• Title/Summary/Keyword: Colon Cancer

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Identification of Selective STAT1 Inhibitors by Computational Approach

  • Veena Jaganivasan;Dona Samuel Karen;Bavya Chandrasekhar
    • Journal of Integrative Natural Science
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    • v.16 no.3
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    • pp.81-95
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    • 2023
  • Colorectal cancer is one of the most common types of cancer worldwide, ranking third after lung and breast cancer in terms of global prevalence. With an expected 1.93 million new cases and 935,000 deaths in 2020, it is more prevalent in males than in women. Evidence has shown that during the later stages of colon cancer, STAT1 promotes tumor progression by promoting cell survival and resistance to chemotherapy. Recent studies have shown that inhibiting STAT1 pathway leads to a reduction in tumor cell proliferation and growth, and can also promote apoptosis in colon cancer cells. One of the recent approaches in the field of drug discovery is drug repurposing. In drug repurposing approach we have virtually screened FDA database against STAT1 protein and their interactions have been studied through Molecular docking. Cross docking was performed with the top 10 compounds to be more specific with STAT1 comparing the affinity with STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6. The drugs that showed higher affinity were subjected to Conceptual - Density functional theory. Besides, the Molecular dynamic simulation was also carried out for the selected leads. We also validated in-vitro against colon cancer cell lines. The results showed mainly Acetyldigitoxin has shown better binding to the target. From this study, we can predict that the drug Acetyldigitoxin has shown noticeable inhibitory efficiency against STAT1, which in turn can also lead to the reduction of tumor cell growth in colon cancer.

Inhibitory effects of Euphorbiae lathyridis Semen extract on cell growth in HT-29 human colon cancer cells (속수자 추출물의 HT-29 대장암세포 증식에 대한 억제효과)

  • Jung, Hyo-Won;Park, Yong-Ki
    • The Journal of Dong Guk Oriental Medicine
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    • v.11
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    • pp.52-57
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    • 2008
  • Objectives. In this study, we investigate that methanol extract of Euphorbiae lathyridis Semen contributes to growth inhibitory effect on the HT-29 human colon cancer cells. Methods. Euphorbiae lathyridis Semen (ELS) was extracted with 80% methanol. HT-29 cells were treated with different concentrations of ELS extract for 24-72 hrs. Growth inhibitory effect was determined by MTT assay. Cell apoptosis was determined by surveying caspases cascades activation using Western blot. Cell cycle arrest was analyzed by flow cytometry with PI staining. Results. Exposure to ELS extract showed in inhibitory effects on HT-29 cell growth as a dose-dependent manner. Cell growth inhibition by ELS extract was related with induction of cell apoptosis with DNA fragmentation through the activation of caspases-3, caspase-9 and PARP cleavage. Conclusion. ELS extract significantly inhibited cell growth and induced cell apoptosis in HT-29 human colon cancer cells, therefore, These results suggest that ELS extract can be used as chemoprevention agent of colon cancers.

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Inferior Mesenteric Plexus Block for Lower Abdominal Cancer Pain (하복부 암성통증에 대한 하 장간막신경총 차단)

  • Oh, Hung-Kun;Yoon, Duck-Mi;Chung, So-Young
    • The Korean Journal of Pain
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    • v.6 no.2
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    • pp.199-203
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    • 1993
  • Inferior mesenteric plexus block(IMPB) is a nerve block for lower abdominal pain originating from GI tract of distal transverse colon to sigmoid colon and other polvic organ where the inferior mesenteric plexus contains visceral afferent fibers of that organ. We performed IMPB on two patients with lower abdominal pain. Case I: 61 year old female diagnosed with cancer of stomach and uterine cervix and carcinomatosis, experienced complete relief from pain for a period of 7 months after IMPB. Case II: male, 28 years old, who had contracted cancer of the descending colon with obstructive jaundice and pancreatitis had complained of pain in the whole of the abdominal area. IMPB was performed for lower abdominal pain. Seven days after, a celiac plexus block was also performed for upper abdominal pain. The patient complained of recurring pain in the left & upper lower abdomen 30 days after the IMPB. The intensity of the pain was visual analogue scale 4 and it was managed by continuous epidural block. Conclusion: It is our recommendation that IMPB is a reliable method for treatment of lower abdominal pain originating from malignant condition of GI tract from distal transverse colon to sigmoid colon and urinary bladder.

