• Investigative Magnetic Resonance Imaging
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• 제17권2호
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• pp.133-143
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• 2013

목적 : 직결장암 조직의 자기공명영상과 고주파 초음파검사를 시행한 후 종양의 탐지와 침윤 깊이에 대해 각각의 영상 소견과 병리 소견을 비교하여 진단적 정확도를 두 영상 기기 간 비교하고, 자기공명영상의 경우 종양의 침윤 깊이를 주변 정상 조직과 가장 명확히 보여주는 펄스 연쇄 (pulse sequence)에 대해 알아보았다. 대상 및 방법 : 직결장암으로 절제술을 시행한 45명의 환자에서 얻은 45예의 제거된 종양 조직을 수조에 넣고 생리 식염수에 담가서 고주파수 (5-17 MHz)의 선형 탐촉자를 이용하여 초음파영상을 얻었으며 8-channel 두경부 코일에 넣어 자기공명영상을 얻었다. 이 연구에 대하여 기관감사위원회의 공지에 입각한 동의는 면제되었다. 자기공명영상은 정- 및 탈위상 경사에코 T1 강조영상, 급속스핀에코 T2 강조영상 및 이의 지방억제 영상, fast imaging employing steady-state acquisition (FIESTA)와 이의 지방억제영상, 확산강조영상 등 일곱 가지 펄스 연쇄를 시행하였다. 각 조직의 자기공명영상과 초음파영상 소견을 각각 독립적으로 종양의 탐지와 침윤 깊이에 대하여 두 명의 영상의학과 의사가 합의 하에 평가하였고 각각의 영상 소견을 병리 조직 소견과 비교하여 두 영상 기기 간 진단적 정확도를 비교하였다. 자기공명영상의 일곱 가지 펄스 연쇄 중에 종양의 침윤 깊이를 주변 정상 조직과 구분하여 명확히 보여주는 펄스 연쇄에 대해 알아보았다. 결과 : 직결장암 조직의 종양 탐지와 침윤 깊이를 평가하는데 있어 자기공명영상과 초음파의 진단적 정확도는 각각 91.1%와 86.7%로 높게 나타났다. 조기 직결장암의 경우 초음파 검사의 정확도는 87.5%, 자기공명영상 검사의 정확도는 75.0%로 나왔다. 두 영상 기기 간에 통계적으로 유의한 차이는 없었다 (p > 0.05). MR의 펄스 연쇄 중에 종양의 침윤 깊이를 주변 정상 조직과 구분하여 명확하게 보여주는 영상은 직결장암 및 조기 직결장암 모두 급속 스핀에코 T2 강조영상이었다. 결론 : 자기공명영상과 초음파 검사는 직결장암 조직의 종양 탐지와 침윤 깊이를 평가하는데 높은 진단적 정확도를 가지고 있으며, 자기공명영상의 급속스핀에코 T2 강조영상이 직결장암 조직의 종양 침윤 깊이를 평가하는데 가장 우수하였다.

• Journal of Microbiology and Biotechnology
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• 제32권7호
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• pp.938-948
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• 2022

Gastric cancers (GC) are generally malignant tumors, occurring with high incidence and threatening public health around the world. Circular RNAs (circRNAs) play crucial roles in modulating various cancers, including GC. However, the functions of circRNAs and their regulatory mechanism in colorectal cancer (CRC) remain largely unknown. This study focuses on both the role of circCOL1A2 in CRC progression as well as its downstream molecular mechanism. Quantitative polymerase chain reaction (qPCR) and western blot were adopted for gene expression analysis. Functional experiments were performed to study the biological functions. Fluorescence in situ hybridization (FISH) and subcellular fraction assays were employed to detect the subcellular distribution. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), RNA pull-down, and immunofluorescence (IF) and immunoprecipitation (IP) assays were used to explore the underlying mechanisms. Our results found circCOL1A2 to be not only upregulated in GC cells, but that it also propels the migration and invasion of GC cells. CircCOL1A2 functions as a competing endogenous RNA (ceRNA) by sequestering microRNA-1286 (miR-1286) to modulate ubiquitin-specific peptidase 10 (USP10), which in turn spurs the migration and invasion of GC cells by regulating RFC2. In sum, CircCOL1A2 sponges miR-1286 to promote cell invasion and migration of GC by elevating the expression of USP10 to downregulate the level of RFC2 ubiquitination. Our study offers a potential novel target for the early diagnosis and treatment of GC.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1637-1641
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• 2016

Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

• 대한수의학회지
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• 제52권2호
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• pp.115-124
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• 2012

Colorectal cancer (CRC) is one of the leading causes of cancer death in western countries or in the developed countries. Zinc intake has been associated with decreased risk of CRC. We investigated the effect of zinc on the formation of colonic aberrant crypt foci (ACF) induced by azoxymethane followed by dextran sodium sulfate in mice. Five-week old ICR mice were fed with the different zinc levels (0.01, 0.1, 1 ppm) for 12 weeks. The numbers of ACF were measured in the colonic mucosa. The ACF number of HZn group was significantly low compared with LZn group or MZn group. Cytosolic superoxide dismutase activity was the highest in HZn group, while thiobarbituric acid reactive substance level for lipid peroxidation was the highest in LZn group. There was no difference in number of PCNA-positive proliferative cells among the groups. TUNEL-positive apoptotic cells were increased in HZn group compared with LZn group. The HZn group exhibited a decrease of ${\beta}$-catenin immunostaining areas compared with the LZn or MZn group. These findings indicate that dietary zinc might exert a protecting effect against colon carcinogenesis by inhibiting the development of ACF in the mice.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2833-2838
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• 2015

