastases (p Myb protein level in the tumor tissue correlated with its mRNA level, no significant association between MYB mRNA and any clinicopathological characteristics was observed. We conclude that albeit overexpression of c-Myb is considered as an important factor contributing to early phases of CRC tumorigenesis, it may later have negative effect on tumor cell dissemination as observed recently in breast cancer as well. Further studies are required to explain the role of c-Myb during formation of CRC distant metastases.

  3. Colonoscopic prioritization in colorectal carcinoma screening using quantitative immunochemical faecal occult blood test: a pilot study.

    Science.gov (United States)

    Chong, H Y; Roslani, A C; Law, C W

    2013-01-01

    Screening for colorectal cancer (CRC) improves outcomes and reduces its incidence. However, population-based screening in Malaysia continues to be a challenge, in view of cost and limited availability of colonoscopic skills and facilities. Conventional qualitative faecal occult blood tests help to prioritize those who require earlier colonoscopies, but cannot distinguish between benign and malignant causes. Recently, quantitative immunochemical faecal occult blood tests (qFOBT) have demonstrated some discriminatory ability in distinguishing benign and malignant causes. We aim to assess feasibility of qFOBT as a tool for stratification of colonoscopic priority in asymptomatic patients. A health awareness exhibition was held in a major shopping complex in Kuala Lumpur on 6 and 7 Feb 2010. All asymptomatic individuals> 40 years, and those Chinese (60%), followed by Malay (25%), Indian (12%) and others (3%). Twelve (10%) participants were tested positive and were advised to undergo colonoscopy but 9 (75%) declined colonoscopy and further investigations citing lack of time as the reason. Of the 3 participants (all in the moderately positive group) who underwent colonoscopy, 2 had a family history of CRC. Colonoscopic findings revealed haemorrhoids in one participant and two participants had histologically proven benign sigmoid colonic polyps. The use of qFOBT as a tool to screen and prioritize asymptomatic patients for early colonoscopy in CRC screening is logistically feasible. However, in order for it to be effective, measures to improve compliance to colonoscopy need to be taken.

  4. Determination of boron concentration in blood and tissue samples from patients with liver metastases of colorectal carcinoma using Prompt Gamma Ray Activation Analysis (PGAA)

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Appelman, K., E-mail: k.appelman@hetnet.n [Institute for Energy, Joint Research Centre of the European Commission, Petten (Netherlands); Kudejova, P., E-mail: petra.kudejova@frm2.tum.d [Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universitaet Muenchen, D-85748 Garching (Germany); Schuetz, C., E-mail: schuetc@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Kratz, J.V., E-mail: jvkratz@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Moss, R., E-mail: raymond.moss@ec.europa.e [Institute for Energy, Joint Research Centre of the European Commission, Petten (Netherlands); Otto, G., E-mail: gerd.otto@unimedizin-mainz.d [Department of Hepatobiliary, Pancreatic and Transplantation Surgery, University of Mainz, Langenbeckstr. 1, D-55131 Mainz (Germany); Hampel, G., E-mail: gabriele.hampel@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany)

    2011-07-15

    As part of the studies on Boron Neutron Capture Therapy at the University of Mainz, Germany, a clinical trial has been started in which, four patients suffering from liver metastases of colorectal carcinoma have been enrolled. Specimens of blood and healthy tissue samples taken from the patients were measured at the PGAA facilities at the HFR in Petten, The Netherlands, and at the FRM II in Munich, Germany. From the measured boron concentrations, pharmacokinetic curves and blood-to-tissue concentration ratios were produced.

  5. The colorectal carcinoma prognosis factors: Significance of diagnosis delay Factores pronósticos en carcinoma colorrectal: Importancia de la demora diagnóstica

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    E. Gómez-Domínguez

    2006-05-01

    Full Text Available Introduction: detection of early-stage colorectal carcinoma (CRC -( Dukes' A or B- provides better survival rates in these patients. Thus, the effectiveness of screening programs in asymptomatic patients or of early diagnosis in symptomatic individuals has been postulated. The aim of this study was to establish whether a delay in diagnosis or other factors are related to CRC stage. Patients and methods: a retrospective study was performed on 96 patients with CRC. Age at diagnosis, gender distribution, intestinal disorders, diagnosis delay, primary sign and -regarding CRC- localization, stage (Dukes' and grade of differentiation (well differentiated; non-well differentiated; poorly differentiated were recorded. Results: diagnosis delay was 185 ± 190 days. Patients delay in obtaining a diagnosis was 119 ± 158 days. In 40% of patients CRC was diagnosed at an early stage (Dukes' A or B, and in 13% CRC was poorly differentiated. The only factor with an independent effect on Dukes' stage was tumor differentiation (p: 0.0012. Distal location was associated with less advanced tumors without statistical significance (p: 0.156. Conclusion: based on the presented data, a greater effort regarding screening programs for healthy people seems warranted, as improved survival has been demonstrated when diagnosis delay is reduced, particularly in patients with the highest mean delay.Introducción: el diagnóstico precoz del cáncer colorrectal (estadios A y B de Dukes consigue mejorar las tasas de supervivencia de estos pacientes. Con este objetivo se ha propuesto como estrategia acelerar el diagnóstico de enfermos sintomáticos o realizar cribados en enfermos asintomáticos. El objetivo de este trabajo es identificar los factores que influyen en la extensión tumoral del carcinoma colorrectal, especialmente la demora en el diagnóstico. Material y métodos: estudio prospectivo de una serie de 99 pacientes diagnosticados de carcinoma colorrectal en los que se

  6. CTNNB1-mutant colorectal carcinomas with immediate invasive growth: a model of interval cancers in Lynch syndrome.

    Science.gov (United States)

    Ahadova, Aysel; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

    2016-10-01

    The implementation of regular colonoscopy programs has significantly decreased the mortality associated with colorectal cancer (CRC) in Lynch syndrome patients. However, interval CRCs in Lynch syndrome that remain undetected by colonoscopy still represent a substantial problem in the management of the syndrome. One possible reason of interval cancers could be a non-polypous pathway of cancer development. To examine the possibility of a non-polypous pathway of CRC development in Lynch syndrome, we analyzed the histological appearance of 46 Lynch syndrome-associated CRCs and compared them to 34 sporadic microsatellite unstable cancers. We observed that 25 (62.5 %) out of 40 assessable Lynch syndrome-associated carcinomas lacked evidence of polypous growth, compared to 17 (50 %) out of 34 sporadic MSI-H cancers. We detected CTNNB1 mutations in 8 (17.4 %) out of 46 Lynch syndrome-associated cancers compared to 0 out of 34 sporadic MSI-H cancers (p = 0.01). The majority of CTNNB1-mutant cancers presented with a histological appearance suggesting immediate invasive growth. Our results suggest that a distinct subgroup of CRCs in Lynch syndrome may in fact emerge from a non-polypous precursor, thus potentially explaining the phenomenon of interval cancers. Such a non-polypous precursor may be the recently described mismatch repair-deficient crypt focus, which remains invisible for the examiner during colonoscopy. This calls for considering the implementation of active, primary preventive measures in the management of Lynch syndrome. Future studies on pathogenic pathways and precursor lesions in Lynch syndrome are strongly encouraged, and the clinical efficacy of new prevention approaches should be evaluated in prospective clinical trials.

  7. Genetic association of deleted in colorectal carcinoma variants with breast cancer risk: A case-control study.

    Science.gov (United States)

    Liu, Xinghan; Wang, Xijing; Fu, Sidney W; Wang, Meng; Kang, Huafeng; Guan, Haitao; Zhang, Shuqun; Ma, Xiaobin; Lin, Shuai; Liu, Kang; Feng, Yanjing; Dai, Cong; Dai, Zhijun

    2016-05-31

    Deleted in colorectal carcinoma (DCC), a netrin-1 dependence receptor, is correlated with cell progression, migration, and adhesion. Evidence indicated that DCC was frequently down-regulated in many cancers. However, the association of DCC with breast cancer remains uncertain. We conducted a case-control study to investigate the impact of three DCC gene variants (rs2229080, rs7504990, and rs4078288) on breast cancer susceptibility in Chinese women. This study included 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. The three gene variants were genotyped via Sequenom MassARRAY. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to evaluate the associations. We found that individuals with the rs2229080 C/G, C/C, and C/G-CC genotypes had a higher breast cancer risk, and the minor allele C was associated with increased breast cancer risk in an allele model. We observed a significantly decreased breast cancer risk with the rs7504990 C/T, T/T, and C/T-T/T genotypes, and the minor allele T was protective against breast cancer in an allele model. In addition, rs2229080 was associated with the axillary lymph node (LN) metastasis status. An age-stratified analysis revealed an association between rs2229080 and reduced breast cancer risk among older patients (≥ 49 years). Furthermore, the haplotype analysis showed that the Crs2229080Crs7504990Ars4078288 haplotype was associated with a decreased breast cancer risk. However, the results indicated a lack of association between rs4078288 and breast cancer risk. These findings affirmed that rs2229080 and rs7504990 polymorphisms in DCC might be related with breast cancer susceptibility in Chinese women.

  8. Oxidative stress with altered element content and decreased ATP level of erythrocytes in hepatocellular carcinoma and colorectal liver metastases.

    Science.gov (United States)

    Váli, László; Hahn, Oszkár; Kupcsulik, Péter; Drahos, Agnes; Sárváry, Eniko; Szentmihályi, Klára; Pallai, Zsolt; Kurucz, Timea; Sípos, Péter; Blázovics, Anna

    2008-05-01

    Our aim was to study the possible alterations of redox status (enzymatic and nonenzymatic parameters and metal elements) in erythrocytes of patients with hepatocellular carcinoma (HCC), colorectal liver metastases (CRLM) and benign liver neoplasms. The function of redox homeostasis is closely connected to the energy level of erythrocytes, therefore, the ATP level was also determined. Antioxidant parameters, enzyme activities of superoxide dismutase and glutathione peroxidase were estimated in the erythrocytes of 11 patients with benign tumour, 23 patients with primary malignant and 37 metastatic liver tumour patients and 30 age-matched and sex-matched healthy controls. Element content with inductively coupled plasma optical emission spectrometer and ATP level by the chemiluminometric method were also determined from the samples. Free radical intensity was significantly increased, whereas erythrocyte glutathione peroxidase and superoxide dismutase activities were significantly decreased in the HCC and CRLM groups versus benign groups and controls. Se, Mn and Zn levels were lowered in HCC and CRLM groups versus benign and control groups. The content of Cu, Mg, Se and Zn changed significantly between HCC and CRLM groups. Similarly, ATP concentration decreased in HCC and CRLM versus controls and benign groups. The lowest levels of ATP and antioxidant enzyme activities were found in the case of CRLM patients. These results reveal an alteration in the ATP level of erythrocytes with concomitant changes in the antioxidant defence system in hepatic cancer patients. Altered redox homeostasis (oxidative damage) may lead to decreased ATP level and consequently may play an important role in primary carcinogenesis and generation of metastases, as well.

  9. Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Chun [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Jin, Zhao [Department of Coloproctology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 325000 (China); Chen, Nian-zhao [Department of Medicine, The Chinese Medicine Hospital of Wenzhou, Wenzhou 325000 (China); Lu, Min; Liu, Chang-bao; Hu, Wan-Le [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Zheng, Chen-guo, E-mail: zhengchenguo80@163.com [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China)

    2016-01-29

    Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. - Highlights: • IRE1 was determined to be an independent predictor of overall survival in CRC patient. • IRE1-XBP1 pathway promoted CRC cell proliferation through regulating Cyclin D1 expression. • IRE1-XBP1 pathway played important role in EMT of CRC cells.

  10. NUBPL, a novel metastasis-related gene, promotes colorectal carcinoma cell motility by inducing epithelial-mesenchymal transition.

    Science.gov (United States)

    Wang, Yuhui; Wu, Nan; Sun, Donglin; Sun, Haiming; Tong, Dandan; Liu, Duo; Pang, Bo; Li, Su; Wei, Jia; Dai, Jialin; Liu, Yang; Bai, Jing; Geng, Jingshu; Fu, Songbin; Jin, Yan

    2017-06-01

    Nucleotide binding protein-like, NUBPL, is an assembly factor for human mitochondrial complex I, which is the biggest member of the mitochondrial respiratory chain. However, the relationship between NUBPL and carcinoma progression remains unknown. In this study, NUBPL was characterized for its role in colorectal cancer (CRC) and the underlying molecular mechanisms. Data (n = 197) from the Oncomine database revealed that mRNA levels of NUBPL were remarkably overexpressed in CRC tissues compared with normal tissues. In addition, immunohistochemical analysis of 75 pairs of CRC and non-tumor tissues showed that the expression level of NUBPL was significantly higher in CRC tissues, and its expression level was positively associated with lymph node metastasis (P = 0.028) and advanced staging (P = 0.030). Expression of NUBPL in metastatic lymph nodes of CRC patients was also detected by immunohistochemical staining and high expression levels of NUBPL were observed. Overexpression of NUBPL significantly promoted the migration and invasion ability of CRC cell lines SW480 and SW620, whereas knockdown of NUBPL lead to an opposite effect. Our further study found that NUBPL could induce epithelial-mesenchymal transition (EMT), characterized by downregulation of epithelial markers (E-cadherin) and upregulation of mesenchymal markers (N-cadherin and vimentin). Moreover, NUBPL was able to activate ERK, which is believed to promote EMT and tumor metastasis. Inhibition of ERK suppressed the NUBPL-induced changes in EMT and cell motility. These data showed that NUBPL plays a vital role in CRC migration and invasion by inducing EMT and activating ERK. It might be a novel therapeutic target for CRC. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  11. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status.

    Science.gov (United States)

    Widel, Maria; Lalik, Anna; Krzywon, Aleksandra; Poleszczuk, Jan; Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna

    2015-08-01

    Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0-8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at lower doses whereas wild type cells only at higher doses. Secretion of IL-8 by TP53-/- control cells was many times lower than that by TP53+/+ but increased significantly after irradiation. Transcription of the NFκBIA was induced in irradiated TP53+/+ mainly, but in bystanders a higher level was observed in TP53-/- cells, suggesting that TP53 is required for induction of NFκB pathway after irradiation but another mechanism of activation must operate in

  12. Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy can be predicted by molecular subtype.

    Science.gov (United States)

    Kwon, Yujin; Park, Minhee; Jang, Mi; Yun, Seongju; Kim, Won Kyu; Kim, Sora; Paik, Soonmyung; Lee, Hyun Jung; Hong, Sungpil; Kim, Tae Il; Min, Byungsoh; Kim, Hoguen

    2017-06-13

    Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a CMS group, which shows a 79% correlation between the CMS classification and our four molecular subtypes. We found that two of our subtypes showed significantly higher disease-free survival and overall survival than the others. Group 2, in particular, which showed no disease recurrence or death, was characterized by high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21), and right-sided location (12/21); this group strongly correlated with CMS1 (microsatellite instability immune type). We further identified the molecular characteristics of each group and selected 10 potential biomarker genes from each. When these were compared to the previously reported molecular classifier genes, we found that 31 out of 40 selected genes were matched with those previously reported. Our findings indicate that molecular classification can reveal specific molecular subtypes correlating with clinicopathologic features of CRCs and can have predictive value for the prognosis for stage III CRCs with FOLFOX adjuvant chemotherapy.

  13. Tucatinib (ONT-380) and Trastuzumab in Treating Patients With HER2+ Metastatic Colorectal Cancer

    Science.gov (United States)

    2018-02-08

    Colorectal Adenocarcinoma; ERBB2 Gene Amplification; HER2/Neu Positive; KRAS wt Allele; NRAS wt Allele; Recurrent Colorectal Carcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  14. Endoscopic mucosal resection in colorectal lesion: a safe and effective procedure even in lesions larger than 2 cm and in carcinomas

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos Santos

    2011-12-01

    Full Text Available CONTEXT: Endoscopic mucosal resection is a minimally invasive technique used in the treatment of colorectal neoplasms, including early carcinomas of different size and morphology. OBJECTIVES: To evaluate procedure safety, efficacy, outcomes, and recurrence rate in endoscopic mucosal resection of colorectal lesions. METHODS: A total of 172 lesions in 156 patients were analyzed between May 2003 and May 2009. All lesions showed pit pattern suggestive of neoplasia (Kudo types III-V at high-magnification chromocolonoscopy with indigo carmine. The lesions were evaluated for macroscopic classification, size, location, and histopathology. Lesions 20 mm or smaller were resected en bloc and lesions larger than 20 mm were removed using the piecemeal technique. Complications and recurrence were analyzed. Patients were followed up for 18 months. RESULTS: There were 83 (48.2% superficial lesions, 57 (33.1% depressed lesions, 44 (25.6% laterally spreading tumors, and 45 (26.2% protruding lesions. Mean lesion size was 11.5 mm ± 9.6 mm (2 mm-60 mm. Patients' mean age was 61.6 ± 12.5 years (34-93 years. Regarding lesion site, 24 (14.0% lesions were located in the rectum, 68 (39.5% in the left colon, and 80 (46.5% in the right colon (transverse, ascending, and cecum. There were 167 (97.1% neoplasms: 142 (82.5% adenomatous lesions, 24 (14.0% intramucosal carcinomas, and 1 (0.6% invasive carcinoma. En bloc resection was performed in 158 (91.9% cases and piecemeal resection in 14 (8.1%. Bleeding occurred in 5 (2.9% cases. Recurrence was observed in 4.1% (5/122 of cases and was associated with lesions larger than 20 mm (P<0.01, piecemeal resection (P<0.01, advanced neoplasm (P = 0.01, and carcinoma compared to adenoma (P = 0.04. CONCLUSIONS: Endoscopic mucosal resection of colorectal lesions is a safe and effective procedure, with low complication and local recurrence rates. Recurrence is associated with lesions larger than 20 mm and carcinomas.

  15. Assessment of tumor budding in colorectal carcinoma: correlation with β-catenin nuclear expression.

    Science.gov (United States)

    El-Gendi, S; Al-Gendi, A

    2011-03-01

    Tumor budding (TB) is showing increasing promise as a colorectal cancer (CRC) prognosticator that is independent of TNM staging. β-Catenin is a component of the Wingless/Wnt signaling pathway that is bound to membrane-associated E-cadherin and is essential for its correct position and function. This study was designed to detect TB in 44 resected primary CRC cases and also to compare β-catenin expression in the tumor budding sites (TBS) and in the tumor center. Tumor budding was assessed in both H&E and pankeratin immunostained sections. Agreement between TB scoring using pancytokeratin and H&E was tested. Also, typing of the tumor margin and determination of degree of cytoplasmic pseudo-fragmentation was done. Tumor budding, cytoplasmic pseudofragments and β-catenin expression were related to known CRC prognosticators. Ten tumors (22.7%) showed low grade (LG) budding and 34 tumors (77.3%) showed high grade (HG) budding. The 34 HG budding tumors were further subdivided into moderate and severe (n=13, n=21, respectively) budding cancers. Twenty nine tumors (65.9%) showed LG cytoplasmic pseudofragments and 15 tumors (34.1%) showed HG pseudofragments. Scoring of TB on H&E and pankeratin stained sections revealed moderate agreement (Kappa=.558; p=tumor center (p=.005, p=.000, respectively). In opposition, membranous β-catenin expression was significantly higher in the tumor center than in TBS (p=.001). Although, nuclear β-catenin accumulation at TBS was noted, yet, it did not relate significantly with both TB and cytoplasmic pseudofragments around TBS (p=.649; p=.675, respectively). Also, nuclear β-catenin immunoreactivity did not relate significantly with the various clinicopathological variables. Pankeratin immunostaining facilitates typing of CRC invasive margin, and determination of the degree of TB and cytoplasmic pseudo-fragmentation. β-Catenin expression differs significantly between tumor center and TBS in CRC. Cut-offs for TB assessment should be unified

  16. Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells

    Directory of Open Access Journals (Sweden)

    Roemer Klaus

    2002-10-01

    Full Text Available Abstract Background The natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis. Recent work has suggested that the cancer chemoprotective effect of the compound is primarily linked to its ability to induce cell division cycle arrest and apoptosis, the latter possibly through the activation of pro-apoptotic proteins such as Bax. Methods The expression, subcellular localization, and importance of Bax for resveratrol-provoked apoptosis were assessed in human HCT116 colon carcinoma cells and derivatives with both bax alleles inactivated. Results Low to moderate concentrations of resveratrol induced co-localization of cellular Bax protein with mitochondria, collapse of the mitochondrial membrane potential, activation of caspases 3 and 9, and finally, apoptosis. In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent. Resveratrol inhibited the formation of colonies by both HCT116 and HCT116 bax -/- cells. Conclusion Resveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis. Both can limit the ability of the cells to form colonies.

  17. Change in anatomic distribution and incidence of colorectal carcinoma over a period of 15 years - Clinical considerations

    NARCIS (Netherlands)

    Mensink, PBF; Kolkman, JJ; van Baarlen, J; Kleibeuker, JH

    2002-01-01

    PURPOSE: Colorectal cancer is the second most common cancer in the Netherlands. Its incidence rates are among the highest in Europe. In the past decades, a right-sided shift of the subsite location of colorectal cancer has been reported. These changes in anatomic distribution might have clinical

  18. Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells.

    Science.gov (United States)

    Cengel, Keith A; Voong, K Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B; Stanbridge, Eric; Kao, Gary D; McKenna, W Gillies; Bernhard, Eric J

    2007-04-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor alpha was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  19. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells1

    Science.gov (United States)

    Cengel, Keith A.; Voong, K. Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B.; Stanbridge, Eric; Kao, Gary D.; McKenna, W. Gillies; Bernhard, Eric J.

    2007-01-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor α was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers. PMID:17460778

  20. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Keith A. Cengel

    2007-04-01

    Full Text Available Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor o was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFRactivated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  1. Absence of non-alcoholic fatty liver disease in the presence of insulin resistance is a strong predictor for colorectal carcinoma

    Science.gov (United States)

    Basyigit, Sebahat; Uzman, Metin; Kefeli, Ayse; Sapmaz, Ferdane Pirincci; Yeniova, Abdullah Ozgür; Nazligul, Yasar; Asiltürk, Zeliha

    2015-01-01

    Background: Colorectal carcinoma (CRC) and non-alcoholic fatty liver disease (NAFLD) share common risk factors. Insulin resistance (IR) has an important role in both diseases. It has been speculated that the prevalence of colorectal neoplasms might be increased in patients with NAFLD. However, It is unclear whether NAFLD is an actual risk factor or any association is incidental coexistance due to the role of IR in both disease. We aimed to assess the risk for CRC in patients with NAFLD in relation to IR. Method: This study was designed prospectively and cross-sectionally. We determined NAFLD by ultrasonography and measured IR by the homeostatic model of assessment-insulin resistance model. Results: The prevalences of CRC and adenoma were shown to be significantly higher in patients with IR (respectively; P: 0.005, P: 0.008). But prevalence of CRC was found to be significantly lower in subjects with NAFLD (P: 0.001). On multivariate logistic regression analysis, the risks of colorectal adenoma and carcinoma were significantly associated with the presence of IR (respectively; OR: 2.338, 95% CI: 1.080-4.993, P: 0.003 and : 5.023, 95% CI: 1.789-9.789, P: 0.001). The risk for CRC was significantly associated with the absence of NAFLD (OR: 7.380, 95% CI: 3.069-7.961, P: 0.010). The absence of NAFLD in the presence of IR was associated with significantly high risk for CRC (OR: 5.218, 95% CI: 1.538-7.448, P: 0.017). Conclusion: The risk of CRC can increased in subjects with IR but without NAFLD. The absence of NAFLD in the presence of IR may predict the CRC. PMID:26770473

  2. The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE2 synthesis and cytotoxicity in human colorectal carcinoma cell lines

    NARCIS (Netherlands)

    Dommels, Y.E.M.; Haring, M.M.G.; Keestra, N.G.M.; Alink, G.M.; Bladeren, P.J. van; Ommen, B. van

    2003-01-01

    This study was conducted to investigate the role of the enzyme cyclooxygenase (COX) and its prostaglandin product PGE2 in n-6 and n-3 polyunsaturated fatty acid (PUFA)-mediated effects on cellular proliferation of two human colorectal carcinoma cell lines. The long chain PUFAs eicosapentaenoic acid

  3. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Widel, Maria, E-mail: maria.widel@polsl.pl [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Lalik, Anna; Krzywon, Aleksandra [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Poleszczuk, Jan [College of Inter-faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, 93 Zwirki i Wigury Street, 02-089 Warsaw (Poland); Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida (United States); Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland)

    2015-08-15

    Highlights: • We tested radiation response and bystander effect on HCT116p53+/+ and p53−/− cells. • The p53+/+ cells developed premature senescence in exposed and bystander neighbors. • Directly exposed and bystander p53−/− cells died profoundly through apoptosis. • Interleukins 6 and 8 were differently generated by both cell lines. • NFκB path was activated mainly in p53+/+ hit cells, in p53 −/− in bystanders only. - Abstract: Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0–8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at

  4. A comparative study of the expression of Wnt-1, WISP-1, survivin and cyclin-D1 in colorectal carcinoma.

    Science.gov (United States)

    Khor, Tin Oo; Gul, Yunus A; Ithnin, Hairuszah; Seow, Heng Fong

    2006-05-01

    It is well accepted that activation of Wnt signalling occurs in colorectal carcinoma (CRC), but the correlation amongst the various proteins involved in primary tumours are still unclear. The expression of the inducer of this pathway, Wnt-1, and the downstream effectors, WISP-1, cyclin-D1 and survivin proteins, was compared in a series of CRC tissues with the apparently normal adjacent tissues to determine the relationship of these proteins. Formalin-fixed, paraffin-embedded tissue samples of 47 CRCs surgically resected at the Kuala Lumpur Hospital (KLH) between 1999 and 2000 were used. Immunohistochemical staining with monoclonal antibodies against cyclin-D1 and survivin and polyclonal antibodies against Wnt-1 and WISP-1 was performed. Results of immunohistochemistry were analysed for correlation between biomolecules and histopathological data of the patients. Of the 47 CRCs, 26 (55.3%), 15 (31.9%), 5 (10.6%) and 28 (59.6%) of the tumours exhibited positivity for Wnt-1, WISP-1, cyclin D1 and survivin, respectively. A lower percentage of the 40 apparently normal adjacent tissues were found to be positive for Wnt-1 (7, 17.5%), WISP-1 (+/-5, 12.5%) and survivin (13, 32.5%), but cyclin D1 was not detected in any of them. Interestingly, the total scores of Wnt-1, WISP-1 and survivin were significantly higher in CRC tissues (p=0.001, 0.034 and 0.044, respectively). Using the Spearman rank correlation test, a positive linear relationship was found between total Wnt-1 score with total WISP-1 score (rho=0.319, p=0.003) and total survivin score (rho=0.609, p=orWISP-1 in the CRC tissues was found to be positively correlated with patients older than 60 years old (p=0.011). In addition, nuclear cyclin-D1 expression was found to be associated with poorly differentiated CRC tissues (pWISP-1 score was associated with well-differentiated CRC tissues (p=0.029). Overexpression and interplay between Wnt-1, WISP-1, survivin and cyclin-D1 may play a role in tumorigenesis, possibly by

  5. Molecular genetic changes in benign colorectal tumors synchronous with microsatellite unstable carcinomas do not support a field defect

    Science.gov (United States)

    Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

    2017-01-01

    Background: A colorectal cancer may develop through a particular molecular genetic pathway, raising the question of whether the particular molecular changes are random, or are unique to the particular segment of colon. We wanted to determine whether molecular changes found within a colorectal cancer might also be detected in separate adenomas and polyps removed from the same area of colon at surgery. Microsatellite instability was chosen as a marker for a pathway of colon carcinogenesis. Methods: We studied a total of 46 primary colorectal cancers with microsatellite instability and 77 synchronous adenomas and polyps. All tumors were evaluated for microsatellite instability, BRAF and KRAS mutations, and methylation using standard polymerase chain reaction based methods. Results: Forty-nine benign tumors did not follow a pathway similar to that of their 31 synchronous primary cancers. For two distinct subsets of the microsatellite unstable colorectal cancers, those with acquired methylation and BRAF mutation, and those without methylation suggestive of an underlying germ line mutation, the molecular changes in the majority of their synchronous benign tumors were different from the colorectal cancer. Conclusions: These differences suggest a stochastic process within the colon regarding the particular molecular carcinogenic pathways followed by the synchronous tumors, rather than a ‘field defect’ within the colon segments. Variability in molecular findings was present for colorectal cancers arising from acquired methylation, as well as those cancers suggestive of a germ line origin. PMID:28694923

  6. The distribution of blood group antigens in experimentally produced carcinomas of rat palate

    DEFF Research Database (Denmark)

    Reibel, J; Philipsen, H P; Fisker, A V

    1986-01-01

    palate induced by a chemical carcinogen (4NQO). The H antigen, normally expressed on spinous cells in rats, was absent in malignant epithelium, whereas staining for the B antigen, normally expressed on basal cells, was variable. These changes are equivalent to those seen in human squamous cell carcinomas....... The blood group antigen staining pattern in experimentally produced verrucous carcinomas showed an almost normal blood group antigen expression. This may have diagnostic significance. Localized areas of hyperplastic palatal epithelium with slight dysplasia revealed loss of H antigen and the presence of B...

  7. A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma

    DEFF Research Database (Denmark)

    Overgaard, M; Bertelsen, K; Dalmark, M

    1993-01-01

    The effect of radiotherapy alone or given simultaneously with 5-FU in the treatment of locally recurrent or inoperable colorectal carcinoma was investigated in a randomized feasibility trial. Twenty-nine patients were randomized to radiotherapy alone (50 Gy/5 weeks + 10-20 Gy boost), and 30...... patients to the same radiotherapy with weekly 5-FU (600 mg/m2) given before treatment every Monday during the first 5 weeks. The two groups were comparable with regard to age, sex, previous treatment, symptoms, tumour size and performance status. Treatment compliance to radiotherapy was the same in both...... groups with 87% receiving at least 50 Gy. Drug treatment was completed in 18/30 patients. Overall the treatment resulted in a significant palliative effect in 73% of evaluable patients with a median duration of 26 months, and objective response in 32% (8 CR, 11 PR), with a median duration of 18 months...

  8. Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin.

    Science.gov (United States)

    Pinheiro, Manuela; Ahlquist, Terje; Danielsen, Stine A; Lind, Guro E; Veiga, Isabel; Pinto, Carla; Costa, Vera; Afonso, Luís; Sousa, Olga; Fragoso, Maria; Santos, Lúcio; Henrique, Rui; Lopes, Paula; Lopes, Carlos; Lothe, Ragnhild A; Teixeira, Manuel R

    2010-10-27

    Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel. Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for BAX, IGF2R, TGFBR2, MSH3, and MSH6 microsatellite sequence alterations, BRAF and KRAS mutations, and MLH1 promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate. In the test series, IGFR2 and BAX mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in TGFBR2, MSH3, and MSH6. We confirmed these findings in the validation series, with TGFBR2 and MSH3 microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (P = 0.00005 and P = 0.0000005, respectively, when considering all MSI-carcinomas of both series). No MLH1 promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (P = 0.004). KRAS and BRAF mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively. The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease.

  9. Is the clinicopathological pattern of colorectal carcinoma similar in the state and private healthcare systems of South Africa? Analysis of a Durban colorectal cancer database.

    Science.gov (United States)

    Ntombela, Xolani H; Zulu, Babongile Mw; Masenya, Molikane; Sartorius, Ben; Madiba, Thandinkosi E

    2017-10-01

    Previous state hospital-based local studies suggest varying population-based clinicopathological patterns of colorectal cancer (CRC). Patients diagnosed with CRC in the state and private sector hospitals in Durban, South Africa over a 12-month period (January-December 2009) form the basis of our study. Of 491 patients (172 state and 319 private sector patients), 258 were men. State patients were younger than private patients. Anatomical site distribution was similar in both groups with minor variations. Stage IV disease was more common in state patients. State patients were younger, presented with advanced disease and had a lower resection rate. Black patients were the youngest, presented with advanced disease and had the lowest resection rate.

  10. High ABCC2 and Low ABCG2 Gene Expression Are Early Events in the Colorectal Adenoma-Carcinoma Sequence

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Vogel, Lotte K.; Kopp, Tine Iskov

    2015-01-01

    Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (P-glycoprotein, Multidrug resistance protein 1, MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) are involved in transport of various compounds...

  11. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: proof of principle study

    NARCIS (Netherlands)

    de Meij, Tim G.; Larbi, Ilhame Ben; van der Schee, Marc P.; Lentferink, Yvette E.; Paff, Tamara; Terhaar Sive Droste, Jochim S.; Mulder, Chris J.; van Bodegraven, Adriaan A.; de Boer, Nanne K.

    2014-01-01

    In the course and prognosis of colorectal cancer (CRC), early detection and treatment are essential factors. Fecal immunochemical tests (FITs) are currently the most commonly used non-invasive screening tests for CRC and premalignant (advanced) adenomas, however, with restricted sensitivity. We

  12. Active TGF-β1 correlates with myofibroblasts and malignancy in the colorectal adenoma-carcinoma sequence

    NARCIS (Netherlands)

    Hawinkels, L.J.A.C.; Verspaget, H.W.; Reijden, J.J. van der; Zon, J.M. van der; Verheijen, J.H.; Hommes, D.W.; Lamers, C.B.H.W.; Sier, C.F.M.

    2009-01-01

    Transforming growth factor-β1 (TGF-β1), a cytokine involved in various stages of cancer, is produced as a latent complex and requires processing to become active. We have determined total and active TGF-β1 levels in homogenates of colorectal neoplasia. In contrast to total TGF-β levels, showing a

  13. Herbal Formulation C168 Attenuates Proliferation and Induces Apoptosis in HCT 116 Human Colorectal Carcinoma Cells: Role of Oxidative Stress and DNA Damage

    Directory of Open Access Journals (Sweden)

    Lek Mun Leong

    2016-01-01

    Full Text Available The use of herbal formulations has gained scientific interest, particularly in cancer treatment. In this study, the herbal formulation of interest, denoted as C168, is a mixture of eight genera of plants. This study aims to investigate the antiproliferative effect of C168 methanol extract (CME on various cancer cells and its underlying mechanism of action on the most responsive cell line, namely, HCT 116 cells. CME exerted antiproliferative activities on HCT 116 colorectal carcinoma cells and HepG2 hepatocellular carcinoma cells but not on CCD-841-CoN normal colon epithelial cells, Jurkat E6.1 lymphoblastic leukemic cells, and V79-4 Chinese hamster lung fibroblasts. Further investigation on HCT 116 cells showed that CME induced G2/M cell-cycle arrest and apoptosis. Treatment of CME induced oxidative stress in HCT 116 cells by increasing the superoxide anion level and decreasing the intracellular glutathione. CME also increased tail moment value and H2AX phosphorylation in HCT 116 cells, suggesting DNA damage as an early signal of CME induced apoptosis. Loss of mitochondrial membrane potential in CME-treated cells also indicated the involvement of mitochondria in CME induced apoptosis. This study indicated the selectivity of CME toward colon cancer cells with the involvement of oxidative damage as its possible mechanism of action.

  14. DNA aneuploidy in colorectal adenomas: Role in the adenoma-carcinoma sequence Aneuploidía del ADN en adenomas colónicos: Papel en la secuencia adenoma-carcinoma

    Directory of Open Access Journals (Sweden)

    M. Alcántara Torres

    2005-01-01

    Full Text Available Introduction: aneuploidy has been observed in 6-27% of lesions known to be precursors of colorectal cancer, such as adenomas or ulcerative colitis. It has been suggested that aneuploidy may predispose to malignancy in these cases. However, its role in the adenoma-carcinoma sequence has not been definitely established. The objective of this study was to assess the incidence of aneuploidy in colon adenomas, as well as to study its possible role in the adenoma-carcinoma sequence. Material and methods: the study was performed on a series of 57 large bowel adenomas measuring 10 mm or more, collected from 54 consecutive patients. All specimens were obtained either by endoscopic or by surgical resection. There were 49 adenomas with low-grade dysplasia, two with high-grade dysplasia, two intramucous carcinomas, and four microinvasive carcinomas. A flow cytometric DNA analysis was performed in fresh specimens following Vindelov´s method. Results: aneuploid DNA was detected in five out of 49 low-grade dysplasia adenomas (10%, in all four high-grade dysplasia adenomas or intramucous carcinomas (100%, and in three out of four microinvasive carcinomas (75%. The association between aneuploidy and high-grade dysplasia adenomas, intramucous, or microinvasive carcinoma was statistically significant (p Introducción: en patología benigna de intestino grueso precursora del cáncer colorrectal, como adenomas o colitis ulcerosa, se ha observado aneuploidía en el 6-27% de los casos y se ha sugerido que su presencia predispone al desarrollo de malignidad. Sin embargo, su papel en la secuencia adenoma-carcinoma no se ha demostrado de forma concluyente. El objetivo de nuestro trabajo fue valorar la incidencia de aneuploidía en adenomas colónicos, con y sin signos de malignidad, y estudiar su posible papel en la secuencia adenoma-carcinoma. Material y métodos: el estudio se realizó en una serie de 57 adenomas de intestino grueso, de 10 o más mil

  15. Hemidesmosome integrity protects the colon against colitis and colorectal cancer

    OpenAIRE

    Hamade, Hussein; Alpy, Fabien; Normand, Sylvain; Bruyere, Emilie; Lefebvre, Olivier; Mechine-Neuville, Agnes; Siebert, Stefanie; Pfister, Véronique; Lepage, Patricia; Laquerriere, Patrice; Dembele, Doulaye; Delanoye-Crespin, Anne; Rodius, Sophie; Robine, Sylvie; Kedinger, Michele

    2017-01-01

    Objective Epidemiological and clinical data indicate that patients suffering from IBD with long-standing colitis display a higher risk to develop colorectal high-grade dysplasia. Whereas carcinoma invasion and metastasis rely on basement membrane (BM) disruption, experimental evidence is lacking regarding the potential contribution of epithelial cell/BM anchorage on inflammation onset and subsequent neoplastic transformation of inflammatory lesions. Herein, we analyse the role of the alpha 6 ...

  16. Anterior sacral meningocele infected with Fusobacterium in a patient with recently diagnosed colorectal carcinoma - a case report.

    Science.gov (United States)

    Braczynski, Anne K; Brockmann, Marc A; Scholz, Torben; Bach, Jan-Philipp; Schulz, Jörg B; Tauber, Simone C

    2017-12-08

    Anterior sacral meningoceles are rare, and usually occur with other malformations of the posterior lower spine. While these are more frequently reported in pediatric cohorts, we report a case in an elderly woman. We report on a 71 year-old woman with a recently diagnosed colorectal adenocarcinoma who presented with a severe bacterial meningitis. The cerebrospinal fluid cell count revealed a pleocytosis of 80,000 cells/μl and a severe disturbance of the blood-brain-barrier. Fusobacterium nucleatum was cultured as the causing pathogen. A lumbar MRI showed, in addition to contrast-enhancing meninges as sign of inflammation, a presacral mass. In the next step, the mass was diagnosed as an anterior sacral meningocele connected to the gut. An adequate antibiotic was used to treat the leptomeningitis. The connection between gut and meningocele was closed surgically and the patient recovered well and underwent further treatment of her colorectal adenocarcinoma. We report on a case of meningitis with an anterior sacral meningocele that was connected to the gut in a patient with a infiltrative colorectal adenocarcinoma. Anatomic variants have to be considered as rare causes of meningitis with typical intestinal germs.

  17. Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma [v2; ref status: indexed, http://f1000r.es/4k6

    Directory of Open Access Journals (Sweden)

    Tianhua Guo

    2014-10-01

    Full Text Available Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female had a mean age of 69.9 years (+/- 12.7 years at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients. Although the mean platelet count increased with the depth of tumor invasion (pT, its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57 had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4% with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery. The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.

  18. Colorectal carcinoma in the frail surgical patient. Implementation of a Work Area focused on the Complex Surgical Patient improves postoperative outcome.