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Clinical Outcomes of Reduced-Port Laparoscopic Surgery for Patients With Sigmoid Colon Cancer: Surgery With 1 Surgeon and 1 Camera Operator

  • Oh, Jung Ryul;Park, Sung Chan;Park, Sung Sil;Sohn, Beonghoon;Oh, Hyoung Min;Kim, Bun;Kim, Min Jung;Hong, Chang Won;Han, Kyung Su;Sohn, Dae Kyung;Oh, Jae Hwan
    • Annals of Coloproctology
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    • v.34 no.6
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    • pp.292-298
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    • 2018
  • Purpose: This study compared the perioperative clinical outcomes of reduced-port laparoscopic surgery (RPLS) with those of conventional multiport laparoscopic surgery (MPLS) for patients with sigmoid colon cancer and investigated the safety and feasibility of RPLS performed by 1 surgeon and 1 camera operator. Methods: From the beginning of 2010 until the end of 2014, 605 patients underwent a colectomy for sigmoid colon cancer. We compared the characteristics, postoperative outcomes, and pathologic results for the patients who underwent RPLS and for the patients who underwent MPLS. We also compared the clinical outcomes of single-incision laparoscopic surgery (SILS) and 3-port laparoscopic surgery. Results: Of the 115 patients in the RPLS group, 59 underwent SILS and 56 underwent 3-port laparoscopic surgery. The MPLS group included 490 patients. The RPLS group had shorter operating time ($137.4{\pm}43.2minutes$ vs. $155.5{\pm}47.9minutes$, P < 0.001) and shorter incision length ($5.3{\pm}2.2cm$ vs. $7.8{\pm}1.2cm$, P < 0.001) than the MPLS group. In analyses of SILS and 3-port laparoscopic surgery, the SILS group showed younger age, longer operating time, and shorter incision length than the 3-port surgery group and exhibited a more advanced T stage, more lymphatic invasion, and larger tumor size. Conclusion: RPLS performed by 1 surgeon and 1 camera operator appears to be a feasible and safe surgical option for the treatment of patients with sigmoid colon cancer, showing comparable clinical outcomes with shorter operation time and shorter incision length than MPLS. SILS can be applied to patients with favorable tumor characteristics.

Esophageal Reconstruction with Isoperistaltic Interposition of Left Colon (동연동성 좌측결장을 이용한 식도재건술)

  • 성시찬
    • Journal of Chest Surgery
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    • v.24 no.9
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    • pp.895-902
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    • 1991
  • The surgical experience on 18 patients with benign or malignant stricture of the esophagus who underwent isoperistaltic interposition of left colon from April 1989 to July 1991 was reviewed. During same period 22 esophageal reconstructions with colon were performed, but 3 patients who had intraabdominal adhesion in the left upper quadrant and one patient who had uncertainty of blood supply of left colic artery could not undergo iso-peristaltic interposition of left colon. There were 12 male and 6 female patients ranging from 16 to 65 years of age. 12 patients had corrosive esophageal stricture, two had cancer of esophagus, and another two had hypopharyngeal cancer. The postoperative complications developed in 7 patients [38.8%] and most frequently encountered complication was cervical anastomotic leakage, which was successfully managed with simple drainage in all cases but one malignant patient. There was no operative mortality. The esophageal reconstruction with isoperistaltic left colon resulted in good function in 14 patients[77.8%], fair in 3 patients[16.7], and poor in 1 patient[5.6%]. In this experience esophageal reconstruction using isoperistaltic left colon is a satisfactory method that can be accomplished with acceptable morbidity and mortality.