Background: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin-based regimens as rechallenge third and fourth-line therapy. Materials and Methods: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meire and Cox-regression methods. Results: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.68 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy ${\geq}12months$ (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. Conclusions: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ${\geq}12months$ PFS onreceiving first line therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7179-7188
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• 2015

Cancer is a major health obstacle around the world, with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) as major causes of morbidity and mortality. Nowadays, there isgrowing interest in the therapeutic use of natural products for HCC and CRC, owing to the anticancer activity of their bioactive constituents. Boswellia serrata oleo gum resin has long been used in Ayurvedic and traditional Chinese medicine to alleviate a variety of health problems such as inflammatory and arthritic diseases. The current study aimed to identify and explore the in vitro anticancer effect of B. Serrata bioactive constituents on HepG2 and HCT 116 cell lines. Phytochemical analysis of volatile oils of B. Serrata oleo gum resin was carried out using gas chromatography-mass spectrometry (GC/MS). Oleo-gum-resin of B. Serrata was then successively extracted with petroleum ether (extract 1) and methanol (extract 2). Gas-liquid chromatography (GLC) analysis of the lipoidal matter was also performed. In addition, a methanol extract of B. Serrata oleo gum resin was phytochemically studied using column chromatography (CC) and thin layer chromatography (TLC) to obtain four fractions (I, II, III and IV). Sephadex columns were used to isolate ${\beta}$-boswellic acid and identification of the pure compound was done using UV, mass spectra, $^1H$ NMR and $^{13}C$ NMR analysis. Total extracts, fractions and volatile oils of B. Serrata oleo-gum resin were subsequently applied to HCC cells (HepG2 cell line) and CRC cells (HCT 116 cell line) to assess their cytotoxic effects. GLC analysis of the lipoidal matter resulted in identification of tricosane (75.32%) as a major compound with the presence of cholesterol, stigmasterol and ${\beta}$-sitosterol. Twenty two fatty acids were identified of which saturated fatty acids represented 25.6% and unsaturated fatty acids 74.4% of the total saponifiable fraction. GC/MS analysis of three chromatographic fractions (I,II and III) of B. Serrata oleo gum resin revealed the presence of pent-2-ene-1,4-dione, 2-methyl- levulinic acid methyl ester, 3,5- dimethyl- 1-hexane, methyl-1-methylpentadecanoate, 1,1- dimethoxy cyclohexane, 1-methoxy-4-(1-propenyl)benzene and 17a-hydroxy-17a-cyano, preg-4-en-3-one. GC/MS analysis of volatile oils of B. Serrata oleo gum resin revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. The anti-cancer effect of two extracts (1 and 2) and four fractions (I, II, III and IV) as well as volatile oils of B. Serrata oleo gum resin on HepG2 and HCT 116 cell lines was investigated using SRB assay. Regarding HepG2 cell line, extracts 1 and 2 elicited the most pronounced cytotoxic activity with $IC_{50}$ values equal 1.58 and $5.82{\mu}g/mL$ at 48 h, respectively which were comparable to doxorubicin with an $IC_{50}$ equal $4.68{\mu}g/mL$ at 48 h. With respect to HCT 116 cells, extracts 1 and 2 exhibited the most obvious cytotoxic effect; with $IC_{50}$ values equal 0.12 and $6.59{\mu}g/mL$ at 48 h, respectively which were comparable to 5-fluorouracil with an $IC_{50}$ equal $3.43{\mu}g/mL$ at 48 h. In conclusion, total extracts, fractions and volatile oils of B. Serrata oleo gum resin proved their usefulness as cytotoxic mediators against HepG2 and HCT 116 cell lines with different potentiality (extracts > fractions > volatile oil). In the two studied cell lines the cytotoxic acivity of each of extract 1 and 2 was comparable to doxorubicin and 5-fluorouracil, respectively. Extensive in vivo research is warranted to explore the precise molecular mechanisms of these bioactive natural products in cytotoxicity against HCC and CRC cells.

• Nutrition Research and Practice
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• 제16권6호
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• pp.700-715
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• 2022

BACKGROUND/OBJECTIVES: Chronic colitis is a risk factor for colorectal cancer (CRC) development in both animals and humans. Previously, we reported that a diet rich in protein (with casein as the protein source) significantly increased the risk of mouse CRC development in a dose-dependent manner. In this study, we investigated the effects of different protein sources on the risk of colitis development. MATERIALS/METHODS: Balb/c mice were divided into 7 experimental groups: 20% casein (20C), 20C-dextran sulfate sodium (DSS), 40% casein-DSS (40CD), 40% whey protein-DSS (40WD), 40% soy protein-DSS (40SD), 40% white meat-DSS (40WMD), and 40% red meat-DSS (40RMD). Mice were fed an experimental diet for 4 wk and received 3% DSS in their drinking water for 6 days during the 4th wk of the experimental period. RESULTS: Compared to other groups, the 40CD group showed the most aggravated colitis with increased disease activity and inflammatory markers. In the 40RMD group, interleukin (IL)-6 levels were the highest among all the groups. The 40SD group showed conflicting effects, for example, elevated mortality and disease activity but decreased nitric oxide (NO) levels. The 40WD group showed attenuated colitis with increased IL-10 levels and decreased NO levels. The 40WMD group showed conflicting effects, including decreased NO levels and elevated fecal lipocalin-2 and IL-6 levels. CONCLUSIONS: These results suggest that, at levels of 40% in the diet, casein and red meat exacerbate colitis, whereas whey protein mitigates it the most effectively.