• Korean Journal of Radiology
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• v.24 no.9
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• pp.849-859
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• 2023

Objective: The prognostic value of the volume and density of skeletal muscles in the abdominal waist of patients with colon cancer remains unclear. This study aimed to investigate the association between the automated computed tomography (CT)-based volume and density of the muscle in the abdominal waist and survival outcomes in patients with colon cancer. Materials and Methods: We retrospectively evaluated 474 patients with colon cancer who underwent surgery with curative intent between January 2010 and October 2017. Volumetric skeletal muscle index and muscular density were measured at the abdominal waist using artificial intelligence (AI)-based volumetric segmentation of body composition on preoperative pre-contrast CT images. Patients were grouped based on their skeletal muscle index (sarcopenia vs. not) and muscular density (myosteatosis vs. not) values and combinations (normal, sarcopenia alone, myosteatosis alone, and combined sarcopenia and myosteatosis). Postsurgical disease-free survival (DFS) and overall survival (OS) were analyzed using univariable and multivariable analyses, including multivariable Cox proportional hazard regression. Results: Univariable analysis showed that DFS and OS were significantly worse for the sarcopenia group than for the non-sarcopenia group (P = 0.044 and P = 0.003, respectively, by log-rank test) and for the myosteatosis group than for the non-myosteatosis group (P < 0.001 by log-rank test for all). In the multivariable analysis, the myosteatotic muscle type was associated with worse DFS (adjusted hazard ratio [aHR], 1.89 [95% confidence interval, 1.25-2.86]; P = 0.003) and OS (aHR, 1.90 [95% confidence interval, 1.84-3.04]; P = 0.008) than the normal muscle type. The combined muscle type showed worse OS than the normal muscle type (aHR, 1.95 [95% confidence interval, 1.08-3.54]; P = 0.027). Conclusion: Preoperative volumetric sarcopenia and myosteatosis, automatically assessed from pre-contrast CT scans using AI-based software, adversely affect survival outcomes in patients with colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.749-755
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• 2014

Background: Purple rice has become a natural product of interest which is widely used for health promotion. This study investigated the preventive effect of purple rice extract (PRE) mixed diet on DMH initiation of colon carcinogenesis. Materials and Methods: Rats were fed with PRE mixed diet one week before injection of DMH (40 mg/kg of body weight once a week for 2 weeks). They were killed 12 hrs after a second DMH injection to measure the level of $O^6$-methylguanine and xenobiotic metabolizing enzyme activities. Results: In rats that received PRE, guanine methylation was reduced in the colonic mucosa, but not in the liver, whereas PRE did not affect xenobiotic conjugation, with reference to glutathione-S-transferase or UDP-glucuronyl transferase. After 5 weeks, rats that received PRE with DMH injection had fewer ACF in the colon than those treated with DMH alone. Interestingly, a PRE mixed diet inhibited the activity of bacterial ${\beta}$-glucuronidase in rat feces, a critical enzyme for free methylazoxymethanol (MAM) release in the rat colon. These results indicated that purple rice extract inhibited ${\beta}$-glucuronidase activity in the colonic lumen, causing a reduction of MAM-induced colonic mucosa DNA methylation, leaded to decelerated formation of aberrant crypt foci in the rat colon. Conclusions: The supplemented purple rice extract might thus prevent colon carcinogenesis by the alteration of the colonic environment, and thus could be further developed for neutraceutical products for colon cancer prevention.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.320-327
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• 2016

Columbianadin (CBN), a natural coumarin from Angelica decursiva (Umbelliferae), is known to have various biological activities including anti-inflammatory and anti-cancer effects. In this study, the anti-proliferative mechanism of actions mediated by CBN was investigated in HCT-116 human colon cancer cells. CBN effectively suppressed the growth of colon cancer cells. Low concentration (up to $25{\mu}M$) of CBN induced apoptosis, and high concentration ($50{\mu}M$) of CBN induced necroptosis. The induction of apoptosis by CBN was correlated with the modulation of caspase-9, caspase-3, Bax, Bcl-2, Bim and Bid, and the induction of necroptosis was related with RIP-3, and caspase-8. In addition, CBN induced the accumulation of ROS and imbalance in the intracellular antioxidant enzymes such as SOD-1, SOD-2, catalase and GPx-1. These findings demonstrate that CBN has the potential to be a candidate in the development of anti-cancer agent derived from natural products.