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Chemopreventive effects of polysaccharides extract from Asterina pectinifera on HT-29 human colon adenocarcinoma cells

  • Nam, Kyung-Soo;Shon, Yun-Hee
    • BMB Reports
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    • v.42 no.5
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    • pp.277-280
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    • 2009
  • We examined the effects of polysaccharides extracted from Asterina pectinifera on the activities of quinone reductase (QR), glutathione S-transferase (GST), ornithine decarboxylase (ODC), cyclooxygenase (COX)-2 and glutathione (GSH) levels in HT-29 human colon adenocarcinoma cells. We found that the polysaccharides extract induced QR activity in a dose-dependent manner over a concentration range of $20-60\;{\mu}g/ml$ and increased GST activity as much as 1.4-fold over controls. GSH levels were increased 1.3- and 1.5-fold with the extract at 40 and $60\;{\mu}g/ml$, respectively. The activity and protein expression of ODC in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colon cancer cells was inhibited by the extract. The polysaccharides suppressed TPA-induced prostaglandin (PG) production. These data indicate that polysaccharides from A. pectinifera increase phase II detoxification enzyme activity and inhibit ODC and COX-2 activities in HT-29 human colon adenocarcinoma cells. Consequently, this effect may contribute to the protective effect of polysaccharides from A. pectinifera against colon cancer.

Gelam and Nenas Honeys Inhibit Proliferation of HT 29 Colon Cancer Cells by Inducing DNA Damage and Apoptosis while Suppressing Inflammation

  • Wen, Christinal Teh Pey;Hussein, Saba Zuhair;Abdullah, Shailah;Karim, Norwahidah Abdul;Makpol, Suzana;Yusof, Yasmin Anum Mohd
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1605-1610
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    • 2012
  • Gelam and Nenas monofloral honeys were investigated in this study for their chemopreventive effects against HT 29 colon cancer cells. MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolim) assays showed more effective inhibition of colon cancer cells proliferation by Gelam honey with $IC_{50}$ values of 39.0 mg/ml and 85.5 mg/ml respectively after 24 hours of treatment. Alkali comet assays revealed both honeys increased DNA damage significantly in a dose dependent manner. In addition, annexin V-FITC/PI flow cytometry demonstrated that at $IC_{50}$ concentrations and above, both Gelam and Nenas honeys induced apoptosis significantlyat values higher than for necrosis (p<0.05). Measurement of prostaglandin $E_2$ ($PGE_2$) confirmed that Gelam and Nenas honeys reduced its production in $H_2O_2$ inflammation-induced colon cancer cells. In conclusion, our study indicated and confirmed that both Gelam and Nenas honeys are capable of suppressing the growth of HT 29 colon cancer cells by inducing apoptosis and suppressing inflammation.

Study on the expression and detection of the p53 mutation in Korean colon cancer cell lines (한국인의 대장암 세포주에서 p53 돌연변이의 발견과 발현에 관한 연구)

