• Title/Summary/Keyword: Colorectal carcinoma

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High and Low Dose Folinic Acid, 5-Fluorouracil Bolus and Continuous Infusion for Poor-Prognosis Patients with Advanced Colorectal Carcinoma

  • Bano, Nusrat;Najam, Rahila;Mateen, Ahmed;Qazi, Faaiza
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3589-3593
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    • 2012
  • Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy. Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma. Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid ($200mg/m^2$), glucose 5%, 5-FU ($400mg/m^2$) and 22 hr. CIV ($600mg/m^2$) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid ($20mg/m^2$)for five days, 5FU($425mg/m^2$) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria. Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ${\geq}2$ events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV. Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.

Multiplicity of Advanced T Category-Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma

  • Park, Hye Eun;Yoo, Seungyeon;Bae, Jeong Mo;Jeong, Seorin;Cho, Nam-Yun;Kang, Gyeong Hoon
    • Journal of Pathology and Translational Medicine
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    • v.52 no.6
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    • pp.386-395
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    • 2018
  • Background: Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods: Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results: SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p=.003) and distant metastasis (p=.001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p<.001), but not for recurrence-free survival (p=.151). Conclusions: Findings suggested that multiplicity of advanced T category-tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer's tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC.

Fentanyl Increases Colorectal Carcinoma Cell Apoptosis by Inhibition of NF-κB in a Sirt1-dependent Manner

  • Zhang, Xiu-Lai;Chen, Min-Li;Zhou, Sheng-Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.10015-10020
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    • 2014
  • Background: Fentanyl is used as an analgesic to treat pain in a variety of patients with cancer and recently it has become considered to also act as an antitumor agent. The study present was designed to investigate the effects of fentanyl on colorectal cancer cell growth and plausible mechanisms. Materials and Methods: The human colorectal carcinoma cell line HCT116 was subcutaneously injected into nude mice. The viability of HCT116 was tested by MTT assay, and apoptosis by flow cytometry and caspase-3 activity. The expression of Sirt1 and NF-${\kappa}B$ were evaluated by Western blotting and the levels of Sirt1 and NF-${\kappa}B$ by fluorescence method. SiRNA was used to silence and Ad-Sirt1 to overexpress Sirt1. Results: Our data showed that fentanyl could inhibit tumor growth, with increased expression of Sirt1 and down-regulation of Ac-p65 in tumors. Compared with control cells without treatment, HCT116 cells that were incubated with fentanyl had a higher apoptotic rate. Moreover, fentanyl could increase expression and activity of Sirt1 and inhibitor expression and activity of NF-${\kappa}B$, which might be mechanisms of fentanyl action. Conclusions: Fentanyl increased colorectal carcinoma cell apoptosis by inhibition of NF-${\kappa}B$ activation in a Sirt1-dependent manner.

Schistosomiasis Combined with Colorectal Carcinoma Diagnosed Based on Endoscopic Findings and Clinicopathological Characteristics: A Report on 32 Cases

  • Liu, Wei;Zeng, Hong-Ze;Wang, Qi-Ming;Yi, Hang;Mou, Yi;Wu, Chun-Cheng;Hu, Bing;Tang, Cheng-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4839-4842
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    • 2013
  • Aims and Background: To improve understanding of the relationship between schistosome-related enteropathy and colorectal carcinoma with particular focus on endoscopic findings and clinicopathological characteristics of colonic schistosomiasis. Materials and Methods: All cases of intestinal schistosomiasis diagnosed at West China Hospital, Chengdu, China, between October 2006 and October 2012 were included in this study. A total of 179 cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected for analysis and the demographics, symptoms, endoscopic findings and clinicopathological characteristics were retrospectively evaluated. Results: Of the 179 colonic schistosomiasis patients, 32 combined with colorectal cancer (CRC) were found, between the ages of 44 and 85 years (24 males, 75%). These 32 lesions were classified as 12 endophytic/ulcerative (37.5%), 10 exophytic/fungating (31.2%), 4 annular (12.5%), 3 giant polypus (9.4%), and 3 IIc (superficial depressed type) (9.4%). The segments of rectum and sigmoid colon were involved in 19 patients (59.4%) and 6 patients (18.8%), respectively. The histopathologic types were classified as follows: 30 welldifferentiated adenocarcinomas, one mucinous adenocarcinoma and one poorly differentiated adenocarcinoma. The pathological findings suggest colorectal malignancy with deposited schistosome ova. Conclusions: Chronic schistosomal infestation has a probable etiological role in promoting genesis of colorectal neoplasms.

