• Radiation Oncology Journal
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• v.35 no.3
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• pp.208-216
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• 2017

Purpose: To evaluate the feasibility of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for preoperative concurrent chemoradiotherapy (PCRT) in locally advanced rectal cancer (LARC), by comparing with 3-dimensional conformal radiotherapy (3D-CRT). Materials and Methods: Patients who were treated with PCRT for LARC from 2015 January to 2016 December were retrospectively enrolled. Total doses of 45 Gy to 50.4 Gy with 3D-CRT or SIB-IMRT were administered concomitantly with 5-fluorouracil plus leucovorin or capecitabine. Surgery was performed 8 weeks after PCRT. Between PCRT and surgery, one cycle of additional chemotherapy was administered. Pathologic tumor responses were compared between SIB-IMRT and 3D-CRT groups. Acute gastrointestinal, genitourinary, hematologic, and skin toxicities were compared between the two groups based on the RTOG toxicity criteria. Results: SIB-IMRT was used in 53 patients, and 3D-CRT in 41 patients. After PCRT, no significant differences were noted in tumor responses, pathologic complete response (9% vs. 7%; p = 1.000), pathologic tumor regression Grade 3 or higher (85% vs. 71%; p = 0.096), and R0 resection (87% vs. 85%; p = 0.843). Grade 2 genitourinary toxicities were significantly lesser in the SIB-IMRT group (8% vs. 24%; p = 0.023), but gastrointestinal toxicities were not different across the two groups. Conclusion: SIB-IMRT showed lower GU toxicity and similar tumor responses when compared with 3D-CRT in PCRT for LARC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3015-3021
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• 2015

Background: Colorectal cancer (CRC) is a major cause of mortality in developed countries, and it is the third most frequent malignancy in Turkey. There are many biological, genetic, molecular, and tissue-derived prognostic factors for CRCs. In this study, we evaluated prognostic factors in patients who were metastatic at diagnosis or progressed to metastatic disease during follow-up. Patients and Methods: This study included 116 patients with malignancies either in the colon or rectum. Of these, 65 had metastatic disease at diagnosis, and 51 progressed to metastatic disease during the course of the disease. The parameters evaluated were age, gender, comorbidity, performance status and stage of the disease at the beginning, localization, history of surgery, chemotherapy regimen, response to first-line treatment, K-RAS status, site and number of metastases, expression of tumor predictors (CEA, CA19-9), and survival times. A multivariate analysis conducted with factors that considered statistically significant in the univariate analysis. Findings: Median age was 56 (32-82) years and the male/female ratio was 80/36. Eleven patients were at stage II, 40 at stage III, and 65 at stage IV at diagnosis. Twenty three patients had tumor in the right colon, 48 in the left colon, and 45 in the rectum. Ninety seven patients were operated, and 27 had surgical metastasectomy. Ninety three patients received targeted therapy. At the end of follow-up, 61 patients had died, and 55 survived. Metastatic period survival times were longer in the adjuvant group, but the difference did not reach the level of statistical significance (adjuvant group: median 29 months, metastatic group: median 22 months; p=0.285). In the adjuvant group before the metastatic first-line therapy, CEA and CA 19-9 levels were significiantly lower compared to the metastatic group (p<0.005). We also found that patients with elevated tumor predictor (CEA, CA 19-9) levels before the first-line therapy had significiantly poorer prognosis and shorter survival time. Survival was significiantly better with the patients who were younger than 65 years of age, had better initial performance status, a history of primary surgery and metastatectomy, and single site of metastasis. Those who benefitted from the first-line therapy were K-RAS wild type and whose tumor markers (CEA, CA 19-9) were not elevated before the first line therapy. Conclusions: Among the patients with metastatic CRC, those who benefited from first-line therapy, had history of metastasectomy, were K-RAS wild type and had low CA 19-9 levels before the first-line therapy, showed better prognosis independent of other factors.

• Annals of Coloproctology
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• v.34 no.6
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• pp.286-291
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• 2018