  • Jung, Ji-Yeon;Oh, Sang-Jin
    • IMMUNE NETWORK
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    • v.1 no.2
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    • pp.151-161
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    • 2001
  • Background: Inactivation in p53 tumor suppressor gene through a point mutation and deletion is one of the most frequent genetic changes found in human cancer, with 50% of an incidence. This high rate of mutation mostly suggests that the gene plays a central role in the development of cancer and the mutations detected so far were found in exons 5 to 8. Mutation of p53 locus produced accumulation of abnormal p53 protein, and negative regulation of cell proliferation and transcriptional activation as a suppressor of transformation were lost. In addition, inhibition of its normal cellular function of wild-type by mutant is an important step in tumorigenesis. Method: 4 colon cancer cell lines (SNU C1, C2A, C4, C5) were examined for mutation in exons 5 to 8 of the p53 tumor suppressor gene by PCR-SSCP analysis and expression pattern by western blotting and immunoprecipitation. p53-mediated transactivation ability were examined by CAT assay and base substitution of p53 in SNU C2A cell were detected by DNA sequencing. Results: 1) SNU C2A cell and SNU C5 cell were detected mobility shifts each in exon 5 and exon 7 of p53 gene by the PCR-SSCP method, implicating being of p53 mutation. 2) 3 colon cancer cell lines (SNU C1, SNU C2A, SNU C5) expressed wild type and mutant type p53 protein. 3) In northern blot experiment, SNU C2A and SNU C5 cell expressed high level of p53 mRNA. 4) Results of p53-mediated transactivation in colon cancer cell lines by CAT assay represented only SNU C2A cell has transcriptional activity. 5) DNA sequencing in SNU C2A cell showed missense mutation in codon 179 of one allele, histidine to arginine and wild type p53 in the other allele. Conclusion: Colon cancer cell lines showed correlation with mutation in p53 gene and accumulation of abnormal p53 protein. Colon cancer cell SNU C2A retained p53-mediated transactivation as heterozygous p53 with one mutant allele in 179 codon and the other wild-type allele.

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Morphologic change of rectosigmoid colon using belly board and distended bladder protocol

  • Cho, Yeona;Chang, Jee Suk;Kim, Mi Sun;Lee, Jaehwan;Byun, Hwakyung;Kim, Nalee;Park, Sang Joon;Keum, Ki Chnag;Koom, Woong Sub
    • Radiation Oncology Journal
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    • v.33 no.2
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    • pp.134-141
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    • 2015
  • Purpose: This study investigates morphologic change of the rectosigmoid colon using a belly board in prone position and distended bladder in patients with rectal cancer. We evaluate the possibility of excluding the proximal margin of anastomosis from the radiation field by straightening the rectosigmoid colon. Materials and Methods: Nineteen patients who received preoperative radiotherapy between 2006 and 2009 underwent simulation in a prone position (group A). These patients were compared to 19 patients treated using a belly board in prone position and a distended bladder protocol (group B). Rectosigmoid colon in the pelvic cavity was delineated on planning computed tomography (CT) images. A total dose of 45 Gy was planned for the whole pelvic field with superior margin of the sacral promontory. The volume and redundancy of rectosigmoid colon was assessed. Results: Patients in group B had straighter rectosigmoid colons than those in group A (no redundancy; group A vs. group B, 10% vs. 42%; p = 0.03). The volume of rectosigmoid colon in the radiation field was significantly larger in group A (56.7 vs. 49.1 mL; p = 0.009). In dose volume histogram analysis, the mean irradiated volume was lower in patients in group B (V45 27.2 vs. 18.2 mL; p = 0.004). In Pearson correlation coefficient analysis, the in-field volume of rectosigmoid colon was significantly correlated with the bladder volume (R = 0.86, p = 0.003). Conclusion: Use of a belly board and distended bladder protocol could contribute to exclusion of the proximal margin of anastomosis from the radiation field.

Adjuvant Chemotherapy and Prognostic Factors in Stage II Colon Cancer - Izmir Oncology Group Study

  • Kucukzeybek, Yuksel;Dirican, Ahmet;Demir, Lutfiye;Yildirim, Serkan;Akyol, Murat;Yildiz, Yasar;Bayoglu, Ibrahim Vedat;Alacacioglu, Ahmet;Varol, Umut;Salman, Tarik;Yildiz, Ibrahim;Can, Huseyin;Tarhan, Mustafa Oktay
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2413-2418
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    • 2015
  • Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefit is not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patients with low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancer patients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patients who were diagnosed with stage II colon cancer between January 2006 and December 2011 were included in the study. Patients were stratified into two groups as being low-risk and high-risk according to risk factors for stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with risk factors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23 were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival and overall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysis demonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowel perforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions: The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was found that adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact that prognosis of stage II patients is good, many more patients will be needed for statistically significant differences in survival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients although it is not a standard treatment approach.