• Bulletin of the Korean Chemical Society
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• v.35 no.11
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• pp.3181-3187
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• 2014

A series of 3,4-dihydroquinazoline derivatives with anti-cancer activities against human colon cancer HT-29 cell were subjected to three-dimensional quantitative structure-activity relationship (3D-QSAR) studies using the comparative molecular similarity indices analysis (CoMSIA) approaches. The most potent compound, BK10001 was used to align the molecules. As a result, the best prediction was obtained with CoMSIA combined electrostatic, hydrophobic, and hydrogen-bond acceptor fields ($q^2=0.648$, $r^2=0.882$). This model was validated by an external test set of six compounds giving satisfactory predictive $r^2$ values of 0.879. This model would guide the design of potent 3,4-dihydroquinazoline derivatives as anti-cancer agent for the treatment of human colon cancer.

• Animal cells and systems
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• v.15 no.1
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• pp.9-17
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• 2011

Colorectal cancer is the third leading cause of cancer-related death in Western countries. Chemotherapeutic agents with different mechanisms of action have shown an increase in cure rates. In the present study, we investigated the effect of a combination of low concentration of paclitaxel (taxol, 5 nM) and topoisomerase 1 inhibitor camptothecin (CPT) on HCT116 colon cancer cells. Although the viability of cells treated with taxol alone was similar to that of control cells, sequential treatment with taxol and CPT exhibited high cytotoxicity. However, the opposite sequence of treatment did not exert cytotoxic effects on HCT116 cells. This enhanced cytotoxicity of the sequential combination therapy was the result of mitotic arrest, which increased the level of $p21^{Cip1/WAF1}$ through the p38 mitogen-activated protein kinase (MAPK) pathway. Knockdown by $p21^{Cip1/WAF1}$ siRNA or treatment with a p38 inhibitor reduced the viability of cells sequentially exposed to taxol and CPT. Taken together, a low taxol concentration in combination with CPT induced mitotic arrest in HCT116 cells, leading to synergistic cell death through enhanced expression of $p21^{Cip1/WAF1}$ and p38 MAPK pathway. Therefore, taxol could playa role as a sensitizer of CPT in colon cancer cells.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.210-215
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• 2019

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.

• The Korean Journal of Nuclear Medicine
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• v.15 no.2
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• pp.1-9
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• 1981

Bone scans with $^{99m}Tc-MDP$ (methylene diphosphonate) were obtained and analysed in 574 patients with biopsy-proven malignancy, who visited Seoul National University Hospital from April, 1979 to June, 1931. Clinical staging was done in all patients without bone scan information and compared with bone scan to determine the predictive value of bone scanning. 1. Primary site of the maligancies were lung in 152, breast in 97, stomach in 43, colon in 15, esophagus in 9, liver and pancreas in 11, kidney in 14, bladder in 27, prostate in 22, thyroid in 20, skin in 11, bone in 9, head and neck in 36, ovary and uterus in 17, hematopoietic and lymphoretic ular system in 33, nervous system in 10, and others in 9 cases. Primary site was not defined in 39 cases. 2. Bone scans were positive in 186 cases (32.4%), which, included 48 cases (31.6%) of lung cancer, 27 cases (27.8%) of breast cancer, 12 cases(28%) of stomach cancer, 6 cases(40%) of colon cancer, 6 cases(43%) of kidney tumor, 4 cases(15%) of bladder cancer, 14 cases(64%) of prostate cancer, 3 cases(15%) of thyroid cancer and 66 other cases. 3. Bone scans were suspicious in 64 cases (11.2%) which included 29 cases (19.1%) of lung cancer, 10 cases (10.3%) of breast cancer, 4 cases (9.3%) of stomach cancer, one case (7%) of colon cancer, 3 cases(11%) of bladder cancer, 2 cases(10%) of thyroid cancer and 15 other cases. 4. Out of 121 cases with early stage of malignancy (which included 20 cases of lung cancer in stage I, II, 38 cases of breast cancer, 13 cases of stomach cancer, 8 cases of kidney tumor, 14 cases of thyroid cancer in stage $I{\sim}III$, and 6 cases of colon cancer, 14 cases of bladder cancer, 8 cases of prostate cancer in stage $A{\sim}C$, bone scans were positive in 5 cases (4.1%) which included 3 cases of lung cancer one case of breast cancer and one case of prostate cancer, and considered as further advanced stage. Out of 121 cases with early stage of malgnancy, bone scans were suspicious in 21 cases (17.4%) which inlcuded 9 cases of lung cancer, 4 cases of breast cancer, 2 cases of stomach cancer, one case of colon cancer, 3 cases of bladder cancer, and 2 cases of thyroid cancer. From these results, we concluded bone scan was useful in detecting bone metastasis in patients of early stage of malignancy, determining prognosis and establishing therapentic plan.