Purpose: Stage-IIIC colon cancer is an advanced disease; however, its oncologic outcomes and prognostic factors remain unclear. In this study, we aimed to determine the predictors of disease-free survival (DFS) in patients with stage-IIIC colon cancer. Methods: From a multicenter database, we retrospectively enrolled 611 patients (355 men and 256 women) who had undergone a potentially curative resection for a stage-IIIC colon adenocarcinoma between 2003 and 2011. The primary endpoint was the 5-year DFS. Results: The median age was 62 years; 213 and 398 patients had right-sided colon cancer (RCC) and left-sided colon cancer (LCC), respectively. The 5-year DFS in all patients was 52.0%; median follow-up time was 35 months (range, 1-134 months). A multivariate Cox regression revealed that female sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.19-1.90; P < 0.01), right-sided tumor location (HR, 1.65; 95% CI, 1.29-2.11; P < 0.01), lymphatic invasion (HR, 1.52; 95% CI, 1.08-2.15; P < 0.01) and a high (${\geq}0.4$) metastatic lymph node ratio (HR, 3.72; 95% CI, 2.63-5.24; P < 0.01) were independent predictors of worse 5-year DFS. Female patients with RCC were 1.79 fold more likely to experience recurrence than male patients with LCC. Conclusion: Female sex and right-sided tumor location are associated with higher tumor recurrence rates in patients with stage-IIIC colon cancers. Aggressive treatment and close surveillance should be planned for patients in these groups.

• BMB Reports
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• v.51 no.11
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• pp.563-571
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• 2018

Colorectal cancer (CRC), the third most common cancer in the world, has no specific biomarkers that facilitate its diagnosis and subsequent treatment. The miRNAs, small single-stranded RNAs that repress the mRNA translation and trigger the mRNA degradation, show aberrant levels in the CRC, by which these molecules have been related with the initiation, progression, and drug-resistance of this cancer type. Numerous studies show the microRNAs influence the cellular mechanisms related to the cell cycle, differentiation, apoptosis, and migration of the cancer cells through the post-transcriptionally regulated gene expression. Specific patterns of the upregulated and down-regulated miRNA have been associated with the CRC diagnosis, prognosis, and therapeutic response. Concretely, the downregulated miRNAs represent attractive candidates, not only for the CRC diagnosis, but for the targeted therapies via the tumor-suppressing microRNA replacement. This review shows a general overview of the potential uses of the miRNAs in the CRC diagnosis, prognosis, and treatment with a special focus on the downregulated ones.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5047-5056
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• 2016

Colorectal cancer (CRC) is a major worldwide health problem owing to its high prevalence and mortality rates. Carcinogenesis in the colon is a multistage and multifactorial process. An imbalance between free radical exposure and anti-oxidant defense systems may leads to oxidative stress and attack of macromolecules which can alter signal transduction pathways and gene expression. Consequently, oxidative damage can lead to cellular dysfunction and contribute to pathophysiological processes in a variety of diseases including CRC. One factor tightly associated with CRC is chronic inflammation, which can be present from the earliest stage of tumor onset. Unpolished rice is an attractive chemoprevention in CRC due to their anti-oxidant and anti-inflammatory activities. The aim of this paper is to review evidence linking oxidative stress and inflammation to CRC and to provide essential background information for understanding future research on oxidative stress and inflammation on CRC. Mechanisms of action of unpolished rice in CRC carcinogenesis are also discussed.

• Journal of Yeungnam Medical Science
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• v.37 no.3
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• pp.246-249
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• 2020

Synchronous gastric cancer and adenomatous colorectal polyp in patients with Klebsiella pneumoniae-induced pyogenic liver abscess (KP-PLA) and bacteremia is a rare presentation. A 58-year-old man with a 6-month history of diabetes mellitus (DM) presented with febrile sensation and dull abdominal pain in the right upper quadrant of the abdomen. Subsequent to laboratory test results and abdominal computed tomography findings, KP-PLA with bacteremia was diagnosed. After intravenous antibiotic administration, his symptoms improved, and upper endoscopy and colonoscopy were performed to evaluate the cause of KP-PLA. Biopsy specimens of the prepyloric anterior wall revealed a moderately differentiated adenocarcinoma. Endoscopic mucosal resection of the colon revealed high-grade dysplasia. Early gastric cancer (EGC) and adenomatous colorectal polyps with high-grade dysplasia concomitant with KP-PLA and bacteremia were diagnosed in our patient who had DM. Intravenous antibiotic treatment for KP-PLA, subtotal gastrectomy for EGC, and colonoscopic mucosal resection for the colon polyp were performed. After 25 days of hospitalization, subtotal gastrectomy with adjacent lymph node dissection was performed. Follow-up ultrasound imaging showed resolution of the abscess 5 weeks post-antibiotic treatment, as well as no tumor metastasis. Upper gastrointestinal endoscopy and colonoscopy should be performed to evaluate gastric cancer in patients with PLA or bacteremia, accompanied with DM or an immunocompromised condition.