    Science.gov (United States)

    Castellví Valls, Jordi; Borrell Brau, Núria; Bernat, María José; Iglesias, Patricia; Reig, Lluís; Pascual, Lluís; Vendrell, Marina; Santos, Pilar; Viso, Lorenzo; Farreres, Núria; Galofre, Gonzalo; Deiros, Carmen; Barrios, Pedro

    2017-12-09

    Advanced age and comorbidity impact on post-operative morbi-mortality in the frail surgical patient. The aim of this study is to assess the impact of a comprehensive, multidisciplinary and individualized care delivered to the frail patient by implementation of a Work Area focused on the Complex Surgical Patient (CSPA). Retrospective study with prospective data collection. Ninety one consecutive patients, classified as frail (ASAIII or IV, Barthel3) underwent curative radical surgery for colorectal carcinoma between 2013 and 2015. GroupI: 35 patients optimized by the CSPA during 2015. GroupII: 56 No-CSPA patients, treated prior to CSPA implementation, during 2014-2015. Group homogeneity, complication rate, length of stay, reoperations, readmissions, costs and overall mortality were analyzed and adjusted by Diagnosis-Related Group (DRG). There were no statistically significant differences in term of age, gender, ASA classification, body mass index, tumor staging and type of surgical intervention between the two groups. Major complications (Clavien-DindoIII-IV) (12.5% vs. 28.5%, P=.04), hospital stay (12.6±6days vs. 15.2±6days, P=0.041), readmissions (12.5% vs. 28.3%, P<0.041), and patient episode cost weighted according to DRG (3.29±1 vs. 4.3±1, P=0.008) were statistically inferior in Group CSPA. There were no differrences in reoperations (6.2% vs. 5.3%) or mortality (6.2% vs. 7.1%). 96.9% of patients of GroupI manifested having received a satisfactory attention and quality of life. Implementation of a CSPA, delivering surgical care to frail colorectal cancer patients, involves a reduction of complications, length of stay and readmissions, and is a cost-effective arrangement. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression--a pilot study.

    Science.gov (United States)

    Zalata, Khaled Refaat; Elshal, Mohamed Farouk; Foda, Abd AlRahman Mohammad; Shoma, Ashraf

    2015-08-01

    The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. This study investigated the changes in the level of expression of a well-defined panel of cell proliferation, differentiation, and apoptosis markers between the primary colorectal cancer (CRC) and the corresponding synchronous lymph node (LN) metastasis from the same patients. DNA flow cytometry and immunostaining of p53, bcl-2, and c-myc were carried out on 36 cases of CRC radical resection specimens with their corresponding LN metastases. There was very low probability that the histological patterns of primary tumors and LN metastases are independent (p < 0.001). Metastatic tumors were significantly more diffusely positive for p53 than the primary tumors (p < 0.001). Conversely, primary tumors were significantly more diffusely positive for c-myc than metastatic tumors (p = 0.011). No significant difference was found between the LNs and the primary tumors in bcl-2 positivity (p = 0.538) and DNA aneuploidy (p = 0.35), with a tendency towards negative bcl-2 and less aneuploidy in LN metastases than primary tumors. In conclusion, LN metastatic colorectal carcinomas have a tendency of being less differentiated, with a higher incidence of diffuse p53 staining, lower incidence of bcl-2 staining, and less aneuploidy in comparison to their primary counterparts suggesting a more aggressive biological behavior, which could indicate the necessity for more aggressive adjuvant therapy.

  20. Papilomavírus humano e sua associação com o carcinoma colorretal Human papillomavirus and its association with colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Carmen Ruth Manzione

    2010-12-01

    Full Text Available Atualmente, sabe-se que 15% dos tumores malignos humanos têm associação com infecções virais. Destes, 80% correspondem aos carcinomas da cérvix uterina, associados ao papilomavírus humano (HPV, e aos hepatocarcinomas. Nos últimos anos, entretanto, artigos da literatura especializada vêm mostrando a presença do DNA do HPV em amostras de tecido de carcinomas do esôfago, estômago, pulmão, da mama e do cólon e reto, o que foi negado por outros autores. O HPV vem sendo encontrado entre 41,7 e 82,1% dos adenocarcinomas e entre 28 e 56% dos adenomas do cólon. Embora o DNA viral esteja integrado ao tumoral, a maneira de contaminação não é evidente. As vias linfáticas e hematogênicas não são reconhecidas. Fica a dúvida quanto à especificidade dos exames de detecção viral e quanto às formas de disseminação viral para os segmentos mais proximais do cólon. De qualquer forma, a literatura não é categórica em afirmar se esse vírus pode ser agente causal da doença, sendo necessários mais estudos para definir esse assunto.Nowadays, we know that 15% of all malignancies have association with viral infections; 80% of them are cervical carcinomas, provoked by human papillomavirus (HPV, and liver carcinomas. However, in the last years, many articles are revealing HPV types occurrence in specimens of carcinomas from esophagus, stomach, lung, breast and colon and rectum, which was denied by other authors. HPV DNA was found in 41.7 to 82.1% of colon carcinomas and in 28 to 56% of colon adenomas. Although viral DNA is integrated with tumoral DNA, the way of contamination is not evident. Hematogenic and lymphatic routes are not well defined. There is doubt concerning the specificity of the exams of viral detection and the ways of viral dissemination in proximal colonic segments. Anyway, literature is not sure to affirm if this virus could be causal agent of this kind of cancer, and more studies are necessary.

  1. Clonal karyotypic abnormalities in colorectal adenomas: clues to the early genetic events in the adenoma-carcinoma sequence

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N

    1994-01-01

    and together with other numerical changes in another. A +7 was also present in one case with structural aberrations. Other recurrent numerical aberrations were -14 and -18, both found in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14 was lost in one of the tumors with only...... with a normal karyotype. All adenomas with a tubulovillous or villous architecture had structural rearrangements. Our findings confirm that a subset of colorectal adenomas exists that have only numerical chromosome aberrations. They also support our previous conclusion that loss of material from distal 1p...

  2. Renal-cell carcinoma risk estimates based on participants in the prostate, lung, colorectal, and ovarian cancer screening trial and national lung screening trial.

    Science.gov (United States)

    Lotan, Yair; Karam, Jose A; Shariat, Shahrokh F; Gupta, Amit; Roupret, Morgan; Bensalah, Karim; Margulis, Vitaly

    2016-04-01

    Current knowledge regarding risk of renal-cell carcinoma (RCC) is based on meta-analyses of case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and National Lung Screening Trial (NLST) provide robust prospective databases with clinical information and rates of cancer development. PLCO and NLST were used to identify risk factors for RCC. Data were extracted from PLCO and NLST to stratify risk of RCC by sex, race, age at inclusion, obesity, and smoking status. Incidence rates between groups were compared using the chi-square test. We excluded urothelial carcinomas. Overall, 701/154,118 and 190/53,242 RCCs were detected in PLCO and NLST, respectively. Incidence rates were higher in men (PLCO: 0.56 vs. 0.28/1000 person y, NLST: 0.73 vs. 0.35/1000 person y; both with P60 years, obesity, and intensity of smoking were associated with higher risk of developing RCC. In the NLST, sex and morbid obesity increased the risk for RCC but age, ethnicity, and smoking intensity were not predictors. There was no effect of screening for other cancers on detection of RCC. High-grade (grades ≥3) RCCs were diagnosed in 145 (20.7%) and 60 (31.6%) in the PLCO and NLST. In PLCO, age (60-64y), male sex, obesity, and current smokers with>50 pack years were at increased risk for high-grade RCC. In NLST, only male sex was an independent predictor of high-grade RCC. Age over 60 years, male sex, smoking intensity, and obesity affect the risk of RCC. Identification of a high-risk population may allow a pilot study of rational screening for RCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Lack of Association between Membrane-Type 1 Matrix Metalloproteinase Expression and Clinically Relevant Molecular or Morphologic Tumor Characteristics at the Leading Edge of Invasive Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Annette Arndt

    2015-01-01

    Full Text Available Colorectal cancer (CRC is one of the leading causes of death from cancer in the western world, but tumor biology and clinical course show great interindividual variation. Molecular and morphologic tumor characteristics, such as KRAS/BRAF mutation status, mismatch repair (MMR protein expression, tumor growth pattern, and tumor cell budding, have been shown to be of key therapeutic and/or prognostic relevance in CRC. Membrane-type 1 matrix metalloproteinase (MT1-MMP is a membrane-anchored zinc-binding endopeptidase that is expressed at the leading edge of various invasive carcinomas and promotes tumor cell invasion through degradation of the extracellular matrix. The aim of this study was to investigate possible associations between MT1-MMP expression and molecular tumor characteristics as well as morphologic features of tumor aggressiveness in a consecutive series of 79 CRC tissue samples. However, although MT1-MMP was expressed in 41/79 samples (52%, there was no significant association between MT1-MMP expression and KRAS/BRAF mutation status, MMR protein expression, presence of lymphovascular invasion, tumor growth pattern, tumor-infiltrating lymphocytes, or tumor cell budding in our sample cohort (P>0.05. Thus, we conclude that although MT1-MMP may play a role in CRC invasion, it is not of key relevance to the current models of CRC invasion and aggressiveness.

  4. Comprehensive and Holistic Analysis of HT-29 Colorectal Cancer Cells and Tumor-Bearing Nude Mouse Model: Interactions Among Fractions Derived From the Chinese Medicine Formula Tian Xian Liquid in Effects on Human Colorectal Carcinoma.

    Science.gov (United States)

    Leigh, Annballaw Bridget; Cheung, Ho Pan; Lin, Li-Zhu; Ng, Tzi Bun; Lao, Lixing; Zhang, Yanbo; Zhang, Zhang-Jin; Tong, Yao; Sze, Stephen Cho Wing

    2017-09-01

    The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 m

  5. 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...... and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine...... contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic....

  6. The dark side of the moon: the PI3K/PTEN/AKT pathway in colorectal carcinoma.

    Science.gov (United States)

    Silvestris, Nicola; Tommasi, Stefania; Petriella, Daniela; Santini, Daniele; Fistola, Ettore; Russo, Antonio; Numico, Gianmauro; Tonini, Giuseppe; Maiello, Evaristo; Colucci, Giuseppe

    2009-01-01

    Wild-type KRAS status is required but not sufficient to confer sensitivity to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in colorectal cancer patients. As a consequence, one of the major challenges is to identify, in non-mutant KRAS patients, other markers that can predict lack of response to this therapy. Small series have investigated the clinical effect of PIK3CA mutations on resistance to anti-EGFR mAbs and discrepant results have been observed. Furthermore, PTEN loss in metastases may be predictive of resistance to anti-EGFR mAbs, even if PTEN determination is far from an immediate clinical application. The introduction of modulators of the PI3K/AKT/mTOR pathway as potential targeted anticancer drugs is encouraging, but this attractive therapy option is still at an early stage of development. Copyright 2010 S. Karger AG, Basel.

  7. Influence of chronic low-dose/dose-rate high-LET irradiation from radium-226 in a human colorectal carcinoma cell line.

    Science.gov (United States)

    Vo, Nguyen T K; Sokeechand, Bibi S H; Seymour, Colin B; Mothersill, Carmel E

    2017-07-01

    To evaluate potential damages of chronic environmentally relevant low-dose/dose-rate high-LET irradiation from a naturally occurring alpha-emitting radionuclide (radium-226, (226)Ra) on a human colorectal carcinoma HCT116 p53(+/+) cell line. Clonogenic survival assays and mitochondrial membrane potential (MMP) measurement with a sensitive fluorescent MMP probe JC-1 were performed in HCT116 p53(+/+) cells chronically exposure to low doses/dose rates of (226)Ra with high-LET. Comparisons were made with the human non-transformed keratinocyte HaCaT cell line and acute low-dose direct low-LET gamma radiation. The chronic low-dose/dose-rate alpha radiation (CLD/DRAR) did not reduce the clonogenic survival of HCT116 p53(+/+) cells over the period of 70 days of exposure. Only one significant reduction in the HCT116 p53(+/+) cells' clonogenic survival was when cells were grown with 10,000mBq/mL (226)Ra for 40 days and progeny cells were clonogenically assessed in the presence of 10,000mBq/mL (226)Ra. The cumulative doses that cells received during this period ranged from 0.05 to 46.2mGy. The mitochondrial membrane potential (MMP) dropped initially in both HCT116 p53(+/+) and HaCaT cells in response to CLD/DRAR. The MMP in HCT116 p53(+/+) cells recovered more quickly at all dose points than and that in HaCaT cells until the end of the exposure period. The highest dose rate of 0.66mGy/day depolarized the HaCaT's mitochondria more consistently during the exposure period. The faster recovery status of the MMP in HCT116 p53(+/+) cells than that in HaCaT cells was also observed after exposure to acute low-dose gamma rays. Overall, it was found that CLD/DRAR had little impact on the MMP of human colorectal cancer and keratinocyte cell lines. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Gadopentetate dimeglumine and FDG uptake in liver metastases of colorectal carcinoma as determined with MR imaging and PET.

    Science.gov (United States)

    van Laarhoven, Hanneke W M; de Geus-Oei, Lioe-Fee; Wiering, Bastiaan; Lok, Jasper; Rijpkema, Mark; Kaanders, Johannes H A M; Krabbe, Paul F M; Ruers, Theo; Punt, Cornelis J A; van der Kogel, Albert J; Oyen, Wim J G; Heerschap, Arend

    2005-10-01

    To examine the in vivo relationship between fluorine 18 fluorodeoxyglucose (FDG) uptake, as measured with positron emission tomography (PET), and functional tumor vasculature, as measured with dynamic contrast material-enhanced magnetic resonance (MR) imaging, in patients with liver metastases of colorectal cancer. All patients provided written informed consent, and the study was approved by the institutional review board. A total of 26 patients (12 men and 14 women; mean age, 59 years) who were suspected of having liver metastases of histologically proved colorectal cancer and underwent work-up for liver metastasectomy were included. Patients underwent whole-body FDG PET, and tumor-to-nontumor ratio of FDG uptake in metastases was calculated. Dynamic contrast-enhanced MR imaging was performed, and the rate constant k(ep) (s(-1)) of gadopentetate dimeglumine uptake in metastases was determined. Pimonidazole was used to determine tumor hypoxia and vascular density of metastases. To assess the relationship between FDG uptake, rate constant k(ep) of gadopentetate dimeglumine uptake, hypoxic fraction, and vascular density, the Pearson correlation coefficient was calculated. Negative correlation between tumor-to-nontumor ratio of FDG uptake and rate constant k(ep) was observed (r = -0.421, P = .082). No correlation between tumor hypoxia and tumor-to-nontumor ratio of FDG uptake or rate constant k(ep) was found. A positive correlation was observed between vascular density and rate constant k(ep) (r = 0.458, P = .034) but not between tumor-to-nontumor ratio of FDG uptake. Negative correlation between tumor-to-nontumor ratio of FDG uptake and rate constant k(ep) suggests that lower values of gadopentetate dimeglumine uptake imply an acutely reduced supply of oxygen, which necessitates a higher uptake of glucose to maintain tumor energy levels. The positive correlation of vascular density with rate constant k(ep), but not with tumor-to-nontumor ratio of FDG uptake

  9. Elephantopus scaber induces apoptosis through ROS-dependent mitochondrial signaling pathway in HCT116 human colorectal carcinoma cells.

    Science.gov (United States)

    Chan, Chim Kei; Supriady, Hadi; Goh, Bey Hing; Kadir, Habsah Abdul

    2015-06-20

    Elephantopus scaber also known as Elephant's foot (Asteraceae family) has a plethora of traditional applications including dysuria, diarrhea, dysentery, leukemia and cancer. This study aimed to investigate the apoptosis inducing effects of E. scaber and the underlying mechanisms in HCT116 colorectal cell line. The MTT assay was used to determine the IC50 values on cancer cell lines by the ethanol, hexane, ethyl acetate and water fractions. Apoptosis was detected by cell morphologic observation through Hoechst 33342/PI dual staining, phosphatidylserine externalization by Annexin V/PI staining and DNA fragmentation by TUNEL assay. The caspase activity, Bcl-2 family and p53 proteins were determined by flow cytometric analysis. The cleaved PARP protein expression was assessed by western blot analysis The ethanol extract of E. scaber and its fractions significantly inhibited the growth of HCT116 and HT-29 cells and induced apoptosis. The E. scaber ethyl acetate fraction (ESEAF) was the most potent on HCT116 cell line with the IC50 value of 1.42 ± 0.10 µg/mL. The induction of apoptosis was marked by nuclear shrinkage accompanied with chromatin condensation, DNA fragmentation and phosphatidylserine externalization. The results showed that ESEAF-induced apoptosis was associated with an upregulation of proapoptotic Bax, elevation of Bax/Bcl-2 ratio, dissipation of mitochondrial membrane potential, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, a compromised mitochondrial membrane potential and overproduction of ROS demonstrated the involvement of the mitochondrial signaling pathway. Mechanistic studies further revealed that ESEAF caused the augmentation of the intracellular ROS, subsequently incited the increase in p53 protein expression and led to oligomerization of Bax, depolarization of mitochondrial membrane potential and caspases cascade (caspase-3/7 and -9) in a time-dependent manner. The attenuation of intracellular ROS

  10. Experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle.

    Science.gov (United States)

    Campo, M S; O'Neil, B W; Barron, R J; Jarrett, W F

    1994-08-01

    Bovine papillomavirus type 4 (BPV-4) is the aetiological agent of epithelial papillomas of the upper alimentary canal in cattle. These benign tumours can become a focus for transformation to squamous cell carcinomas in animals feeding on bracken fern. Strong epidemiological evidence suggests that the progression to malignancy is due to the interplay between BPV-4 and mutagenic and immunosuppressing chemicals present in the fern. The carcinomas of the upper alimentary canal are often accompanied by adenomas and adenocarcinomas of the lower intestine and bracken-grazing animals are also heavily immunosuppressed. To elucidate the individual roles and the concerted action of the viral and chemical factors involved in tumorigenesis and malignant conversion, we attempted to reproduce experimentally the cancer syndrome observed in the field. Florid persistent papillomatosis of the upper alimentary canal was reproduced in animals infected with BPV-4 and immunosuppressed either by a diet of bracken or by treatment with azathioprine; cancer of the upper alimentary tract or of the lower intestine developed only in animals infected with virus and fed on bracken fern. As in field cases, BPV-4 DNA was detected in papillomas but not in cancers. We conclude that immunosuppression is necessary for persistence and spread of viral papillomas, that the fern mutagens are responsible for neoplastic conversion of papilloma cells, and that continuous expression of viral functions is not required for the maintenance of the malignant state.

  11. Mitigation of DMBA-induced mammary carcinoma in experimental rats by antiangiogenic property of Kalpaamruthaa.

    Science.gov (United States)

    Sathish, Sivaprakasam; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2011-06-01

    Extra cellular matrix (ECM) and basement membrane (BM) are important layers that regulate cell structure, cell migration, and cellular proliferation. Degradation of both ECM and BM mediated by proteases favors the tumor invasion and promotes angiogenesis. Female Sprague-Dawley rats weighing 180 ± 10 g were categorized into 6 groups. Group-1 animals served as vehicle control. Group-2 to Group-4 animals were administered with 7,12-dimethylbenz(a)anthracene (25 mg/rat dissolved in olive oil, orally) on day 1 of experimental period to induce mammary carcinoma. (After 90 days, mammary carcinoma was confirmed by histopathological examination). Group-3 and Group-4 rats were subsequently treated with Semecarpus anacardium nut milk extract (SA) and Kalpaamruthaa (KA), respectively. Group-5 and Group-6 animals served as drug control for SA and KA, respectively. Pro-angiogenic factors like proteases, cyclooxygenase-2, and vascular endothelial growth factor were elevated in tumor-bearing animals and decreased in SA- and KA-supplemented rats. Increased levels of these angiogenic factors in tumor-bearing rats indicate the progression of mammary tumor. The decreased levels of these angiogenic in SA- and KA-treated rats may be due to the ameliorative effect of phenolic compounds such as flavonoids, tannins, and other compounds present in the drug.

  12. The Cytotoxic Effect of Essential Oil of Syrian Citrus limon Peel on Human Colorectal Carcinoma Cell Line (Lim1863

    Directory of Open Access Journals (Sweden)

    Mohammad Eyad Chatty

    2012-01-01

    Full Text Available Background: Essential oils are the volatile fraction of aromatic and medicinal plants created after extraction by steam or water distillation. Species of the genus Citrus(Rutaceae have been widely used in traditional medicine as volatile oils and are currently the subject of numerous research. Citrus essential oil consists of different terpens that have antitumor activities. This study determines the cytotoxic effect of the essential oils of Citrus limon L. peels on a colorectal cancer cell line (LIM1863.Methods: We harvested four samples from four locations in Syria. Essential oils were prepared by hydrodistillation and analyzed by Gas chromatography-mass spectrometry (GC-MS.Various concentrations ofessential oils (0.5-48 μg/ml were added to cultured cells and incubated for 72 h. Cell viability was evaluated byMTT-basedcytotoxicity assay.Results: We noted 18 components that represented 98.81% of the total oil content. The major components were: limonene (61.8%-73.8%, γ-terpinene (9.4%-10.4%, β-pinene (3.7%-6.9%, O-cymene(1%-2.4%,and citral (0.8%-5.4%.The obtained IC50 value range of Citrus limon essential oils was 5.75-7.92 μg/ml against LIM1863.Conclusion: This study revealed that Syrian Citrus limon essential oil has a cytotoxic effect on the human colorectalcarcinoma cell line LIM1863 when studied in vitro.

  13. Electronic nose can discriminate colorectal carcinoma and advanced adenomas by fecal volatile biomarker analysis: proof of principle study.

    Science.gov (United States)

    de Meij, Tim G; Larbi, Ilhame Ben; van der Schee, Marc P; Lentferink, Yvette E; Paff, Tamara; Terhaar Sive Droste, Jochim S; Mulder, Chris J; van Bodegraven, Adriaan A; de Boer, Nanne K

    2014-03-01

    In the course and prognosis of colorectal cancer (CRC), early detection and treatment are essential factors. Fecal immunochemical tests (FITs) are currently the most commonly used non-invasive screening tests for CRC and premalignant (advanced) adenomas, however, with restricted sensitivity. We hypothesized that fecal volatile organic compounds (VOCs) may serve as a diagnostic biomarker of CRC and adenomas. In this proof of concept study, we aimed to assess disease-specific VOC smellprints in fecal gas to distinguish patients with CRC and advanced adenomas from healthy controls. Fecal samples of patients who were scheduled to undergo an elective colonoscopy were collected. An electronic nose (Cyranose 320) was used to measure VOC patterns in fecal gas from patients with histopathologically proven CRC, with advanced adenomas and from controls (no abnormalities seen at colonoscopy). Receiver operator characteristic curves and corresponding sensitivity and specificity for detection of CRC and advanced adenomas were calculated. A total of 157 stool samples (40 patients with CRC, 60 patients with advanced adenomas, and 57 healthy controls) were analyzed by electronic nose. Fecal VOC profiles of patients with CRC differed significantly from controls (area under curve ± 95%CI, p-value, sensitivity, specificity; 0.92 ± 0.03, advanced adenomas could be discriminated from controls (0.79 ± 0.04, electronic nose seems to hold promise as a novel screening tool for the (early) detection of advanced neoplasia and CRC. © 2013 UICC.

  14. Baicalin Induces Apoptosis in SW620 Human Colorectal Carcinoma Cells in Vitro and Suppresses Tumor Growth in Vivo

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    Yi-Shiuan Tzeng

    2012-03-01

    Full Text Available In the United States, colorectal cancer (CRC is the second most frequent malignancy and the fourth most common cause of cancer death. Baicalin, a flavone derivative isolated and purified from the dry root of Scutellaria, was assessed for its antitumor effects in human SW620 CRC cells. Baicalin (200 μM inhibited proliferation of SW620 cells. Baicalin (200 μM increased activities of caspase-3, -8, and -9 in SW620 cells. Furthermore, flow cytometric analysis of baicalin-treated SW620 cells showed an increase in sub-G1 cells, and the dihydroethidium assay showed significant enhancement of intracellular peroxide production in baicalin-treated cells. Addition of N-acetylcysteine prevented most of the baicalin-induced apoptosis, which in turn mediated cytotoxicity in human SW620 cells. In vivo, baicalin (50 mg/kg/day, i.p. treatment inhibited 55% of tumor growth in xenografted nude mice by 4 weeks, compared to that of the vehicle control (p < 0.05. Baicalin had no noteworthy influence on body weight. Thus, we suggest the development of baicalin as a potential leading antitumor agent in CRC.

  15. 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.

  16. 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.

  17. 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....

  18. Adjuvant postoperative radiation therapy for colorectal carcinoma above the peritoneal reflection. II. Antimesenteric wall ascending and descending colon and cecum

    Energy Technology Data Exchange (ETDEWEB)

    Kopelson, G.

    1983-08-15

    From 1970 to 1981, 50 patients had curative surgery for carcinoma of the cecum, ascending, or descending colon and were Stage greater than or equal to B2. In 15 cases, the lesion originated on the antimesenteric (posterolateral) bowel wall. Of seven cases (with minimum three-year follow-up) not receiving adjuvant postoperative regional irradiation, four recurred in the tumor bed/abdominal wall versus 0/3 irradiated patients. Similarly, the five-year survival was improved in the irradiated group (2/3) versus only 2/9 in the unirradiated group. Patients with transmural extension of right or left colon cancers originating on the anti mesenteric (posterolateral) bowel wall may have a high incidence of postoperative regional failure which may be decreased by adjuvant postoperative regional irradiation.

  19. MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells

    Science.gov (United States)

    2013-01-01

    Background Colorectal carcinoma (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs, miRs) play important roles in carcinogenesis. MiR-32 has been shown to be upregulated in CRC. In this study, we identified the potential effects of miR-32 on some important biological properties of CRC cells, and clarified the regulation of PTEN by miR-32. Methods The effect of miR-32 on PTEN expression was assessed in CRC cell lines with miR-32 mimics/inhibitor to increase/decrease miR-32 expression. Furthermore, the roles of miR-32 in regulating CRC cells biological properties were analyzed with miR-32 mimics/inhibitor-transfected cells. The 3′-untranslated region (3′-UTR) of PTEN combined with miR-32 was verified by dual-luciferase reporter assay. Results Gain-of-function and loss-of-function studies showed that overexpression of miR-32 promoted SW480 cell proliferation, migration, and invasion, reduced apoptosis, and resulted in downregulation of PTEN at a posttranscriptional level. However, miR-32 knock-down inhibited these processes in HCT-116 cells and enhanced the expression of PTEN protein. In addition, we further identified PTEN as the functional downstream target of miR-32 by directly targeting the 3′-UTR of PTEN. Conclusions Our results demonstrated that miR-32 was involved in tumorigenesis of CRC at least in part by suppression of PTEN. PMID:23617834

  20. Comparison of SPECT imaging using monoclonal antibodies with computed tomography (CT) and ultrasonography (US) for detection of recurrences of colorectal carcinoma: A prospective clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Chatal, J.F.; Saccavini, J.C.; Douillard, J.Y.; Curtet, C.; Kremer, M.; Le Mevel, B.

    1985-05-01

    A prospective clinical study compared SPECT imaging, ultrasonography (US), and computed tomography (CT) in 22 patients clinically or biologically (increased CEA and/or CA 19-9 serum concentration) suspected of recurrence of colorectal carcinoma. The recordings were performed 3 to 5 days after injection of 111 to 129.5 MBq of cocktail of I-131-labeled anti-CEA and 19-9 (F(ab')2 fragments) monoclonal antibodies. Twenty nine tumor sites were demonstrated by surgery or concordant results of conventional diagnostic methods. SPECT visualized 21 of these 29 tumor sites (72%). It was negative in 4 cases with no demonstrated recurrence (by any method and follow-up). With respect to localization of tumor sites, SPECT visualized 7/12 liver metastases, 8/8 local pelvic recurrences and 6/8 abdominal recurrences. CT and US, systematically performed blind after SPECT, respectively visualized 9/10 and 9/12 liver metastases, 7/12 and 4/13 pelvic and abdominal recurrences. Image interpretation of SPECT was difficult due to poor tumor contrast and the large number of low-intensity, nonspecific radioactive foci. A focus had to recur in at least 3 successive slices to be considered pathological. Four tumor sites were visualized with SPECT and not with US and CT (negative or uncertain results). SPECT would appear to be useful for localizing pelvic or abdominal recurrences in cases in which interpretation of US and CT images is difficult, often because their nonspecific approach does not make it possible to differentiate a tumor recurrence from post-operative anatomical changes.

  1. Germline mutations in PMS2 and MLH1 in individuals with solitary loss of PMS2 expression in colorectal carcinomas from the Colon Cancer Family Registry Cohort.

    Science.gov (United States)

    Rosty, Christophe; Clendenning, Mark; Walsh, Michael D; Eriksen, Stine V; Southey, Melissa C; Winship, Ingrid M; Macrae, Finlay A; Boussioutas, Alex; Poplawski, Nicola K; Parry, Susan; Arnold, Julie; Young, Joanne P; Casey, Graham; Haile, Robert W; Gallinger, Steven; Le Marchand, Loïc; Newcomb, Polly A; Potter, John D; DeRycke, Melissa; Lindor, Noralane M; Thibodeau, Stephen N; Baron, John A; Win, Aung Ko; Hopper, John L; Jenkins, Mark A; Buchanan, Daniel D

    2016-02-19

    Immunohistochemistry for DNA mismatch repair proteins is used to screen for Lynch syndrome in individuals with colorectal carcinoma (CRC). Although solitary loss of PMS2 expression is indicative of carrying a germline mutation in PMS2, previous studies reported MLH1 mutation in some cases. We determined the prevalence of MLH1 germline mutations in a large cohort of individuals with a CRC demonstrating solitary loss of PMS2 expression. This cohort study included 88 individuals affected with a PMS2-deficient CRC from the Colon Cancer Family Registry Cohort. Germline PMS2 mutation analysis (long-range PCR and multiplex ligation-dependent probe amplification) was followed by MLH1 mutation testing (Sanger sequencing and multiplex ligation-dependent probe amplification). Of the 66 individuals with complete mutation screening, we identified a pathogenic PMS2 mutation in 49 (74%), a pathogenic MLH1 mutation in 8 (12%) and a MLH1 variant of uncertain clinical significance predicted to be damaging by in silico analysis in 3 (4%); 6 (9%) carried variants likely to have no clinical significance. Missense point mutations accounted for most alterations (83%; 9/11) in MLH1. The MLH1 c.113A> G p.Asn38Ser mutation was found in 2 related individuals. One individual who carried the MLH1 intronic mutation c.677+3A>G p.Gln197Argfs*8 leading to the skipping of exon 8, developed 2 tumours, both of which retained MLH1 expression. A substantial proportion of CRCs with solitary loss of PMS2 expression are associated with a deleterious MLH1 germline mutation supporting the screening for MLH1 in individuals with tumours of this immunophenotype, when no PMS2 mutation has been identified. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Alterations in IQGAP1 expression and localization in colorectal carcinoma and liver metastases following oxaliplatin-based chemotherapy

    Science.gov (United States)

    Rotoli, Deborah; Morales, Manuel; Maeso, María Del Carmen; García, María Del Pino; Gutierrez, Ricardo; Valladares, Francisco; Ávila, Julio; Díaz-Flores, Lucio; Mobasheri, Ali; Martín-Vasallo, Pablo

    2017-01-01

    IQGAP1 is a scaffolding protein that serves a key role in cell dynamics by integrating internal and external stimuli to distinct signal outputs. Previous studies have identified several genes that are significantly up- or downregulated in the peripheral white cells (PWCs) of patients with colorectal adenocarcinoma (CRC), who underwent oxaliplatin-based chemotherapy (CT). In addition, screening studies have reported that IQ-motif containing GTPase activating protein 1 (IQGAP1) transcriptional expression levels varied from ‘off’ to ‘on’ following oxaliplatin CT. In order to determine if variations previously described in PWCs are able to be observed at the protein level in tumors and in metastases following CT, the present study performed an immunohistochemical analysis of IQGAP1 in CRC and primary metastases. IQGAP1 expression was observed in the nuclear envelope and in lateral cell membranes and cytoplasm in normal colon tissue. However, in tumor tissue, cells exhibited a diffuse pattern, with variable expression levels of staining in the nuclear membrane and cytoplasm, with the highest expression intensity observed at the invasive front. In healthy and metastasized liver tissue and in the metastases themselves, expression levels varied from cell to cell from no expression to a high level. In the majority of cells, IQGAP1 co-localized with microtubules at the cytoplasmic face of the nuclear envelope. Strong positive expression was observed in areas of the lesion where cells were detaching from the lesion into the lumen. Despite the homogeneous IQGAP1 staining pattern observed in healthy colon tissue sections, CRC demonstrated heterogeneity in staining, which was more marked in metastasized liver tissue resected following CT. However, the most notable findings were the observed effects on the cellular and subcellular distribution and its implications for cancer biology. These results suggest that IQGAP1 may be a putative biomarker, a candidate for clinical

  3. Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Cobbs Gary A

    2007-05-01

    Full Text Available Abstract Background N-acetyltransferase 1 (NAT1 and 2 (NAT2 are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD consist of Crohn's disease (CD and ulcerative colitis (UC, both are associated with increased colorectal cancer (CRC risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD. Methods A case control study was performed with 729 Caucasian participants, 123 CRC, 201 CD, 167 UC, 15 IBD dysplasia/cancer and 223 controls. NAT1 and NAT2 genotyping were performed using Taqman based techniques. Eight single nucleotide polymorphisms (SNPs were characterized for NAT1 and 7 SNPs for NAT2. Haplotype frequencies were estimated using an Expectation-Maximization (EM method. Disease groups were compared to a control group for the frequencies at each individual SNP separately. The same groups were compared for the frequencies of NAT1 and NAT2 haplotypes and deduced NAT2 phenotypes. Results No statistically significant differences were found for any comparison. Strong linkage disequilibrium was present among both the NAT1 SNPs and the NAT2 SNPs. Conclusion This study did not demonstrate an association between NAT1 and NAT2 polymorphisms and IBD or sporadic CRC, although power calculations indicate this study had sufficient sample size to detect differences in frequency as small as 0.05 to 0.15 depending on SNP or haplotype.

  4. NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder carcinoma outgrowth by inhibiting tumor cell proliferation.

    NARCIS (Netherlands)

    Smakman, N.; Schaap, N.P.M.; Snijckers, C.M.; Rinkes, M.J.; Kranenburg, O.

    2005-01-01

    OBJECTIVES: To evaluate the efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 in treating experimental T24 bladder carcinoma, and to assess its effect on tumor cell proliferation and survival and tumor vascularization. COX-2 overexpression is frequently observed in bladder

  5. Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudia Maletzki

    Full Text Available BACKGROUND: Colorectal cancer (CRC represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113 along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113 were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total. Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt, B-raf(mut, HROC87: K-ras(wt, B-raf(mut, whereas the HROC113 cell line (K-ras(mut, B-raf(wt was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+ tumor cells, showing surface tumor marker expression (CEACAM(+. MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the

  6. The cost of systemic therapy for metastatic colorectal carcinoma in Slovenia: discrepancy analysis between cost and reimbursement.

    Science.gov (United States)

    Mesti, Tanja; Boshkoska, Biljana Mileva; Kos, Mitja; Tekavčič, Metka; Ocvirk, Janja

    2015-06-01

    The aim of the study was to estimate the direct medical costs of metastatic colorectal cancer (mCRC) treated at the Institute of Oncology Ljubljana and to question the healthcare payment system in Slovenia. Using an internal patient database, the costs of mCRC patients were estimated in 2009 by examining (1) mCRC direct medical related costs, and (2) the cost difference between payment received by Slovenian health insurance and actual mCRC costs. Costs were analysed in the treatment phase of the disease by assessing the direct medical costs of hospital treatment with systemic therapy together with hospital treatment of side effects, without assessing radiotherapy or surgical treatment. Follow-up costs, indirect medical costs, and nonmedical costs were not included. A total of 209 mCRC patients met all eligibility criteria. The direct medical costs of mCRC hospitalization with systemic therapy in Slovenia for 2009 were estimated as the cost of medications (cost of systemic therapy + cost of drugs for premedication) + labor cost (the cost of carrying out systemic treatment) + cost of lab tests + cost of imaging tests + KRAS testing cost + cost of hospital treatment due to side effects of mCRC treatment, and amounted to €3,914,697. The difference between the cost paid by health insurance and actual costs, estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009, was €1,900,757.80. The costs paid to the Institute of Oncology Ljubljana by health insurance for treating mCRC with systemic therapy do not match the actual cost of treatment. In fact, the difference between the payment and the actual cost estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009 was €1,900,757.80. The model Australian Refined Diagnosis Related Groups (AR-DRG) for cost assessment in oncology being currently used

  7. Ginkgo biloba L. leaf extract offers multiple mechanisms in bridling N-methylnitrosourea - mediated experimental colorectal cancer.

    Science.gov (United States)

    Ahmed, Hanaa H; El-Abhar, Hanan S; Hassanin, Elsayed Abdul Khalik; Abdelkader, Noha F; Shalaby, Mohamed B

    2017-11-01

    In Egypt, colorectal cancer (CRC) is the 6th cancer in both gender and CRC rates are high in subjects under 40 years of age. This study goaled to determine the development of CRC using relevant biochemical markers and to elucidate the potent mechanism of Ginkgo biloba L. leaf extract in retrogression of experimental CRC. Adult male Sprague-Dawley rats were administered N-methylnitrosourea (N-MNU; 2mg in 0.5ml water/rat) intrarectally thrice a week for five weeks to induce CRC, followed by treatment with either 5-fluorouracil (5-FU; 12.5mg/kg, i.p.) or Ginkgo biloba L. leaf extract in a dose of 0.675 and 1.35g/kg, p.o. respectively. The developed tumor enhanced plasma TGF-β, and Bcl 2 , serum EGF, CEA, CCSA, and MMP-7 significantly. Also, gene expression analysis showed significant upregulation of colonic β-Catenin, K-ras and C-myc genes. Besides, immunohistochemical findings revealed significant increase in COX-2, cyclin D1 and survivin content in colon tissue. These data were further supported by the histological observations. Ginkgo biloba L. leaf extract-treated rats; particularly those treated with dose of 1.35g/kg, exhibited significant reduction in the aforementioned parameters and improvement in the histological organization of the colon tissue. The therapeutic effect of Ginkgo biloba L. leaf extract was comparable with that mediated by 5-FU. The current research proved that Ginkgo biloba L. leaf extract could suppress tumor cell proliferation, promote apoptosis, and mitigat inflammation in vivo. The amelioration of these key events might be linked with the inhibition of Wnt/β-Catenin signaling module. The outcomes of the present investigation encourage the use of Ginkgo biloba L. leaf extract as a complementary and alternative therapeutic approach to abate CRC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. MSH2 and MLH1 mutations in sporadic replication error-positive colorectal carcinoma as assessed by two-dimensional DNA electrophoresis

    NARCIS (Netherlands)

    Wu, Y; NystromLahti, M; Osinga, J; Looman, MWG; Peltomaki, P; Aaltonen, LA; delaChapelle, A; Hofstra, RMW; Buys, CHCM

    Replication errors (RER) are frequently seen in both sporadic and hereditary forms of colorectal cancer. In hereditary nonpolyposis colorectal cancer (HNPCC), RER is associated with defects in DNA mismatch repair genes. Two of these genes, MSH2 and MLH1, account for a major share of this cancer

  9. Distinct patterns of KRAS mutations in colorectal carcinomas according to germline mismatch repair defects and hMLH1 methylation status

    NARCIS (Netherlands)

    Oliveira, C; Westra, JL; Arango, D; Ollikainen, M; Domingo, E; Ferreira, A; Velho, S; Niessen, R; Lagerstedt, K; Alhopuro, P; Laiho, P; Veiga, [No Value; Teixeira, MR; Ligtenberg, M; Kleibeuker, JH; Sijmons, RH; Plukker, JT; Imai, K; Lage, P; Hamelin, R; Albuquerque, C; Schwartz, S; Lindblom, A; Peltomaki, P; Yamamoto, H; Aaltonen, LA; Seruca, R; Hofstra, RMW

    2004-01-01

    In sporadic colorectal tumours the BRAF(V600E) is associated with microsatellite instability (MSI-H) and inversely associated to KRAS mutations. Tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients carrying germline mutations in hMSH2 or hMLH1 do not show BRAF(V600E), however no

  10. [Molecular biology in the development of colorectal cancer].