• Biomolecules & Therapeutics
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• v.15 no.2
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• pp.95-101
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• 2007

Resveratrol (3,5,4’-trihydroxy-trans-stilbene), a naturally occurring phytoallexin abundant in grapes and several plants, has been shown to be active in inhibiting proliferation and inducing apoptosis in several human cancer cell lines. On the line of the biological activity of resveratrol, a variety of resveratrol analogs were synthesized and evaluated for their growth inhibitory effects against several human cancer cell lines. In the present study, we found that one of the resveratrol analogs, 3,4,5-trimethoxy-4’-bromo-cis-stilbene, markedly suppressed human colon cancer cell proliferation (EC$_{50}$ = 0.01 ${\mu}$g/ml), and the inhibitory activity was superior to its corresponding trans-isomer (EC$_{50}$ = 1.6 ${\mu}$g/ml) and resveratrol (EC$_{50}$ = 18.7 ${\mu}$g/ml). Prompted by the strong growth inhibitory activity in cultured human colon cancer cells (Col2), we investigated its mechanism of action. 3,4,5-Trimethoxy-4’-bromo-cis-stilbene induced arrest of cell cycle progression at G2/M phase and increased at sub-G1 phase DNA contents of the cell cycle in a time- and dose-dependent manner. Colony formation was also inhibited in a dose-dependent manner, indicating the inhibitory activity of the compound on cell proliferation. Moreover, the morphological changes and condensation of the cellular DNA by the treatment of the compound were well correlated with the induction of apoptosis. These data suggest the potential of 3,4,5-trimethoxy-4’-bromo-cis-stilbene might serve as a cancer chemotherapeutic or chemopreventive agent by virtue of arresting the cell cycle and inducing apoptosis for the human colon cancer cells.

• Nutrition Research and Practice
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• v.9 no.2
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• pp.111-116
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• 2015

BACKGROUND/OBJECTIVES: Inonotus obliquus (I. obliquus, Chaga mushroom) has long been used as a folk medicine to treat cancer. In the present study, we examined whether or not ethanol extract of I. obliquus (EEIO) inhibits cell cycle progression in HT-29 human colon cancer cells, in addition to its mechanism of action. MATERIALS/METHODS: To examine the effects of Inonotus obliquus on the cell cycle progression and the molecular mechanism in colon cancer cells, HT-29 human colon cancer cells were cultured in the presence of $2.5-10{\mu}g/mL$ of EEIO, and analyzed the cell cycle arrest by flow cytometry and the cell cycle controlling protein expression by Western blotting. RESULTS: Treatment cells with $2.5-10{\mu}g/mL$ of EEIO reduced viable HT-29 cell numbers and DNA synthesis, increased the percentage of cells in $G_1$ phase, decreased protein expression of CDK2, CDK4, and cyclin D1, increased expression of p21, p27, and p53, and inhibited phosphorylation of Rb and E2F1 expression. Among I. obliquus fractions, fraction 2 (fractionated by dichloromethane from EEIO) showed the same effect as EEIO treatment on cell proliferation and cell cycle-related protein levels. CONCLUSIONS: These results demonstrate that fraction 2 is the major fraction that induces $G_1$ arrest and inhibits cell proliferation, suggesting I. obliquus could be used as a natural anti-cancer ingredient in the food and/or pharmaceutical industry.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2987-2991
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• 2014

Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (p<0.05) with the histological type and tumor invasion properties of the cancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.