• Development and Reproduction
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• v.18 no.4
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• pp.225-231
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• 2014

Autophagy is a homeostatic degradation process that is involved in tumor development and normal development. Autophagy is induced in cancer cells in response to chemotherapeutic agents, and inhibition of autophagy results in enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial drug, is a lysosomotropic agent and is currently used as a potential anticancer agent as well as an autophagy inhibitor. Here, we evaluate the characteristics of these dual activities of CQ using human colorectal cancer cell line HCT15. The results show that CQ inhibited cell viability in dose- and time-dependent manner in the range between 20 to 80 uM, while CQ did not show any antiproliferative activity at 5 and 10 uM. Cotreatment of CQ with antitumor agent NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability at low concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced the lethal effect at high concentrations. Acridine orange staining revealed that CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses of CQ produced cellular reactive oxygen species (ROS) and cotreatment of antioxidants, such as NAC and trolox, with high doses of CQ rescued the cell viability. These results suggest that CQ may exert its dual activities, as autophagy inhibitor or LMP inducer, in concentration-dependent manner.

• Journal of Digestive Cancer Research
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• v.11 no.1
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• pp.49-54
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• 2023

Colorectal cancers often invade adjacent organs; however, direct duodenal invasion is rare. Adenocarcinoma is the most common type of colorectal cancer, but an undifferentiated carcinoma type is unusual. Herein, we present a case of undifferentiated carcinoma of the colon that directly invaded the duodenum and metastasized to distant lymph nodes. An 85-year-old female patient was admitted with a 7-cm-sized colonic mass invading the duodenum, detected by computed tomography. Positron emission tomography revealed fluorodeoxyglucose uptake in the colon, duodenum, and aortocaval lymph nodes. A large encircling mass in the ascending colon and an ulcerated mass in the duodenum were revealed by colonoscopy and esophagogastroduodenoscopy, respectively. Pathologic examinations of the colon and the duodenum revealed nonglandular, diffusely infiltrating atypical round cells, confirming undifferentiated carcinoma of the colon. The histologic type of this tumor was distinguished using immunohistochemical (IHC) markers. Finally, microscopic characteristics and IHC markers aided in identifying the histologic type of colorectal cancer.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.655-660
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• 2023

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

• The Korean Journal of Nuclear Medicine
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• v.24 no.1
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• pp.29-36
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• 1990

Most of the diagnostic methods currently used for the detection of neoplastic masses provide indirect evidence. To obtain greater specificity in the interpretation of neoplasias by in vivo methods, the immunological approach appears to be most promising. Two problems that interfered with progress in this field were the lack of tumor specific antigen and the lack of well-defined and reproducible antibodies. To improve the sensitivity and specificity of radioimmunoscintigraphy as a technique for tumor localization, the use of monoclonal antibodies, fragments of antibodies and single photon emission computerized tomography (SPECT) are reasonable. The obvious advantages of monoclonal antibodies are their homogeneity, their specificity for the immunizing antigen and the reaction with a single determinant-thus no large immunecomplexes with antigen are formed. Monoclonal antibody technique has recently provided an opportunity to reevaluate the role of nuclear medicine for the diagnosis of malignant diseases by using the immunological approach. Out first results by means of radioimmunoscintigraphy of CEA and CA 19-9 producing tumors using a cocktail of fragments F $(ab')_2$, of mocolonal antibodies to CA 19-9 and CEA labeled with $^{131}I$ (IMACIS-1) are reported. The aims of this investigation was to evaluate the role of immunoscintigraphy in patients with colorectal and other cancers for diagnosis of local recurrences and metastasis. This report contains results of the first 8 colorectal and pancreas cancer patients with the elevation of the level of serum CEA and/or CA 19-9. IMACIS-1 was injected intravenously during 30 minutes in 100 ml saline solution after skin test. Planar scintigrams were recorded 3, 5 and 7 days after the injection of the IMACIS-1. Anterior, lateral and posterior views of the liver as well as anterior and posterior views of the pelvis were obtained in each patients as an $^{131}I-antibody$ image. We were able to localize exactly the malignant process with the double-nuclide double-compound $^{99m}Tc\;^{131}I$ (Tc+l) scintigrams. In Tc & I double-nuclide scintigraphy, computer subtraction display provided more clear localization of the tumor. We compared the results of radioimmunoscintigraphy with CT, ultrasonograms, conventional scintigrams. The results were as follows: 1) The sensitivity and specificity of radioimmunoscintigraphy using the fragments $F(ab')_2$ of the cocktails of CEA and CA 19-9 monoclonal antibodies were 80% and 100% respectively. 2) Tumor detection rate was not proportionated to the level of serum tumor markets. 3) Second tracer technique was essential for tumor localization as an anatomic landmark using double-nuclide scintigraphy. 4) A slow infusion of the antibodies was necessary to prevent the formation of large immune complexes. 5) Tumor/non-tumor radioactivity was most elevated at 7 days delayed imaging. 6) Using planar scintigraphic technique of $^{131}I$ labeled monoclonal antibodies are possible for imaging most of the tumors.