    Science.gov (United States)

    Nagawa, H; Muto, T

    1999-12-01

    In 1988, Vogelstein and colleagues published a paper entitled "Genetic alterations during colorectal-tumor development." This marked the beginning of a series of advances in our understanding of how colorectal cancer develops. This paper also provided evidence for the adenoma-carcinoma sequence. Furthermore, the importance of DNA mismatch repair genes in hereditary nonpolyposis colorectal cancer has been recognized. We herein discuss the development of colorectal cancer on the basis of molecular biology, including specific abnormalities of related genes.

  11. Ureteroscopic management of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (hereditary nonpolyposis colorectal cancer syndrome).

    Science.gov (United States)

    Hubosky, Scott G; Boman, Bruce M; Charles, Sarah; Bibbo, Marluce; Bagley, Demetrius H

    2013-10-01

    To report our experience with ureteroscopic laser ablation of upper tract urothelial carcinoma (UTUC) in patients with Lynch Syndrome (LS), as defined by a documented germline mutation in the MSH-2 gene. To increase awareness among urologists about UTUC in this unique patient population and refer to genetic counselling when appropriate. Demographic, clinical and pathological data on 13 consecutive patients with UTUC and documented MSH-2 mutation comprising 15 involved renal units were retrospectively collected. Ureteroscopic evaluations involved biopsy and laser treatment with combination holmium/neodymium yttrium aluminum garnet (YAG) lasers. Tumours were graded from 1 to 3 according to the 1973 World Health Organisation classification by a single pathologist evaluating cell block preparations. The mean patient age at initial presentation was 56.5 years, with six of 13 patients having metachronous bilateral UT disease. The mean follow-up was 59 months with a mean number of surveillances of 12. Of 15 affected renal units, 10/15 (67%) of initial tumours involved the ureter with mean lesion size of 17.5 mm, while five of 15 (33%) involved the intrarenal collecting system with mean lesion size of 25 mm. Ureteroscopy cleared 13/15 (87%) lesions and four of those 13 (31%) needed staged procedures. Renal preservation rate was 14/15 (93%) with one nephroureterectomy and one segmental ureterectomy performed. One patient developed metastatic UTUC after 40 months surveillance. No patient presented with bladder tumours but seven of the 13 (54%) developed them within 10 months of the initial ureteroscopy. Patients with LS who develop UTUC present at younger ages and appear to be more likely to have bilateral UT disease over their lifetimes vs sporadic UTUC patients. Ureteroscopic laser ablation offers a good renal preservation rate with reasonable cancer control in patients willing to undergo endoscopic surveillance. Development of new bladder tumours is common. © 2013

  12. Does the application of Ankaferd Blood Stopper rectally have positive effects on the healing of colorectal anastomosis and prevention of anastomotic leakage? An experimental study.

    Science.gov (United States)

    Kuru, Serdar; Kismet, Kemal; Bag, Yusuf Murat; Barlas, Aziz Mutlu; Senes, Mehmet; Durak, Murat; Yumusak, Nihat; Urhan, Mustafa Kemal; Cavusoglu, Turgut; Pekcici, Recep

    2017-12-01

    The purpose of this experimental study was to evaluate the potential effects on the healing of colorectal anastomoses of the rectal administration of Ankaferd Blood Stopper (ABS). Thirty Wistar-Albino male rats were randomly separated into 3 groups. In the sham group, only laparotomy and colonic mobilization was performed. In the other 2 groups, colon transection and anastomosis were carried out. Saline (2 mL, 0.9% NaCl) was given rectally via a feeding tube for 10 days after the surgical procedure in the sham and control groups. In Group 3 (ABS group), the rats were treated with rectally administered ABS (2 mL/day) for 10 days. In all groups, after the measurement of bursting pressures, tissue samples were collected for the measurement of tissue hydroxyproline and prolidase levels, and for histopathological evaluation on postoperative day 11. The rectal administration of ABS showed positive effects on bursting pressures, tissue prolidase and hydroxyproline levels, and the histopathological findings of colonic anastomosis. The rectal application of ABS had positive effects on the healing of colorectal anastomosis. As a natural product, it may be used effectively and safely to achieve better healing results after colorectal anastomosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  13. Determinação do antígeno carcinoembrionário biliar na detecção das metástases hepáticas do carcinoma colorretal Carcinoembryonic antigen (CEA determination in detection of hepatic metastasis from colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Adriana Polycarpo

    2003-01-01

    Full Text Available OBJETIVO: Analisar, prospectivamente, os resultados da determinação do antígeno carcinoembriário (CEA na bile vesicular, relacionando-os com os aspectos morfológicos e clínicos da neoplasia e recidiva hepática. MÉTODOS: Os níveis do CEA foram estudados na bile vesicular e no sangue periférico de 44 doentes com carcinoma colorretal e 10 com colelitíase não complicada, a partir de amostras do CEA colhidas imediatamente antes da extirpação da neoplasia colo-retal e da colecistectomia (considerou-se valor normal até 5 ng/ml. RESULTADOS: Os 44 carcinomas colorretais extirpados com intenção curativa tiveram nível médio do CEA sérico de 8,5 ng/ml e CEA biliar, 74,5 ng/ml. Nas colelitíases não complicadas submetidas a colecistectomia, o nível médio do CEA sérico foi de 1,9 ng/ml e CEA biliar, 1,2 ng/ml. Quatro doentes submetidos à extirpação do carcinoma colo-retal, sem evidências de metástases hepáticas e com valor médio de CEA biliar de 213,2 ng/ml apresentaram metástases hepáticas entre três a 17 meses após a extirpação. CONCLUSÃO: o nível elevado de CEA biliar dos operados por carcinoma colo-retal pode indicar presença de metástases hepáticas e esses enfermos devem ser acompanhados com especial atenção para diagnosticar essas lesões.PURPOSE: Carcinoembryonic antigen (CEA determination in gallbladder bile was used in a prospective study concerning the morphological and clinical features of the neoplasm and the occurrence of hepatic metastasis. METHODS: CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis from samples collected immediately before extirpating the colorectal neoplasms or cholecystectomy (values of up to 5 ng/ml were considered normal. RESULTS: In the 44 patients with colorectal carcinoma who underwent operation with curative intent, the average level of serum CEA was 8.5 ng/ml and for bile

  14. 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 ...

  15. An experimental study on the anti-Ehrlich ascites carcinoma effect of ...

    African Journals Online (AJOL)

    The objective of this paper was to study the anti-Ehrlich ascites carcinoma effect of purified toad venom extract and its mechanism. Mouse model of Ehrlich ascites carcinoma was established with cisplatin as the control to observe the inhibitory effect of purified toad venom extract on malignant peritoneal effusion in mice.

  16. Recuperative effect of Semecarpus anacardium linn. nut milk extract on carbohydrate metabolizing enzymes in experimental mammary carcinoma-bearing rats.

    Science.gov (United States)

    Sujatha, Venugopal; Sachdanandam, Panchanatham

    2002-03-01

    Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. We have tested the antitumour activity of Semecarpus anacardium nut extract against experimental mammary carcinoma in animals. As there is a direct relationship between the proliferation of tumour cells and the activities of the glycolytic and gluconeogenic enzymes, we studied changes in the activities of enzymes involved in this metabolic pathway in the liver and kidney. The enzymes investigated were glycolytic enzymes, namely hexokinase, phosphoglucoisomerase, aldolase and the gluconeogenic enzymes, namely glucose-6-phosphatase and fructose-1,6-biphosphatase in experimental rats. A significant rise in glycolytic enzyme activities and a simultaneous fall in gluconeogenic enzyme activities were found in mammary carcinoma bearing rats. Drug administration returned these enzyme activities to their respective control activities. Copyright 2002 John Wiley & Sons, Ltd.

  17. Effect of Semecarpus anacardium Linn. nut milk extract on glutathione and its associated enzymes in experimentally induced mammary carcinoma.

    Science.gov (United States)

    Mathivadhani, P; Shanthi, P; Sachdanandam, P

    2006-01-01

    Reduced glutathione (GSH) is a ubiquitous thiol-containing tripeptide that plays a key role in the etiology of many diseases and, in particular, cancer. GSH, the foremost internal protective system, participates directly in the destruction of free radical compounds and detoxification of carcinogens. The effect of Semecarpus anacardium nut milk extract was studied for gaining insight into the disease relationship to GSH and its metabolizing enzymes. Mammary carcinoma was induced by giving 7,12-dimethylbenz[a]anthracene (DMBA) (25 mg/mL of olive oil) perorally by gastric intubation, and nut milk extract of S. anacardium was administered orally (200 mg/kg of body weight/day) for 14 days to mammary carcinoma-bearing rats. The levels of GSH and its metabolizing enzyme activities were determined in liver and kidney homogenates. Significant decreases in GSH, glutathione peroxidase, glutathione S-transferase, glutathione reductase, and gamma-glutamylcysteine synthetase and a concomitant increase in oxidized glutathione, gamma-glutamyl transpeptidase, and glucose 6-phosphate dehydrogenase were observed in DMBA-induced mammary carcinoma in rats, while drug treatment reversed the conditions to near normal levels. There was a marked increase in GSH level and gamma-glutamylcysteine synthetase activity in drug control rats. These findings suggest that S. anacardium can exert its protective effect in maintaining the glutathione redox status by restoring the associated enzymes against oxidative stress in experimental mammary carcinoma.

  18. Antiangiogenic activity of vitexicarpine in experimentally induced hepatocellular carcinoma: Impact on vascular endothelial growth factor pathway.

    Science.gov (United States)

    Hassoun, Shimaa M; Abdel-Rahman, Noha; Eladl, Entsar I; El-Shishtawy, Mamdouh M

    2017-06-01

    Angiogenesis plays important roles in progression of hepatocellular carcinoma. The antiangiogenic mechanisms of vitexicarpine are not fully defined. Therefore, we conducted the following study to evaluate the antiangiogenic mechanism and antitumor activity of vitexicarpine in vivo model of hepatocellular carcinoma through modulation of vascular endothelial growth factor signaling pathway. Hepatocellular carcinoma was induced in Sprague Dawley rats by thioacetamide. Hepatocellular carcinoma was assessed by measuring serum alpha-fetoprotein and investigating liver sections stained with hematoxylin/eosin. Hepatocellular carcinoma rats were injected with vitexicarpine (150 mg/kg) for 2 weeks. Hepatic vascular endothelial growth factor was measured by enzyme-linked immunosorbent assay. Protein and expression of hepatic phospho-Ser473-AKT (p-AKT) and phospho-Tyr419-Src (p-Src) were determined. The apoptotic pathway was evaluated by assessment of protein expression of caspase-3. Vitexicarpine increased rats' survival time and decreased serum alpha-fetoprotein as well as it ameliorated fibrosis and massive hepatic tissue breakdown. It attenuated hepatocellular carcinoma-induced protein and gene expression of vascular endothelial growth factor, p-AKT, p-Src, and caspase-3. In conclusion, this study suggests that vitexicarpine possesses both antiangiogenic and antitumor activities through inhibition of vascular endothelial growth factor, p-AKT/AKT, and p-Src with subsequent inhibition of apoptotic pathway.

  19. Wnt-pathway activation in two molecular classes of hepatocellular carcinoma and experimental modulation by sorafenib.

    Science.gov (United States)

    Lachenmayer, Anja; Alsinet, Clara; Savic, Radoslav; Cabellos, Laia; Toffanin, Sara; Hoshida, Yujin; Villanueva, Augusto; Minguez, Beatriz; Newell, Philippa; Tsai, Hung-Wen; Barretina, Jordi; Thung, Swan; Ward, Stephen C; Bruix, Jordi; Mazzaferro, Vincenzo; Schwartz, Myron; Friedman, Scott L; Llovet, Josep M

    2012-09-15

    Hepatocellular carcinoma (HCC) is a heterogeneous cancer with active Wnt signaling. Underlying biologic mechanisms remain unclear and no drug targeting this pathway has been approved to date. We aimed to characterize Wnt-pathway aberrations in HCC patients, and to investigate sorafenib as a potential Wnt modulator in experimental models of liver cancer. The Wnt-pathway was assessed using mRNA (642 HCCs and 21 liver cancer cell lines) and miRNA expression data (89 HCCs), immunohistochemistry (108 HCCs), and CTNNB1-mutation data (91 HCCs). Effects of sorafenib on Wnt signaling were evaluated in four liver cancer cell lines with active Wnt signaling and a tumor xenograft model. Evidence for Wnt activation was observed for 315 (49.1%) cases, and was further classified as CTNNB1 class (138 cases [21.5%]) or Wnt-TGFβ class (177 cases [27.6%]). CTNNB1 class was characterized by upregulation of liver-specific Wnt-targets, nuclear β-catenin and glutamine-synthetase immunostaining, and enrichment of CTNNB1-mutation-signature, whereas Wnt-TGFβ class was characterized by dysregulation of classical Wnt-targets and the absence of nuclear β-catenin. Sorafenib decreased Wnt signaling and β-catenin protein in HepG2 (CTNNB1 class), SNU387 (Wnt-TGFβ class), SNU398 (CTNNB1-mutation), and Huh7 (lithium-chloride-pathway activation) cell lines. In addition, sorafenib attenuated expression of liver-related Wnt-targets GLUL, LGR5, and TBX3. The suppressive effect on CTNNB1 class-specific Wnt-pathway activation was validated in vivo using HepG2 xenografts in nude mice, accompanied by decreased tumor volume and increased survival of treated animals. Distinct dysregulation of Wnt-pathway constituents characterize two different Wnt-related molecular classes (CTNNB1 and Wnt-TGFβ), accounting for half of all HCC patients. Sorafenib modulates β-catenin/Wnt signaling in experimental models that harbor the CTNNB1 class signature. ©2012 AACR.

  20. Significado prognóstico das metástases nos linfonodos regionais do adenocarcinoma colo-retal Prognostic significance of regional lymph node metastases in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Sansom Henrique Bromberg

    1997-03-01

    Full Text Available Trezentos e vinte doentes com adenocarcinoma colo-retal submetidos a ressecção curativa foram estudados com o intuito de verificar, nas peças ressecadas, o comprometimento ou não dos linfonodos, o número dos acometidos e a área ocupada peia neoplásicas. Chamou-se de linfonodos invadidos aqueles com raros focos de células neoplásicas presentes, que não interferiam na estrutura do nodo e de destruídos àqueles que apresentavam sua estrutura em grande parte ou totalmente ocupada pelo tumor. Os linfonodos positivos foram agrupados em subgrupos contendo 1 a 4 e em mais de 4.120 (38,6% doentes apresentaram linfonodos comprometidos, dos quais 24,2% eram invadidos e 75,8% destruídos. Portadores de linfonodos livres apresentaram sobrevivência de cinco anos de 71,7%; a sobrevivência de doentes com nodos invadidos - 58,6%- foi significantemente maior que a dos com nodos destruídos - 29,7%, mas não diferiu estatisticamente da apresentada pelos portadores de linfonodos livres. Doentes com mais de 4 linfonodos comprometidos sobreviveram significantemente menos (20,0% que aqueles com 1 a 4 linfonodos acometidos (43,5%. Entre os portadores de linfonodos invadidos a sobrevivência de 5 anos foi a mesma para os com 1 a 4 ou mais de 4 linfonodos invadidos. Isto não aconteceu com portadores de linfonodos destruídos, onde os com 1 a 4 sobreviveram em cerca de 37,7% e os com mais de 4, 13,3%. Faz-se necessário identificar adequadamente a área ocupada pela neoplasia no linfonodo, pois o comportamento biológico do tipo invadido diferiu substancialmente do destruído. O melhor prognóstico dos portadores de linfonodos invadidos pode explicar a sobrevivência aparentemente paradoxal observada em alguns doentes estadiados na classe C de DUKES.320 patients submitted to eurative ressection for colorectal carcinoma was analysed with reference to involved lymph nodes, with the number of their and with the area taken by the tumor. The involved lymph nodes

  1. Frequent detection of K-ras mutation in stool samples of colorectal carcinoma patients after improved DNA extraction: comparison with tissue samples.

    Science.gov (United States)

    Ito, Yasushi; Kobayashi, Susumu; Taniguchi, Tetsushi; Kainuma, Osamu; Hara, Tsuyosi; Ochiai, Takenori

    2002-06-01

    Fecal occult blood testing is widely used in the clinical screening of colorectal tumors. However, this method has so frequent false-positive results that more accurate screening-strategy should be established. Although the molecular screening using K-ras gene mutation in stools has been attempted to improve the results, the low rate of DNA extraction from stools leaves this measurement under utility value. In this study, we investigated whether or not our applied DNA extraction method from stools could produce enough DNA for the molecular screening of colorectal tumors by K-ras gene mutations in stools. We applied cetyltrimethylammonium bromide (CTAB) solution to improve human DNA extraction from stools and a mutant-allele-sensitive amplification (MASA) method to detect K-ras mutation within codon 12. We were able to confirm the stool DNA by identifying K-ras fragments in all the 20 patients. Tissue K-ras mutation was identified in 4 (2 cancers and 2 adenomas) of 20 patients. Stool K-ras mutations were found in 6 patients, 3 tissue K-ras mutation positive patients (2 cancers and an adenoma) and 3 tissue K-ras mutation negative patients. These results indicate that it is possible to extract enough DNA from human stool samples of all patients with colorectal tumors for K-ras mutation studies. K-ras mutations are more frequently detected in stools than in resected colorectal tumors. This study indicates that K-ras mutation screening in stools for colorectal cancer may include not only a primary colorectal cancer but also precancerous lesions in all parts of a gastrointestinal tract.

  2. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Wark, P.A.; Saritas, A.M.; Roemen, G.M.; Muijen, G.N.P. van; Bruine, A.P. de; Brandt, P.A. van den; Goeij, A.F. de

    2005-01-01

    BACKGROUND: The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of

  3. Mutations in APC, CTNNBI en K-ras genes and expression of hMLHI in sporadic colorectal carcinomas from the Netherlands Cohort Study

    NARCIS (Netherlands)

    Luchtenborg, M.; Weijenberg, M.P.; Wark, P.A.; Merdan Saritas, M.

    2005-01-01

    Background - The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1) and Ras (K-ras) pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of

  4. Cytogenetic findings in metastases from colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor...... colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process....

  5. Nutrients, Foods, and Colorectal Cancer Prevention

    Science.gov (United States)

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

    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, folate, fruits and vegetables. Nutrients and foods may also interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of over-nutrition and obesity—risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. PMID:25575572

  6. Mutations in APC, CTNNB1 and K-ras genes and expression of hMLH1 in sporadic colorectal carcinomas from the Netherlands Cohort Study

    Directory of Open Access Journals (Sweden)

    de Bruïne Adriaan P

    2005-12-01

    Full Text Available Abstract Background The early to intermediate stages of the majority of colorectal tumours are thought to be driven by aberrations in the Wnt (APC, CTNNB1 and Ras (K-ras pathways. A smaller proportion of cancers shows mismatch repair deficiency. The aim of this study was to analyse the co-occurrence of these genetic alterations in relation to tumour and patient characteristics. Methods In a group of 656 unselected sporadic colorectal cancer patients, aberrations in the APC, K-ras, CTNNB1 genes, and expression of hMLH1 were investigated. Additionally, tumours were divided in groups based on molecular features and compared with respect to patient's age at diagnosis, sex, family history of colorectal cancer, tumour sub-localisation, Dukes' stage and differentiation. Results Mutations at the phosphorylation sites (codons 31, 33, 37, and 45 in the CTNNB1 gene were observed in tumours from only 5/464 patients. Tumours with truncating APC mutations and activating K-ras mutations in codons 12 and 13 occurred at similar frequencies (37% (245/656 and 36% (235/656, respectively. Seventeen percent of tumours harboured both an APC and a K-ras mutation (109/656. Nine percent of all tumours (58/656 lacked hMLH1 expression. Patients harbouring a tumour with absent hMLH1 expression were older, more often women, more often had proximal colon tumours that showed poorer differentiation when compared to patients harbouring tumours with an APC and/or K-ras mutation. Conclusion CTNNB1 mutations seem to be of minor importance in sporadic colorectal cancer. The main differences in tumour and patient characteristics are found between groups of patients based on mismatch repair deficiency.

  7. Recent advances in Oral Oncology 2008; squamous cell carcinoma aetiopathogenesis and experimental studies.

    Science.gov (United States)

    Bagan, Jose V; Scully, Crispian

    2009-07-01

    This paper provides a synopsis of the main papers related to the aetiopathogenesis of oral and oropharyngeal squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC) published in 2008 in Oral Oncology - an international interdisciplinary journal which publishes high quality original research, clinical trials and review articles, and all other scientific articles relating to the aetiopathogenesis, epidemiology, prevention, clinical features, diagnosis, treatment, and management of patients with neoplasms in the head and neck, and orofacial disease in patients with malignant disease.

  8. Genomic instability measured by inter-(simple sequence repeat) PCR and high-resolution microsatellite instability are prognostic of colorectal carcinoma survival after surgical resection.

    Science.gov (United States)

    Brenner, Bruce M; Swede, Helen; Jones, Beth A; Anderson, Garth R; Stoler, Daniel L

    2012-01-01

    During the multiyear progression to colorectal cancer, numerous genomic alterations arise in events ranging from single base mutations to gains or losses of entire chromosomes. A single genetic change might not stand out as an independent predictor of outcome. The goal of this study was to determine if more comprehensive measurements of genomic instability provide clinically relevant prognostic information. Our study included 65 sporadic colorectal cancer patients diagnosed from 1987 to 1991 with last follow-up ascertained in 2006. We estimated an overall tally of alterations using the genome-wide sampling technique of inter-(simple sequence repeat [SSR]) polymerase chain reaction (PCR), and evaluated its relationship with all-cause survival. We also extended and sensitized the Bethesda criteria for microsatellite instability (MSI), by analyzing 348 microsatellite markers instead of the normal five. We expanded the MSI categories into four levels: MSI stable (MSS), very low-level MSI, moderately low-level MSI, and classical high-level MSI. Tumors with genomic instability above the median value of 2.6% as measured by inter-SSR PCR, were associated with far greater risk of death compared to tumors with lower levels of genomic instability. Adverse outcome was most pronounced for patients presenting with stage 3 disease. A gradient of increased survival was observed across increasing MSI levels but did not reach statistical significance. Our findings suggest genomic instabilities quantified by inter-SSR PCR and increased precision in MSI values may be clinically useful tools for estimating prognosis in colorectal cancer.

  9. Therapeutic effect of coenzyme Q10 against experimentally-induced hepatocellular carcinoma in rats.

    Science.gov (United States)

    Fouad, Amr A; Al-Mulhim, Abdulruhman S; Jresat, Iyad

    2013-01-01

    The therapeutic potential of coenzyme Q10 was investigated in rats with hepatocellular carcinoma induced by trichloroacetic acid (0.5g/kg/day, p.o., for five days). Coenzyme Q10 treatment (0.4mg/kg/day, i.p.) was applied for four weeks following trichloroacetic acid administration. Coenzyme Q10 significantly suppressed lipid peroxidation, prevented the depletion of reduced glutathione and superoxide dismutase activity, and decreased the elevations of tumor necrosis factor-α and nitric oxide in liver tissue of rats with hepatocellular carcinoma. Also, the histopathological dysplastic changes induced by trichloroacetic acid in liver tissue were ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the expression of hepPar-1, alpha-fetoprotein, inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-κB in liver tissue of rats with hepatocellular carcinoma. It was concluded that coenzyme Q10 may represent a potential therapeutic option for liver carcinogenesis. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Colorectal Cancer

    Science.gov (United States)

    ... detected by optical colonoscopy. Virtual colonoscopy uses virtual reality technology to produce three-dimensional images of the ... that if current trends in reducing risk factors, increased screening, and better treatment persist, colorectal cancer mortality ...

  11. Using Positron Emission Tomography with [18F]FDG to Predict Tumor Behavior in Experimental Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Bryan M. Burt

    2001-01-01

    Full Text Available This study investigates the relationship between FDG uptake as determined by positron emission tomography (PET imaging and rates of tumor growth, cellular GLUT1 transporter density, and the activities of hexokinase and glucose-6-phosphatase in a solid tumor implant model. Five different human colorectal xenografts of different growth properties were implanted in athymic rats and evaluated by dynamic 18F-FDG-PET. The phosphorylating and dephosphorylating activities of the key glycolytic enzymes, hexokinase and glucose-6-phosphatase, were measured in these tumor types by spectrophotometric assays and the expression of GLUT1 glucose transporter protein was determined by immunohistochemistry. Correlations among FDG accumulation, hexokinase activity, and tumor doubling time are reported in these colon xenografts. The results indicate that the activity of tumor hexokinase may be a marker of tumor growth rate that can be determined by 18F-FDG-PET imaging. PET scanning may not only be a useful tool for staging patients for extent of disease, but may provide important prognostic information concerning the proliferative rates of malignancies.

  12. No difference in the occurrence of mismatch repair defects and APC and CTNNB1 genes mutation in a multi-racial colorectal carcinoma patient cohort.

    Science.gov (United States)

    Tan, Lu Ping; Ng, Ban Kim; Balraj, Pauline; Lim, Patricia Kim Chooi; Peh, Suat Cheng

    2007-04-01

    Colorectal cancers of different subtypes involve different pathogenic pathways like the Wnt and the mutator pathways. In this study, we screened 73 colorectal cancer cases from a multi-racial group for genetic and expression profile defects with the aim of correlating these with patients' clinicopathological characteristics. Mutation screening of the entire coding region of APC and exon 3 of CTNNB1, loss of heterozygosity (LOH) of APC, and microsatellite instability (MSI) status were assessed for 44 patients with available paired frozen normal and tumour tissues. In addition, 29 cases with available paraffin embedded tumour blocks were screened for mutation in exon 3 of CTNNB1, the APC mutation cluster region (codon 1286-1513), and hMLH1, hMSH2, hMSH6 protein expressions by immunohistochemistry method. In our study, 15/73 cases showed APC mutations (20.5%), 1/73 cases had CTNNB1 mutation (1.4%), 5/32 cases had APC LOH (15.6%), and 16/70 (22.9%) cases revealed at least some form of mismatch repair (MMR) defect. Tumour grade (poor differentiation) was found to correlate significantly with right-sided tumour and mucinous histology (p = 0.01879 and 0.00320, respectively). Patients of younger age (below 45 years) more often had tumours of mucinous histology (p = 0.00014), while patients of older age (above 75 years) more often had tumours on the right side of the colon (p = 0.02448). Tumours of the mucinous histology subtype often had MMR defects (p = 0.02686). There was no difference in the occurrence of APC and CTNNB1 mutations and MMR defects found within our multi-racial colorectal cancer patient cohort. Our findings support the notion that racial factor may not be related to the occurrence of MMR defects and APC and CTNNB1 mutations in our multi-racial patient cohort.

  13. A prospective cohort study on the relationship between onion and leek consumption, garlic supplement use and the risk of colorectal carcinoma in the Netherlands

    NARCIS (Netherlands)

    Dorant, E.; Brandt, P.A. van den; Goldbohm, R.A.

    1996-01-01

    The association between onion and leek consumption, garlic supplement use and colon and rectum carcinoma among men and women was evaluated in the Netherlands Cohort Study, a large-scale prospective cohort study on diet and cancer. Onions, leeks, and garlic belong to the Allium genus and contain

  14. Streptococcus sanguis endocarditis associated with colonic carcinoma.

    Science.gov (United States)

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    Infective endocarditis caused by Streptococcus bovis is known to be associated with colorectal malignancy. Other less common streptococci, specifically Streptococcus sanguis, can be similarly associated with gastrointestinal carcinoma. We present a case of disseminated colorectal carcinoma occurring after a confirmed S sanguis endocarditis, that required mitral valve surgery. There may be a need for gastrointestinal surveillance in patients presenting with bacteraemia caused by less common streptococci.

  15. Effects of Promotional Materials on Attitudes and Fear towards Colorectal Cancer Screening among Chinese Older Adults: An Experimental Study.

    Science.gov (United States)

    Leung, Doris Y P; Chen, Joanne M T; Lou, Vivian W Q; Wong, Eliza M L; Chan, Aileen W K; So, Winnie K W; Chan, Carmen W H

    2017-07-13

    Colorectal cancer (CRC) screening is a cost-effective prevention and control strategy. However, the promotion of CRC screening for older adults may be difficult because reading CRC prevention information may evoke embarrassment, fear, and anxiety towards the screening procedure and cancer diagnosis. This study aims to (1) examine the effects of three promotional materials for CRC screening on the attitudes toward CRC screening tests (screening interest, screening effectiveness, and trust in the screening results) and cancer fear, and (2) to explore the interaction effect of cancer fear with screening effectiveness and trust in the screening results on screening interest of the three screening tests (fecal occult blood test (FOBT), flexible sigmoidoscopy, and colonoscopy) among Chinese older adults. A total of 114 community-dwelling older adults were asked to look at the corresponding promotional materials (pamphlet, cartoon, and video) of one of the three study groups. The pamphlet and video represent convention strategies and the cartoon represents an innovative strategy. No significant difference was observed in the screening interest and cancer fear across groups. FOBT was the most preferred screening modality. The video group has a large proportion agreed screening effectiveness of flexible sigmoidoscopy than pamphlet and cartoon groups and trusted in the screening results for FOBT and flexible sigmoidoscopy than the pamphlet group. Logistic regression results showed that the effect of trust in the screening results on screening interest for colonoscopy was greater among participants with higher cancer fear than those with lower cancer fear level. In conclusion, the three promotional groups had produced similar results in their attitudes toward CRC screening and cancer fear. The use of cartoons may be a comparable approach with conventional methods in the promotion of CRC screening. Additional components that can arouse fear and boost response efficacy

  16. Towards the human colorectal cancer microbiome

    NARCIS (Netherlands)

    Marchesi, J.R.; Dutilh, B.E.; Hall, N.; Peters, W.H.M.; Roelofs, R.; Boleij, A.; Tjalsma, H.

    2011-01-01

    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

  17. 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.

  18. Distribution of basal lamina type IV collagen and laminin in normal rat tongue mucosa and experimental oral carcinoma: ultrastructural immunolocalization and immunogold quantitation.

    Science.gov (United States)

    Jiang, D J; Wilson, D F; Smith, P S; Pierce, A M; Wiebkin, O W

    1994-07-01

    The relationship of basal lamina, a form of specialised extracellular matrix which separates epithelial cells and other cell types from adjacent stroma, to the behaviour of malignant neoplasms of epithelial origin is not well understood. However, it is widely acknowledged that the properties of local invasion and metastasis of carcinomas are linked to extracellular matrix (including basal lamina) changes. In the present study, the distribution of the major basal lamina components, type IV collagen and laminin, in normal rat tongue mucosa and experimentally induced oral carcinomas was investigated using post-embedding immunogold techniques and electron microscopy. The expression of these components was also quantitatively analysed using morphometry and immunocytochemistry. Results indicated that type IV collagen and laminin were confined to the lamina densa of normal oral epithelial basal lamina, and that both components were also detected in the lamina densa of basal lamina associated with carcinomas, and in the extracellular matrix of tumours. Furthermore, laminin was detected within stromal fibroblasts in normal tissues and experimental carcinomas. Quantitative analysis indicated that expression of laminin was significantly increased in carcinomas. In contrast, type IV collagen expression was significantly decreased. The quantitative changes observed in the two basal lamina constituents may be related to the process of tumour invasion, reflecting altered metabolic activities of tumour and stromal cells. These observations may be of use in understanding the architectural characteristics of oral mucosa basal lamina and in assessing the malignant potential of epithelial dysplasias or "premalignant" lesions.

  19. Aberrant Expression of Calretinin, D2-40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis.

    Science.gov (United States)

    Foda, Abd AlRahman Mohammad; El-Hawary, Amira Kamal; Hamed, Hazem

    2016-10-01

    CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2-40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2-40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2-40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2-40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2-40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2-40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.

  20. [Experimental study on hepatitis B-virus X gene expression in adenoid cystic carcinoma].

    Science.gov (United States)

    Xie, Ling; Wang, Weihong; Xu, Biao; Liu, Yu

    2014-08-01

    To explore the expression of hepatitis B-virus X gene (HBX) in adenoid cystic carcinoma (ACC) and determine its clinical significance. Between June 2008 and October 2012, in-hospital patients with salivary gland tumors who were treated at the Department of Oral and Maxillofacial Surgery, Affiliated Stomatology Hospital of Kunming Medical University, were enrolled to this study. HBeAb-positive patients were defined as those exposed to hepatitis B virus (HBV) or harboring persistent HBV infection regardless of being HBeAg positive or negative. According to the pathological results, all patients were divided into ACC group and control group. Immunohistochemical staining and polymerase chain reaction (PCR) were used to detect HBX expression in ACC group and control group. HBX expression was mostly detected in the cytoplasm of ACC cells. Minimal HBX expression was detected in the nucleus. HBX expression was significantly higher in ACC than in Warthin's tumor. A significant difference was observed between the two groups. HBX is expressed in ACC and may be associated with the development of ACC. HBX might serve important functions in the carcinogenesis and development of ACC.

  1. [Experimental study of percutaneous hot ethanol injection therapy (PHEIT) by continuous heating device for hepatocellular carcinoma].

    Science.gov (United States)

    Kawai, N; Sato, M; Sonomura, T; Kishi, K; Terada, M; Tanaka, K; Tanaka, H; Nosaka, M; Takata, H; Nakanishi, H; Yoshikawa, A

    1998-06-01

    Percutaneous ethanol injection therapy (PEIT) is widely used as a local treatment for hepatocellular carcinoma (HCC). However, because only a small amount of ethanol can be used in one PEIT session and because the antitumor effect is limited, this modality is indicated only when there are three or fewer tumors and when the tumor diameter is liquid is inserted into the syringe heater, which heats the liquid to a desired temperature by adjusting the voltage. The needle thermocontroller is a puncture guide needle to which a heating device has been attached. The needle-tip thermosensor constantly measures, displays and records the temperature of the liquid at the needle tip during injection. Also, because the Continuous Heating Device is a closed-circuit system, there is no risk of accidental a fire, which ensures procedural safety. It is also possible to use this device to safely heat and inject a variety of other liquids, such as physiological saline and anticancer agents and thus contribute to the widespread development of ultrasound-guided injection therapy.

  2. Experimental evidence of Migfilin as a new therapeutic target of hepatocellular carcinoma metastasis.

    Science.gov (United States)

    Gkretsi, Vasiliki; Bogdanos, Dimitrios P

    2015-06-10

    Migfilin is a novel cell-matrix adhesion protein known to interact with Vasodilator Stimulated Phosphoprotein (VASP) and be localized both at cell-matrix and cell-cell adhesions. To date there is nothing known about its role in hepatocellular carcinoma (HCC). As matrix is important in metastasis, we aimed to investigate the Migfilin׳s role in HCC metastasis using two human HCC cell lines that differ in their metastatic potential; non-invasive Alexander cells and the highly invasive HepG2 cells. We silenced Migfilin by siRNA and studied its effect on signaling and metastasis-related cellular properties. We show that Migfilin׳s expression is elevated in HepG2 cells and its silencing leads to upregulation of actin reorganization-related proteins, namely phosphor-VASP (Ser157 and Ser239), Fascin-1 and Rho-kinase-1, promoting actin polymerization and inhibiting cell invasion. Phosphor-Akt (Ser473) is decreased contributing to the upregulation of free and phosphor-β-catenin (Ser33/37Thr41) and inducing proliferation. Migfilin elimination upregulates Extracellular Signal-regulated kinase, which increases cell adhesion in HepG2 and reduces invasiveness. This is the first study to reveal that Migfilin inhibition can halt HCC metastasis in vitro, providing the molecular mechanism involved and presenting Migfilin as potential therapeutic target against HCC metastasis. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Colorectal Cancer

    African Journals Online (AJOL)

    Peter Donald

    history, young age at onset and presence of other specific tumours and defects. Among these defects are ... medical advice. Only 2 (6.3%) patients completed their treatment regimen. Conclusion: The incidence of colorectal cancer is still low in our environment but treatment outcome remains poor due to late presentation.

  4. HISTOMORPHOLOGICAL STUDY OF COLORECTAL MALIGNANCIES

    Directory of Open Access Journals (Sweden)

    Sarvesh

    2015-07-01

    Full Text Available BACKGROUND: Colorectal cancer is the most common cancer in men and in women worldwide. Incidence rates of colorectal cancer vary 10 - fold in both sexes worldwide, Within Asia, the incidence rates vary widely and are uniformly low in all south Asian countries and high i n all developed Asian countries. Fortunately, the age adjusted incidence rates of colorectal cancer in all the Indian cancer registries are very close to the lowest rates in the world. The present study is under taken to study the prevalence and types of c olorectal cancer among the patients in the rural population in and around Chidambaram. OBJECTIVES: To study the prevalence of malignant colorectal neoplasms among the speci mens received in the Department of Pathology and the gross and histomorphological pa ttern of the lesions and finally to correlate the findings with clinical data. METHOD: The materials consisted of 68 specimens who were submitted to the Department of Pathology, during the period of Jan 2008 - Dec 2012. Data collected and entered in MS - Excel and were analyzed using SPSS - 16. RESULTS : Out of 8454 colonoscopic specimens, 68(0.8% showed colorectal malignancy. A higher frequency of colorectal was seen in 6 th decade. Out of 68 specimens of malignant neoplasms majority were Carcinoma of the Rectum (79.41% followed in decreasing order of frequency by malignant lesions of descending colon(8.82%, ascending and Sigmoid colon (4.41% each, recto - sigmoid (2.94% and cecum (2.63%, and transverse colon (2.63%. Youngest patient was 19 years old and the o ldest patient was 80 years old with a mean age of 49.5 years and median age of 50 years. CONCLUSION: Colorectal cancer is a common and lethal disease. The adenoma carcinoma. S equence offers a window of opportunity in which the precursor lesion or early car cinoma can be removed endoscopically to prevent systematic disease. The result of a careful and systematic examination of surgical specimens from patients with

  5. Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study

    Directory of Open Access Journals (Sweden)

    Sum-Fu Chiang

    2015-01-01

    Full Text Available Background. The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC. This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2, tetraspanin-6 (TSPAN6, bone marrow stromal antigen 2 (BST2, and tumor necrosis factor receptor superfamily member 16 (NGFR as potential plasma CRC biomarkers. Methods. The study population comprises 152 CRC patients and 152 controls. Target protein levels in plasma and tissue samples were assessed by ELISA and immunohistochemistry, respectively. Results. Among the four candidate proteins examined by ELISA in a small sample set, only BST2 showed significantly elevated plasma levels in CRC patients versus controls. Immunohistochemical analysis revealed the overexpression of BST2 in CRC tissues, and higher BST2 expression levels correlated with poorer 5-year survival (46.47% versus 65.57%; p=0.044. Further verification confirmed the elevated plasma BST2 levels in CRC patients (2.35 ± 0.13 ng/mL versus controls (1.04 ± 0.03 ng/mL (p<0.01, with an area under the ROC curve (AUC being 0.858 comparable to that of CEA (0.867. Conclusion. BST2, a membrane protein selectively detected in CRC cell secretome, may be a novel plasma biomarker and prognosticator for CRC.

  6. Microsatellite instability affecting the T17 repeats in intron 8 of HSP110, as well as five mononucleotide repeats in patients with colorectal carcinoma.

    Science.gov (United States)

    Markovic, Srdjan; Antic, Jadranka; Dimitrijevic, Ivan; Zogovic, Branimir; Bojic, Daniela; Svorcan, Petar; Markovic, Velimir; Krivokapic, Zoran

    2013-08-01

    To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T17, KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. Allelic variations of HSP110T17 were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T17 were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T17. Patients with high-frequency MSI CRC had allelic variations of HSP110T17. BRAF mutations occur along with greater shortening in HSP110T17 during oncogenesis via the MSI pathway.

  7. Tumor expression of calcium sensing receptor and colorectal cancer survival: Results from the nurses' health study and health professionals follow-up study.