Chemotherapeutic Response and Survival for Patients With an Anal Squamous Cell Carcinoma and Low Hemoglobin Levels

  • Naqvi, A.;Platt, E.;Jitsumura, M.;Evans, M.;Coleman, M.;Smolarek, S.
    • Annals of Coloproctology
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    • v.34 no.6
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    • pp.312-316
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    • 2018
  • Purpose: Anemia is associated with poor treatment results for a variety of cancers. The effect of low hemoglobin levels on long-term outcomes after the treatment of patients with an anal squamous cell carcinoma (SCC) remains unclear. For that reason, this study aimed to investigate the effect of anemia on treatment outcomes following chemoradiation for an anal SCC. Methods: This was a retrospective study of all patients who underwent curative treatment for an anal SCC between 2009 and 2015 at 2 trusts in the United Kingdom. Data were collated from prospectively collected cancer databases and were cross-checked with operating-room records and records in the hospitals' patient management systems. Results: We identified 103 patients with a median age of 63 years (range, 36-84 years). The median overall survival was 39 months (range, 9-90 months), and the disease-free survival was 36 months (range, 2-90 months). During the follow-up period, 16.5% patients died and 13.6% patients developed recurrence. Twenty-two people were anemic prior to treatment, with a female preponderance (20 of 22). No differences in disease-free survival (P = 0.74) and overall survival (P = 0.12) were noted between patients with anemia and those with normal hemoglobin levels. On regression the analysis, the combination of anemia, the presence of a defunctioning colostomy, lymph-node involvement and higher tumor stage correlated with poor overall survival. Conclusion: In this study, anemia did not influence disease-free survival or overall survival. We suggest that the interaction between anemia and survival is more complex than previously demonstrated and potentially reliant on other coexisting factors.

Anti-HER-2×anti-CD3 Bi-specific Antibodies Inhibit Growth of HCT-116 Colorectal Carcinoma Cells in Vitro and in Vivo

  • Ren, Hui;Li, Jun;Liu, Jing-Jing;Guo, Hui-Ling;Jiang, Tao
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2795-2798
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    • 2012
  • Objective: This study is conducted to evaluate the effects of anti-HER-2${\times}$anti-CD3 bi-specific antibodies(BsAb) on HER-2/neuover-expressing human colorectal carcinoma cells. Methods: Growth was assessed by MTT assays after exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was applied to test the HER-2 level of HCT-116. In a nude mouse model, HER-2${\times}$CD3 BsAb was combined with effector cells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors. Results: Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin or HER2${\times}$CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkably in the HER2${\times}$CD3 BsAb case. The growth of xenografts with HER2${\times}$CD3 BsAb combined with effector cells was also significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05). Conclusion: HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2${\times}$anti-CD3 BsAb exerting clear anti-tumor effects.

Lack of Relation of AKAP12 with p53 and Bcl-2 in Colorectal Carcinoma

  • Suren, Dinc;Yildirim, Mustafa;Alikanoglu, Arsenal Sezgin;Kaya, Vildan;Yildiz, Mustafa;Dilli, Utku Donem;Sezer, Cem
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3415-3418
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    • 2014
  • Background: AKAP12 inhibits oncogenic proliferation, invasion, chemotaxis and neovascularization. Bcl-2 and p53 are two important apoptotic markers that play roles in apoptotic processes. It has been found that AKAP12 blocks the cell cycle and induces apoptosis in fibrosarcoma cells. In our study we assessed the relationship of AKAP12 with apoptotic markers, Bcl-2 and p53. Materials and Methods: Our study included 45 cases that were histopathologically diagnosed with colorectal carcinoma from the tissue samples acquired by surgical resection. AKAP 12, Bcl-2, and p53 expression was examined by immunohistochemistry. Results: A total of 45 colorectal adenocarcinoma patients - 17 (37.8%) females and 28 (62.2%) males - were included in this study. AKAP12 expression was found to be negative in 8 patients (17.8%), and positive in 37 patients (82.2%). Bcl-2 was found positive in 6 patients (13.3%) and p53 in 29 patients (55.6%). AKAP12 expression had no significant relation with Bcl-2 and p53 expression (p:0.939, p:0.079, respectively). Conclusions: Although various studies have pointed to apoptotic activity of AKAP12, the literature is limited regarding relations with p53 or Bcl-2 expression. In the present study, we found no relation in colorectal carcinomas.