    Science.gov (United States)

    Momen-Heravi, Fatemeh; Masugi, Yohei; Qian, Zhi Rong; Nishihara, Reiko; Liu, Li; Smith-Warner, Stephanie A; Keum, NaNa; Zhang, Lanjing; Tchrakian, Nairi; Nowak, Jonathan A; Yang, Wanshui; Ma, Yanan; Bowden, Michaela; da Silva, Annacarolina; Wang, Molin; Fuchs, Charles S; Meyerhardt, Jeffrey A; Ng, Kimmie; Wu, Kana; Giovannucci, Edward; Ogino, Shuji; Zhang, Xuehong

    2017-12-15

    Although experimental evidence suggests calcium-sensing receptor (CASR) as a tumor-suppressor, the prognostic role of tumor CASR expression in colorectal carcinoma remains unclear. We hypothesized that higher tumor CASR expression might be associated with improved survival among colorectal cancer patients. We evaluated tumor expression levels of CASR by immunohistochemistry in 809 incident colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. We used Cox proportional hazards regression models to estimate multivariable hazard ratio (HR) for the association of tumor CASR expression with colorectal cancer-specific and all-cause mortality. We adjusted for potential confounders including tumor biomarkers such as microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, expressions of PTGS2, VDR and CTNNB1 and mutations of KRAS, BRAF and PIK3CA. There were 240 colorectal cancer-specific deaths and 427 all-cause deaths. The median follow-up of censored patients was 10.8 years (interquartile range: 7.2, 15.1). Compared with patients with no or weak expression of CASR, the multivariable HRs for colorectal cancer-specific mortality were 0.80 [95% confidence interval (CI): 0.55-1.16] in patients with moderate CASR expression and 0.50 (95% CI: 0.32-0.79) in patients with intense CASR expression (p-trend = 0.003). The corresponding HRs for overall mortality were 0.85 (0.64-1.13) and 0.81 (0.58-1.12), respectively. Higher tumor CASR expression was associated with a lower risk of colorectal cancer-specific mortality. This finding needs further confirmation and if confirmed, may lead to better understanding of the role of CASR in colorectal cancer progression. © 2017 UICC.

  8. Incidence of colorectal cancer in Kashmir valley, India.

    Science.gov (United States)

    Javid, Gul; Zargar, Showkat Ali; Rather, Shabir; Khan, Abdul Rashid; Khan, Bashir Ahmad; Yattoo, Ghulam Nabi; Shah, Altaf; Gulzar, Ghulam Mohamad; Sodhi, Jaswinder Singh; Khan, Mushtaq Ahmad; Bashir, Abid Shoukat-Deeba

    2011-02-01

    There is wide variation in the incidence of colorectal cancer globally and also within the same country among different racial or ethnic groups. The present population-based study was undertaken to determine the incidence of colorectal cancer in Kashmiri population which is non-migratory and ethnically homogeneous having stable food habits. Over a period of one year, all newly diagnosed and histological proved cases of colorectal cancer in all possible areas, where such patients are diagnosed and treated were prospectively registered. A total of 212 cases of colorectal cancers were registered; of them 113 (53.3%) originated in the colon and other 99 (46.7%) in rectum. Male to female ratio was 1.2:1. The crude incidence rate of colorectal cancer was 3.65/100,000; it was 3.78 in males, and 3.50/100,000 in females. The incidence rates for colorectal cancer in Muslims and Hindus were different. The crude incidence rate for colorectal carcinoma was highest for district Srinagar 6.19/100,000 (urban area) and lowest for district Kupwara (rural area) 1.59/100,000. The highest numbers of cases were detected in the age group 55-59 years (n = 34). The age-specific rate for colorectal carcinoma was highest in the age group 55-59 years (17.21/100,000), followed by 65-69 years (14.86/100,000). The age standardized incidence rate was 4.52/100,000 per year. The truncated age adjusted incidence rates in age group 35-64 years was 8.31/100,000; while that for colorectal carcinoma was 8.77/100,000 in males and 7.66/100,000 in females. We conclude that the incidence of colorectal cancer in Kashmir valley is similar to that reported in the rest of India.

  9. Subnuclear proteomics in colorectal cancer

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Knol, Jaco C; Piersma, Sander R

    2010-01-01

    Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers...... for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we...... established the reproducibility of the entire work flow. In a reproducibility analysis of three nuclear matrix fractions independently isolated from the same colon tumor homogenate, 889 of 1,047 proteins (85%) were reproducibly identified at high confidence (minimally two peptides per protein at 99...

  10. Diagnostic Ultrasound in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rafaelsen, Søren Rafael

    2014-01-01

    tumour stage and whether there is distant spread of the disease at the time of diagnosis. Ultrasound Diagnostics is non-unionized and less costly than MDCT, MRI and PET/CT. Although MRI in recent years has gained ground in diagnostics in Denmark, there are still patients who have contraindications to MRI...... or are non-compliant. Also, patient movement during the MRI sequence acquisition degrades image quality on MRI and decreases accuracy. Over the last years, the ultrasound technique has improved further by Power Doppler, intravenous contrast enhancement, and elastography. Ultrasound diagnostics has...... the potential to contribute to the staging of colorectal cancer. The purpose of these studies was to determine the usefulness of ultrasound diagnostics in patients with colorectal cancer.The purpose of the TRUS studies was to compare staging of rectal carcinomas using digital rectal exploration...

  11. Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia.

    Science.gov (United States)

    Palomba, Grazia; Colombino, Maria; Contu, Antonio; Massidda, Bruno; Baldino, Giovanni; Pazzola, Antonio; Ionta, MariaTeresa; Capelli, Francesca; Trova, Vittorio; Sedda, Tito; Sanna, Giovanni; Tanda, Francesco; Budroni, Mario; Palmieri, Giuseppe; Cossu, Antonio; Contu, Marta; Cuccu, Angelo; Farris, Antonio; Macciò, Antonio; Mameli, Giuseppe; Olmeo, Nina; Ortu, Salvatore; Petretto, Elisabetta; Pusceddu, Valeria; Virdis, Luciano

    2012-08-29

    Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC) has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia. From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478) were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. Overall, KRAS tumour mutation rate was 30% (145/478 positive cases). Distribution of mutation carriers was surprisingly different within the island: 87/204 (43%) in North Sardinia vs. 58/274 (21%) in Middle-South Sardinia (p<0.001). Among 384 CRC cases whose DNA was available, only one (0.3%) patient carried a mutation in BRAF gene; PIK3CA was found mutated in 67 (17%) patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10%) cases from northern vs. 48/201 (24%) cases from central-southern island (p<0.001). This heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy. Our findings support the hypothesis that differences in patients' origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.

  12. Prevalence of KRAS, BRAF, and PIK3CA somatic mutations in patients with colorectal carcinoma may vary in the same population: clues from Sardinia

    Directory of Open Access Journals (Sweden)

    Palomba Grazia

    2012-08-01

    Full Text Available Abstract Background Role of KRAS, BRAF and PIK3CA mutations in pathogenesis of colorectal cancer (CRC has been recently investigated worldwide. In this population-based study, we evaluated the incidence rates and distribution of such somatic mutations in genetically isolated population from Sardinia. Methods From April 2009 to July 2011, formalin-fixed paraffin-embedded tissues (N = 478 were prospectively collected from Sardinian CRC patients at clinics across the entire island. Genomic DNA was isolated from tissue sections and screened for mutations in KRAS, BRAF, and PIK3CA genes by automated DNA sequencing. Results Overall, KRAS tumour mutation rate was 30% (145/478 positive cases. Distribution of mutation carriers was surprisingly different within the island: 87/204 (43% in North Sardinia vs. 58/274 (21% in Middle-South Sardinia (pBRAF gene; PIK3CA was found mutated in 67 (17% patients. A significant inverse distribution of PIK3CA mutation rates was observed within Sardinian population: 19/183 (10% cases from northern vs. 48/201 (24% cases from central-southern island (pKRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population. Preliminary clinical evaluation of 118 KRAS wild-type patients undergoing anti-EGFR-based treatment indicated lack of role for PIK3CA in predicting response to therapy. Conclusions Our findings support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in candidate cancer genes.

  13. The plant alkaloid and anti-leukemia drug homoharringtonine sensitizes resistant human colorectal carcinoma cells to TRAIL-induced apoptosis via multiple mechanisms.

    Science.gov (United States)

    Beranova, Lenka; Pombinho, Antonio R; Spegarova, Jarmila; Koc, Michal; Klanova, Magdalena; Molinsky, Jan; Klener, Pavel; Bartunek, Petr; Andera, Ladislav

    2013-06-01

    TNF-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic ligand from the TNF-alpha family that is under consideration, along with agonistic anti-TRAIL receptor antibodies, as a potential anti-tumor agent. However, most primary human tumors are resistant to monotherapy with TRAIL apoptogens, and thus the potential applicability of TRAIL in anti-tumor therapy ultimately depends on its rational combination with drugs targeting these resistances. In our high-throughput screening for novel agents/drugs that could sensitize TRAIL-resistant colorectal cancer cells to TRAIL-induced apoptosis, we found homoharringtonine (HHT), a cephalotaxus alkaloid and tested anti-leukemia drug, to be a very effective, low nanomolar enhancer of TRAIL-mediated apoptosis/growth suppression of these resistant cells. Co-treatment of TRAIL-resistant RKO or HT-29 cells with HHT and TRAIL led to the effective induction of apoptosis and the complete elimination of the treated cells. HHT suppressed the expression of the anti-apoptotic proteins Mcl-1 and cFLIP and enhanced the TRAIL-triggered activation of JNK and p38 kinases. The shRNA-mediated down-regulation of cFLIP or Mcl-1 in HT-29 or RKO cells variably enhanced their TRAIL-induced apoptosis but it did not markedly sensitize them to TRAIL-mediated growth suppression. However, with the notable exception of RKO/sh cFLIP cells, the downregulation of cFLIP or Mcl-1 significantly lowered the effective concentration of HHT in HHT + TRAIL co-treatment. Combined HHT + TRAIL therapy also led to the strong suppression of HT-29 tumors implanted into immunodeficient mice. Thus, HHT represents a very efficient enhancer of TRAIL-induced apoptosis with potential application in TRAIL-based, anti-cancer combination therapy.

  14. Oncogenic RAS alters the global and gene-specific histone modification pattern during epithelial-mesenchymal transition in colorectal carcinoma cells.

    Science.gov (United States)

    Peláez, Ignacio Mazón; Kalogeropoulou, Margarita; Ferraro, Angelo; Voulgari, Angeliki; Pankotai, Tibor; Boros, Imre; Pintzas, Alexander

    2010-06-01

    The presence of different forms of histone covalent modifications, such as phosphorylation, acetylation and methylation in localized promoter regions are markers for chromatin packing and transcription. Activation of RAS signalling pathways through oncogenic RAS mutations is a hallmark of colorectal cancer. Overexpression of Harvey-Ras oncogene induces epithelial-mesenchymal transition (EMT) in Caco-2 cells. We focused on the role of epigenetic modifications of histone H3 and its dependence on RAS signal transduction pathways and oncogenic transformation. Using cell lines stably overexpressing oncogenic Harvey-RAS with EMT phenotype, we studied the acquired changes in the H3 histone modification patterns. Two genes show inverse protein expression patterns after Ha-RAS overexpression: Cyclin D1, a cell cycle-related gene, and the EMT marker-gene E-cadherin. We report that these two genes demonstrate matching inverse histone repression patterns on their promoter, while histone markers associated with an active state of genes were affected by the RAS-activated signalling pathway MEK-ERK-MSK1. Furthermore, we show that though the level of methyltransferases enzymes was increased, the status of H3 three-methylation at lysine 27 (H3K27me(3)), associated with gene repression on the promoter of Cyclin D1, was lower. Together, these results suggest that histone covalent modifications can be affected by oncogenic RAS pathways to regulate the expression of target genes like Cyclin D1 or E-cadherin and that the dynamic balance of opposing histone-modifying enzymes is critical for the regulation of cell proliferation. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. Immunohistochemical staining for p16 and BRAFV600E is useful to distinguish between sporadic and hereditary (Lynch syndrome-related) microsatellite instable colorectal carcinomas.

    Science.gov (United States)

    Boissière-Michot, Florence; Frugier, Hélène; Ho-Pun-Cheung, Alexandre; Lopez-Crapez, Evelyne; Duffour, Jacqueline; Bibeau, Frédéric

    2016-08-01

    DNA mismatch repair (MMR) protein analysis by immunohistochemistry (IHC) can identify colorectal cancer (CRC) with microsatellite instability (MSI). As MLH1-deficient CRC can be hereditary or sporadic, markers to distinguish between them are needed. MLH1 promoter methylation assay is the reference method; however, sometimes, it is challenging on formalin-fixed paraffin-embedded tissue samples. We assessed by IHC the expression of BRAFV600E, p16, MGMT, and CDX2 in 55 MLH1-deficient MSI CRC samples (of which 8 had a germline MLH1 mutation) to determine whether this panel differentiates between sporadic and hereditary CRCs. We also analyzed MLH1 promoter methylation by methylation-specific PCR and pyrosequencing and BRAF status by genotyping. None of the hereditary CRCs showed MLH1 methylation, BRAF mutation, BRAFV600E-positive immunostaining, or loss of p16 expression. We detected MLH1 promoter methylation in 67 % and a BRAF mutation in 42 % of CRC, all showing MLH1 promoter methylation. BRAFV600E IHC and BRAF genotyping gave concordant results in all but two samples. Loss of expression of p16 was found in 30 % of CRC with methylation of the MLH1 promoter, but its expression was retained in all non-methylated and part of MLH1-methylated tumors (100 % specificity, 30 % sensitivity). CDX2 and MGMT expression was not associated with MLH1 status. Thus, BRAFV600E and p16 IHC may help in differentiating sporadic from hereditary MLH1-deficient CRC with MSI. Specifically, p16 IHC might be used as a surrogate marker for MLH1 promoter methylation, because all p16-negative CRCs displayed MLH1 methylation, whereas hereditary CRCs were all p16-positive.

  16. A novel single-port technique for transanal rectosigmoid resection and colorectal anastomosis on an ex vivo experimental model.

    Science.gov (United States)

    Bhattacharjee, Hemanga K; Buess, Gerhard F; Becerra Garcia, Francisco Cesar; Storz, Pirmin; Sharma, Mousumi; Susanu, Sidonia; Kirschniak, Andreas; Misra, Mahesh C

    2011-06-01

    In the context of natural orifice translumenal endoscopic surgery (NOTES), we developed a new set of rigid instruments according to the principles of transanal endoscopic microsurgery (TEM).These instruments are long, curved, and steerable by rotating two wheels near its handle. Our success in transvaginal cholecystectomy in human with these instruments motivated us to explore the feasibility of rectosigmoid resection through the anus. The young bovine large bowel with attached organs is collected en bloc and reintegrated into an anatomically designed trainer to reproduce the human anatomy. The technique comprises the following: (1) closure of the rectal lumen by an endolumenal pursestring suture; (2) transection of the rectal wall 1 cm distal to the pursestring suture and continuation of the dissection toward the fascia and upward excising the mesorectal tissue; (3) inferior mesenteric artery is divided near its origin; (4) the colon is mobilized up to the splenic flexure; (5) the mobilized colon is brought down to the pelvis, ligated twice at the intended proximal resection site, and divided between the ligatures; (6) specimen is delivered transanally; and (7) intestinal continuity is restored by stapled or hand-sutured anastomosis. Twelve rectosigmoid resections, 20 stapled, and 27 hand-sutured anastomoses were performed in two experimental setups. Mean operation time for the resection part was 78.6 min (standard deviation (SD)=9.9). The average specimen length was 37.2 cm. During dissection in the pelvis, as the specimen was pushed upward and toward abdomen, an "empty pelvis" view of the working field was achieved, facilitating dissection. The mean operation time for hand-sutured and stapled anastomoses were 47.7 (SD=6.9) and 43.3 (SD=7.1) min, respectively. Both groups had one anastomotic leak. Transanal rectosigmoid resection is feasible with TEM technology. The unobstructed "empty pelvis" view is likely to enhance the quality of mesorectal dissection.

  17. Determination of carcinoembryonic antigen levels in peripheral and draining venous blood in patients with colorectal carcinoma Determinação dos níveis do antígeno carcinoembriônico no sangue periférico e no efluente venoso em doentes com carcinoma colorretal

    Directory of Open Access Journals (Sweden)

    Jaques Waisberg

    2004-06-01

    Full Text Available BACKGROUND: The problem of the relationship between blood carcinoembryonic antigen (CEA levels and tissue CEA content in colorectal carcinoma, and the mechanisms for CEA release from tumor cells in tissue adjacent to the neoplasm is important to understanding the biology of colorectal carcinoma. It has not been adequately explained whether CEA in the peripheral blood is drained mainly by portal system blood or by the lymphatic system, or indeed by both systems. AIM: To study the behavior of CEA levels in peripheral blood (CEA-p and venous effluent blood (CEA-d among patients with colorectal tumors, who underwent curative operation. METHOD: A total of 28 patients were studied (12 male [42.9%] and 16 female [57.1%], mean age 66.1 years [range: 43 - 84]. Immediately after laparotomy, peripheral venous blood was extracted by antecubital venous puncture and venous effluent blood was collected from the main drainage vein of the lesions. Values of CEA-p, CEA-d and the gradient between CEA-d and CEA-p that were less than 5.0 ng/mL were considered normal. RESULTS: Eight (28.6% patients were stage A in Duke's classification, nine (32.1% stage B and 11 (39.3% stage C. The neoplasm was located in the rectum of 14 patients (50.0%, in the transverse colon in five (17.9%, in the sigmoid in four (14.3%, in the cecum and/or ascending colon in three (10.7%, and in the descending colon in two (7.1%. The histopathological examination revealed well-differentiated adenocarcinoma in all the patients. Only one patient (3.6%, Duke's classification stage C, presented neoplasm with venous invasion. The gradient between the CEA-p and CEA-d levels were normal in 25 patients (88.3% and high in three (10.7%. The mean value for CEA-p was 3.8 ± 4.1 ng/mL (0.1-21.1 ng/mL and for the drained CEA (CEA-d it was 4.5 ± 4.3 ng/mL (0.3-20.2 ng/mL, without significant difference between these values. There was a significant difference between the mean value for CEA-p and CEA-d levels

  18. Polimorfismos das isoformas M1, T1 e P1 da glutationa S-transferase e associação com os aspectos clínico-patológicas no carcinoma colorretal Polymorphism of glutathione S-transferase M1, T1 and P1 and association with clinicopathological aspects in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Poliana L Ansolin

    2010-09-01

    increased neoplasia risks, including colorectal cancer. In this retrospective study 50 biopsies of patients with colorectal carcinoma of South Brazilian were analyzed polymorphisms in the genes GSTM1, GSTT1 and GSTP1 by Multiplex PCR and RFLP for the clinical and pathological variables: location, stage and differentiation. There were no significant p values for the variables: stage (p=0,28, p=0,93 e p=0,67, differentiation (p=0,70 e p=0,37 and location (p= 0,23. p= 0,58 e p= 0,60 respectively and the presence of polymorphism of GSTM1, GSTT1 and GSTP1 in variables staging and location. The only clinicopathological variable that showed significant value in the differentiation of CCR was the polymorphism GSTP1 ile/val and val/val (p= 0,046, however, more research is needed to confirm these findings, since these results may have been influenced by the reduced number of biopsies analyzed.

  19. Molecular Cytogenetics: Genomic Imbalances in Colorectal Cancer and their Clinical Impact

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    Marian Grade

    2006-01-01

    Full Text Available Chromosomal aberrations play a dominant role in colorectal carcinogenesis. The application of fluorescence in situ hybridization (FISH based techniques such as comparative genomic hybridization (CGH and spectral karyotyping (SKY revealed that colorectal carcinomas are characterized by a specific pattern of chromosomal imbalances which sequentially accumulate during cancer progression. This review aims to summarize molecular cytogenetic studies, provides a background on the functional relevance of chromosomal aberrations for colorectal cancer progression and discusses their potential clinical impact.

  20. Quantitative analysis of wild-type and V600E mutant BRAF proteins in colorectal carcinoma using immunoenrichment and targeted mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hang [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122 (China); Hsiao, Yung-Chin [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Department of Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Chiang, Sum-Fu [Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Wu, Chia-Chun; Lin, Yu-Tsun [Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Liu, Hsuan [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan (China); Zhao, Hong [Experimental Center of Functional Subjects, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110122 (China); Chen, Jinn-Shiun [Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan (China); Chang, Yu-Sun [Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan (China); Department of Otolaryngology, Chang Gung Memorial Hospital, Linkou, Taiwan (China); and others

    2016-08-24

    The BRAF V600E mutation is one of the most common mutations implicated in the development of several types of cancer including colorectal cancer (CRC), where it is associated with aggressive disease phenotypes and poor outcomes. The status of the BRAF V600E mutation is frequently determined by direct DNA sequencing. However, no previous study has sought to quantify the BRAF V600E protein in cancer specimens. Here, we evaluated immunoenrichment coupled with two MS-based quantitative techniques, namely multiple reaction monitoring (MRM) and single ion monitoring conjugated accurate inclusion mass screening (SIM-AIMS), to detect and precisely quantify wild-type (WT) and V600E mutant BRAF proteins in DNA sequence-confirmed CRC tissue specimens. WT and V600E BRAF proteins were immunoprecipitated from a CRC cell line (HT-29), and their representative peptides ({sup 592}IGDFGLATVK{sup 601} and {sup 592}IGDFGLATEK{sup 601}, respectively) were confirmed by LC-MS/MS analysis and then quantified by MRM or SIM-AIMS with spiked stable isotope-labeled peptide standards. Both assays worked well for measuring WT BRAF from different amounts of HT-29 cell lysates, but the MRM assay was more sensitive than SIM-AIMS assay for quantifying lower levels of V600E BRAF. In protein extracts (2 mg) from 11 CRC tissue specimens, the MRM assay could measure WT BRAF in all 11 cases (0.32–1.66 ng) and the V600E BRAF in two cases (0.1–0.13 ng; mutant-to-WT ratio, 0.16–0.17). The SIM-AIMS assay could also detect WT and V600E BRAF in CRC specimens, but the measured levels of both targets were lower than those determined by MRM assay. Collectively, this study provides an effective method to precisely quantify WT and V600E BRAF proteins in complex biological samples using immunoenrichment-coupled targeted MS. Since the V600E BRAF protein has emerged as an important therapeutic target for cancer, the developed assay should facilitate future BRAF-related basic and clinical studies

  1. Mediterranean Diet: Prevention of Colorectal Cancer

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    Micah G. Donovan

    2017-12-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer diagnosis and the second and third leading cause of cancer mortality in men and women, respectively. However, the majority of CRC cases are the result of sporadic tumorigenesis via the adenoma–carcinoma sequence. This process can take up to 20 years, suggesting an important window of opportunity exists for prevention such as switching toward healthier dietary patterns. The Mediterranean diet (MD is a dietary pattern associated with various health benefits including protection against cardiovascular disease, diabetes, obesity, and various cancers. In this article, we review publications available in the PubMed database within the last 10 years that report on the impact of a MD eating pattern on prevention of CRC. To assist the reader with interpretation of the results and discussion, we first introduce indexes and scoring systems commonly used to experimentally determine adherence to a MD, followed by a brief introduction of the influence of the MD pattern on inflammatory bowel disease, which predisposes to CRC. Finally, we discuss key biological mechanisms through which specific bioactive food components commonly present in the MD are proposed to prevent or delay the development of CRC. We close with a discussion of future research frontiers in CRC prevention with particular reference to the role of epigenetic mechanisms and microbiome related to the MD eating pattern.

  2. MALIGNANCY IN LARGE COLORECTAL LESIONS

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    Carlos Eduardo Oliveira dos SANTOS

    2014-09-01

    Full Text Available Context The size of colorectal lesions, besides a risk factor for malignancy, is a predictor for deeper invasion Objectives To evaluate the malignancy of colorectal lesions ≥20 mm. Methods Between 2007 and 2011, 76 neoplasms ≥20 mm in 70 patients were analyzed Results The mean age of the patients was 67.4 years, and 41 were women. Mean lesion size was 24.7 mm ± 6.2 mm (range: 20 to 50 mm. Half of the neoplasms were polypoid and the other half were non-polypoid. Forty-two (55.3% lesions were located in the left colon, and 34 in the right colon. There was a high prevalence of III L (39.5% and IV (53.9% pit patterns. There were 72 adenomas and 4 adenocarcinomas. Malignancy was observed in 5.3% of the lesions. Thirty-three lesions presented advanced histology (adenomas with high-grade dysplasia or early adenocarcinoma, with no difference in morphology and site. Only one lesion (1.3% invaded the submucosa. Lesions larger than 30 mm had advanced histology (P = 0.001. The primary treatment was endoscopic resection, and invasive carcinoma was referred to surgery. Recurrence rate was 10.6%. Conclusions Large colorectal neoplasms showed a low rate of malignancy. Endoscopic treatment is an effective therapy for these lesions.

  3. Colonoscopia com magnificação de imagem no diagnóstico de carcinoma colorretal invasivo da submucosa na polipose adenomatosa familiar Magnifying colonoscopy diagnosis of submucosal invasive colorectal carcinoma in familial adenomatous polyposis

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    Cláudio TARTA

    2000-04-01

    Full Text Available O desenvolvimento da colonoscopia com magnificação de imagem possibilitou o estudo detalhado da mucosa colônica e o diagnóstico diferencial entre lesões neoplásicas e não-neoplásicas, a partir da observação dos pit patterns. Os resultados são comparáveis à estereomicroscopia, sendo possível, assim, presumir o diagnóstico histológico. Foi realizada colonoscopia com magnificação de imagem em paciente portadora de polipose adenomatosa familiar, demonstrando-se com este método, a diversidade de lesões polipóides benignas e as apresentações morfológicas do câncer colorretal precoce. Nesta paciente, a avaliação por magnificação (videocolonoscópio FUJINON 410 - CM -- 40X, combinada à cromoscopia com indigo carmine 0,4%, demonstrou ampla variedade de lesões distribuídas por todo o cólon: lesão de espalhamento lateral no ceco com padrão IIIL + IV, pólipos subpediculados e sésseis distribuídos pelo cólon com padrão tipo IIIL, pólipo subpediculado no cólon transverso com diâmetro aproximado de 2,0 cm e padrão IV + V, lesões plano-elevadas tipo IIIL e no cólon sigmóide lesão IIa + IIc, com padrão V de Kudo. A avaliação dos pit patterns de lesões no cólon transverso e sigmóide permitiu o diagnóstico endoscópico de lesão com invasão de submucosa.The development of colonoscopy with image magnification has enable to study the colonic mucosa in detail and to do differential diagnosis between neoplastic and non-neoplastic lesions from the observation of pit patterns. The results are comparable to stereomicroscopy being possible to predict the histologic diagnosis. In a patient with familial adenomatous polyposis magnifying colonoscopy was performed and this method demonstrated a wide variaton of benign polypoid lesions and the morphological features of early colorectal cancer. In this patient, the evaluation by image magnification, together with indigo carmin 0,4% chromoscopy, showed a wide variety of

  4. Correlation of perfusion MRI and 18F-FDG PET imaging biomarkers for monitoring regorafenib therapy in experimental colon carcinomas with immunohistochemical validation.

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    Ralf S Eschbach

    Full Text Available To investigate a multimodal, multiparametric perfusion MRI / 18F-fluoro-deoxyglucose-(18F-FDG-PET imaging protocol for monitoring regorafenib therapy effects on experimental colorectal adenocarcinomas in rats with immunohistochemical validation.Human colorectal adenocarcinoma xenografts (HT-29 were implanted subcutaneously in n = 17 (n = 10 therapy group; n = 7 control group female athymic nude rats (Hsd:RH-Foxn1rnu. Animals were imaged at baseline and after a one-week daily treatment protocol with regorafenib (10 mg/kg bodyweight using a multimodal, multiparametric perfusion MRI/18F-FDG-PET imaging protocol. In perfusion MRI, quantitative parameters of plasma flow (PF, mL/100 mL/min, plasma volume (PV, % and endothelial permeability-surface area product (PS, mL/100 mL/min were calculated. In 18F-FDG-PET, tumor-to-background-ratio (TTB was calculated. Perfusion MRI parameters were correlated with TTB and immunohistochemical assessments of tumor microvascular density (CD-31 and cell proliferation (Ki-67.Regorafenib significantly (p<0.01 suppressed PF (81.1±7.5 to 50.6±16.0 mL/100mL/min, PV (12.1±3.6 to 7.5±1.6% and PS (13.6±3.2 to 7.9±2.3 mL/100mL/min as well as TTB (3.4±0.6 to 1.9±1.1 between baseline and day 7. Immunohistochemistry revealed significantly (p<0.03 lower tumor microvascular density (CD-31, 7.0±2.4 vs. 16.1±5.9 and tumor cell proliferation (Ki-67, 434.0 ± 62.9 vs. 663.0 ± 98.3 in the therapy group. Perfusion MRI parameters ΔPF, ΔPV and ΔPS showed strong and significant (r = 0.67-0.78; p<0.01 correlations to the PET parameter ΔTTB and significant correlations (r = 0.57-0.67; p<0.03 to immunohistochemical Ki-67 as well as to CD-31-stainings (r = 0.49-0.55; p<0.05.A multimodal, multiparametric perfusion MRI/PET imaging protocol allowed for non-invasive monitoring of regorafenib therapy effects on experimental colorectal adenocarcinomas in vivo with significant correlations between perfusion MRI parameters and 18F

  5. Stabilization of lysosomal membrane and cell membrane glycoprotein profile by Semecarpus anacardium linn. nut milk extract in experimental hepatocellular carcinoma.

    Science.gov (United States)

    Premalatha, B; Sachdanandam, P

    2000-08-01

    Semecarpus anacardium Linn. nut milk extract administered orally at a dose of 200 mg/kg/day for 14 days exerted an in vivo stabilizing effect on lysosomal membrane and glycoprotein content in rat hepatocellular carcinoma. This was demonstrated in normal rats and in animals whose biomembranes were rendered fragile by induction of hepatocellular carcinoma with aflatoxin B(1) and subsequent treatment with Semecarpus anacardium nut extract. In this condition, the discharge of lysosomal enzymes increased significantly with a subsequent increase in glycoprotein components. The nut extract administration reversed these adverse changes to near normal in treated animals. The possible reason for this reversal is discussed. Such stabilization of biomembranes by Semecarpus anacardium nut extract may have a beneficial effect in the treatment of hepatocellular carcinoma and other cancers involving abnormal fragility of lysosomes and glycoprotein content providing the extract demonstrates safety in a full toxicity study. Copyright 2000 John Wiley & Sons, Ltd.

  6. Is height a risk factor for colorectal adenoma?

    Science.gov (United States)

    Pyo, Jeung Hui; Hong, Sung Noh; Min, Byung-Hoon; Chang, Dong Kyung; Son, Hee Jung; Rhee, Poong-Lyul; Kim, Jae J; Kim, Young-Ho

    2016-07-01

    Although it is generally known that the risk for all types of cancer increases with adult height, combined and for several common site-specific cancers (including colon and rectal), evidence is limited for adenomas, which are precursors to colorectal cancer. We evaluated the association between height and risk of colorectal adenoma at various stages of the adenoma-carcinoma pathway. We conducted a retrospective study using data from patients who had undergone a complete colonoscopy as part of a health examination at the Health Promotion Center of Samsung Medical Center between October 13, 2009 and December 31, 2011. A total of 1,347 male subjects were included in our study. Multivariate logistic regression analysis was used to evaluate the association between height and colorectal adenoma. Each 5-cm increase in height was associated with 1.6% and 5.3% higher risks of advanced colorectal adenoma and high-risk colorectal adenoma, respectively, but associations were not significant after adjusting for age, body mass index, metabolic syndrome, alcohol intake, smoking, family history of colorectal cancer, and regular aspirin use (p = 0.840 and p = 0.472, respectively). No clear association was found between colorectal adenoma risk and height. Unlike other site-specific tumors reported to have a consistent relationship with height, the association between colorectal tumor and height remains controversial.

  7. Hereditary non-polyposis colorectal cancer: clinical features and survival. Results from the Danish HNPCC register

    DEFF Research Database (Denmark)

    Myrhøj, T; Bisgaard, M L; Bernstein, Inge Thomsen

    1997-01-01

    BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited syndrome characterized by the development of colorectal cancer (CRC) and other carcinomas. Our aim was to evaluate tumour parameters and survival in HNPCC. METHODS: One hundred and eight Danish HNPCC patients...... were compared with 870 patients with sporadic colorectal cancer. RESULTS: The median age at CRC diagnosis was 41 years in the HNPCC group. HNPCC patients had significantly more carcinomas located to the right colon (68% against 49% in controls), more synchromous tumours (7% versus 1%), more...

  8. In vivo monitoring of sorafenib therapy effects on experimental prostate carcinomas using dynamic contrast-enhanced MRI and macromolecular contrast media.

    Science.gov (United States)

    Cyran, Clemens C; Schwarz, Bettina; Paprottka, Philipp M; Sourbron, Steven; von Einem, Jobst C; Dietrich, Olaf; Hinkel, Rabea; Clevert, Dirk A; Bruns, Christiane J; Reiser, Maximilian F; Nikolaou, Konstantin; Wintersperger, Bernd J

    2013-12-16

    To investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with macromolecular contrast media (MMCM) to monitor the effects of the multikinase inhibitor sorafenib on subcutaneous prostate carcinomas in rats with immunohistochemical validation. Copenhagen rats, implanted with prostate carcinoma allografts, were randomized to the treatment group (n = 8) or the control group (n = 8). DCE-MRI with albumin-(Gd-DTPA)35 was performed at baseline and after 1 week using a clinical 3-Tesla system. The treatment group received sorafenib, 10 mg/kg body weight daily. Kinetic analysis yielded quantitative parameters of tumor endothelial permeability-surface area product (PS; ml/100 ml/min) and fractional blood volume (Vb, %). Tumors were harvested on day 7 for immunohistochemical analysis. In sorafenib-treated tumors, PS (0.62 ± 0.20 vs 0.08 ± 0.09 ml/100 ml/min; P effects of a 1-week, daily treatment course of sorafenib on experimental prostate carcinoma allografts.

  9. Colorectal Cancer Prevention

    Science.gov (United States)

    ... cancer: Age Family history of colorectal cancer Personal history Inherited risk Alcohol Cigarette smoking Obesity The following protective factors decrease the risk of colorectal cancer: Physical activity Aspirin Combination hormone replacement therapy Polyp removal It is ...

  10. Nutrients, foods, and colorectal cancer prevention.

    Science.gov (United States)

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

    2015-05-01

    Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity-risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Colorectal neoplasm characterization based on swept-source optical coherence tomography

    Science.gov (United States)

    Lu, Chih-Wei; Chiu, Han-Mo; Sun, Chia-Wei

    2009-07-01

    Most of the colorectal cancer has grown from the adenomatous polyp. Adenomatous lesions have a well-documented relationship to colorectal cancer in previous studies. Thus, to detect the morphological changes between polyp and tumor can allow early diagnosis of colorectal cancer and simultaneous removal of lesions. In this paper, the various adenoma/carcinoma in-vitro samples are monitored by our swept-source optical coherence tomography (SS-OCT) system. The significant results indicate a great potential for early detection of colorectal adenomas based on the SS-OCT imaging.

  12. Cavernous sinus syndrome associated with metastatic colorectal cancer and perineural spread along the trigeminal nerve.

    Science.gov (United States)

    Nassrallah, Georges; Sun, Vincent; Guiot, Marie-Christine; Mikhail, Mikel; Arthurs, Bryan

    2017-06-01

    We report the case of a patient with cavernous sinus syndrome associated with biopsy-confirmed metastasis from colorectal cancer. A patient known for laryngeal carcinoma and metastatic colorectal carcinoma presented with symptoms of left trigeminal neuralgia and progressive, near-complete ophthalmoplegia. Magnetic resonance imaging (MRI) revealed a mass in the left cavernous sinus, extending into Meckel's cave with perineural spread along the mandibular branch of the left trigeminal nerve. A transsphenoidal biopsy was performed and demonstrated metastatic colon adenocarcinoma. We review the existing literature on colorectal cancer associated cavernous sinus syndrome. Cavernous sinus metastasis from colorectal cancer is exceedingly rare. We report the second case of this entity with histopathologic confirmation, and the first case with concurrent perineural spread involving the trigeminal nerve. Cavernous sinus metastasis may represent a poor prognostic factor in colorectal cancer.

  13. Microscopical evaluation of prognostic factors in colorectal cancer

    NARCIS (Netherlands)

    Mesker, Wilhelmina Engelina

    2008-01-01

    Aims and outline of the thesis. Since Fearon and Vogelstein in 1990 presented the genetic model for the adeno-carcinoma sequence of colorectal cancer, many prognostic studies varying from early stage markers to markers involved in late progression and liver metastases have followed. As has become

  14. Colorectal cancer in South Africa: A heritable cause suspected in ...

    African Journals Online (AJOL)

    Background. Colorectal carcinoma (CRC) has a low incidence among the black African population. Largely unrecognised in the scientific literature is the fact that a disproportionately large number of young black patients (<50 years old) present with CRC. Objectives. To analyse those tumours, which we propose may link ...

  15. [Aspirin and colorectal cancer].

    Science.gov (United States)

    Grancher, Adrien; Michel, Pierre; Di Fiore, Frédéric; Sefrioui, David

    2018-02-01

    Colorectal cancer is a worldwide public health problem. Aspirin has been identified as a protective factor against the apparition of colorectal cancer. There are several mechanisms about the actions by aspirin on colorectal tumorogenesis. These are not perfectly known nowadays. On one hand, there are direct mechanisms on colorectal mucosa, on the other hand there are indirect mechanisms through platelet functions. Aspirin also plays a role by its anti-inflammatory action and the stimulation of antitumor immunity. Several studies show that long-term treatment with low-doses of aspirin decreases the incidence of adenomas and colorectal cancers. In the United States, aspirin is currently recommended for primary prevention of the risk of colorectal cancer in all patients aged 50 to 59, with a 10-year risk of cardiovascular event greater than 10 %. However, primary prevention with aspirin should not be a substitute for screening in colorectal cancer. Furthermore, aspirin seems to be beneficial when used in post-diagnosis of colorectal cancer. It could actually decrease the risk of metastasis in case of a localized colorectal cancer, and increase the survival in particular, concerning PIK3CA mutated tumors. The association of aspirin with neoadjuvant treatment of colorectal cancer by radiochimiotherapy seems to have beneficial effects. French prospective randomized study is currently being conducted to investigate postoperative aspirin in colorectal cancers with a PIK3CA mutation. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  16. hereditary non-polyposis colorectal carcinoma (hnpcc)

    African Journals Online (AJOL)

    2011-08-08

    Aug 8, 2011 ... Construction of the family tree showed a very striking picture of colonic cancers in three generations. (Figure 1). Only the two youngest (twins) out of 8 siblings in the second generation had been spared from colon cancer. The ages of the siblings at diagnosis is shown in Table 2. Paraffin tissue blocks from ...

  17. Role of colonic microbiota in colorectal carcinogenesis: a systematic review

    Directory of Open Access Journals (Sweden)

    Marta Borges-Canha

    2015-11-01

    Full Text Available Background and aim: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile. Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. Methods: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. Results: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales, while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema. Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. Conclusion: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

  18. Cancer-associated stroma affects FDG uptake in experimental carcinomas. Implications for FDG-PET delineation of radiotherapy target

    Energy Technology Data Exchange (ETDEWEB)

    Farace, Paolo; Merigo, Flavia; Galie, Mirco; Sbarbati, Andrea; Marzola, Pasquina [University of Verona, Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, Verona (Italy); D' Ambrosio, Daniela; Nanni, Cristina; Spinelli, Antonello; Fanti, Stefano [Policlinico ' S. Orsola-Malpighi' , Department of Nuclear Medicine, Bologna (Italy); Degrassi, Anna [Nerviano Medical Sciences, Milan (Italy); Rubello, Domenico [' S. Maria della Misericordia' Hospital, PET Centre, Department of Nuclear Medicine, Rovigo (Italy)

    2009-04-15

    To analyse the influence of cancer-associated stroma on FDG-uptake in two carcinoma models characterized by different stromal degrees. Eight nude mice were subcutaneously injected with DU-145 prostate cancer cells or BXPC-3 pancreatic cancer cells, and underwent FDG-PET imaging about 2 weeks after implantation. After the mice were killed, histology, and CD31 and GLUT1 immunohistochemistry were performed. To further evaluate the highly stromalized carcinoma using perfusion-sensitive imaging, four BXPC-3 tumours underwent two successive albumin-binding (MS-325) MRI scans during tumour growth. FDG uptake was significantly higher in the DU-145 than in the BXPC-3 tumours, which were hardly distinguishable from adjacent normal tissue. In the BXPC-3 tumours, histology confirmed the widespread presence of aberrant infiltrated stroma, embedded with numerous vessels marked by CD31. In both tumour types, the stromal matrix was negative for GLUT1. In DU-145 tumour cells, GLUT1 immunostaining was greater than in BXPC-3 tumour cells, but not homogeneously, since it was less evident in the tumour cells which were nearer to vessels and stroma. Finally, MS-325 MRI always clearly showed areas of enhancement in the BXPC-3 tumours. Cancer-associated stroma has been reported to be capable of aerobic metabolism with low glucose consumption. Furthermore, it has been proposed that regions with high vascular perfusion exhibit a significantly lower FDG uptake, suggesting some vascular/metabolic reciprocity. Since our results are consistent with these recent findings, they signal a risk of tumour volume underestimation in radiotherapy if FDG uptake alone is used for target delineation of carcinomas, which suggests that additional evaluation should be performed using vasculature/perfusion-sensitive imaging. (orig.)

  19. Gastrins, iron and colorectal cancer.

    Science.gov (United States)

    Baldwin, Graham S

    2009-09-01

    This minireview explores the connections between circulating gastrins, iron status and colorectal cancer. The peptide hormone gastrin is a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. Gastrins bind two ferric ions with μM affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity. The ferric ion ligands have been identified as glutamates 7, 8 and 9 in the 18 amino acid peptide glycine-extended gastrin. An interaction between gastrin and transferrin was first demonstrated by covalent crosslinking techniques, and has been recently confirmed by surface plasmon resonance. We have therefore proposed that gastrins act as catalysts in the loading of transferrin with iron. Several recent lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease haemochromatosis, and that transferrin saturation positively correlates with circulating gastrin concentrations, suggest that gastrins may be involved in iron homeostasis. In addition the recognition that ferric ions may play an unexpected role in the biological activity of non-amidated gastrins may assist in the development of new therapies for colorectal carcinoma.

  20. Inflammatory bowel disease and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Andreja Ocepek

    2006-12-01

    Full Text Available Background: Colorectal cancer is one of the most frequent cancers in developed countries and Slovenia, and the incidence is still rising. Groups of people with higher risk for colorectal cancer are well defined. Among them are patients with inflammatory bowel disease. The risk is highest in patients in whom whole large bowel is affected by inflammation, it rises after 8 to 10 years and increases with the duration of the disease. Precancerous lesion is a displastic, chronically inflammed mucosa and not an adenoma as in cases of sporadic colorectal carcinoma.Conclusions: Many studies suggest that the influence of genetic factors differs between sporadic and inflammatory bowel disease related colorectal cancer. Symptomatic patients at the time of diagnosis have a much worse prognosis. The goal of prevention programes is therefore discovering early precancerous lesions. Established screening protocols are based on relatively frequent colonoscopies which are inconvinient for the patient as well as the endoscopist. Use of specific genetic markers, mutations of candidate genes, as a screening method and a prognostic predictor could greatly lighten therapeutic decisions.

  1. Combined anti-angiogenic therapy targeting PDGF and VEGF receptors lowers the interstitial fluid pressure in a murine experimental carcinoma.

    Directory of Open Access Journals (Sweden)

    Agnieszka Kłosowska-Wardega

    Full Text Available Elevation of the interstitial fluid pressure (IFP of carcinoma is an obstacle in treatment of tumors by chemotherapy and correlates with poor drug uptake. Previous studies have shown that treatment with inhibitors of platelet-derived growth factor (PDGF or vascular endothelial growth factor (VEGF signaling lowers the IFP of tumors and improve chemotherapy. In this study, we investigated whether the combination of PDGFR and VEGFR inhibitors could further reduce the IFP of KAT-4 human carcinoma tumors. The tumor IFP was measured using the wick-in-needle technique. The combination of STI571 and PTK/ZK gave an additive effect on the lowering of the IFP of KAT-4 tumors, but the timing of the treatment was crucial. The lowering of IFP following combination therapy was accompanied by vascular remodeling and decreased vascular leakiness. The effects of the inhibitors on the therapeutic efficiency of Taxol were investigated. Whereas the anti-PDGF and anti-VEGF treatment did not significantly inhibit tumor growth, the inhibitors enhanced the effect of chemotherapy. Despite having an additive effect in decreasing tumor IFP, the combination therapy did not further enhance the effect of chemotherapy. Simultaneous targeting of VEGFR and PDGFR kinase activity may be a useful strategy to decrease tumor IFP, but the timing of the inhibitors should be carefully determined.

  2. New core-shell nanoparticules for the intravenous delivery of siRNA to experimental thyroid papillary carcinoma.

    Science.gov (United States)

    de Martimprey, Henri; Bertrand, Jean-Rémi; Malvy, Claude; Couvreur, Patrick; Vauthier, Christine

    2010-03-01

    Development of efficient in vivo delivery nanodevices remains a major challenge to achieve clinical application of siRNA. The present study refers to the conception of core-shell nanoparticles aiming to make possible intravenous administration of chemically unmodified siRNA oriented towards the junction oncogene of the papillary thyroid carcinoma. Nanoparticles were prepared by redox radical emulsion polymerization of isobutylcyanoacrylate and isohexylcyanoacrylate with chitosan. The loading of the nanoparticles with siRNA was achieved by adsorption. The biological activity of the siRNA-loaded nanoparticles was assessed on mice bearing a papillary thyroid carcinoma after intratumoral and intravenous administration. Chitosan-coated nanoparticles with a diameter of 60 nm were obtained by adding 3% pluronic in the preparation medium. siRNA were associated with the nanoparticles by surface adsorption. In vivo, the antisense siRNA associated with the nanoparticles lead to a strong antitumoral activity. The tumor growth was almost stopped after intravenous injection of the antisense siRNA-loaded nanoparticles, while in all control experiments, the tumor size was increased by at least 10 times. This work showed that poly(alkylcyanoacrylate) nanoparticles coated with chitosan are suitable carriers to achieve in vivo delivery of active siRNA to tumor including after systemic administration.

  3. A novel transcript, VNN1-AB, as a biomarker for colorectal cancer.

    Science.gov (United States)

    Løvf, Marthe; Nome, Torfinn; Bruun, Jarle; Eknaes, Mette; Bakken, Anne C; Mpindi, John P; Kilpinen, Sami; Rognum, Torleiv O; Nesbakken, Arild; Kallioniemi, Olli; Lothe, Ragnhild A; Skotheim, Rolf I

    2014-11-01

    Colorectal cancer is a global health challenge with high incidence rate and mortality. The patients' prognosis is strongly associated with disease stage and currently there is a need for improved prognostic and predictive biomarkers. In this study, novel colorectal cancer-specific transcript structures were nominated from whole transcriptome sequencing of seven colorectal cancer cell lines, two primary colorectal carcinomas with corresponding normal colonic mucosa and 16 normal tissues. The nominated transcripts were combined with gene level outlier expression analyses in a cohort of 505 colorectal cancers to identify biomarkers with capacity to stratify colorectal cancer subgroups. The transcriptome sequencing data and outlier expression analysis revealed 11 novel colorectal cancer-specific exon-exon junctions, of which 3 were located in the gene VNN1. The junctions within VNN1 were further characterized using rapid amplification of cDNA ends (RACE) and the prevalence of the subsequently characterized novel transcript, VNN1-AB, was investigated by real-time RT-PCR in 291 samples of miscellaneous origins. VNN1-AB was not present in any of the 43 normal colorectal tissue samples investigated, but in 5 of the 6 polyps, and 102 of the 136 (75%) colorectal cancers. We have identified a novel transcript of the VNN1 gene, with an organ-confined complete specificity for colorectal neoplasia. © 2014 UICC.

  4. Early detections of cancer in family practice – a case of colorectal cancer

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    Ksenija Tušek-Bunc

    2007-12-01

    Full Text Available Background: Malignant diseases present a serious public health problem in the world as well in Slovenia. In the last years, colon and rectum are (with the exception of skin the most common cancer sites in the developed world, including Slovenia. Colorectal carcinoma is the most frequent cancer of the gastrointestinal tract occurring in Slovenia and it is second leading cause of mortality due to malignancies. The incidence of colorectal carcinoma is rising in the past few years. In spite of better five-year survival rates in patients with the disease, there are many patients diagnosed in advanced stages with worse prognosis.Conclusions: Early detection of colorectal carcinoma in Slovenia has not been introduced in a systematic way yet. There is no doubt that screening is feasible in family practice. Family doctors have a unique role in preventing, early detection and screening of colorectal carcinoma. Guidelines for management of predisposing factors, for early detection of the disease and for healthier life style are an important tool in the hands of family doctors with the aim to reduce morbidity and mortality due to colorectal carcinoma.

  5. Epigenetics and Colorectal Cancer

    Science.gov (United States)

    Lao, Victoria Valinluck; Grady, William M.

    2012-01-01

    Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer. PMID:22009203

  6. Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  7. DCE-MRI using small-molecular and albumin-binding contrast agents in experimental carcinomas with different stromal content

    Energy Technology Data Exchange (ETDEWEB)

    Farace, Paolo; Merigo, Flavia; Fiorini, Silvia; Nicolato, Elena; Tambalo, Stefano; Daducci, Alessandro [Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona (Italy); Degrassi, Anna [Nerviano Medical Sciences Institute, Milan (Italy); Sbarbati, Andrea [Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona (Italy); Rubello, Domenico, E-mail: domenico.rubello@libero.it [Department of Radiology, Nuclear Medicine, Medical Physics, Services of Radiology and Nuclear Medicine, ' S. Maria della Misericordia' Hospital, Viale Tre Martiri 140, 45100 Rovigo (Italy); Marzola, Pasquina [Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona (Italy)

    2011-04-15

    Objectives: To compare DCE-MRI experiments performed using a standard small-molecular (Gd-DTPA) and an albumin-binding (MS-325) contrast agent in two carcinoma models with different stromal content. Materials and methods: DU-145 or BXPC-3 cancer cells were subcutaneously injected into nude mice. DCE-MRI was performed by a bolus injection of Gd-DTPA or MS-325 about 2 weeks after inoculation. For quantitative analysis a volume of interest was manually drawn over each tumor. To address the heterogeneous enhancement, each tumor volume was then divided into the 20% most-enhancing and the remaining 80% least-enhancing fractions. Mean tumor enhancement was calculated over these selected tumor volumes and compared between tumor groups and contrast agents. Maps of differential enhancement, peak enhancement and time-to-peak were used for visual evaluation. CD31 and VEGF immunohistochemistry were performed in excised tumors. Results: In the 80% least-enhancing volume, at late time points of the dynamic scan, the mean enhancement elicited by MS-325 was higher in BXPC-3 than in DU-145 tumors. In the 20% most-enhancing volume, using either contrast agents, significant difference between the two tumors types were observed only early, while at later time points of the dynamic scan the difference were obscured by the faster washout observed in the BXPC-3 tumors. Enhancement maps confirmed that BXPC-3 tumors were characterized by marked washout rate using either contrast agent, particularly in the higher enhancing peripheral rim. With MS-325 this washout pattern appeared to be specific to the BXPC-3 carcinomas, since it was not observed in the DU-145 tumors. Finally, in both tumor types, MS-325 produced significantly higher enhancement than Gd-DTPA in the late phase of the dynamic scan. Ex vivo analysis confirmed the marked presence of aberrant infiltrative stroma in BXPC-3 tumors, in which tumor vessels were embedded. In all tumors the central portion was less viable and less

  8. Promoter Methylation Precedes Chromosomal Alterations in Colorectal Cancer Development

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    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.

  9. The Russian drug glyciphon, a representative of organophosphorus epoxides, for the treatment of basal cell carcinoma – clinical and experimental studies

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    L. N. Zalyalyutdinova

    2015-01-01

    Full Text Available The review deals with the results of clinical and experimental studies of the original Russian drug glyciphon used to treat basal cell carcinoma (BCC. Glyciphon is diglycidyl ether of methylphosphonic acid, which has been synthesized at the A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences, belongs to a class of organophosphors epoxides. The drug has been experimentally tested by Kazan scientists who revealed the selectivity of its antiblastoma activity, relatively low toxicity, and high safety when it was used long. The antiproliferatve activity of glyciphon in inhibiting DNA synthesis, retarding all mitotic phases, and blocking the entry of cells into S and M phases plays an important role in its mechanism of antiblastoma action. Glyciphon ointment 30 % is effective in the treatment of primary BCC (solitary tumors and polyneoplasms and its recurrences after radiation and surgery in the absence of a side skin resorption effect. It may be successfully used to treat BCC that are refractory to radiotherapy and surgical dissection and to detect latent foci of multiple BCC. The ointment is registered as an agent for the treatment of Stage I squamous cell carcinoma, as well as basaliomas (including recurrences after surgery and radiotherapy, Bowen,s disease, senile keratosis. Glyciphon is manufactured by OAO “Tatchempharmpreparaty” (Kazan (as 30 % ointment from the substance made by the affiliate of the A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences.

  10. Modeling high-grade serous carcinoma: how converging insights into pathogenesis and genetics are driving better experimental platforms

    Directory of Open Access Journals (Sweden)

    Paul Michael Jones

    2013-08-01

    Full Text Available Recent developments in the study of epithelial ovarian cancer have called into question the traditional views regarding the site of tumor initiation. Histopathologic studies and genomic analyses suggest that extra-ovarian sites, like the fallopian tube, may harbor the coveted cell of origin and could therefore contribute significantly to the development of high-grade serous ovarian carcinoma (HG-SOC. Our ability to validate these emerging genomic and pathologic observations and characterize the early transformation events of HG-SOC hinges on the development of novel model systems. Currently, there are only a handful of new model systems that are addressing these concerns. This review will chronicle the convergent evolution of these ovarian cancer model systems in the context of the changing pathologic and genomic understanding of HG-SOC.

  11. Modeling High-Grade Serous Carcinoma: How Converging Insights into Pathogenesis and Genetics are Driving Better Experimental Platforms

    Science.gov (United States)

    Jones, Paul Michael; Drapkin, Ronny

    2013-01-01

    Recent developments in the study of epithelial ovarian cancer have called into question the traditional views regarding the site of tumor initiation. Histopathologic studies and genomic analyses suggest that extra-ovarian sites, like the fallopian tube, may harbor the coveted cell of origin and could therefore contribute significantly to the development of high-grade serous ovarian carcinoma (HG-SOC). Our ability to validate these emerging genomic and pathologic observations and characterize the early transformation events of HG-SOC hinges on the development of novel model systems. Currently, there are only a handful of new model systems that are addressing these concerns. This review will chronicle the convergent evolution of these ovarian cancer model systems in the context of the changing pathologic and genomic understanding of HG-SOC. PMID:23986883

  12. LICC: L-BLP25 in patients with colorectal carcinoma after curative resection of hepatic metastases--a randomized, placebo-controlled, multicenter, multinational, double-blinded phase II trial

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    Schimanski Carl

    2012-04-01

    Full Text Available Abstract Background 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC. Methods/Design This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 μg once weekly for 8 weeks, followed by s.c. L-BLP25 930 μg maintenance doses at 6-week (years 1&2 and 12-week (year 3 intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS time between groups. Secondary endpoints are overall survival (OS time, safety, tolerability, RFS/OS in MUC-1 positive

  13. Antitumor magnetic hyperthermia induced by RGD-functionalized Fe3O4 nanoparticles, in an experimental model of colorectal liver metastases

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    Oihane K. Arriortua

    2016-10-01

    Full Text Available This work reports important advances in the study of magnetic nanoparticles (MNPs related to their application in different research fields such as magnetic hyperthermia. Nanotherapy based on targeted nanoparticles could become an attractive alternative to conventional oncologic treatments as it allows a local heating in tumoral surroundings without damage to healthy tissue. RGD-peptide-conjugated MNPs have been designed to specifically target αVβ3 receptor-expressing cancer cells, being bound the RGD peptides by “click chemistry” due to its selectivity and applicability. The thermal decomposition of iron metallo-organic precursors yield homogeneous Fe3O4 nanoparticles that have been properly functionalized with RGD peptides, and the preparation of magnetic fluids has been achieved. The nanoparticles were characterized by transmission electron microscopy (TEM, vibrating sample magnetometry (VSM, electron magnetic resonance (EMR spectroscopy and magnetic hyperthermia. The nanoparticles present superparamagnetic behavior with very high magnetization values, which yield hyperthermia values above 500 W/g for magnetic fluids. These fluids have been administrated to rats, but instead of injecting MNP fluid directly into liver tumors, intravascular administration of MNPs in animals with induced colorectal tumors has been performed. Afterwards the animals were exposed to an alternating magnetic field in order to achieve hyperthermia. The evolution of an in vivo model has been described, resulting in a significant reduction in tumor viability.

  14. Diagnosing lynch syndrome in absence of colorectal cancer.

    Science.gov (United States)

    Lynch, Henry T; Knezetic, Joseph; Lanspa, Stephen

    2012-11-01

    There are many ways in which a diagnosis of Lynch syndrome can be made, most prominent of which is family history, presence of cancer, high microsatellite instability, immunohistochemistry, and a mismatch repair germline mutation. There are at least four molecular pathways for colorectal cancer carcinogenesis: 1) adenoma-carcinoma sequence; 2) hereditary microsatellite instability; 3) serrated pathway; 4) epidermal growth factor receptor. The answer to diagnosing Lynch syndrome in the absence of colorectal cancer may be partially based upon the phenotypic characteristics of the colonic polyps should they be identified at colonoscopy, specifically their phenotypic characteristics of location, size, histology, number, and age of polyp onset.

  15. Synchronous colorectal liver metastases

    NARCIS (Netherlands)

    A.E.M. van der Pool (Anne)

    2011-01-01

    textabstractColorectal cancer is one of the most common malignancies worldwide and ranks second in cancer-related deaths in many parts of the Western world. Once in the lymph or blood vessels, colorectal cancer can quickly spread and the liver is known to be a favourable site for metastases. The

  16. Can colorectal cancer mass-screening organization be evidence-based? Lessons from failures: The experimental and pilot phases of the Lazio program

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    Valle Sabrina

    2008-09-01

    Full Text Available Abstract Background Screening programmes should be organized to translate theoretical efficacy into effectiveness. An evidence-based organizational model of colorectal cancer screening (CRCS should assure feasibility and high compliance. Methods A multidisciplinary Working Group (WG, reviewed literature and guidelines to define evidence-based recommendations. The WG identified the need for further local studies: physicians' CRCS attitudes, the effect of test type and provider on compliance, and individual reasons for non-compliance. A survey of digestive endoscopy services was conducted. A feasibility study on a target population of 300.000 has begun. Results Based on the results of population trials and on literature review the screening strategy adopted was Faecal Occult Blood Test (FOBT every two years for 50–74 year olds and, for positives, colonoscopy. The immunochemical test was chosen because it has 20% higher compliance than the Guaiac. GPs were chosen as the preferred provider also for higher compliance. Since we observed that distance is the major determinant of non-compliance, we choose GPs because they are the closest providers, both geographically and emotionally, to the public. The feasibility study showed several barriers: GP participation was low, there were administrative problems to involve GPs; opportunistic testing by the GPs; difficulties in access to Gastroenterology centres; difficulties in gathering colonoscopy results; little time given to screening activity by the gastroenterology centre. Conclusion The feasibility study highlighted several limits of the model. Most of the barriers that emerged were consequences of organisational choices not supported by evidence. The principal limit was a lack of accountability by the participating centres.

  17. Potential Antioxidant Role of Tridham in Managing Oxidative Stress against Aflatoxin-B(1)-Induced Experimental Hepatocellular Carcinoma.

    Science.gov (United States)

    Ravinayagam, Vijaya; Jaganathan, Ravindran; Panchanadham, Sachdanandam; Palanivelu, Shanthi

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most fatal cancers due to delayed diagnosis and lack of effective treatment options. Significant exposure to Aflatoxin B(1) (AFB(1)), a potent hepatotoxic and hepatocarcinogenic mycotoxin, plays a major role in liver carcinogenesis through oxidative tissue damage and p53 mutation. The present study emphasizes the anticarcinogenic effect of Tridham (TD), a polyherbal traditional medicine, on AFB(1)-induced HCC in male Wistar rats. AFB(1)-administered HCC-bearing rats (Group II) showed increased levels of lipid peroxides (LPOs), thiobarbituric acid substances (TBARs), and protein carbonyls (PCOs) and decreased levels of enzymic and nonenzymic antioxidants when compared to control animals (Group I). Administration of TD orally (300 mg/kg body weight/day) for 45 days to HCC-bearing animals (Group III) significantly reduced the tissue damage accompanied by restoration of the levels of antioxidants. Histological observation confirmed the induction of tumour in Group II animals and complete regression of tumour in Group III animals. This study highlights the potent antioxidant properties of TD which contribute to its therapeutic effect in AFB(1)-induced HCC in rats.

  18. Potential Antioxidant Role of Tridham in Managing Oxidative Stress against Aflatoxin-B1-Induced Experimental Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Vijaya Ravinayagam

    2012-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most fatal cancers due to delayed diagnosis and lack of effective treatment options. Significant exposure to Aflatoxin B1 (AFB1, a potent hepatotoxic and hepatocarcinogenic mycotoxin, plays a major role in liver carcinogenesis through oxidative tissue damage and p53 mutation. The present study emphasizes the anticarcinogenic effect of Tridham (TD, a polyherbal traditional medicine, on AFB1-induced HCC in male Wistar rats. AFB1-administered HCC-bearing rats (Group II showed increased levels of lipid peroxides (LPOs, thiobarbituric acid substances (TBARs, and protein carbonyls (PCOs and decreased levels of enzymic and nonenzymic antioxidants when compared to control animals (Group I. Administration of TD orally (300 mg/kg body weight/day for 45 days to HCC-bearing animals (Group III significantly reduced the tissue damage accompanied by restoration of the levels of antioxidants. Histological observation confirmed the induction of tumour in Group II animals and complete regression of tumour in Group III animals. This study highlights the potent antioxidant properties of TD which contribute to its therapeutic effect in AFB1-induced HCC in rats.

  19. Sorafenib modulates the gene expression of multi-drug resistance mediating ATP-binding cassette proteins in experimental hepatocellular carcinoma.

    Science.gov (United States)

    Hoffmann, Katrin; Franz, Clemens; Xiao, Zhi; Mohr, Elvira; Serba, Susanne; Büchler, Markus W; Schemmer, Peter

    2010-11-01

    High ATP-binding cassette (ABC) protein expression leads to intrinsic drug resistance of hepatocellular carcinoma (HCC). The aim of this study was to investigate the potential chemosensitizing effects of sorafenib on the multi-drug resistance (MDR) phenotype. The ABC-protein gene expression and the cellular survival were determined by RT-PCR analysis and MTT assay in HUH7 cells. Sorafenib inhibits MDR. The ABC-protein mRNA expression decreased by up to 51% (p ≤ 0.01). Addition of sorafenib to conventional chemotherapy restored the chemosensitivity. Combination of gemcitabine plus sorafenib decreased the ABC-protein mRNA levels by up to 77%, compared to gemcitabine monotherapy (p ≤ 0.001). Doxorubicin plus sorafenib decreased the ABC-protein mRNA levels up to 74% compared to doxorubicin monotherapy (p ≤ 0.001). This study provides evidence that the MDR phenotype of HCC cells can be modulated by the multi-kinase inhibitor sorafenib and consequentially may lead towards personalized therapies in patients with highly resistant tumors.

  20. Protective effects of mastic oil from Pistacia lentiscus variation chia against experimental growth of lewis lung carcinoma.

    Science.gov (United States)

    Magkouta, Sophia; Stathopoulos, Georgios T; Psallidas, Ioannis; Papapetropoulos, Andreas; Kolisis, Fragiskos N; Roussos, Charis; Loutrari, Heleni

    2009-01-01

    Mastic oil from Pistacia lentiscus variation chia, a traditionally used dietary flavoring agent with medicinal properties, has been shown to exert in vitro antitumor activities, but no study has addressed in vivo efficacy and mechanisms of action. Presently, we demonstrated that treatment of immunocompetent mice with mastic oil (45 mg/kg body weight, intraperitoneally, 3 times a wk for approximately 3 wk) significantly inhibited tumor growth (56.4% +/- 5.7 maximum reduction in tumor volumes) without toxicity. Analysis of tumors by immunohistochemistry and ELISA indicated that this effect is associated with increased apoptosis, reduced neovascularization, and inhibition of chemokine expression. Likewise mastic oil reduced vascular endothelial growth factor and chemokine release by Lewis lung carcinoma (LLC) cells. Furthermore, mastic oil administration decreased small guanosine triphosphatases (GTPases) Ras, RhoA and nuclear factor-kappa-B-dependent reporter gene expression in vivo and in vitro, indicating a mechanistic link between mastic oil activities and blocking of relevant signaling and transcription pathways. A dose-response comparison with perillyl alcohol and alpha-pinene, two of its components, revealed a higher efficacy of mastic oil, pointing to a beneficial collective interaction among its ingredients. Conclusively, our results provide novel in vivo evidence of mastic oil inhibitory effects on tumor growth and set a rational basis for its future application in cancer prevention.

  1. Effect of New Water-Soluble Dendritic Phthalocyanines on Human Colorectal and Liver Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ebru YABAŞ

    2017-08-01

    Full Text Available Human hepatocellular carcinoma (HepG2 cells and colorectal adenocarcinoma (DLD-1 cells were treated with the synthesized water soluble phthalocyanine derivatives to understand the effect of the compounds both on colorectal and liver cancer cells. The compounds inhibited cell proliferation and displayed cytotoxic effect on these cancer cell lines however; the effect of the compounds on healthy control fibroblast cell line was comparatively lower. The compounds can be employed for cancer treatment as anticancer agents.

  2. Evolução do carcinoma colorretal, comparando doentes com idades acima e abaixo de 40 anos, quanto à diferenciação tumoral e ao estádio do tumor Colorectal cancer evolution, comparing patients yourger and older than 40 years old, according to tumoral differentiation and tumor stage

    Directory of Open Access Journals (Sweden)

    Luis Roberto Manzione Nadal

    2009-09-01

    Full Text Available OBJETIVO: A incidência elevada do carcinoma colorretal o torna problema de saúde pública no nosso país. Os poucos trabalhos na literatura, bem como as dúvidas relacionando a idade com a evolução da doença, estimularam-nos a realizar esse trabalho para conhecer as divergências quanto à diferenciação tumoral e o estádio na evolução dessa neoplasia, comparando doentes com idades acima e abaixo de 40 anos. MÉTODO: Comparar 205 doentes de adenocarcinoma colorretal com idades acima e abaixo de 40 anos quanto ao tempo de sintomas, história familiar, localização do tumor, estádio do tumor, diferenciação, morte operatória, local de metástases e mortalidade até 3 anos. RESULTADOS: Eram 20 no grupo mais jovem e 185 entre os mais idosos. Não houve diferença em relação ao sexo, ao tempo de início de sintomas, à história familiar, ao local de tumor no cólon, ao estádio, ao aparecimento de recidivas, à mortalidade operatória e à sobrevivência até o terceiro ano pós-operatório. No grupo mais jovem os tumores foram mais indiferenciados e as metástases abdominais predominaram. No grupo mais velho houve maior incidência de metástases hepáticas e pulmonares. CONCLUSÃO: Os resultados obtidos nas condições de execução do presente estudo, em que comparamos doentes portadores de adenocarcinoma colorretal com idades acima e abaixo de 40 anos, permitiram concluir que os tumores foram mais indiferenciados entre os mais jovens embora a evolução pós-tratamento tenha sido semelhante.OBJECTIVE: High incidence of colorectal carcinoma turns it into a public health problem in our country. A few articles, as well as some doubts about patients age and disease evolution, made us study these features to know about tumor cells differentiation and tumor staging in the post-operative follow-up, comparing patients younger and older than 40 years old. METHOD: Comparison of 205 colorectal carcinoma patients younger and older than 40

  3. Medullary carcinoma of the colon

    DEFF Research Database (Denmark)

    Fiehn, Anne-Marie Kanstrup; Grauslund, Morten; Glenthøj, Anders

    2015-01-01

    Medullary carcinoma of the colon is a rare variant of colorectal cancer claimed to have a more favorable prognosis than conventional adenocarcinomas. The histopathologic appearance may be difficult to distinguish from poorly differentiated adenocarcinoma. The study aimed to evaluate the diagnostic...... interobserver agreement and to characterize the immunohistochemical and molecular differences between these two subgroups. Fifteen cases initially classified as medullary carcinoma and 30 cases of poorly differentiated adenocarcinomas were included. Two pathologists reviewed the slides independently without...... differences in CK20 (p = 0.005) expression and in the rate of BRAF mutations (p = 0.0035). In conclusion, medullary carcinomas of the colon are difficult to discriminate from poorly differentiated adenocarcinoma even with the help of immunohistochemical and molecular analyses. This raises the question whether...

  4. The role of selected matrix metalloproteinases and their inhibitors in colorectal cancer developme

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    Magdalena Groblewska

    2010-01-01

    Full Text Available Colorectal cancer is one of the most common malignant tumors of the gastrointestinal tract. The development of this tumor is a complex, long-term, and multi-step process, from small dysplastic lesions of normal colorectal mucosa, through adenomatous polyps, to carcinoma in situ. Matrix metalloproteinases (MMPs and their tissue inhibitors (TIMPs play an important role in colorectal carcinogenesis. MMP-9 is able to degrade collagen IV from basement membranes and extracellular matrix, which is associated with tumor progression, including invasion, metastasis, growth, migration, and angiogenesis. It was demonstrated that increased expression of MMP-9 plays a crucial role in the development of several human malignancies, including colorectal cancer. Increased expression of MMP-9 correlated with tumor stage, invasiveness, and poor survival of colorectal cancer patients.

  5. COL11A1 in FAP polyps and in sporadic colorectal tumors

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    Iselius Lennart

    2001-10-01

    Full Text Available Abstract Background We previously reported that the α-1 chain of type 11 collagen (COL11A1, not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of β-catenin. Methods We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/β-catenin pathway. Results In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/β-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. Conclusions Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/β-catenin pathway in FAP and sporadic colorectal cancer.

  6. Instability of a dinucleotide repeat in the 3'-untranslated region (UTR) of the microsomal prostaglandin E synthase-1 (mPGES-1) gene in microsatellite instability-high (MSI-H) colorectal carcinoma.

    Science.gov (United States)

    Cherukuri, Durga Prasad; Deignan, Joshua L; Das, Kingshuk; Grody, Wayne W; Herschman, Harvey

    2015-08-01

    DNA mismatch-repair gene mutations, with consequent loss of functional protein expression, result in microsatellite instability (MSI). Microsatellite sequences are found in coding regions and in regulatory regions of genes (i.e., 5'-UTRs and 3'-UTRs). In addition to being a surrogate marker of defective mismatch repair, deletion or insertion microsatellite sequences can dysregulate gene expression in MSI-H (microsatellite instability-high) tumors. The microsomal prostaglandin E synthase-1 (mPGES-1) gene product, mPGES-1, participates in prostaglandin E2 (PGE2) production. Moreover, mPGES-1 is often overexpressed in human colorectal tumors, and is thought to contribute to progression of these tumors. Here we identified a dinucleotide repeat, (GT)24, in the mPGES-1 gene 3' untranslated region (3'-UTR), and analyzed its mutation frequencies in MSI-H and microsatellite stable (MSS) tumors. The (GT)24 repeat exhibited instability in all MSI-H tumors examined (14), but not in any of the MSS tumors (13). In most cases, (GT)24 repeat instability resulted in insertion of additional GT units. We also determined mPGES-1 mRNA levels in MSI-H and MSS colorectal cancer cell lines. Three of four previously designated "MSI-H" cell lines showed higher mPGES-1 mRNA levels compared to MSS cell lines; correlations between elevated mPGES-1 mRNA levels and microsatellite (GT)24 repeat characteristics are present for all six cell lines. Our results demonstrate that mPGES-1 is a target gene of defective mismatch repair in human colorectal cancer, with functional consequence. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  7. Modulatory effect of Pleurotus ostreatus on oxidant/antioxidant status in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats--A dose-response study.

    Science.gov (United States)

    Krishnamoorthy, Deepalakshmi; Sankaran, Mirunalini

    2016-01-01

    Worldwide, breast cancer is the second most prevalent cancer among women and its incidence is increasing alarmingly. To determine a dose-response effect of Pleurotus ostreatus on oxidant/antioxidant status in 7,12-dimethylbenz. (a) antheracene induced. (DMBA) mammary carcinoma in experimental rats. Cancer bearing female Sprague Dawley rats were orally treated with Pleurotus ostreatus ethanolic extract (POEet) (150, 300 and 600 mg/kg body weight) for 16 weeks. By means of high performance liquid chromatography (HPLC) analysis, ergosterol (48.82%) were identified and quantified in POEet. Body weight of experimental rats in each groups and the biochemical parameters of plasma, liver and mammary tissues were carried out. Histopathological analyses were also determined. Results were analyzed using SPSS software package, version 16.0. The values were analyzed by one way analysis of variance (ANOVA) followed by Duncan's multiple range test (DMRT). The result showed that depleted activities of enzymatic and non-enzymatic antioxidant level and significant elevated TBARS level were observed in DMBA group of plasma, mammary and liver tissues of experimental rats. The effects were dose.dependent and the above noted parameters were renovated to near normal after supplementation with different dose of POEet (150 mg, 300 mg and 600 mg/kg bwt). The data obtained from the study indicate that POEet at a dose of 600 mg/kg bwt possesses optimum anticancer effects against DMBA induced mammary carcinogenesis. Based on the scientific appraisal, we conclude that the POEet is having a potent antioxidant capacity; thereby it offers maximum protection against DMBA-induced mammary carcinogenesis.

  8. [Detection of T-antigen in colorectal adenocarcinoma and polyps].

    Science.gov (United States)

    Xu, S; Lu, Y; Wang, Q

    1995-10-01

    Galactose oxidase method was employed to detect the beta-D-Gal (1-->3) -D-Gal NAc residue of T-antigen present in the large intestinal mucus of 156 subjects. The positive rates of the test were 84.4%, 29.1%, and 7.2% in the mucus samples obtained from 32 patients with colorectal adenocarcinomas, 55 with polyps and 69 controls respectively. Chi-square test demonstrated that there were significant differences between the group of carcinoma and control (P < 0.001) as well as between also polyp and control (P < 0.01). The test had a high sensitivity (84.4%) and specificity (92.8%) in the diagnosis of colorectal cancer and may be used as a practical mass screening test for colorectal neoplasms.

  9. Detection of colorectal neoplasia

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Christensen, Ib J.; Rasmussen, Louise

    2017-01-01

    Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA...... value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC....

  10. Antagonists of growth hormone-releasing hormone inhibit the proliferation of experimental non-small cell lung carcinoma.

    Science.gov (United States)

    Szereday, Zoltan; Schally, Andrew V; Varga, Jozsef L; Kanashiro, Celia A; Hebert, Francine; Armatis, Patricia; Groot, Kate; Szepeshazi, Karoly; Halmos, Gabor; Busto, Rebeca

    2003-11-15

    Recent studies show that antagonists of growth hormone-releasing hormone (GH-RH) inhibit proliferation of various cancers indirectly through blockage of the endocrine GH-insulin-like growth factor (IGF) I axis and directly by an action on tumor cells involving the suppression of autocrine/paracrine IGF-I, IGF-II, or GH-RH. The effectiveness of therapy with GH-RH antagonist JV-1-38 and its mechanisms of action were investigated in NCI-H838 non-small cell lung carcinoma (NSCLC) xenografted s.c. into nude mice and in vitro. Treatment with GH-RH antagonist JV-1-38 significantly (P < 0.05-0.001) inhibited tumor growth as demonstrated by a 58% decrease in final tumor volume, 54% reduction in tumor weight, and the extension of tumor-doubling time from 8.5 +/- 1.38 to 12 +/- 1.07 days as compared with controls. Using ligand competition assays with (125)I-labeled GH-RH antagonist JV-1-42, specific high-affinity binding sites for GH-RH were found on tumor membranes. Reverse transcription-PCR revealed the expression of mRNA for GH-RH and splice variant 1 (SV(1)) of GH-RH receptor in H838 tumors. Reverse transcription-PCR analysis also demonstrated that H838 tumors express IGF-I and IGF-I receptors. Tumoral concentration of IGF-I and its mRNA expression were significantly decreased by 25% (P = 0.05) and 65% (P < 0.001), respectively, in animals receiving JV-1-38, whereas serum IGF-I levels remained unchanged. In vitro studies showed that H838 cells secreted GH-RH and IGF-I into the medium. The growth of tumor cells in vitro was stimulated by IGF-I and inhibited by GH-RH antagonist JV-1-38 and a GH-RH antiserum. Our results extend the findings on the involvement of IGF-I in NSCLC and suggest that GH-RH may be an autocrine growth factor for H838 NSCLC. The antitumorigenic action of GH-RH antagonists could be partly direct and mediated by SV(1) of tumoral GH-RH receptors. The finding of GH-RH and SV(1) of GH-RH receptors in NSCLC provides a new approach to the treatment of this

  11. Classifications of multispectral colorectal cancer tissues using convolution neural network

    Directory of Open Access Journals (Sweden)

    Hawraa Haj-Hassan

    2017-01-01

    Full Text Available Background: Colorectal cancer (CRC is the third most common cancer among men and women. Its diagnosis in early stages, typically done through the analysis of colon biopsy images, can greatly improve the chances of a successful treatment. This paper proposes to use convolution neural networks (CNNs to predict three tissue types related to the progression of CRC: benign hyperplasia (BH, intraepithelial neoplasia (IN, and carcinoma (Ca. Methods: Multispectral biopsy images of thirty CRC patients were retrospectively analyzed. Images of tissue samples were divided into three groups, based on their type (10 BH, 10 IN, and 10 Ca. An active contour model was used to segment image regions containing pathological tissues. Tissue samples were classified using a CNN containing convolution, max-pooling, and fully-connected layers. Available tissue samples were split into a training set, for learning the CNN parameters, and test set, for evaluating its performance. Results: An accuracy of 99.17% was obtained from segmented image regions, outperforming existing approaches based on traditional feature extraction, and classification techniques. Conclusions: Experimental results demonstrate the effectiveness of CNN for the classification of CRC tissue types, in particular when using presegmented regions of interest.

  12. Colorectal cancer screening with virtual colonoscopy

    Science.gov (United States)

    Ge, Yaorong; Vining, David J.; Ahn, David K.; Stelts, David R.

    1999-05-01

    Early detection and removal of colorectal polyps have been proven to reduce mortality from colorectal carcinoma (CRC), the second leading cause of cancer deaths in the United States. Unfortunately, traditional techniques for CRC examination (i.e., barium enema, sigmoidoscopy, and colonoscopy) are unsuitable for mass screening because of either low accuracy or poor public acceptance, costs, and risks. Virtual colonoscopy (VC) is a minimally invasive alternative that is based on tomographic scanning of the colon. After a patient's bowel is optimally cleansed and distended with gas, a fast tomographic scan, typically helical computed tomography (CT), of the abdomen is performed during a single breath-hold acquisition. Two-dimensional (2D) slices and three-dimensional (3D) rendered views of the colon lumen generated from the tomographic data are then examined for colorectal polyps. Recent clinical studies conducted at several institutions including ours have shown great potential for this technology to be an effective CRC screening tool. In this paper, we describe new methods to improve bowel preparation, colon lumen visualization, colon segmentation, and polyp detection. Our initial results show that VC with the new bowel preparation and imaging protocol is capable of achieving accuracy comparable to conventional colonoscopy and our new algorithms for image analysis contribute to increased accuracy and efficiency in VC examinations.

  13. 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....

  14. 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...

  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. Tumor microvasculature observed using different contrast agents: a comparison between Gd-DTPA-Albumin and B-22956/1 in an experimental model of mammary carcinoma.