Public Awareness of Colorectal Cancer in a Turkish Population: Importance of Fecal Occult Blood Testing

  • Bas, Koray;Guler, Tolga;Gunay, Levent Mert;Besim, Hasan;Uygur, Dilek
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.195-198
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    • 2012
  • To date, there was no controlled-study regarding awareness and knowledge of colorectal cancer in the Turkish population. We therefore designed a questionnaire consisting of items related to socio-demographic parameters, medical and family history and questions of awareness and knowledge about colorectal cancer for use in a descriptive cross-sectional study. An interviewer-administered technique was applied and 450 subjects were interviewed in the outpatient clinics at Near East University Hospital. Among all subjects, 337 were found to be eligible for the study group. Exclusion criteria were age below 18 years, any cancer history, family history of colorectal cancer, current colorectal problems, history of any diagnostic or therapeutic interventions for colorectal diseases. All participants stated that they heard about colorectal cancer. When asked about the lifetime risk of colorectal carcinoma, only 25.4% of women and 37.9% of men estimated correctly. Univariate analysis revealed that the total awareness score was significantly correlated with age, marital status, parenthood and fecal occult blood testing history. On multivariate analysis of independent predictors for awareness of colorectal cancer were found to be history of fecal occult blood testing, age and marital status were found to be the most important determinants. As a conclusion, opportunistic screening with fecal occult blood test by physicians from non-gastrointestinal specialties not only helps to reduce the mortality but also increases the awareness of colorectal cancer.

Gastrointestinal Adverse Effects in Advanced Colorectal Carcinoma Patients Treated with Different Schedules of FOLFOX

  • Bano, Nusrat;Najam, Rahila;Qazi, Faaiza;Mateen, Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8089-8093
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    • 2014
  • Background: To assess the frequency and severity of gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with four different schedules of FOLFOX. Materials and Methods: Patients (median age 61 years) who underwent surgery were included in the study. All had measureable disease at CT scan, ultrasonography or clinical examination. Toxicity was graded on a scale of 1-5 according to the general grade definition of CTC v2.0. The severity of adverse effects (Grade 3 and 4) assessed in each treatment arm was compared. Results: Differences between the incidence rates of 3 and 4 toxicity and all grades of toxicity for all parameters in GI toxicity were very highly significant (p<0.001). Severe gastrointestinal symptoms of toxicity were noted with FOLFOX7 (oxaliplatin $130mg/m^2$). Grade 3 diarrhea was reported in 25% patients and grade 4 diarrhea in 4% in the FOLFOX7 treatment arm. Grade 2 vomiting was very frequently reported in the FOLFOX4 treatment arm (oxaliplatin $85mg/m^2$). Grade 2 stomatitis was reported in 42% patients treated with mFOLFOX6 (oxaliplatin $100mg/m^2$). Differences in the incidence rate of nausea, diarrhea and stomatitis among all treatment arms of FOLFOX were significant (p<0.05). Conclusions: Severe diarrhea is associated with FOLFOX7 treatment. No grade 3 or 4 GI toxicity was reported in patients of the mFOLFOX6 arm.

Anti-proliferative Effect of a Novel Anti-oxidative Peptide in Hanwoo Beef on Human Colorectal Carcinoma Cells

  • Kim, Hye-Jin;Yang, Se-Ran;Jang, Aera
    • Food Science of Animal Resources
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    • v.38 no.6
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    • pp.1168-1178
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    • 2018
  • The present study aimed to characterise anti-oxidant peptides from water-soluble protein extracts of Hanwoo beef and evaluate their anti-proliferative effect on human colorectal carcinoma cells (HCT116). Antioxidant peptides were purified from the low-molecular-weight fraction (<3 kDa) of Hanwoo beef extract. Antioxidant activity of peptide fractions was determined using the oxygen radical absorbance capacity (ORAC) assay. Purified peptide (P3) displayed higher ORAC activity than the low-molecular-weight fraction ($202.66{\mu}M\;TE/g$ vs $167.38{\mu}M\;TE/g$ of dry matter, respectively) (p<0.05). The peptide sequence of P3 was Cys-Cys-Cys-Cys-Ser-Val-Gln-Lys (888.30 Da). The novel peptide P3, at $250{\mu}g/mL$, also significantly inhibited HCT116 cell proliferation up to 25.24% through phosphorylation of ERK, JNK, and p38 kinase (p<0.05). Hence, antioxidant peptide P3 from Hanwoo beef extract can be used as an antioxidative and anticancer agent in the functional food industry.