    Science.gov (United States)

    Boschi, Federico; Marzola, Pasquina; Sandri, Marco; Nicolato, Elena; Galiè, Mirco; Fiorini, Silvia; Merigo, Flavia; Lorusso, Vito; Chaabane, Linda; Sbarbati, Andrea

    2008-05-01

    The aim of this study was to compare a pure macromolecular contrast agent (Gd-DTPA-albumin) with a new protein-binding blood pool contrast agent (B22956/1) in terms of their capacity to investigate the microvasculature in an experimental model of mammary carcinoma. Tumors were induced by subcutaneous injection of 5 x 10(5) BB1 cells into the backs of 5-7 week-old female FVB/neuNT233 mice. The animals were observed using DCE-MRI when the longest diameter of the tumor was 10.2+/-2.0 mm. DCE-MRI experiments were carried out using B22956/1 and (24 h later) Gd-DTPA-albumin. DCE-MRI data showed that vasculature in the tumor rim was characterized by greater fractional plasma volume and transendothelial permeability than vasculature in the tumor core as measured by both contrast agents. Permeability to Gd-DTPA-albumin in the tumor core was hardly measurable while permeability to B22956/1 was substantial. Histologically the tumor core showed areas of well vascularized, viable tissue surrounded by necrotic regions. DCE-MRI experiments performed with B22956/1 are useful in the investigation of vasculature in those tumor regions that are characterized by low permeability to macromolecules.

  17. Experimental validation of the complement protein C3a down expression in the plasma of patients with squamous cell carcinoma of the penis.

    Science.gov (United States)

    Ornellas, Paulo; Ribeiro-Carvalho, Marilza de M; Ornellas, Antonio Augusto; Scherrer, Luciano; Koifman, Leandro; Magni, Fulvio; Ornellas, Maria Helena; Alves, Gilda

    2017-09-01

    We have previously shown the importance of the complement system in differentiating between patients with squamous cell carcinoma of the penis (SCCP) and controls. These patients had low expression of C3a and C4 fragments. Therefore, in this study, we investigated the complement protein C3a as a potential circulating biomarker in these patients by a commercially available enzyme-linked immunosorbent assay (ELISA) test. Plasma samples from 39 patients with SCCP, 15 patients with prostate cancer, and 50 healthy male subjects were evaluated using the ELISA-Bioscience OptEIA Kit human anti-C3a (BD). The nonparametric Mann-Whitney test was used for comparison of means among the groups. The complement protein C3a was found down expressed in patients with SCCP (P<0.05) in comparison to either subjects with good health or subjects with prostate cancer. Experimental validation of the down expression of C3a was well succeeded using a commercial ELISA kit. Complement system fragment C3a is down expressed in patients with SCCP. Besides, C3a is also low expressed in the plasma of patients with initial prostate cancer when compared to healthy subjects. These results suggest that the innate immune response might be suppressed in patients with these malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Colorectal polyps in childhood.

    Science.gov (United States)

    Thakkar, Kalpesh; Fishman, Douglas S; Gilger, Mark A

    2012-10-01

    Colorectal polyps are a common cause of gastrointestinal bleeding in children. This review updates the information on colorectal polyps and summarizes the recent advances in genetics, diagnosis, and treatment of polyps in the large intestine. A review of recent literature regarding colorectal polyps demonstrates an estimated detected prevalence of 6.1% overall and 12.0% among those with lower gastrointestinal bleeding during pediatric colonoscopy. Non-Caucasian races (e.g., black and Hispanic) are at higher risk for colorectal polyps in childhood. Recent data show juvenile polyps may recur in approximately 45% of children with multiple polyps and 17% of children with solitary polyps. A clinical trial showed that celecoxib, a cyclooxygenase (COX)-2 inhibitor, significantly reduced the number of colorectal polyps in children with familial adenomatous polyposis (FAP). Ethical challenges related to genetic tests for FAP have been newly examined. The utility of novel endoscopic techniques (e.g., enteroscopy) in Peutz-Jeghers Syndrome to prevent intussusception have been newly described. Although colorectal polyps in children are generally benign and easily removed, careful clinical evaluation and ongoing research are needed to identify the small proportion of children at risk for cancer. The current paradigm of using the polyp number at presentation as a primary determinant of subsequent surveillance may be inadequate for many patients.

  19. Expression of cyclooxygenase-2 and its relationship with mismatch repair and microsatellite instability in hereditary nonpolyposis colorectal cancer.

    Science.gov (United States)

    Peng, Jin; Jian-qiu, Sheng; Ying-hui, Zhang; Ai-qin, Li; Zi-tao, Wu; Shi-rong, Li

    2010-12-01

    To investigate cyclooxygenase-2 (COX-2) expression and its relationship with mismatch repair (MMR) protein expression and microsatellite instability (MSI) in hereditary nonpolyposis colorectal cancer (HNPCC). A total of 28 cases of colorectal adenoma and 14 cases of colorectal carcinoma were collected between July 2003 and July 2007 from 33 HNPCC families. Sporadic colorectal adenoma (n=32) and carcinoma patients (n=24) served as controls. With samples of tumor tissues and normal colonic mucosa collected from the patients, the protein expressions of COX-2 and MMR (hMLH1, hMSH2, and hMSH6) were examined with immunohistochemical assay. Frequency of MSI in five standard MSI loci BAT25, BAT26, D2S123, D5S346, and D17S250 were analyzed by means of polymerase chain reaction. The rate of COX-2 high-expression was 53.6% (15/28) and 42.9% (6/14) in HNPCC adenoma and carcinoma; 62.5% (20/32) and 91.7% (22/24) in sporadic adenoma and carcinoma, respectively. That rate was lower in HNPCC carcinoma than in sporadic carcinoma (Pü0.05). MMR-deletion rate and percentage of high-frequency MSI (MSI-H) in HNPCC carcinoma were higher than those in sporadic colorectal carcinoma [both 71.4% (10/14) vs. 12.5% (3/24), both Pü0.01]. Among the 10 MMR-deficient HNPCC carcinoma patients, COX-2 low-expression was observed in 8 cases (80.0%), while COX-2 high-expression was observed in all of the 4 MMR-positive HNPCC carcinoma cases (Pü0.05). In comparison to MMR positive HNPCC carcinoma, HNPCC adenoma, and sporadic carcinoma, COX-2 expression was significantly lower in corresponding MMR-deficient cases (all Pü0.05). The rates of COX-2 low-expression in HNPCC adenoma, HNPCC carcinoma, and sporadic carcinoma with MSI-H were significantly higher than those in the cases with microsatellite stability (all Pü0.05). COX-2 is expressed at a low level in HNPCC carcinoma, different from the high COX-2 expression in sporadic carcinoma.

  20. Iodide kinetics and experimental (131)I therapy in a xenotransplanted human sodium-iodide symporter-transfected human follicular thyroid carcinoma cell line.

    Science.gov (United States)

    Smit, Jan W A; Schröder-van der Elst, Janny P; Karperien, Marcel; Que, Ivo; Stokkel, Marcel; van der Heide, Daan; Romijn, Johannes A

    2002-03-01

    Uptake of iodide is a prerequisite for radioiodide therapy in thyroid cancer. However, loss of iodide uptake is frequently observed in metastasized thyroid cancer, which may be explained by diminished expression of the human sodium-iodide symporter (hNIS). We studied whether transfection of hNIS into the hNIS-deficient follicular thyroid carcinoma cell line FTC133 restores the in vivo iodide accumulation in xenografted tumors and their susceptibility to radioiodide therapy. In addition, the effects of low-iodide diets and thyroid ablation on iodide kinetics were investigated. Tumors were established in nude mice injected with the hNIS-transfected cell line FTC133-NIS30 and the empty vector transfected cell line FTC133-V4 as a control. Tumors derived from FTC133-NIS30 in mice on a normal diet revealed a high peak iodide accumulation (17.4% of administered activity, measured with an external probe) as compared with FTC133-V4 (4.6%). Half-life in FTC133-NIS30 tumors was 3.8 h. In mice kept on a low-iodide diet, peak activity in FTC133-NIS30 tumors was diminished (8.1%), whereas thyroid iodide accumulation was increased. In thyroid-ablated mice kept on a low-iodide diet, half-life of radioiodide was increased considerably (26.3 h), leading to a much higher area under the time-radioactivity curve than in FTC133-NIS30 tumors in mice on a normal diet without thyroid ablation. Experimental radioiodide therapy with 2 mCi (74 MBq) in thyroid-ablated nude mice, kept on a low-iodide diet, postponed tumor development (4 wk after therapy, one of seven animals revealed tumor vs. five of six animals without therapy). However, 9 wk after therapy, tumors had developed in four of the seven animals. The calculated tumor dose was 32.2 Gy. We conclude that hNIS transfection into a hNIS-defective thyroid carcinoma cell line restores the in vivo iodide accumulation. The unfavorable iodide kinetic characteristics (short half-life) can be partially improved by conventional conditioning with

  1. Signature Celebration of Gastroenterology, Colorectal Cancer.

    Science.gov (United States)

    Chan, Andrew T; Moayyedi, Paul

    2017-11-23

    Gastroenterology has published many seminal articles that have transformed our understanding of colorectal cancer (CRC) as well as being influential in promoting colorectal cancer screening which has saved many people from developing the disease. CRC has a hereditary component most notably highlighted in Lynch syndrome. A key paper reported that the majority of mutations in patients with hereditary nonpolyposis colorectal cancer harbored mutations in the MLH1 or MSH2 mismatch repair proteins. Continuing on the gene mutation theme, another paper. highlighted that serrated polyps accounted for approximately 9% of all colon polyps and the majority of these harbored BRAF mutations, a mutation rarely seen in the traditional adenoma to carcinoma sequence. The journal also published key work outlining the role of COX-2 in the development of CRC and this led to the concept that CRC may be prevented by COX-2 inhibition. Gastroenterology has published many influential guidelines to promote screening for colorectal cancer. Initially Gastroenterology guidelines emphasized the need for offering any screening modality either alone or in combination such as fecal occult blood test, flexible sigmoidoscopy, CT colography or colonoscopy. These guidelines were very influential in persuading governments around the world of the importance of CRC and now many countries in the developed world offer national CRC screening programs. More recently guidelines have emphasized the need to offer screening programs that prevent CRC as well as early detection and colonoscopy would be the gold standard approach. Gastroenterology has also led the way in developing the concept of developing quality measures. The journal has published evidence as to which measures lead to improvement in adenoma detection and reduced interval CRC rates. These papers have been instrumental in current recommendations on quality colonoscopy practice. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights

  2. Thymic carcinoma

    Directory of Open Access Journals (Sweden)

    Vitória Homem Machado

    2016-10-01

    Full Text Available Thymic carcinomas are a heterogeneous group of aggressive, invasive epithelial malignancies. Their incidence is rare, occurring predominantly in middle-aged men. Here we present the typical imaging findings of a thymic carcinoma. The combination of imaging characteristics with tumor location and patient age provides a roadmap for approaching the differential diagnosis. Keywords: Thymus Gland; carcinoma; mediastinal neoplasms

  3. Is peritoneal reflection the best anatomical repair landmark in experimental colorectal surgery on rats? A reflexão peritoneal é o melhor reparo anatômico na cirurgia experimental colorretal em ratos?

    Directory of Open Access Journals (Sweden)

    Denise Gonçalves Priolli

    2009-12-01

    Full Text Available PURPOSE: To validate Peyer's patch as an anatomical repair landmark for colorectal surgery in rats and to measure the collagen content in segments of the colon containing or not containing Peyer's patch. METHODS: The distance between Peyer's patch and the peritoneal reflection was measured in forty-five Wistar rats. The colon and rectum were resected for quantification of collagen content by means of computer-assisted image analysis in regions of the colon with and without Peyer's patch. RESULTS: There was great variation in the distance between Peyer's patch and the peritoneal reflection when the male and female rats were considered as a single group (p=0.04. Comparison between the genders showed that the distance between the patch and the peritoneal reflection was greater in female than in male rats (p=0.001. The colonic segment containing Peyer's patch was observed to have lower tissue collagen content than the segment in which this structure was not present (p=0.02. CONCLUSION: Peyer's patch can be indicated as an anatomical repair landmark, and there is a need to study the healing of colorectal anastomoses in rats based on differing quantities of tissue collagen existing in the colonic wall with or without this structure.OBJETIVO: Validar a placa de Peyer como reparo anatômico para a cirurgia colorretal em ratos e mensurar a quantidade de colágeno em segmentos da parede cólica que contém ou não a placa de Peyer. MÉTODOS: Foi aferida a distância entre a placa de Peyer e a reflexão peritoneal em 45 ratos Wistar. O cólon e o reto foram ressecados, para a quantificação do colágeno, por meio de análise de imagem assistida por computador, em regiões do cólon que continham ou não a placa de Peyer. RESULTADOS: Existe grande variação entre a distância da placa de Peyer e a reflexão peritoneal quando se consideraram os animais de ambos os gêneros como grupo único (p= 0.04, sendo a distância entre a placa e a reflex

  4. Growth inhibition by 8-chloro cyclic AMP of human HT29 colorectal and ZR-75-1 breast carcinoma xenografts is associated with selective modulation of protein kinase A isoenzymes.

    Science.gov (United States)

    Ramage, A D; Langdon, S P; Ritchie, A A; Burns, D J; Miller, W R

    1995-06-01

    Significant dose-related inhibition of growth of HT29 human colorectal cancer xenografts and ZR-75-1 breast cancer xenografts in immune-suppressed mice was induced by the cyclic AMP analogue, 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cyclic AMP) when given by alzet mini-pumps over a 7-day period at doses of either 50 or 100 mg/kg/day. Levels and types of cyclic AMP binding proteins were measured by ligand binding and photoaffinity labelling, respectively, in tumours harvested at the end of the treatment period. Compared with levels in tumours from control animals, values of tumour cyclic AMP binding proteins from treated animals were significantly reduced. These effects were associated with an apparent modulation of the types of cyclic AMP binding proteins, 8-Cl-cyclic AMP-treated xenografts displaying a reduced ratio of RI/RII isoforms compared with untreated control tumours.

  5. 6 Common Cancers - Colorectal Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... of colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  6. Developments in Colorectal Cancer Screening

    Science.gov (United States)

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

  7. Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia

    Directory of Open Access Journals (Sweden)

    Mansukhani Mahesh

    2003-11-01

    Full Text Available Abstract Background The p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS, and intramucosal carcinoma. Methods We examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG2a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508. Results p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9 but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6. Heavy beer consumption (8+ bottles per week was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0 but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7. Conclusion Our findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence.

  8. Parotid carcinoma

    DEFF Research Database (Denmark)

    Sørensen, Kristine Bjørndal; Godballe, Christian; de Stricker, Karin

    2006-01-01

    OBJECTIVES: Our aim is to investigate the expression of kit protein (KIT) and epidermal growth factor receptor (EGFR) in parotid carcinomas in order to correlate the expression to histology and prognosis. Further we want to perform mutation analysis of KIT-positive adenoid cystic carcinomas....... PATIENTS AND METHODS: Formalin-fixed paraffin-embedded sections from 73 patients with parotid gland carcinomas were used for the study. The sections were stained with both KIT and EGFR polyclonal antibodies. Twelve KIT-positive adenoid cystic carcinomas were examined for c-kit mutation in codon 816....... RESULTS: Of all carcinomas 25% were KIT-positive and 79% were EGFR-positive. Ninety-two percentage of the adenoid cystic carcinomas were KIT-positive. None of the adenoid cystic carcinomas had mutations in codon 816 of the c-kit gene. CONCLUSION: Neither KIT- nor EGFR-expression seem to harbour...

  9. 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 ...

  10. Colorectal Cancer: A Personal Journey

    Science.gov (United States)

    ... be as fortunate as we are.” Reflecting what research has proven, Valvo’s message is clear. “Screening is so important! Early detection is early cure!” Read More "Colorectal Cancer" Articles Colorectal Cancer: A Personal Journey / The Importance of Early Detection / Developments in Colorectal ...

  11. Microsatellite Instability Markers Status in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Giti Esmailnia

    2014-12-01

    Full Text Available Background: Colorectal cancer (CRC is the third most prevalent and the third leading cause of cancer-related deaths in Iran. Our aim was to investigate five mononucleotide statuses among Iranian patients with sporadic colorectal cancer. Materials and Methods: In this experimental study 80 sporadic CRC patients were evaluated for microsatellite instability (MSI. The pentaplex panel including 5 quasi mononucleotide microsatellite markers (NR-21, BAT-26, BAT-25, NR-27 and NR-24 was used. The MSI analysis was performed on paired tumoral DNA from cancerous tissues and genomic DNA from whole blood. MSI carriers were identified by analysis of tumor tissue using polymerase chain reaction. Results: Our findings showed that microsatellite instability was detected in 36 of 80 cases (45% with colorectal cancer. MSI analysis revealed that 17 cases of MSI-H (21%, 19 MSI-L (23% and 44 microsatellite stable tumors (55%. Instability is observed in the tumoral DNA compared to the DNA from the normal DNA sample. The most instable markers were NR-21, NR-24 in which instability was detected in 45% of patients. Conclusion: Using a panel including 3 mentioned MSI markers should be more promising markers for identifying MSI status in patients with sporadic colorectal cancer.

  12. 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.

  13. Prospective derivation of a living organoid biobank of colorectal cancer patients

    NARCIS (Netherlands)

    van de Wetering, Marc; Francies, Hayley E; Francis, Joshua M; Bounova, Gergana; Iorio, Francesco; Pronk, Apollo; van Houdt, Winan; van Gorp, Joost; Taylor-Weiner, Amaro; Kester, Lennart; McLaren-Douglas, Anne; Blokker, Joyce; Jaksani, Sridevi; Bartfeld, Sina; Volckman, Richard; van Sluis, Peter; Li, Vivian S W; Seepo, Sara; Sekhar Pedamallu, Chandra; Cibulskis, Kristian; Carter, Scott L; McKenna, Aaron; Lawrence, Michael S; Lichtenstein, Lee; Stewart, Chip; Koster, Jan; Versteeg, Rogier; van Oudenaarden, Alexander; Saez-Rodriguez, Julio; Vries, Robert G J; Getz, Gad; Wessels, Lodewyk; Stratton, Michael R; McDermott, Ultan; Meyerson, Matthew; Garnett, Mathew J; Clevers, Hans

    2015-01-01

    In Rspondin-based 3D cultures, Lgr5 stem cells from multiple organs form ever-expanding epithelial organoids that retain their tissue identity. We report the establishment of tumor organoid cultures from 20 consecutive colorectal carcinoma (CRC) patients. For most, organoids were also generated from

  14. Sennosides and aloin do not promote dimethylhydrazine-induced colorectal tumors in mice.

    Science.gov (United States)

    Siegers, C P; Siemers, J; Baretton, G

    1993-10-01

    In a model of dimethylhydrazine-induced colorectal tumors in male mice aloin- or sennoside-enriched diets (0.03%) did not promote incidence and growth of adenomas and carcinomas after 20 weeks. Furthermore, in anthranoid-fed mice no significant changes in serum electrolytes as well as parameters of hepato- and nephrotoxicity were observed.

  15. Mononucleotide precedes dinucleotide repeat instability during colorectal tumour development in Lynch syndrome patients

    NARCIS (Netherlands)

    Ferreira, Ana M.; Westers, Helga; Sousa, Sonia; Wu, Ying; Niessen, Renee C.; Olderode-Berends, Maran; van der Sluis, Tineke; Reuvekamp, Peter T. W.; Seruca, Raquel; Kleibeuker, Jan H.; Hollema, Harry; Sijmons, Rolf H.; Hofstra, Robert M. W.

    A progressive accumulation of genetic alterations underlies the adenoma-carcinoma sequence of colorectal cancer. This accumulation of mutations is driven by genetic instability, of which there are different types. Microsatellite instability (MSI) is the predominant type present in the tumours of

  16. Do Microsatellite Instability Profiles Really Differ Between Colorectal and Endometrial Tumors?

    NARCIS (Netherlands)

    Ferreira, Ana M.; Westers, Helga; Wu, Ying; Niessen, Rene C.; Olderode-Berends, Maran; van der Sluis, Tineke; van der Zee, Ate G.; Hollema, Harry; Kleibeuker, Jan H.; Sijmons, Rolf H.; Hofstra, Robert M. W.

    Microsatellite instability (MSI) occurs in more than 90% of the tumors of Lynch syndrome patients, and in 15-25% of sporadic colorectal (CRC) and endometrial carcinomas (EC). Previous studies comparing EC and CRC using BAT markers showed that the frequency of unstable markers is lower in EC, and

  17. New insights into frequency and contents of fear of cancer progression/recurrence (FOP/FCR in outpatients with colorectal carcinoma (CRC receiving oral capecitabine: a pilot study at a comprehensive cancer center

    Directory of Open Access Journals (Sweden)

    Hefner J

    2017-11-01

    Full Text Available Jochen Hefner,1 Sara Berberich,2 Elena Lanvers,3 Maria Sanning,2 Ann-Kathrin Steimer,2 Volker Kunzmann4 1Section of Psychosomatic Medicine, Department of Internal Medicine II, University of Wuerzburg, 2Faculty of Medicine, University of Wuerzburg, Bavaria, 3Children’s Hospital of the City of Cologne, North Rhine-Westphalia, 4Section of Clinical Oncology, Department of Internal Medicine II, University of Wuerzburg, Bavaria, Germany Background: Fear of cancer progression/recurrence (FOP/FCR is considered one of the most prevalent sources of distress in cancer survivors and associated with lower quality of life and functional impairment. Detailed measures of FOP/FCR are needed because little is known about the knowledge of FOP/FCR, its associations with the patient–doctor relationship, and the rate of adequate therapy. Colorectal cancer (CRC is one of the most prevalent cancer entities, and oral capecitabine is widely prescribed as treatment. Therefore, we initiated a pilot study to expand the literature on FOP/FCR in CRC outpatients receiving capecitabine and to generate hypotheses for future investigations. Methods: This study included 58 patients treated at a comprehensive cancer center. FOP/FCR was assessed with the Fear of Progression Questionnaire (FOP-Q-SF. Satisfaction with the relationships with doctors was assessed with the Patient–Doctor Relationship Questionnaire-9 (PRDQ-9. Levels of side effects were rated by the patients on a visual analog scale. Clinical data were extracted from the charts. Results: A total of 19 out of 58 patients (36% suffered from FOP/FCR according to our assessment. Levels of FOP/FCR seemed to be mostly moderate to high. Only four out of the 19 distressed patients (21% were treated accordingly. Typical side effects of oncological treatment were associated with higher FOP/FCR. Satisfaction with doctor–patient relationships was not associated with FOP/FCR. Regarding single items of FOP/FCR, three out of the

  18. CT colonography for synchronous colorectal lesions in patients with colorectal cancer: initial experience.

    Science.gov (United States)

    McArthur, D R; Mehrzad, H; Patel, R; Dadds, J; Pallan, A; Karandikar, S S; Roy-Choudhury, S

    2010-03-01

    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(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.

  19. Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up

    Energy Technology Data Exchange (ETDEWEB)

    Sztrokay, Aniko; Auweter, Sigrid D.; Liebhardt, Susanne; Hellerhoff, Karin; Reiser, Maximilian F. [Ludwig-Maximilians-Universitaet Muenchen, Department of Clinical Radiology, Munich (Germany); Herzen, Julia; Willner, Marian; Hahn, Dieter; Pfeiffer, Franz [Technische Universitaet Muenchen, Department of Physics, Garching (Germany); Mayr, Doris [Ludwig-Maximilians-Universitaet Muenchen, Institute of Pathology, Munich (Germany); Zanette, Irene [Technische Universitaet Muenchen, Department of Physics, Garching (Germany); European Synchrotron Radiation Facility (ESRF), Grenoble (France); Weitkamp, Timm [Synchrotron Soleil, L' Orme des Merisiers, Gif-sur-Yvette (France); Bamberg, Fabian [Ludwig-Maximilians-Universitaet Muenchen, Department of Clinical Radiology, Munich (Germany); LMU Munich, Institute of Clinical Radiology, Munich (Germany)

    2013-02-15

    Limited contrast between healthy and tumour tissue is a limiting factor in mammography and CT of the breast. Phase-contrast computed tomography (PC-CT) provides improved soft-tissue contrast compared with absorption-based techniques. In this study, we assessed the technical feasibility of grating-based PC-CT imaging of the breast for characterisation of ductal carcinoma in situ (DCIS). Grating-based PC-CT was performed on one breast specimen containing an invasive ductal carcinoma and DCIS using monochromatic radiation of 23 keV. Phase-contrast and absorption-based images were compared qualitatively and quantitatively with histopathology in a blinded fashion. Grating-based PC-CT showed improved differentiation of soft-tissue components. Circular structures of high phase-shift contrast corresponding to the walls of the dilated ductuli of the DCIS were visualised with a contrast-to-noise ratio (CNR) of 9.6 using PC-CT but were not detectable on absorption-based images (CNR = 0.27). The high phase-shift structures of the dilated ductuli were identifiable in the PC-CT volume data set allowing for 3D characterisation of DCIS. Our results indicate that unlike conventional CT, grating-based PC-CT may allow the differentiation between invasive carcinoma and intraductal carcinoma and healthy breast tissue and provide 3D visualisation of DCIS. (orig.)

  20. Radioimmunotherapy improves survival of rats with microscopic liver metastases of colorectal origin.

    NARCIS (Netherlands)

    Jong, G.M. de; Hendriks, T.; Eek, A.; Oyen, W.J.G.; Heskamp, S.; Bleichrodt, R.P.; Boerman, O.C.

    2009-01-01

    BACKGROUND: Half of the patients with colorectal cancer develop liver metastases during the course of their disease. The aim of the present study was to assess the efficacy of radioimmunotherapy (RIT) with a radiolabeled monoclonal antibody (mAb) to treat experimental colorectal liver metastases.

  1. Gene expression of IQGAPs and Ras families in an experimental mouse model for hepatocellular carcinoma: a mechanistic study of cancer progression.

    Science.gov (United States)

    Zoheir, Khairy M A; Abd-Rabou, Ahmed A; Harisa, Gamaleldin I; Ashour, Abdelkader E; Ahmad, Sheikh Fayaz; Attia, Sabry M; Bakheet, Saleh A; Abdel-Hamied, Hala E; Abd-Allah, Adel R; Kumar, Ashok

    2015-01-01

    IQGAPs genes play critical role in either induction or suppression of cancer and its progression, however the relationship between Ras genes and these genes are still unclear. In this study, we tried to understand the mechanistic action of IQGAPs genes and its correlation with Ras genes in mouse hepatic cancer model. The genetic expressions of IQGAP1, IQGAP2, IQGAP3, Hras, Kras, Nras, Mras, Caspase3, and BAX were followed in both hepatocellular carcinoma and normal liver cells of Balbc mice. Genotoxic agent diethylnitrosamine (DEN)-induced hepatic cancer model was induced in male mice and recorded the occurrence of hepatocellular carcinoma by morphological and histological changes in the liver. It was observed that mRNA expressions of IQGAP1, Hras, Kras, Nras, Mras, Caspase3, and BAX genes were highly elevated in hepatocellular carcinoma cells when compared with normal liver cells, additionally their expressions increased by concentrating the dose of DEN. While, the expressions of IQGAP2 and IQGAP3 were significantly decreased in hepatocellular carcinoma cells when compared with normal liver cells, as well as their expressions decreased more with increasing the dose of DEN. It was concluded from this study that IQGAP1 has a strong signaling relationship with Ras genes in induction of cancer and it is considered as a key gene for induction or suppression of the hepatocellular carcinoma.

  2. Colorectal cancer among young native Indonesians: A clinicopathological and molecular assessment on microsatellite instability

    Directory of Open Access Journals (Sweden)

    Aru W. Sudoyo

    2010-11-01

    Full Text Available Aim: To obtain clinicopathological characteristics of colorectal cancer among young native Indonesians and to assess MLH1, MSH2, and SMAD4 protein expressions, comparing them with a matched population of colorectal cancer patients aged 60 years old and older.Methods: Medical records of colorectal cancer patients aged 40 years or younger and 60 years or older from several hospitals in three Indonesian cities – Jakarta, Makassar, and Bandung - were reviewed. The “native” ethnic groups were selected from those originating from Java, Makassar (South Celebes,  Minangkabau (West Sumatra. Ethnicity of 121 colorectal  carcinoma patients was confirmed by fulfilling requirements in a questionnaire. Tumor specimens of those patients underwent evaluation for histopathology, tumor grading as well as  immunohistochemical analysis to assess MLH1, MSH2 protein expressions to detect microsatellite instability mutation pathway and SMAD4 protein expression to reconfirm that the specimens were not microsatellite instability origin.Results: There were 121 colorectal carcinoma cases of Sundanese, Javanese, Macassarese and Minangkabau ethnic group. This study indicated that colorectal cancer has statistically different grade (p = 0.001 between the young and the older patients. Immunohistochemical staining for MSH2 protein and MLH1 were done for 92 and 97 specimens respectively. There was no significant difference between the expressions of MLH1 and MSH2 on tumor grading, indicated there was no correlation between microsatellite instability and tumor grading in this study.Conclusion: Colorectal cancer in young native Indonesian patients (40 years old or less was not different in clinicopathological characteristics compared to older patients (60 years old or more in similar ethnic groups. There was also no difference in MSH2 and MLH1 protein expressions, important indicators of microsatellite instability and. (Med J Indones 2010; 19:245-51Keywords: colorectal

  3. [Nationwide colorectal cancer screening].

    NARCIS (Netherlands)

    Rossum, L.G.M. van; Laheij, R.J.F.; Jansen, J.B.M.J.

    2010-01-01

    Usually, colorectal cancer presents with complaints in a late stage, but can be detected in an earlier stage, with better prognosis, by colonoscopy. Using colonoscopy, also precancerous tumours, adenomas, can be detected and excised, but only in a national screening programme. However primary

  4. Laryngeal carcinoma presenting as polymyositis: A paraneoplastic syndrome

    Directory of Open Access Journals (Sweden)

    Ritesh Sahu

    2016-01-01

    Full Text Available Laryngeal carcinoma is rarely associated with paraneoplastic syndrome. Inflammatory myopathy presenting as paraneoplastic event is commonly associated with carcinomas of ovary, lung, pancreas, stomach, colorectal, and non-Hodgkin′s lymphoma. We report a case of elderly male, who presented with proximal muscle weakness and found to be associated with laryngeal carcinoma. Diagnosis of polymyositis (PM was confirmed based on clinical features, laboratory test, and muscle biopsy. Exclusion of other commonly associated malignancies was done. This patient improved gradually after 6 months of immunosuppressive therapy and management of underlying cancer.

  5. Extended RAS Gene Mutation Testing in Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update 2015.

    Science.gov (United States)

    Allegra, Carmen J; Rumble, R Bryan; Hamilton, Stanley R; Mangu, Pamela B; Roach, Nancy; Hantel, Alexander; Schilsky, Richard L

    2016-01-10

    An American Society of Clinical Oncology Provisional Clinical Opinion (PCO) offers timely clinical direction after publication or presentation of potentially practice-changing data from major studies. This PCO update addresses the utility of extended RAS gene mutation testing in patients with metastatic colorectal cancer (mCRC) to detect resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy. Recent results from phase II and III clinical trials in mCRC demonstrate that patients whose tumors harbor RAS mutations in exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146) are unlikely to benefit from therapy with MoAbs directed against EGFR, when used as monotherapy or combined with chemotherapy. In addition to the evidence reviewed in the original PCO, 11 systematic reviews with meta-analyses, two retrospective analyses, and two health technology assessments based on a systematic review were obtained. These evaluated the outcomes for patients with mCRC with no mutation detected or presence of mutation in additional exons in KRAS and NRAS. PCO: All patients with mCRC who are candidates for anti-EGFR antibody therapy should have their tumor tested in a Clinical Laboratory Improvement Amendments-certified laboratory for mutations in both KRAS and NRAS exons 2 (codons 12 and 13), 3 (codons 59 and 61), and 4 (codons 117 and 146). The weight of current evidence indicates that anti-EGFR MoAb therapy should only be considered for treatment of patients whose tumor is determined to not have mutations detected after such extended RAS testing. © 2015 by American Society of Clinical Oncology.

  6. [Nutrition and colorectal cancer].

    Science.gov (United States)

    Ströhle, Alexander; Maike, Wolters; Hahn, Andreas

    2007-01-01

    Diet plays an important role in the pathogenesis of colorectal cancer. Current prospective cohort studies and metaanalysis enable a reevaluation of how food or nutrients such as fiber and fat influence cancer risk. Based on the evidence criteria of the WHO/FAD, risk reduction by a high intake of fruit is assessed as possible, while a lowered risk by a high vegetable intake is probable. Especially raw vegetables and fruits seem to exert anticancer properties. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as probable whereas the evidence of an increased risk by high consumption of refined white flour products and sweets is (still) insufficient despite some evidences. There is a probable risk reducing effect of milk and dairy products. e available data on eggs and red meat indicate a possible risk increasing influence. Stronger clues for a risk increasing effect have been shown for meat products leading to an evidence assessed as probable. Owing to varied interpretations of the data on fiber, the evidence of a risk reducing effect relating to colorectal cancer is assessed as possible or insufficient. The available data on alcohol consumption indicate a possible risk increasing effect. In contrast to former evaluations, diets rich in fat seem to increase colorectal cancer risk only indirectly as part of a hypercaloric diet by advancing the obesity risk. Thus, the evidence of obesity, especially visceral obesity, as a risk of colorectal cancer is judged as convincing today. Prospective cohort studies suggest that people who get higher than average amounts of folic acid from multivitamin supplements have lower risks of colorectal cancer. The evidence for a risk reducing effect of calcium, selenium, vitamin D and vitamin E on colorectal cancer is insufficient. As primary prevention, a diet rich in vegetables, fruits, whole grain products, and legumes added by low-fat dairy products, fish, and poultry can be recommended. In

  7. Imperfect conformation of experimental and epidemiological data for frequency of RET/РТС gene rearrangements in papillary thyroid carcinoma for the Chernobyl accident

    Directory of Open Access Journals (Sweden)

    Ushenkova L.N.

    2013-12-01

    Full Text Available In an overview and analytical study of the epidemiological data on the frequency of RET/РТС gene rearrangements in sporadic and radiogenic (patients after radiotherapy, residents of contaminated after the Chernobyl disaster areas, victims after the atomic bombings, etc. carcinomas of the thyroid gland were examined. In general, the observed epidemiological laws were confirmed in radiobiology experiments by irradiation of different cultures of thyroid cells and ex vivo with the exception of Chernobyl cohorts. Induction of RET/РТС gene rearrangements by 131l exposure in children carcinomas of Chernobyl residents in mice did not observe too. It is concluded that the situation with the frequency of RET/РТС rearrangements in thyroid carcinoma in Chernobyl cohorts once again confirms the multifactorial nature of the induction and development of these tumors with a contribution of radiation and non-radiation factors (iodine deficiency and different stresses.

  8. [Growth inhibitory effects of lipofectamine-mediated DCC gene on ovarian epithelial carcinoma].

    Science.gov (United States)

    Li, Pei-ling; Hu, Chun-jie; Li, Chang-min; Meng, Chun-yan; Gao, Lei

    2006-03-01

    To study the inhibitory effects of lipofectamine-mediated deleted colorectal carcinoma gene on ovarian epithelial carcinoma (ovarian cancer) cell line SKOV3. We constructed a recombinant eukaryotic expression vector pcDNA3.1 (+)-DCC containing exogenous human DCC cDNA and vector with neomycin resistance gene, which were introduced by lipofectamine-mediated gene transfection into SKOV3 cell line that does not express DCC endogenously, thus forming SKOV3/DCC. Therefore, the experimental cells were classified into SKOV3/DCC, SKOV3/Neo and SKOV3. By using reverse transcriptase-polymerase chain reaction and immunocytochemistry, the expression of DCC mRNA and its protein were examined. Exogenous DCC had successfully been transferred into SKOV3 cells and obtained permanent expression. The growth speed of SKOV3/DCC was slower than the other two groups, there was significant difference between them (P < 0.01). SKOV3/DCC clones number was 38 +/- 8, while SKOV3 and SKOV3/Neo were 192 +/- 8 and 186 +/- 10, respectively, there was significant difference between them (P < 0.01). The percentage of G(1) phase cells increased to 78.0%, which that of S phase decreased to 5.3% by analyzing cell cycle, there was significant difference between them (20.0% and 3.2%, P < 0.01). The ultrastructural changes of the cells were observed under electron microscope, revealing growth retardation. DCC gene played an important role in generation and development of ovarian carcinomas.

  9. Detection of Mismatch Repair Deficiency and Microsatellite Instability in Colorectal Adenocarcinoma by Targeted Next-Generation Sequencing.

    Science.gov (United States)

    Nowak, Jonathan A; Yurgelun, Matthew B; Bruce, Jacqueline L; Rojas-Rudilla, Vanesa; Hall, Dimity L; Shivdasani, Priyanka; Garcia, Elizabeth P; Agoston, Agoston T; Srivastava, Amitabh; Ogino, Shuji; Kuo, Frank C; Lindeman, Neal I; Dong, Fei

    2017-01-01

    Mismatch repair protein deficiency (MMR-D) and high microsatellite instability (MSI-H) are features of Lynch syndrome-associated colorectal carcinomas and have implications in clinical management. We evaluate the ability of a targeted next-generation sequencing panel to detect MMR-D and MSI-H based on mutational phenotype. Using a criterion of >40 total mutations per megabase or >5 single-base insertion or deletion mutations in repeats per megabase, sequencing achieves 92% sensitivity and 100% specificity for MMR-D by immunohistochemistry in a training cohort of 149 colorectal carcinomas and 91% sensitivity and 98% specificity for MMR-D in a validation cohort of 94 additional colorectal carcinomas. False-negative samples are attributable to tumor heterogeneity, and next-generation sequencing results are concordant with analysis of microsatellite loci by PCR. In a subset of 95 carcinomas with microsatellite analysis, sequencing achieves 100% sensitivity and 99% specificity for MSI-H in the combined training and validation set. False-positive results for MMR-D and MSI-H are attributable to ultramutated cancers with POLE mutations, which are confirmed by direct sequencing of the POLE gene and are detected by mutational signature analysis. These findings provide a framework for a targeted tumor sequencing panel to accurately detect MMR-D and MSI-H in colorectal carcinomas. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  10. Diet, aberrant crypt foci and colorectal cancer.

    Science.gov (United States)

    Bruce, W R; Archer, M C; Corpet, D E; Medline, A; Minkin, S; Stamp, D; Yin, Y; Zhang, X M

    1993-11-01

    We have used the aberrant crypt focus (ACF) assay to test and develop hypotheses linking diet and colon cancer. The hypotheses were suggested by epidemiological studies that identified possible dietary factors associated with colorectal cancer risk. The ACF assay was used to quantitate the effect of the dietary factors on the initiation and growth of these putative precursors of colon cancers in experimental animals. Using this approach we have developed 3 new hypotheses for the role of diet in colorectal cancer. These are (1) a risk associated with 5-hydroxymethyl-2-furaldehyde in caramelized sugar, (2) a risk associated with some factor in thermolyzed casein, and (3) a risk associated with single nutrient boluses of sucrose and fructose. The importance of these hypotheses has still to be tested in long term carcinogenesis experiments, in analytic epidemiology studies and then, perhaps, in intervention trials.

  11. Basisquamous Carcinoma

    Directory of Open Access Journals (Sweden)

    Yesudian Devakar P

    1997-01-01

    Full Text Available A 50 year old woman presented with an ulceroproliferative mass in the value of 4 month duration. Biopsy of the lesion showed features of a basisquamous cell carcinoma. This is a rare tumour showing histopathological features of both basal cell and squamous cell carcinomas. The clinical, histopathological and histogenetic status of this tumour are discussed.

  12. Gastrins, iron homeostasis and colorectal cancer.

    Science.gov (United States)

    Kovac, Suzana; Anderson, Gregory J; Baldwin, Graham S

    2011-05-01

    The peptide hormone gastrin has been identified as a major regulator of acid secretion and a potent mitogen for normal and malignant gastrointestinal cells. The importance of gastric acid in the absorption of dietary iron first became evident 50 years ago when iron deficiency anemia was recognized as a long-term consequence of partial gastrectomy. This review summarizes the connections between circulating gastrins, iron status and colorectal cancer. Gastrins bind two ferric ions with micromolar affinity and, in the case of non-amidated forms of the hormone, iron binding is essential for biological activity in vitro and in vivo. The demonstration of an interaction between gastrin and transferrin by biochemical techniques led to the proposal that gastrins catalyze the loading of transferrin with iron. Several lines of evidence, including the facts that the concentrations of circulating gastrins are increased in mice and humans with the iron overload disease hemochromatosis and that transferrin saturation positively correlates with circulating gastrin concentration, suggest the potential involvement of gastrins in iron homeostasis. Conversely, recognition that ferric ions play an unexpected role in the biological activity of gastrins may assist in the development of useful therapies for colorectal carcinoma and other disorders of mucosal proliferation in the gastrointestinal tract. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. 2011 Elsevier B.V. All rights reserved.

  13. 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.

  14. Microbiota, Inflammation and Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Cécily Lucas

    2017-06-01

    Full Text Available Colorectal cancer, the fourth leading cause of cancer-related death worldwide, is a multifactorial disease involving genetic, environmental and lifestyle risk factors. In addition, increased evidence has established a role for the intestinal microbiota in the development of colorectal cancer. Indeed, changes in the intestinal microbiota composition in colorectal cancer patients compared to control subjects have been reported. Several bacterial species have been shown to exhibit the pro-inflammatory and pro-carcinogenic properties, which could consequently have an impact on colorectal carcinogenesis. This review will summarize the current knowledge about the potential links between the intestinal microbiota and colorectal cancer, with a focus on the pro-carcinogenic properties of bacterial microbiota such as induction of inflammation, the biosynthesis of genotoxins that interfere with cell cycle regulation and the production of toxic metabolites. Finally, we will describe the potential therapeutic strategies based on intestinal microbiota manipulation for colorectal cancer treatment.

  15. Delayed complications in colo-rectal carcinoma treated by combination radiotherapy and 5-fluorouracil: Eastern Cooperative Oncology Group (E. C. O. G. ) pilot study. [/sup 60/Co-teletherapy

    Energy Technology Data Exchange (ETDEWEB)

    Danjoux, C.E.; Catton, G.E.

    1979-03-01

    From June 1976 to Dec 1977, 24 patients with residual, or recurrent, inoperable rectal carcinoma, were treated by a split-course irradiation and 5-FU. All patients received /sup 60/Co pelvic irradiation, with AP--PA opposed fields. The dose was delivered in 3 courses of 2000 rad in 2 weeks, with 2 weeks rest between each course. 5 Fluorouracil (5-FU)-(500 mg/m/sup 2/), was administered I.V., on the first 3 days of each course of irradiation. The acute reaction was minimal, and was not predictive of the late serious complications which occurred in 7/24 (29%), of our patients, 2/10 with minimal, and 5/14 with bulky pelvic disease. The median follow-up was 12 months--(range 4 to 26 months). The onset of serious complications occurred about 8 months following treatment, and consisted of bowel stenosis, necrosis, fistula formation, and subcutaneous fibrosis. In 5 of 7 patients, predisposing factors accounted for such complications. We believe this to be the first report of such an observation of delayed complications in the absence of serious early reaction with combined chemoradiotherapy. The safety of multimodality therapy cannot be predicted by how well it is tolerated initially.

  16. Risks of Colorectal Cancer Screening

    Science.gov (United States)

    ... Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ...

  17. Mouse models of colorectal cancer as preclinical models

    Science.gov (United States)

    Buczacki, Simon J.A.; Arends, Mark J.; Adams, David J.

    2015-01-01

    In this review, we discuss the application of mouse models to the identification and pre‐clinical validation of novel therapeutic targets in colorectal cancer, and to the search for early disease biomarkers. Large‐scale genomic, transcriptomic and epigenomic profiling of colorectal carcinomas has led to the identification of many candidate genes whose direct contribution to tumourigenesis is yet to be defined; we discuss the utility of cross‐species comparative ‘omics‐based approaches to this problem. We highlight recent progress in modelling late‐stage disease using mice, and discuss ways in which mouse models could better recapitulate the complexity of human cancers to tackle the problem of therapeutic resistance and recurrence after surgical resection. PMID:26115037

  18. Butyrate inhibits seeding and growth of colorectal metastases to the liver in mice.

    Science.gov (United States)

    Velázquez, O C; Jabbar, A; DeMatteo, R P; Rombeau, J L

    1996-08-01

    The short-chain fatty acid butyrate inhibits growth of colorectal carcinoma cells in vitro. Mevalonate, a short-chain fatty acid structurally and metabolically related to butyrate, is important in signal transduction and is essential for cell growth. We investigated butyrate's effects on seeding and growth of colorectal tumor cells metastatic to the liver in vivo and hypothesized that butyrate's antiproliferative effects are associated with inhibition of mevalonate-mediated cell growth. Hepatic metastases were induced by injecting 1 x 10(5) MC-26 (N-methyl-N-nitrosourea-induced murine colorectal carcinoma) cells into the spleen of BALB/c mice. Mice were treated with a continuous intravenous infusion of butyrate (2 gm/kg/day) for 7 days starting 24 hours before tumor cells were injected. Study variables included liver weight and number of hepatic surface metastases. Proliferation studies on MC-26 cells were performed in vitro to examine the effects of butyrate alone or combined with mevalonate or mevastatin (an inhibitor of mevalonate synthesis). Butyrate reduced seeding and growth of colorectal tumor cells in vivo. Mevalonate diminished butyrate's antiproliferative action in vitro, whereas mevastatin potentiated this effect. These studies (1) show that butyrate inhibits seeding and growth of hepatic colorectal metastases in vivo, (2) associate butyrate's antiproliferative effects with inhibition of mevalonate-mediated cell growth, and (3) indicate that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may have synergistic antiproliferative effects when combined with butyrate.

  19. [Colorectal cancer screening].

    Science.gov (United States)

    Castells, Antoni

    2013-10-01

    Colorectal cancer is the paradigm of tumoral growth that is susceptible to preventive measures, especially screening. Various screening strategies with demonstrated efficacy and efficiency are currently available, notable examples being the fecal occult blood test and endoscopic tests. In addition, new modalities have appeared in the last few years that could become viable alternatives in the near future. The present article reviews the most important presentations on colorectal screening at the annual congress of the American Gastroenterological Association held in Orlando in May 2013, with special emphasis on the medium- and long-term results of strategies using the fecal occult blood test and flexible sigmoidoscopy, as well as initial experiences with the use of new biomarkers. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. [Colorectal cancer screening].

    Science.gov (United States)

    Castells, Antoni

    2015-09-01

    Colorectal cancer is one of malignancies showing the greatest benefit from preventive measures, especially screening or secondary prevention. Several screening strategies are available with demonstrated efficacy and efficiency. The most widely used are the faecal occult blood test in countries with population-based screening programmes, and colonoscopy in those conducting opportunistic screening. The present article reviews the most important presentations on colorectal cancer screening at the annual congress of the American Gastroenterological Association held in Washington in 2015, with special emphasis on the medium-term results of faecal occult blood testing strategies and determining factors and on strategies to reduce the development of interval cancer after colonoscopy. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. 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...... colono- and sigmoidoscopy, CT- and MR-colonography, capsule endoscopy, DNA and occult blood in feces, and so on. The pros and cons of the various tests, including economic issues, are debated. Although a plethora of evaluated and validated tests even with high specificities and reasonable sensitivities...... 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...

  2. Improving colorectal cancer referrals

    OpenAIRE

    Gregory, Claire

    2018-01-01

    The colorectal services at The Royal Bournemouth Hospital needed to adapt to meet the extra demand on fast-track patient referrals to the outpatient department, as a consequence of the changes in the National Institute for Health and Care Excellence (NICE) guidance on cancer referrals in June 2015. Learning from other units, a telephone assessment clinic (TAC) triaging patients straight to colonoscopy was trialled. A Plan–Do–Study–Act (PDSA) methodology was used. A baseline study showed that ...

  3. Colorectal cancer screening.

    Science.gov (United States)

    Bessa Caserras, Xavier

    2016-09-01

    In the latest meeting of the American Gastroenterological Association, several clinical studies were presented that aimed to evaluate the various colorectal cancer screening strategies, although most assessed the various aspects of faecal immunochemical testing (FIT) and colonoscopy. Data were presented from consecutive FIT-based screening rounds, confirming the importance of adherence to consecutive screening rounds, achieving a similar or superior diagnostic yield to endoscopic studies. There was confirmation of the importance of not delaying endoscopic study after a positive result. Participants with a negative FIT (score of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the importance of high-quality colonoscopy in colorectal cancer screening programmes. The implementation of high-quality colonoscopies has reduced mortality from proximal lesions and reduced interval cancers in various studies. Finally, participants with a normal colonoscopy result or with a small adenoma are at low risk for developing advanced neoplasms during follow-up. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  4. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma.

    Science.gov (United States)

    ten Kate, J; van den Ingh, H F; Khan, P M; Bosman, F T

    1986-04-15

    Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi-quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane-associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well-differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor.

  5. Impact of family history of gastric cancer on colorectal neoplasias in young Japanese.

    Science.gov (United States)

    Hata, K; Shinozaki, M; Toyoshima, O; Toyoshima, A; Matsumoto, S; Saisho, T; Tsurita, G

    2013-01-01

    The aim of this study was to elucidate risk factors for the development of colorectal neoplasia in the young population. In particular, we focused on the family history of gastric cancer. Young Japanese subjects aged 30-49 years old who underwent colonoscopy for the first time from August 2007 to August 2008 were included in this study. A total of 300 unselected consecutive patients (mean age 40.5 years) were eligible for analysis, and family history of colorectal cancer and gastric cancer, sex, age, body mass index, positivity of faecal occult blood test and the presence of symptoms were evaluated. Risk factors for developing colorectal adenoma and/or carcinoma were assessed. Colorectal neoplasias were detected in 83 (27.7%) cases. Two were found to have invasive carcinoma. Univariate and multivariate analyses revealed that family history of gastric cancer (OR 2.09, 95% CI 1.12-3.92, P = 0.02) was an independent risk factor for the development of colorectal neoplasia, as well as male sex (OR 1.89, 95% CI 1.10-3.27, P = 0.02), older age (OR 2.05, 95% CI 1.18-3.55, P = 0.01) and positive faecal occult blood test (OR 1.99, 95% CI 1.14-3.48, P = 0.02). In the young population under 50 years of age, a family history of gastric cancer is an independent risk factor for the development of colorectal neoplasia. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

  6. CTLA4 gene polymorphism in Italian patients with colorectal adenoma and cancer.

    Science.gov (United States)

    Solerio, E; Tappero, G; Iannace, L; Matullo, G; Ayoubi, M; Parziale, A; Cicilano, M; Sansoè, G; Framarin, L; Vineis, P; Rosina, F

    2005-03-01

    Colorectal cancer is a major health problem. Colonoscopic colorectal cancer screening is cumbersome and expensive. Identification of genetic risk of colorectal cancer may help to select the subjects who could benefit from colonoscopy. The immune system plays a fundamental role in the human-environment interaction, and the carcinogenic effects of many environmental factors are mediated by the chronic activation of the immune system in a genetic-controlled fashion. Cytotoxic T lymphocyte associated antigen 4 (CTLA4) plays an inhibitory role in regulating lymphocyte functions. The loss of CTLA4 function is responsible for loss of mucosal lymphocyte tolerance. The G allele at position +49 of exon 1 of the CTLA4 gene affects the CTLA4 function. We evaluated in an association study the role of CTLA4 A+49G polymorphism as a risk factor for colorectal neoplasm. Five hundred and fifty-six patients (male 295; female 261) who underwent colonoscopy at our Centre were enrolled in the study and divided into three groups: Colorectal cancer (132 patients, M/F 68/64, mean age 66+/-11 years); Colorectal adenoma (186 patients, M/F 110/76, mean age 65+/-11 years); Healthy controls (238 patients, M/F 117/121, mean age 63+/-10 years). DNA was extracted from peripheral blood, CTLA4 gene was amplified by using specific primers, and A+49G polymorphism was analysed by restriction enzyme digestion. No statistically significant differences in the genotype distribution among Control and Adenoma groups (p=0.93), Control and Carcinoma groups (p=0.52), and Adenoma and Carcinoma groups (p=0.53) were observed. There is no significant correlation between CTLA4 A+49G polymorphism and the risk of colorectal neoplasm among Italian Caucasians.

  7. The role of tissue factor in colorectal cancer

    DEFF Research Database (Denmark)

    Lykke, J; Nielsen, Hans Jørgen

    2003-01-01

    The possible role of tissue factor (TF) in colorectal cancer (CRC) is reviewed. A correlation between TF expression and advanced stages of malignancy, and a correlation between TF expression and overall survival have been suggested in CRC. This is supported by experimental studies indicating...

  8. GALLBLADDER CARCINOMA

    Directory of Open Access Journals (Sweden)

    Blaž Trotovšek

    2003-12-01

    Full Text Available Background. Carcinoma of the gallbladder is a tumour with a dismal prognosis and 5-years overall survival rate less than 5%. Among the tumours of the gastrointestinal tract it is fifth in the row and its incidence is approximately 1.2/105. Tumour occurs more often (2–6 times in women and in people over 50 years old (90%. According to the Slovenian Registry of Cancer for year 1998 the incidence of gallbladder carcinoma was 2.7/105 and it occurred 4 times more often among women. The most important risk factors for development of gallbladder carcinoma are: bile stones, chronic inflammation and polyps of the gallbladder. Carcinoma of the gallbladder develops in only 2–3% of the patients with bile stones. When discovered, carcinoma has already invaded the liver in 60%, regional lymph nodes in 45% and the other surrounding organs in 40%. Carcinoma is at time of diagnosis already disseminated in distant organs in 20%. Only in 10% of the patients it is confined to the gallbladder wall. Before the routine use of the ultrasound, computed tomography and tumour markers the disease was discovered preoperatively in 10% versus 90% today. Diagnostic percutaneous biopsy is not recommended. TNM classification and staging of the disease is important for the decision of the modality of treatment.Conclusions. For TNM stage I gallbladder carcinoma, simple cholecystectomy is sufficient. When stage II-IVa is discovered, »en block« resection of gallbladder, liver segments 4b and 5, common bile duct and thorough lymphadenectomy is recommended. Regional radiotherapy and intraarterial chemotherapy with Mitomycin-C are showing promising results. Longterm outcome in patients with gallbladder carcinoma is improving but it is still disappointing.

  9. Tracheal Carcinoma

    Directory of Open Access Journals (Sweden)

    Ashok K Chauhan

    2012-01-01

    Full Text Available Adenoid cystic carcinoma of the trachea is a rare primary tracheal malignancy. Obstructive symptoms such as dyspnoea, hoarseness of voice, dysphasia are commonly seen symptoms. Combined modality treatments including surgery and radiation therapy are considered as optimal treatment for these tumours. A case of adenoid cystic carcinoma in a 35 years old male patient who was treated successfully by surgical excision and external beam radiation therapy is presented.

  10. Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors

    National Research Council Canada - National Science Library

    Fišerová, Anna; Richter, Jan; Čapková, Katarína; Bieblová, Jana; Mikyšková, Romana; Reiniš, Milan; Indrová, Marie

    2016-01-01

    ... (3-methycholanthrene-induced tumor) syngeneic to Balb/c. Furthermore, we induced colorectal carcinoma by azoxymethane-DSS treatment to test the susceptibility to chemically-induced primary cancer...

  11. Undifferentiated salivary gland carcinomas

    DEFF Research Database (Denmark)

    Herbst, H.; Hamilton-Dutoit, S.; Jakel, K.T.

    2004-01-01

    malignant lymphomas, amelanotic melanomas, Merkel cell carcinomas, and adenoid cystic carcinomas, in particular in small biopsy materials. Because of the rarity of undifferentiated salivary gland carcinomas, the differential diagnosis should always include metastases of undifferentiated carcinomas arising...

  12. The dutch surgical colorectal audit

    NARCIS (Netherlands)

    Leersum, N.J. van; Snijders, H.S.; Henneman, D.; Kolfschoten, N.E.; Gooiker, G.A.; Berge, M.G. Ten; Eddes, E.H.; Wouters, M.W.; Tollenaar, R.A.E.M.; Bemelman, W.A.; Dam, R.M. van; Elferink, M.A.; Karsten, T.M.; Krieken, J.H. van; Lemmens, V.E.; Rutten, H.J.; Manusama, E.R.; Velde, C.J. van de; Meijerink, W.J.H.J.; Wiggers, T.; Harst, E. van der; Dekker, J.W.T.; Boerma, D.

    2013-01-01

    INTRODUCTION: In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated

  13. The Dutch surgical colorectal audit

    NARCIS (Netherlands)

    van Leersum, N. J.; Snijders, H. S.; Henneman, D.; Kolfschoten, N. E.; Gooiker, G. A.; ten Berge, M. G.; Eddes, E. H.; Wouters, M. W. J. M.; Tollenaar, R. A. E. M.; Bemelman, W. A.; van Dam, R. M.; Elferink, M. A.; Karsten, Th M.; van Krieken, J. H. J. M.; Lemmens, V. E. P. P.; Rutten, H. J. T.; Manusama, E. R.; van de Velde, C. J. H.; Meijerink, W. J. H. J.; Wiggers, Th; van der Harst, E.; Dekker, J. W. T.; Boerma, D.

    2013-01-01

    In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated by the Dutch

  14. Intestinal stem cell imaging in colorectal cancer screening.

    Science.gov (United States)

    Moossavi, S; Ansari, R

    2013-01-01

    Colorectal cancer (CRC) is a common cancer and cause of cancer-related death worldwide. Although, the step-wise genetic alteration in the course of adenoma-carcinoma progression is well-understood, the mechanism of the tumour initiation and promotion is yet to be elucidated. Murine studies indicate that intestinal tumour originates from normal intestinal stem cells which acquire the oncogenic hits. It is plausible to consider the abnormality of the stem cell compartment as the earliest potentially detectable phenotypic change in the course of intestinal tumourigenesis. Hereby, it is hypothesised that imaging of the abnormal state of the intestinal stem cell compartment could potentially be integrated in CRC screening strategy.

  15. Correlations between cytoplasmic CSE1L in neoplastic colorectal glands and depth of tumor penetration and cancer stage

    Directory of Open Access Journals (Sweden)

    Tai Cheng-Jeng

    2013-01-01

    Full Text Available Abstract Background Colorectal carcinomas spread easily to nearby tissues around the colon or rectum, and display strong potential for invasion and metastasis. CSE1L, the chromosome segregation 1-like protein, is implicated in cancer progression and is located in both the cytoplasm and nuclei of tumor cells. We investigated the prognostic significance of cytoplasmic vs. nuclear CSE1L expression in colorectal cancer. Methods The invasion- and metastasis-stimulating activities of CSE1L were studied by in vitro invasion and animal experiments. CSE1L expression in colorectal cancer was assayed by immunohistochemistry, with tissue microarray consisting of 128 surgically resected specimens; and scored using a semiquantitative method. The correlations between CSE1L expression and clinicopathological parameters were analyzed. Results CSE1L overexpression was associated with increased invasiveness and metastasis of cancer cells. Non-neoplastic colorectal glands showed minimal CSE1L staining, whereas most colorectal carcinomas (99.2%, 127/128 were significantly positive for CSE1L staining. Cytoplasmic CSE1L was associated with cancer stage (P=0.003 and depth of tumor penetration (P=0.007. Cytoplasmic CSE1L expression also correlated with lymph node metastasis of the disease in Cox regression analysis Conclusions CSE1L regulates the invasiveness and metastasis of cancer cells, and immunohistochemical analysis of cytoplasmic CSE1L in colorectal tumors may provide a useful aid to prognosis.

  16. Prevention of Colorectal Cancer by Targeting Obesity-Related Disorders and Inflammation.

    Science.gov (United States)

    Shirakami, Yohei; Ohnishi, Masaya; Sakai, Hiroyasu; Tanaka, Takuji; Shimizu, Masahito

    2017-04-26

    Colorectal cancer is a major healthcare concern worldwide. Many experimental and clinical studies have been conducted to date to discover agents that help in the prevention of this disease. Chronic inflammation in colonic mucosa and obesity, and its related metabolic abnormalities, are considered to increase the risk of colorectal cancer. Therefore, treatments targeting these factors might be a promising strategy to prevent the development of colorectal cancer. Among a number of functional foods, various phytochemicals, including tea catechins, which have anti-inflammatory and anti-obesity properties, and medicinal agents that ameliorate metabolic disorders, might also be beneficial in the prevention of colorectal cancer. In this review article, we summarize the strategies for preventing colorectal cancer by targeting obesity-related disorders and inflammation through nutraceutical and pharmaceutical approaches, and discuss the mechanisms of several phytochemicals and medicinal drugs used in basic and clinical research, especially focusing on the effects of green tea catechins.

  17. Evaluation of an automated immunochemical fecal occult blood test for colorectal neoplasia detection in a Chinese population.

    Science.gov (United States)

    Wong, Wai Man; Lam, Shiu Kum; Cheung, Kwan Lok; Tong, Teresa Sze Man; Rozen, Paul; Young, Graeme P; Chu, Kin Wah; Ho, Judy; Law, Wai Lun; Tung, Hiu Ming; Choi, Hok Kwok; Lee, Yee Man; Lai, Kam Chuen; Hu, Wayne H C; Chan, Chi Kuen; Yuen, Man Fung; Wong, Benjamin Chun-Yu

    2003-05-15

    Most commercial fecal occult blood tests (FOBT) used for colorectal carcinoma screening of Western populations are guaiac-based, manually developed, subjective, and sensitive to dietary components. Preliminary studies demonstrated the unsuitability of these tests for screening a Chinese population. The goal of the current study was to evaluate the performance characteristics of a human hemoglobin-specific automated immunochemical FOBT, the Magstream 1000/Hem SP (Fujirebio, Inc., Tokyo, Japan), in a Chinese population referred for colonoscopy. Two hundred fifty consecutive patients who were referred for colonoscopy and met the study inclusion criteria provided samples for the immunochemical FOBT (without dietary restrictions) from two successive stool specimens. Tests were developed with an automated instrument that had an adjustable sensitivity threshold. The sensitivity, specificity, and positive predictive value for detecting colorectal adenomas and carcinomas were calculated according to the manufacturer's instructions over a range of sensitivity levels. At the optimal threshold level, the sensitivity, specificity, and positive predictive value for detection of significant colorectal neoplasia (adenomas >or= 1.0 cm and carcinomas) were 62%, 93%, and 44%, respectively. The test was easy to use, and results did not depend on operator experience. The automated immunochemical FOBT used in the current study was a robust, convenient, and useful tool for colorectal carcinoma screening in the study population. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11369

  18. Comparing the outcomes of two strategies for colorectal tumor detection: Policy-promoted screening program versus health promotion service

    Directory of Open Access Journals (Sweden)

    Ping-Hsiu Wu

    2013-06-01

    Conclusion: In comparison with the outcomes of the HPS database, the screening efficacy of the PPS database is even for detecting colorectal carcinoma but is limited in detecting advanced adenoma. HPS may provide comprehensive validity indicators and will be helpful in adjusting current policies for improving screening performance.

  19. Retinoblastoma (pRb) protein immunoexpression in colorectal cancer.

    Science.gov (United States)

    Chetty, R; Subramoney, T; Singh, J; Harilal, P

    1997-01-01

    The level of expression of the cell cycle regulatory proteins is an important facet in determining the malignant state. Fifty consecutive colectomy specimens of colorectal carcinoma in patients over 50 years of age, and 25 cases in patients under 30 years, were examined to ascertain retinoblastoma protein expression and to relate this to clinicopathological features. Retinoblastoma protein (pRb) staining was more intense in well differentiated, low stage carcinomas in the over 50 age group (p < 0.001). On the other hand, in the under 30 age group, pRb staining was seen in all tumours grades and stages. No statistical significance was noted with other clinical or pathological features in both age groups.

  20. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    Science.gov (United States)

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  1. Experimental validation of specificity of the squamous cell carcinoma antigen-immunoglobulin M (SCCA-IgM) assay in patients with cirrhosis.

    Science.gov (United States)

    Zuin, Jessica; Veggiani, Gianluca; Pengo, Paolo; Gallotta, Andrea; Biasiolo, Alessandra; Tono, Natascia; Gatta, Angelo; Pontisso, Patrizia; Toth, Radovan; Cerin, Dean; Frecer, Vladimir; Meo, Sabrina; Gion, Massimo; Fassina, Giorgio; Beneduce, Luca

    2010-02-01

    Squamous cell carcinoma antigen-immunoglobulin M (SCCA-IgM) is a useful biomarker for the risk of development of hepatocellular carcinoma (HCC) in patients with cirrhosis due to its progressive increase associated to HCC evolution. In patients with cirrhosis, other assays have been affected by interfering reactivities of IgM. In this study, the analytical specificity of the SCCA-IgM assay was assessed by evaluating SCCA-IgM measurement dependence on different capture phases, and by measuring the recovery of SCCA-IgM reactivity following serum fractionation. Serum samples from 82 patients with cirrhosis were analyzed. SCCA-IgM was measured using the reference test (Hepa-IC, Xeptagen, Italy) that is based on rabbit oligoclonal anti-squamous cell carcinoma antigen (SCCA) and a dedicated ELISA with a mouse monoclonal anti-SCCA as the capture antibody. SCCA-IgM concentrations measured with the reference assay (median value=87 AU/mL) were higher than those measured with the mouse monoclonal test (median value=78 AU/mL). However, the differences in the SCCA-IgM distribution were not statistically significant (p>0.05). When SCCA-IgM concentrations measured with both tests were compared, a linear correlation was found (r=0.77, pSCCA-IgM reactivity was seen only in the fractions corresponding to components with a molecular weight higher than IgM and SCCA (>2000 kDa) with both tests. The equivalence of both SCCA-IgM assays and the absence of reactivity not related to immune complexes support the analytical specificity of SCCA-IgM measurements. The results validate the assessment of SCCA-IgM for prognostic purposes in patients with cirrhosis.

  2. [Genetics of colorectal cancer].

    Science.gov (United States)

    Balaguer, Francesc

    2013-10-01

    Up to 5% of all cases of colorectal cancer (CRC) are due to a known hereditary syndrome. These hereditary forms often require a high degree of suspicion for their diagnosis and specific and specialized management. Moreover, a diagnosis of hereditary CRC has important consequences, not only for patients-for whom highly effective preventive measures are available-, but also for their relatives, who may be carriers of the same condition. The most significant advances in the field of hereditary CRC have been produced in the diagnosis and characterization of these syndromes and in the discovery of new causative genes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  3. [Epigenetics and colorectal cancer].

    Science.gov (United States)

    Menéndez, Pablo; Villarejo, Pedro; Padilla, David; Menéndez, José María; Rodríguez Montes, José Antonio

    2012-05-01

    The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease. Copyright © 2011 AEC. Published by Elsevier Espana. All rights reserved.

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

    Science.gov (United States)

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

    2013-03-01

    The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

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

    Directory of Open Access Journals (Sweden)

    N. Erkasap

    2013-03-01

    Full Text Available The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases and metastatic colon (13 cases cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

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

    Directory of Open Access Journals (Sweden)

    N. Erkasap

    Full Text Available The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases and metastatic colon (13 cases cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

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

    Energy Technology Data Exchange (ETDEWEB)

    Erkasap, N.; Ozkurt, M. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Erkasap, S.; Yasar, F. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uzuner, K. [Department of Physiology, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Ihtiyar, E. [Department of General Surgery, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Uslu, S.; Kara, M. [Department of Biochemistry, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey); Bolluk, O. [Department of Biostatistics, Osmangazi University Medical Faculty, Meselik, Eskisehir (Turkey)

    2013-03-19

    The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis.

  8. Primary Prevention of Colorectal Cancer

    Science.gov (United States)

    Chan, Andrew T.; Giovannucci, Edward L.

    2010-01-01

    Colorectal cancer has been strongly associated with a Western lifestyle. In the past several decades, much has been learned about the dietary, lifestyle, and medication risk factors for this malignancy. Although there is controversy about the role of specific nutritional factors, consideration of the dietary pattern as a whole appears useful for formulating recommendations. For example, several studies have shown that high intake of red and processed meats, highly refined grains and starches, and sugars is related to increased risk of colorectal cancer. Replacing these factors with poultry, fish, and plant sources as the primary source of protein; unsaturated fats as the primary source of fat; and unrefined grains, legumes and fruits as the primary source of carbohydrates is likely to lower risk of colorectal cancer. Although a role for supplements, including vitamin D, folate, and vitamin B6, remains uncertain, calcium supplementation is likely to be at least modestly beneficial. With respect to lifestyle, compelling evidence indicates that avoidance of smoking and heavy alcohol use, prevention of weight gain, and the maintenance of a reasonable level of physical activity are associated with markedly lower risks of colorectal cancer. Medications such as aspirin and non-steroidal anti-inflammatory drugs and post-menopausal hormones for women are associated with significant reductions in colorectal cancer risk, though their utility is affected by associated risks. Taken together, modifications in diet and lifestyle should substantially reduce the risk of colorectal cancer and could complement screening in reducing colorectal cancer incidence. PMID:20420944

  9. Diet, gender, and colorectal neoplasia.

    Science.gov (United States)

    Jacobs, Elizabeth T; Thompson, Patricia A; Martínez, María Elena

    2007-09-01

    The association between diet and colorectal cancer has been studied in depth for many decades, with equivocal results. It has been hypothesized that cancers arising in the distal and proximal colon have different pathologies, and therefore different risk factors. As such, it is possible that diet-related factors might influence colorectal neoplasia differently depending on the subsite. Recent evidence indicates that women may be more likely to develop proximal cancers than men. Additionally, the link between certain dietary factors and colorectal neoplasia in women seems to vary by menopausal status. Given these observations, women may be affected differently than men by diet-related factors. The objective of this article was therefore to review the data for diet and colorectal adenomas and cancer, and then attempt to address the potential differences in the association of diet-related factors and colorectal neoplasia in men and women. For total energy intake, selenium, and fiber, it seems that there may be slightly stronger effects in men as compared with women, whereas calcium and folate seem to affect both sexes similarly. With regard to vitamin D and colorectal cancer, women may exhibit stronger associations than men. Perhaps the most evidence for a sex-specific effect is observed for obesity, where more substantial direct relationships between body size and colorectal neoplasia have been reported for men than for women. However, this observation may be influenced by the differential effects in women by menopausal status. Further research on sex-specific dietary effects is warranted.

  10. [In vivo experimental study on nasopharyngeal carcinoma with combination of pAdKDR-tk/GCV suicide gene therapy system and 60Co radiotherapy].

    Science.gov (United States)

    Qiu, Qianhui; Sun, Wei; Chen, Shaohua; Huang, Xiaoming

    2010-05-01

    To explore the killing effect of pAdKDR-tk/GCV suicide gene therapy system combined with 60Co radiotherapy on human nasopharyngeal carcinoma in vivo. The pAdKDR-tk/GCV suicide gene therapy system and 60Co radiotherapy were used separately or in combination for human nasopharyngeal carcinoma in vivo to compare their effects. The tumor growth curve and inhibition rate of tumor to the cure effects of the combination of the pAdKDR-tk/GCV suicide gene therapy system and 60Co radiotherapy. The inhibition rate of gene therapy alone and radiotherapy alone in curing the transplanted tumor in nude mouse subcutaneously was 58.43% and 70.88% respectively, and the combined application of gene therapy and radiotherapy exhibited stronger therapeutic effects (the inhibition rate was 84.39%, Pgene therapy alone and radiotherapy alone in the twenty-first day. The combined application of gene therapy and radiotherapy has an obviously higher curative effect than simple therapy. This method would establish a theoretic and clinical basis for the research of combination of suicide gene system tumor vascular targeting treating and radiotherapy.

  11. Aberrant DNA methylation of WNT pathway genes in the development and progression of CIMP-negative colorectal cancer.

    Science.gov (United States)

    Galamb, Orsolya; Kalmár, Alexandra; Péterfia, Bálint; Csabai, István; Bodor, András; Ribli, Dezső; Krenács, Tibor; Patai, Árpád V; Wichmann, Barnabás; Barták, Barbara Kinga; Tóth, Kinga; Valcz, Gábor; Spisák, Sándor; Tulassay, Zsolt; Molnár, Béla

    2016-08-02

    The WNT signaling pathway has an essential role in colorectal carcinogenesis and progression, which involves a cascade of genetic and epigenetic changes. We aimed to analyze DNA methylation affecting the WNT pathway genes in colorectal carcinogenesis in promoter and gene body regions using whole methylome analysis in 9 colorectal cancer, 15 adenoma, and 6 normal tumor adjacent tissue (NAT) samples by methyl capture sequencing. Functional methylation was confirmed on 5-aza-2'-deoxycytidine-treated colorectal cancer cell line datasets. In parallel with the DNA methylation analysis, mutations of WNT pathway genes (APC, β-catenin/CTNNB1) were analyzed by 454 sequencing on GS Junior platform. Most differentially methylated CpG sites were localized in gene body regions (95% of WNT pathway genes). In the promoter regions, 33 of the 160 analyzed WNT pathway genes were differentially methylated in colorectal cancer vs. normal, including hypermethylated AXIN2, CHP1, PRICKLE1, SFRP1, SFRP2, SOX17, and hypomethylated CACYBP, CTNNB1, MYC; 44 genes in adenoma vs. NAT; and 41 genes in colorectal cancer vs. adenoma comparisons. Hypermethylation of AXIN2, DKK1, VANGL1, and WNT5A gene promoters was higher, while those of SOX17, PRICKLE1, DAAM2, and MYC was lower in colon carcinoma compared to adenoma. Inverse correlation between expression and methylation was confirmed in 23 genes, including APC, CHP1, PRICKLE1, PSEN1, and SFRP1. Differential methylation affected both canonical and noncanonical WNT pathway genes in colorectal normal-adenoma-carcinoma sequence. Aberrant DNA methylation appears already in adenomas as an early event of colorectal carcinogenesis.

  12. Molecular Features and Methylation Status in Early Onset (≤40 Years Colorectal Cancer: A Population Based, Case-Control Study

    Directory of Open Access Journals (Sweden)

    Giulia Magnani

    2015-01-01

    Full Text Available Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%. KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls (p=0.02. Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

  13. [Evidence-based public health: strategies aimed at increasing adherence to colorectal cancer screening programs].

    Science.gov (United States)

    Tarulli, Sabrina; Lepore, Anna Raffaella; Sansoni, Diana; Viviani, Giancarlo

    2007-01-01

    The ministerial decree 29/11/2001 included colorectal carcinoma screening procedures among the "essential" health care services that should be delivered free of charge to citizens. Secondary prevention programs for colorectal cancer must therefore be implemented in all Italian regions. An international literature search on colorectal cancer screening was performed in order to provide a resource for public health workers and decision makers, for selecting interventions to improve adherence to screening programs. The following interventions have been proven to be effective: reducing structural barriers to screening, active recall systems, multicomponent interventions involving active recall and health education, active reminder systems, periodic dissemination of results, and physician health education. Opportunistic screening by general practitioners, that is, performing faecal occult blood testing in asymptomatic patients consulting a GP for other reasons, is a strategy should also be implemented.

  14. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds.

    Science.gov (United States)

    Pan, Min-Hsiung; Lai, Ching-Shu; Wu, Jia-Ching; Ho, Chi-Tang

    2011-01-01

    Colorectal cancer is one of the major causes of cancer-related mortality in both men and women worldwide. This review focuses on preventing the initiation and promotion of neoplastic growth in colorectal cancer, particularly with natural dietary compounds. Chemoprevention is defined as the use of natural dietary compounds and/or synthetic substances that can delay, prevent, or even reverse the development of adenomas, as well as the progression from adenoma to carcinoma. The molecular mechanisms of their chemopreventive action are associated with the modulation of signaling cascades, gene expressions involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of chronic inflammation, metastasis, and angiogenesis. Here, we summarize the currently known targets and signaling pathways whereby natural dietary compounds interfere with the development of colorectal cancer, and thus providing evidence for these substances in colonic cancer chemopreventive action. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Social media in colorectal surgery.

    Science.gov (United States)

    Wexner, S D; Petrucci, A M; Brady, R R; Ennis-O'Connor, M; Fitzgerald, J E; Mayol, J

    2017-02-01

    The engagement of social media in healthcare continues to expand. For members of the colorectal community, social media has already made a significant impact on practice, education and patient care. The applications are unique such that they provide a platform for instant communication and information sharing with other users worldwide. The purpose of this article is to provide an overview of how social media has the potential to change clinical practice, training, research and patient care in colorectal surgery. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

  16. [Hereditary and familial colorectal cancer].

    Science.gov (United States)

    Balaguer, Francesc

    2014-09-01

    Up to 5% of all colorectal cancer cases are caused by a known hereditary syndrome. These hereditary types often need a higher degree of clinical suspicion to be diagnosed and require specific and specialized management. In addition, diagnosing hereditary colorectal cancer has significant consequences not only for the patient, for whom there are effective preventative measures, but also for their families, who could be carriers of the condition. The most significant advances in the field of colorectal cancer have come from the diagnosis and characterization of these syndromes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  17. Ameloblastic carcinoma

    Directory of Open Access Journals (Sweden)

    Praveen B Kumar

    2009-01-01

    Full Text Available Ameloblastoma of jaws are common and locally destructive tumors originating from odontogenic apparatus. They constitute approximately 1% of all jaw tumors with 80% occurring in the mandible. Ameloblastoma exhibiting a frank malignancy is a rare entity and occurs in less than 1% of all ameloblastomas. Among the two jaws, ameloblastic carcinoma involving maxilla is extremely rare with only few cases reported so far in the literature. Here we report two cases of ameloblastic carcinoma one involving the maxilla and the other involving mandible, with an aggressive clinical course leading to extensive local destruction of the affected jaws.

  18. Early diagnosis of colorectal tumours - significance of the double contrast enema

    Energy Technology Data Exchange (ETDEWEB)

    Roedl, W.

    1985-03-01

    Early diagnosis of cancer in the colon is of a particular importance owing to its increasing morbidity and more favourable prognosis. Malignant degeneration of adenomatous colonic polyps is seen as evidenced according to the adenoma-carcinoma sequence. Malignity rate depends on the size and type of adenoma. Macroscopically, there are no criteria found for an adenoma nor for its malignant degeneration. However, 70% of all colorectal polyps are adenomas. Therefore, early diagnosis of colorectal carcinomas is to aim at detecting minuscule polyps. The hit rate of radiological examination depends on the preparation of the patient, on the examination technique used and on the examiners stage of professional training and experience. Under optimum conditions (good patient preparation, double contrast enema, fully-trained radiologist), our hit rate was 61% in cases of polyps up to 1 cm in diameter, and 85% of those larger than 1 cm.

  19. Colorectal adenocarcinoma metastasizing to the oral mucosa of the upper jaw

    Directory of Open Access Journals (Sweden)

    Baranović Marijan

    2015-01-01

    Full Text Available Introduction. Metastases to the oral cavity are uncommon, accounting for only 1% of all oral malignant tumors. When they occur they mostly originate from primary tumors of the lungs, kidney, breast and prostate. Oral metastases from the primary colorectal carcinoma are much more infrequent. Case Outline. We present an unusual case of a 78-year-old man with a soft tissue oral metastasis originating from the primary colorectal carcinoma. The patient was referred to the Department of Otorhinolaryngology, Head and Neck Surgery with an intraoral mass on the right side of the maxilla. The diagnosis was confirmed by histopathologic examination and immunohistochemical analysis. Conclusion. Oral metastases occur rarely and often can mimic much more common benign lesions, therefore they should be considered as a possibility in a differential diagnosis.

  20. Lactoferrin Deficiency Promotes Colitis-Associated Colorectal Dysplasia in Mice

    Science.gov (United States)

    Ye, Qiurong; Zheng, Ying; Fan, Songqing; Qin, Zailong; Li, Nan; Tang, Anliu; Ai, Feiyan; Zhang, Xuemei; Bian, Yanhui; Dang, Wei; Huang, Jing; Zhou, Ming; Zhou, Yanhong; Xiong, Wei; Yan, Qun; Ma, Jian; Li, Guiyuan

    2014-01-01

    Nonresolving inflammatory processes affect all stages of carcinogenesis. Lactoferrin, a member of the transferrin family, is involved in the innate immune response and anti-inflammatory, anti-microbial, and anti-tumor activities. We previously found that lactoferrin is significantly down-regulated in specimens of nasopharyngeal carcinoma (NPC) and negatively associated with tumor progression, metastasis, and prognosis of patients with NPC. Additionally, lactoferrin expression levels are decreased in colorectal cancer as compared with normal tissue. Lactoferrin levels are also increased in the various phases of inflammation and dysplasia in an azoxymethane–dextran sulfate sodium (AOM-DSS) model of colitis-associated colon cancer (CAC). We thus hypothesized that the anti-inflammatory function of lactoferrin may contribute to its anti-tumor activity. Here we generated a new Lactoferrin knockout mouse model in which the mice are fertile, develop normally, and display no gross morphological abnormalities. We then challenged these mice with chemically induced intestinal inflammation to investigate the role of lactoferrin in inflammation and cancer development. Lactoferrin knockout mice demonstrated a great susceptibility to inflammation-induced colorectal dysplasia, and this characteristic may be related to inhibition of NF-κB and AKT/mTOR signaling as well as regulation of cell apoptosis and proliferation. Our results suggest that the protective roles of lactoferrin in colorectal mucosal immunity and inflammation-related malignant transformation, along with a deficiency in certain components of the innate immune system, may lead to serious consequences under conditions of inflammatory insult. PMID:25057912

  1. Reproducibility of parameter learning with missing observations in naive Wnt Bayesian network trained on colorectal cancer samples and doxycycline-treated cell lines.

    Science.gov (United States)

    Sinha, Shriprakash

    2015-07-01

    In this manuscript the reproducibility of parameter learning with missing observations in a naive Bayesian network and its effect on the prediction results for Wnt signaling activation in colorectal cancer is tested. The training of the network is carried out separately on doxycycline-treated LS174T cell lines (GSE18560) as well as normal and adenoma samples (GSE8671). A computational framework to test the reproducibility of the parameters is designed in order check the veracity of the prediction results. Detailed experimental analysis suggests that the prediction results are accurate and reproducible with negligible deviations. Anomalies in estimated parameters are accounted for due to the representation issues of the Bayesian network model. High prediction accuracies are reported for normal (N) and colon-related adenomas (AD), colorectal cancer (CRC), carcinomas (C), adenocarcinomas (ADC) and replication error colorectal cancer (RER CRC) test samples. Test samples from inflammatory bowel diseases (IBD) do not fare well in the prediction test. Also, an interesting case regarding hypothesis testing came up while proving the statistical significance of the different design setups of the Bayesian network model. It was found that hypothesis testing may not be the correct way to check the significance between design setups, especially when the structure of the model is the same, given that the model is trained on a single piece of test data. The significance test does have value when the datasets are independent. Finally, in comparison to the biologically inspired models, the naive Bayesian model may give accurate results, but this accuracy comes at the cost of a loss of crucial biological knowledge which might help reveal hidden relations among intra/extracellular factors affecting the Wnt pathway.

  2. Immunohistochemistry of colorectal cancer biomarker phosphorylation requires controlled tissue fixation.

    Directory of Open Access Journals (Sweden)

    Abbey P Theiss

    Full Text Available Phosphorylated signaling molecules are biomarkers of cancer pathophysiology and resistance to therapy, but because phosphoprotein analytes are often labile, poorly controlled clinical laboratory practices could prevent translation of research findings in this area from the bench to the bedside. We therefore compared multiple biomarker and phosphoprotein immunohistochemistry (IHC results in 23 clinical colorectal carcinoma samples after either a novel, rapid tissue fixation protocol or a standard tissue fixation protocol employed by clinical laboratories, and we also investigated the effect of a defined post-operative "cold" ischemia period on these IHC results. We found that a one-hour cold ischemia interval, allowed by ASCO/CAP guidelines for certain cancer biomarker assays, is highly deleterious to certain phosphoprotein analytes, specifically the phosphorylated epidermal growth factor receptor (pEGFR, but shorter ischemic intervals (less than 17 minutes facilitate preservation of phosphoproteins. Second, we found that a rapid 4-hour, two temperature, formalin fixation yielded superior staining in several cases with select markers (pEGFR, pBAD, pAKT compared to a standard overnight room temperature fixation protocol, despite taking less time. These findings indicate that the future research and clinical utilities of phosphoprotein IHC for assessing colorectal carcinoma pathophysiology absolutely depend upon attention to preanalytical factors and rigorously controlled tissue fixation protocols.

  3. The natural history of pT1 colorectal cancer

    Directory of Open Access Journals (Sweden)

    Mauro eRisio

    2012-03-01

    Full Text Available Colorectal carcinoma invading the submucosa but not the muscular layer (pT1, early invasive cancer represents the earliest form of clinically relevant colorectal cancer in most patients. Neoplastic invasion of the submucosa, in fact, opens the way to metastasis via the lymphatic and blood vessels, and the choice between surveillance and major surgery will turn on its metastatic potential. The following histological features predict the risk of metastasis and the different clinical outcomes: grade of differentiation of carcinoma, lymphovascular invasion, state of the resection margin. Microstaging of invasive cancer, namely the width and the depth of submucosal invasion, together with tumor budding at the advancing edge allow the metastatic risk to be further stratified in minimal, low, and high. Different, although morphologically undistinguishable, tumorigenic pathways are supposed to lead to the malignant transformation of colonic mucosa and subsequently drive the progression from early to advanced cancer: new biomarkers are needed to identify progressive and non-progressive pT1 neoplasia.

  4. Rapidly resorbable vs. non-resorbable suture for experimental colonic anastomoses in rats--a randomized experimental study

    DEFF Research Database (Denmark)

    Klein, Mads; Pommergaard, Hans-Christian; Gögenur, Ismail

    2011-01-01

    Anastomotic dehiscence remains an important challenge for colorectal surgeons worldwide. Extensive research focused on performing a safe anastomosis is conducted with rats being the most used model when examining colorectal anastomoses. In daily clinical practice resorbable sutures are used when...... hand-sewn anastomoses are performed. However, in the experimental studies examining colorectal anastomoses, non-resorbable sutures have predominantly been used. The aim of this study was to compare a rapidly resorbable suture with a non-resorbable suture in experimental colorectal anastomoses....

  5. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Castanos-Velez Esmeralda

    2006-09-01

    Full Text Available Abstract Background Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression. Results We investigated genome-wide gene expression in colorectal carcinoma (CRC and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC. Conclusion An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.

  6. Microsatellite pathologic score does not efficiently identify high microsatellite instability in colorectal serrated adenocarcinoma.

    Science.gov (United States)

    García-Solano, José; Conesa-Zamora, Pablo; Carbonell, Pablo; Trujillo-Santos, Javier; Torres-Moreno, Daniel; Rodriguez-Braun, Edith; Vicente-Ortega, Vicente; Pérez-Guillermo, Miguel

    2013-05-01

    The microsatellite pathologic score has been proposed as a valuable tool to estimate the probability of a colorectal cancer having high microsatellite instability; however, this score has not been tested in serrated adenocarcinoma. Our aim was to evaluate microsatellite pathologic score in serrated adenocarcinoma, conventional carcinoma, and colorectal cancer with high microsatellite instability histologic features. Eighty-nine serrated adenocarcinoma and 81 matched conventional carcinomas were tested with microsatellite pathologic score, and the results were compared with those of 24 high microsatellite instability histologic features. Validation was performed by microsatellite instability analysis. Although all colorectal cancers with high microsatellite instability histologic features rendered a more than 5.5 score, the microsatellite pathologic score performance was of lower rank in high microsatellite instability serrated adenocarcinoma because none of the cases scored above 5.5 (>77% probability of being high microsatellite instability). High microsatellite instability serrated adenocarcinoma shows pathologic features different from those observed in high microsatellite instability histologic features such as adverse prognostic histologic features at the invasive front. We describe a serrated adenocarcinoma subtype showing high microsatellite instability and some, but not all, high microsatellite instability histologic features that would not be detected if the microsatellite pathologic score cutoff is set at the highest rank. To increase microsatellite pathologic score sensitivity in serrated adenocarcinoma, we propose to set up a 2.1 cutoff score when faced by a right-sided colorectal cancer with serrated features. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Carcinoma vulvar

    Directory of Open Access Journals (Sweden)

    Yamit Peñas Zayas

    2015-11-01

    Full Text Available El carcinoma de la vulva tiene una incidencia de aproximadamente un 3-5% dentro de todas las enfermedades ginecológicas malignas. El 90% de los tumores malignos de la vulva está constituido por carcinoma epidermoide, el resto son adenocarcinomas, carcinomas de células basales y melanomas. Se realiza la presentación de un caso de una paciente femenina de 25 años de edad con antecedentes  de Diabetes Mellitus tipo II y trombopatia, que ingresa en el servicio de ginecología con un cuadro cutáneo polimorfo, localizado en labios mayores y menores, dado por lesiones eritematoerosivas y vegetante, sospechándose clínicamente el diagnóstico  de un carcinoma epidermoide, corroborándose el mismo histológicamente al realizarse biopsia de piel. Se indicó tratamiento con quimioterapia. Por la edad de la paciente y ser menos frecuente en mucosa que en la piel,  motivo la presentación del caso.

  8. Parathyroid carcinoma

    DEFF Research Database (Denmark)

    Qvist, N; Krøll, L; Ladefoged, C

    1986-01-01

    Parathyroid carcinoma is a slow growing tumor, and the patients most often die from complications to the hypercalcemia. Therefore, any attempt should be made to remove local recurrence and metastasis surgically, as medical treatment is disappointing. A case treated with extensive vascular surgery...

  9. Nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Brennan Bernadette

    2006-06-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a tumor arising from the epithelial cells that cover the surface and line the nasopharynx. The annual incidence of NPC in the UK is 0.3 per million at age 0–14 years, and 1 to 2 per million at age 15–19 years. Incidence is higher in the Chinese and Tunisian populations. Although rare, NPC accounts for about one third of childhood nasopharyngeal neoplasms. Three subtypes of NPC are recognized in the World Health Organization (WHO classification: 1 squamous cell carcinoma, typically found in the older adult population; 2 non-keratinizing carcinoma; 3 undifferentiated carcinoma. The tumor can extend within or out of the nasopharynx to the other lateral wall and/or posterosuperiorly to the base of the skull or the palate, nasal cavity or oropharynx. It then typically metastases to cervical lymph nodes. Cervical lymphadenopathy is the initial presentation in many patients, and the diagnosis of NPC is often made by lymph node biopsy. Symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis of the soft palate, hearing loss and cranial nerve palsies. Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Etiological factors include Epstein-Barr virus (EBV, genetic susceptibility and consumption of food with possible carcinogens – volatile nitrosamines. The recommended treatment schedule consists of three courses of neoadjuvant chemotherapy, irradiation, and adjuvant interferon (IFN-beta therapy.

  10. Laryngeal carcinoma

    African Journals Online (AJOL)

    Biological pharyngo-cutaneous fistula could not. One patient died markers of alcohol abuse in patients with from a ruptured carotid following radiotherapy three carcinoma of the larynx. Acta months after surgery, while the remaining eight are still. Otorrinolaringol Esp 1998 Aug- doing well with an average duration of follow ...

  11. Danish Colorectal Cancer Group Database

    DEFF Research Database (Denmark)

    Ingeholm, Peter; Gögenur, Ismail; Iversen, Lene H

    2016-01-01

    AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed......, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal...... diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long...

  12. Lysyl oxidase in colorectal cancer.

    Science.gov (United States)

    Cox, Thomas R; Erler, Janine T

    2013-11-15

    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 advancements in the field of colorectal cancer.

  13. Immunohistochemistry in ocular carcinomas.

    Science.gov (United States)

    Sramek, Brett; Lisle, Allison; Loy, Timothy

    2008-07-01

    The distinction between ocular sebaceous carcinoma, poorly differentiated ocular squamous cell carcinoma and ocular basal cell carcinoma can be challenging. An appropriate immunohistochemical panel may help to differentiate these lesions. To determine the distribution and use of several immunostains in these specimens, formalin-fixed, paraffin-embedded tissue from several of each was studied using an immunohistochemical technique. Positive staining for cytokeratin (CK)7 was seen in 100% of sebaceous carcinomas, 77.8% of basal cell carcinomas and 67.7% of squamous cell carcinomas. One hundred percent of sebaceous and basal cell carcinomas were positive for cytokeratin CAM 5.2, while only 83.3% of squamous cell carcinomas were positive. Using epithelial membrane antigen (EMA), 100% of squamous cell carcinomas and 80% of sebaceous carcinomas were positive, while basal cell carcinomas were uniformly negative. One hundred percent of basal cell carcinomas and 80% of sebaceous carcinomas were positive for Ber-EP4, while all squamous cell carcinomas were negative. Finally, 77.8%, 20% and 16.7% of basal cell carcinomas, sebaceous carcinomas and squamous cell carcinomas showed immunoreactivity for the androgen receptor. An EMA positive, Ber-EP4 positive immunophenotype supports sebaceous carcinoma, EMA positive, Ber-EP4 negative result supports squamous cell carcinoma and an EMA negative, Ber-EP4 positive result supports basal cell carcinoma.

  14. [Colorectal cancer prevention by flavonoids].

    Science.gov (United States)

    Hoensch, Harald; Richling, Elke; Kruis, Wolfgang; Kirch, Wilhelm

    2010-08-01

    Valid, sustained and safe clinical means of colorectal cancer prevention are still lacking, but they are urgently needed to lower the incidence of colorectal cancer. Dietary factors and phytochemicals such as flavonoids play an important role for prevention. A selective search of the literature using PubMed was performed with the following key words: flavonoids, cancer, therapy, colorectal cancer focused on clinical queries. Results of clinical studies including the authors' own were compared. In vivo and in vitro studies with animals, cell cultures and subcellular components provide ample evidence for antimutagenic and anticarcinogenic effects of flavonoids as shown for multiple biological and molecular endpoints. Isoflavonoids in vitro have been shown to induce proliferation of breast cancer cells. Epidemiologic trials (cohort, case-control and cross-sectional studies) yielded inconsistent results for flavonoid protection. Systematic reviews and meta-analyses support the protective role of tea flavonoids on adenoma incidence. An interventional pilot study with sustained flavonoid supplementation was shown to reduce the rate of neoplasia in patients with resected colorectal cancer. Selected flavonoids possess antimutagenic and anticarcinogenic properties and could reduce the incidence of colorectal neoplasias as shown in epidemiologic trials. Randomized controlled clinical studies with flavonoid intervention are necessary to provide evidence for their role in colorectal cancer prevention.

  15. Robotics in Colorectal Surgery

    Science.gov (United States)

    Weaver, Allison; Steele, Scott

    2016-01-01

    Over the past few decades, robotic surgery has developed from a futuristic dream to a real, widely used technology. Today, robotic platforms are used for a range of procedures and have added a new facet to the development and implementation of minimally invasive surgeries. The potential advantages are enormous, but the current progress is impeded by high costs and limited technology. However, recent advances in haptic feedback systems and single-port surgical techniques demonstrate a clear role for robotics and are likely to improve surgical outcomes. Although robotic surgeries have become the gold standard for a number of procedures, the research in colorectal surgery is not definitive and more work needs to be done to prove its safety and efficacy to both surgeons and patients. PMID:27746895

  16. Epigenetics of colorectal cancer.

    Science.gov (United States)

    Goel, Ajay; Boland, C Richard

    2012-12-01

    In the early years of the molecular biology revolution, cancer research was mainly focused on genetic changes (ie, those that altered DNA sequences). Although this has been extremely useful as our understanding of the pathogenesis and biology of cancer has grown and matured, there is another realm in tumor development that does not involve changing the sequence of cellular DNA. This field is called "epigenetics" and broadly encompasses changes in the methylation of cytosines in DNA, changes in histone and chromatin structure, and alterations in the expression of microRNAs, which control the stability of many messenger RNAs and serve as "master regulators" of gene expression. This review focuses on the epigenetics of colorectal cancer and illustrates the impact epigenetics has had on this field. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Inactivation of the retinoblastoma gene yields a mouse model of malignant colorectal cancer.

    Science.gov (United States)

    Parisi, T; Bronson, R T; Lees, J A

    2015-11-26

    The retinoblastoma gene (Rb) is mutated at significant frequency in various human epithelial tumors, including colorectal cancer, and is strongly associated with metastatic disease. However, sole inactivation of Rb in the mouse has so far failed to yield epithelial cancers. Here, we specifically inactivate Rb and/or p53 in the urogenital epithelium and the intestine. We find that the loss of both tumor suppressors is unable to yield tumors in the transitional epithelium lining the bladder, kidneys and ureters. Instead, these mice develop highly metastatic tumors of neuroendocrine, not epithelial, origin within the urogenital tract to give prostate cancer in the males and vaginal tumors in the females. Additionally, we discovered that the sole inactivation of Rb in the intestine was sufficient to induce formation of metastatic colorectal adenocarcinomas. These tumors closely mirror the human disease in regard to the age of onset, histological appearance, invasiveness and metastatic potential. Like most human colorectal carcinomas, our murine Rb-deficient tumors demonstrate genomic instability and they show activation of β-catenin. Deregulation of the Wnt/β-catenin pathway is specific to the intestinal tumors, as genomic instability but not activation of β-catenin was observed in the neuroendocrine tumors. To date, attempts to generate genetically engineered mouse models of colorectal cancer tumors have yielded mostly cancer of the small intestine, which rarely occurs in humans. Our system provides the opportunity to accurately model and study colorectal cancer in the mouse via a single gene mutation.

  18. Epithelial-specific loss of PTEN results in colorectal juvenile polyp formation and invasive cancer.

    Science.gov (United States)

    Marsh Durban, Victoria; Jansen, Marnix; Davies, Emma J; Morsink, Folkert H; Offerhaus, G Johan A; Clarke, Alan R

    2014-01-01

    Cowden syndrome (CS) is a rare autosomal dominant cancer-prone disorder caused by germ-line mutation of the phosphatase and tensin homolog mutated on chromosome 10 (PTEN) tumor-suppressor gene. Affected patients commonly develop juvenile polyps, and show an elevated risk of developing colorectal cancers. The etiology of these peculiar polyps remains unclear, although previous work has suggested somatic PTEN alterations in the stroma of juvenile polyps. After a long latency period, we find epithelial-specific PTEN deletion to cause formation of juvenile polyps in the colorectum without stromal PTEN loss. More important, we find that these lesions closely recapitulate all of the characteristic histopathological features of juvenile polyps seen in patients with CS, including stromal alterations and dysplastic transformation to colorectal carcinoma. The stromal alterations we identify after epithelial-specific PTEN loss suggest that PTEN may be involved in altered epithelial-mesenchymal cross talk, which, in turn, predisposes to colorectal neoplasia and polyposis. Our transgenic model is the first to recapitulate colorectal juvenile polyposis in patients with CS. We conclude that stromal PTEN loss is not a prerequisite for the formation of juvenile polyps, and that colorectal juvenile polyps in CS are bona fide neoplastic precursor lesions. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer.

    Science.gov (United States)

    Arun, C; London, N J M; Hemingway, D M

    2004-01-01

    Prognostic factors from clinical, laboratory and pathological data of patients with colorectal cancer are essential to identify high-risk groups to whom beneficial adjuvant therapy could be given. Endothelin-1, a growth factor, has been associated with the development and spread of solid tumours. This prospective study was performed to determine whether preoperative plasma big ET-1 levels might be useful as a prognostic indicator in patients with colorectal carcinoma. Sixty-five consecutive patients with colorectal cancer confirmed by biopsy were included prospectively into this study over a 12-month period. Plasma samples from a peripheral vein were obtained prior to surgery. Univariate analysis of survival using age ( 70 years), sex, Dukes' stage (A&B versus C), tumour size ( 50 mm), vascular invasion and plasma big ET-1 levels was performed and significant factors were then analysed with the Cox regression model. Three variables, age, Dukes' tumour stage and plasma big ET-1 levels, were found to have prognostic significance (p70 years (p=0.02), Dukes' C tumours (p=0.04) and plasma big ET-1 levels >4.2 pg/mL (p=0.02). The Cox regression model identified the same three variables as having independent prognostic value for overall survival. Preoperative plasma big ET-1 levels may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 levels may be useful in the selection of high-risk lymph node-negative patients with colorectal cancer for adjuvant therapy.

  20. Prevalence of Cytomegalovirus Infection in Patients With Colorectal Cancer by Using PCR Technique

    Directory of Open Access Journals (Sweden)

    Sahar Mehrabani-Khasraghi

    2016-01-01

    Full Text Available Background Colorectal cancer is the most common gastrointestinal cancer and the second leading cause of cancer deaths worldwide. Objectives The purpose of this study is to investigate the prevalence of cytomegalovirus in patients with colorectal carcinomas and polyps in comparison with healthy people. Patients and Methods In this analytical case-control study, 15 patients with colorectal cancer, 20 patients with colorectal polyps and also 35 patients without malignancy as controls were studied. Biopsy specimens were frozen under sterile conditions at -20ºC. After DNA extraction, analysis of polymerase chain reaction (PCR to detect CMV DNA in tissue samples was performed. Statistical analysis was performed with χ2 test. Results CMV DNA were found in 8 (53.3% of tumor samples, in 10 (50% of polyp samples and 13 (37.1% of the non-malignant control group. Statistical analysis showed no significant association between the prevalence of CMV and incidence colorectal cancer and polyps in comparison with the control group. Conclusions The results of the present study has shown the presence of CMV sequences in differentiated cancer tissue, polyp and non-malignant by PCR method reflects the ability of the virus to infect of the different colon cells.

  1. Microsatellite instability in metastatic colorectal cancer: a review of pathology, response to chemotherapy and clinical outcome.

    Science.gov (United States)

    Yim, Kein-Leong

    2012-09-01

    Approximately 10% of colorectal carcinomas demonstrate microsatellite instability (MSI). Distinct from the majority of colorectal cancers with chromosomal instability (CIN) which harbour allelic imbalance from chromosomal polyploidy and aneuploidy, MSI tumours retain intact chromosomal numbers but contain microsatellite repeats due to deficiency in mismatch repair which are thought to contribute to the early steps of tumourigenesis in colorectal cancer. While emerging clinical data has highlighted improved prognosis of tumours with MSI in early colorectal cancer and potentially circumventing the need for adjuvant chemotherapy, the implications of MSI deficiency in metastatic colorectal cancer (mCRC) remain uncertain. In order to assess the significance of MSI in mCRC, a broad literature review was carried out through online PubMed search on published articles encompassing pathological and clinical papers. This included pathological studies identifying the correlation with MSI status between primary sites and metastases, and chemotherapeutic studies assessing the impact of fluoropyrimidine-, irinotecan- and oxaliplatin-based regimens on mCRC with MSI.

  2. Microcystin-LR promotes epithelial-mesenchymal transition in colorectal cancer cells through PI3-K/AKT and SMAD2.

    Science.gov (United States)

    Ren, Yan; Yang, Mengli; Chen, Meng; Zhu, Qiangqiang; Zhou, Lihua; Qin, Wei; Wang, Ting

    2017-01-04

    Increasing evidences suggest that microcystins, a kind of toxic metabolites, produced by cyanobacteria in contaminated water may contribute to the aggravation of the human colorectal carcinoma. Our previous study showed that microcystin-LR (MC-LR) exposure caused significant invasion and migration of colorectal cancer cells. However, the roles of MC-LR in regulating epithelial-mesenchymal transition (EMT) in colorectal cancer cells remain unknown. In our study, we observed that MC-LR treatment decreased epithelial marker E-cadherin expression and up-regulated the levels of mesenchymal markers Vimentin and Snail in colorectal cancer cells. Moreover, MC-LR stimulated protein expression of SMAD2 and phospho-SMAD2 by PI3-K/AKT activation. The activated PI3-K/AKT and SMAD2 signaling largely accounted for MC-LR-induced EMT, which could be reversed by SMAD2 RNA interference or PI3-K/AKT chemical inhibitor in colorectal cancer cells. Our results show that MC-LR could induce SMAD2 expression to promote colorectal cancer cells EMT, which not only provides a mechanistic insight on MC-LR promotes EMT in colorectal cancer cells, but also support to the development of therapies aimed at SMAD2 in colorectal cancer induced by MC-LR. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. The sentinel node procedure in colon carcinoma : a multi-centre study in The Netherlands

    NARCIS (Netherlands)

    Kelder, Wendy; Braat, Andries E.; Karrenbeld, Arend; Grond, Joris A. K.; De Vries, Johannes E.; Oosterhuis, J. Wolter A.; Baas, Peter C.; Plukker, John T. M.

    2007-01-01

    Background Lymph node status is the most important predictive factor in colorectal carcinoma. Recurrences occur in 20% of the patients without lymph node metastases. The sentinel lymph node (SLN) biopsy is a tool to facilitate identification of micrometastatic disease and aberrant lymphatic

  4. Clinical Pattern of Recurrent Disease during the Follow-Up of Rectal Carcinoma

    NARCIS (Netherlands)

    Wieldraaijer, Thijs; Bruin, Pascal; Duineveld, Laura A. M.; Tanis, Pieter J.; Smits, Anke B.; van Weert, Henk C. P. M.; Wind, Jan

    2018-01-01

    Several initiatives have started to transfer colorectal cancer follow-up (FU) from secondary to primary care. For this purpose, it is important to assess when and how recurrences of rectal carcinoma are detected after treatment with curative intent. Retrospective multicentre cohort study. Patients

  5. Increased MUTYH mutation frequency among Dutch families with breast cancer and colorectal cancer.

    Science.gov (United States)

    Wasielewski, Marijke; Out, Astrid A; Vermeulen, Joyce; Nielsen, Maartje; van den Ouweland, Ans; Tops, Carli M J; Wijnen, Juul T; Vasen, Hans F A; Weiss, Marjan M; Klijn, Jan G M; Devilee, Peter; Hes, Frederik J; Schutte, Mieke

    2010-12-01

    Homozygous and compound heterozygous MUTYH mutations predispose for MUTYH-associated polyposis (MAP). The clinical phenotype of MAP is characterised by the multiple colorectal adenomas and colorectal carcinoma. We previously found that female MAP patients may also have an increased risk for breast cancer. Yet, the involvement of MUTYH mutations in families with both breast cancer and colorectal cancer is unclear. Here, we have genotyped the MUTYH p.Tyr179Cys, p.Gly396Asp and p.Pro405Leu founder mutations in 153 Dutch families with breast cancer patients and colorectal cancer patients. Families were classified as polyposis, revised Amsterdam criteria positive (FCRC-AMS positive), revised Amsterdam criteria negative (FCRC-AMS negative), hereditary breast and colorectal cancer (HBCC) and non-HBCC breast cancer families. As anticipated, biallelic MUTYH mutations were identified among 13% of 15 polyposis families, which was significantly increased compared to the absence of biallelic MUTYH mutations in the population (P = 0.0001). Importantly, six heterozygous MUTYH mutations were identified among non-polyposis families with breast and colorectal cancer. These mutations were identified specifically in FCRC-AMS negative and in HBCC breast cancer families (11% of 28 families and 4% of 74 families, respectively; P = 0.02 for both groups combined vs. controls). Importantly, the 11% MUTYH frequency among FCRC-AMS negative families was almost fivefold higher than the reported frequencies for FCRC-AMS negative families unselected for the presence of breast cancer patients (P = 0.03). Together, our results indicate that heterozygous MUTYH mutations are associated with families that include both breast cancer patients and colorectal cancer patients, independent of which tumour type is more prevalent in the family.

  6. Colorectal Cancer: The Importance of Early Detection

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Colorectal Cancer The Importance of Early Detection Past Issues / Summer ... Cancer of the colon or rectum is called colorectal cancer. The colon and the rectum are part of ...

  7. Thyroid cancer - medullary carcinoma

    Science.gov (United States)

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... The cause of medullary carcinoma of the thyroid (MTC) is unknown. ... and adults. Unlike other types of thyroid cancer, MTC is less ...

  8. The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer ...Colorectal Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0273 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Andrea Burnett-Hartman 5d... cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s specific aims are as follows: 1) Estimate the risk of colorectal

  9. GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS.

    Science.gov (United States)

    Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

    2013-01-18

    Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

  10. Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Shuohui Yang

    2017-01-01

    Full Text Available We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI and mean vessel density imaging (Q in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC. Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS and Q were serially measured and compared between the treated (n = 15 and control groups (n = 15. Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05. Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669 and increased at 14 and 21 days (P < 0.05, while Q significantly declined at 7 days (P = 0.028 and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD (r = 0.753, P < 0.001, and ITSS correlated well with MVD (r = 0.742, P = 0.002 after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.

  11. The experimental study on the radioimmunotherapy of the nasopharyngeal carcinoma overexpressing HER2/neu in nude mice model with intratumoral injection of {sup 188}Re-herceptin

    Energy Technology Data Exchange (ETDEWEB)

    Li Guiping [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China) and Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China)]. E-mail: ligp@fimmu.com; Wang Yongxian [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, Shanghai, 201800 (China)]. E-mail: yongxianw@163.com; Huang Kai [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Hui [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Peng Wuhe [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Chunfu [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China)

    2005-01-01

    The therapeutic efficacy of radioimmunotherapy (RIT) of {sup 188}Re-labeled herceptin, which is a humanized anti-p185-HER2/neu monoclonal antibody (mAb), was studied. The nude mice bearing nasopharyngeal carcinoma (NPC) expressing HER2/neu protooncogene were injected with {sup 188}Re-herceptin intratumorally and intravenously. The biodistribution was observed on day 2 (n=3). The tumor growth inhibition rate (IR) was determined by measurement of tumor volume. In the intratumorally treated mice, tumor uptake of {sup 188}Re-herceptin was significantly greater than in the intravenously treated mice [11.53% injected dose (ID)/g vs. 2.79% ID/g at 48 h], and lower normal organ uptake was also seen. The intratumoral administration of {sup 188}Re-herceptin caused greater inhibition of tumor growth at the fourth week as compared to the intravenous administration. It is concluded that intratumoral administration of {sup 188}Re-herceptin makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy for NPC overexpressing HER2/neu.

  12. Pomegranate Bioactive Constituents Suppress Cell Proliferation and Induce Apoptosis in an Experimental Model of Hepatocellular Carcinoma: Role of Wnt/β-Catenin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Deepak Bhatia

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer-related death worldwide, and chemoprevention represents a viable approach in lowering the mortality of this disease. Pomegranate fruit, an abundant source of anti-inflammatory phytochemicals, is gaining tremendous attention for its wide-spectrum health benefits. We previously reported that a characterized pomegranate emulsion (PE prevents diethylnitrosamine (DENA-induced rat hepatocarcinogenesis though inhibition of nuclear factor-kappaB (NF-κB. Since NF-κB concurrently induces Wnt/β-catenin signaling implicated in cell proliferation, cell survival, and apoptosis evasion, we examined antiproliferative, apoptosis-inducing and Wnt/β-catenin signaling-modulatory mechanisms of PE during DENA rat hepatocarcinogenesis. PE (1 or 10 g/kg was administered 4 weeks before and 18 weeks following DENA exposure. There was a significant increase in hepatic proliferation (proliferating cell nuclear antigen and alteration in cell cycle progression (cyclin D1 due to DENA treatment, and PE dose dependently reversed these effects. PE substantially induced apoptosis by upregulating proapoptotic protein Bax and downregulating antiapoptotic protein Bcl-2. PE dose dependently reduced hepatic β-catenin and augmented glycogen synthase kinase-3β expression. Our study provides evidence that pomegranate phytochemicals exert chemoprevention of hepatic cancer through antiproliferative and proapoptotic mechanisms by modulating Wnt/β-catenin signaling. PE, thus, targets two interconnected molecular circuits (canonical NF-κB and Wnt/β-catenin pathways to exert chemoprevention of HCC.

  13. Leptin regulates proliferation and apoptosis of colorectal carcinoma ...

    Indian Academy of Sciences (India)

    The obesity hormone leptin is considered as a key mediator for cancer development and progression. ... The results showed that leptin/Ob-R expression was significantly associated with T stage, TNM stage, lymph node metastasis, distant metastasis, differentiation and expression of p-mTOR, p-70S6 kinase, and p-Akt.

  14. Tumor infiltrating macrophages reduce development of peritoneal colorectal carcinoma metastases

    NARCIS (Netherlands)

    van der Bij, Gerben J.; Bögels, Marijn; Oosterling, Steven J.; Kroon, Jeffrey; Schuckmann, Dénise T. M.; de Vries, Helga E.; Meijer, Sybren; Beelen, Robert H. J.; van Egmond, Marjolein

    2008-01-01

    Macrophages generally constitute a major component of tumor stroma, and possess either tumor growth promoting or inhibiting capabilities. Classically activated macrophages exert cytotoxicity and produce inflammatory cytokines, which limits tumor growth. By contrast, alternatively activated or M2

  15. Leptin regulates proliferation and apoptosis of colorectal carcinoma ...

    Indian Academy of Sciences (India)

    (e.g. prostate, colon, ovarian and breast cancers, etc.) through activating mitogenic and anti-apoptotic signalling pathways (Onuma et al. 2003; Hoda and Popken 2008). Leptin exhibits its activity mainly through binding to its long form, fully active receptor (Ob-Rb), which can induce trans-autophosphorylation of cytoplasmic ...

  16. Morphology of colorectal carcinoma among Nigerians: A 30-year ...

    African Journals Online (AJOL)

    Nigeria, as a result of change in diet and adoption of western lifestyle. Objectives: The aim of this review is to highlight the ... Adoption of western lifestyle including diets in spite of previously documented low level of ... unconnected with the reduced life expectancy in developing countries and possible overrepresentation of ...

  17. Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma

    Science.gov (United States)

    2015-09-01

    downregulation of gluconeogenesis and upregulation of glycolysis. PLoS ONE 2013;8: e74340. [102] Zhong L, D’Urso A, Toiber D, Sebastian C, Henry RE...MJ, Camporez JP, et al. The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis . Mol Cell 2012;48:900–13

  18. Gut microbiome development along the colorectal adenoma-carcinoma sequence

    DEFF Research Database (Denmark)

    Feng, Qiang; Liang, Suisha; Jia, Huijue

    2015-01-01

    factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment...

  19. Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma

    Science.gov (United States)

    2014-09-01

    Figure 2). However, little is known about the metabolic properties of CSCs. Previous work had demonstrated that metformin , a widely used antidiabetic...Keymeulen A, Blanpain C. Tracing epithelial stem cells during development, homeostasis, and repair. J Cell Biol. 2012;197:575-584. 6. Boyer LA , Lee TI...HK, Jang HG, Jha AK, Chen WW, Barrett FG, Stransky N, Tsun ZY, Cowley GS, Barretina J, Kalaany NY, Hsu PP, Ottina K, Chan AM, Yuan B, Garraway LA

  20. Patogénesis molecular del carcinoma de esófago

    Directory of Open Access Journals (Sweden)

    A. M. Jiménez

    2003-06-01

    Full Text Available El carcinoma de esófago existe en dos formas principales: el carcinoma de células escamosas o pavimentoso y el adenocarcinoma. En este artículo se describen las principales alteraciones genéticas halladas en ambos tipos de carcinomas y la implicancia de éstas en la patogénesis de los mismos. La secuencia de estas alteraciones se correlaciona con la histogénesis, lo que permite comprender la progresión tumoral desde el epitelio normal al carcinoma invasor. Se establece también una comparación entre la patogénesis molecular del cáncer de esófago y del desarrollo de estos carcinomas con el modelo de la patogénesis molecular del cáncer colorrectal.Carcinoma of the esophagus is present in two distinct morphological cell types: squamous or pavimentous cell carcinoma and adenocarcinoma. In this article, the main genetic alterations found in both types of carcinomas and their implications are described. The sequence of these alterations is related to histogenesis, making it possible to understand tumor progression from normal epithelium to invasive carcinoma. A comparison is attempted between the molecular development of esophagus carcinomas and that of colorectal carcinoma.

  1. Sequential biphasic changes in claudin1 and claudin4 expression are correlated to colorectal cancer progression and liver metastasis

    Science.gov (United States)

    Georges, Rania; Bergmann, Frank; Hamdi, Hadjar; Zepp, Michael; Eyol, Ergül; Hielscher, Thomas; Berger, Martin R; Adwan, Hassan

    2012-01-01

    Abstract Terminal progression of colorectal cancer (CRC) culminates in liver metastasis. To identify genes that are involved in the metastatic phenotype, cDNA microarrays were used to analyse mRNA expression profiles of colorectal carcinoma (CC)531 rat colon adenocarcinoma cells for changes related to their homing into the liver. Briefly, CC531 cells were intraportally implanted into the liver of Wag-Rij rats and re-isolated after 3, 6, 9, 14 and 21 days. Compared to control CC531 cells, claudin1 and claudin4 were among the ≥8-fold initially down-regulated genes. The co-culture of tumour cells with isolated rat hepatocytes and Kupffer cells did not induce down-regulation of either claudin1 or 4. When the environment effective on circulating tumour cells was simulated by cell culture conditions favouring their adhesion, only claudin4 showed augmented expression. Knockdown of claudin1 and claudin4 mediated by small interfering RNA caused significantly increased migration and decreased clonogenic growth of tumour cells (P < 0.05), but had no effect on their proliferation. These experimental results were paralleled by increased claudin1 and claudin4 expression in human CRC samples in Union for International Cancer Control (UICC) stages I–III, as evaluated by real-time PCR. Increased claudin4 levels were correlated with significantly reduced overall survival (log-rank test, P= 0.018). Further, significantly (P < 0.05) reduced expression of claudin1 and claudin4 was observed in stage IV and liver metastasis by immunohistochemistry. In conclusion, sequential biphasic changes in claudin1 and claudin4 expression occur during the homing of rat CC531 CRC cells to the liver. This modulation is reflected by significant changes in claudin expression in human primary and metastatic CRC. PMID:21388515

  2. Lifetime alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- but not BRAF+ colorectal cancer.

    Science.gov (United States)

    Jayasekara, Harindra; MacInnis, Robert J; Williamson, Elizabeth J; Hodge, Allison M; Clendenning, Mark; Rosty, Christophe; Walters, Rhiannon; Room, Robin; Southey, Melissa C; Jenkins, Mark A; Milne, Roger L; Hopper, John L; Giles, Graham G; Buchanan, Daniel D; English, Dallas R

    2017-04-01

    Ethanol in alcoholic beverages is a causative agent for colorectal cancer. Colorectal cancer is a biologically heterogeneous disease, and molecular subtypes defined by the presence of somatic mutations in BRAF and KRAS are known to exist. We examined associations between lifetime alcohol intake and molecular and anatomic subtypes of colorectal cancer. We calculated usual alcohol intake for 10-year periods from age 20 using recalled frequency and quantity of beverage-specific consumption for 38,149 participants aged 40-69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between lifetime alcohol intake and colorectal cancer risk. Heterogeneity in the HRs across subtypes of colorectal cancer was assessed. A positive dose-dependent association between lifetime alcohol intake and overall colorectal cancer risk (mean follow-up = 14.6 years; n = 596 colon and n = 326 rectal cancer) was observed (HR = 1.08, 95% CI: 1.04-1.12 per 10 g/day increment). The risk was greater for rectal than colon cancer (phomogeneity  = 0.02). Alcohol intake was associated with increased risks of KRAS+ (HR = 1.07, 95% CI: 1.00-1.15) and BRAF-/KRAS- (HR = 1.05, 95% CI: 1.00-1.11) but not BRAF+ tumors (HR = 0.89, 95% CI: 0.78-1.01; phomogeneity  = 0.01). Alcohol intake is associated with an increased risk of KRAS+ and BRAF-/KRAS- tumors originating via specific molecular pathways including the traditional adenoma-carcinoma pathway but not with BRAF+ tumors originating via the serrated pathway. Therefore, limiting alcohol intake from a young age might reduce colorectal cancer originating via the traditional adenoma-carcinoma pathway. © 2016 UICC.

  3. Genetic Testing for Hereditary Colorectal Cancer

    Science.gov (United States)

    ... Facebook Tweet Share Compartir Having a family health history of colorectal (colon) cancer can make you more likely to get colorectal ... Health History? If you have a family health history of colorectal cancer, your doctor may consider your family health history ...

  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

  5. BRAF, KRAS and PIK3CA mutations in colorectal serrated polyps and cancer: Primary or secondary genetic events in colorectal carcinogenesis?