• 제목/요약/키워드: metastatic colorectal cancer

검색결과 97건 처리시간 0.021초

A small molecule approach to degrade RAS with EGFR repression is a potential therapy for KRAS mutation-driven colorectal cancer resistance to cetuximab

  • Lee, Sang-Kyu;Cho, Yong-Hee;Cha, Pu-Hyeon;Yoon, Jeong-Soo;Ro, Eun Ji;Jeong, Woo-Jeong;Park, Jieun;Kim, Hyuntae;Kim, Tae Il;Min, Do Sik;Han, Gyoonhee;Choi, Kang-Yell
    • Experimental and Molecular Medicine
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    • 제50권11호
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    • pp.12.1-12.12
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    • 2018
  • Drugs targeting the epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have been prescribed for metastatic colorectal cancer (CRC), but patients harboring KRAS mutations are insensitive to them and do not have an alternative drug to overcome the problem. The levels of ${\beta}$-catenin, EGFR, and RAS, especially mutant KRAS, are increased in CRC patient tissues due to mutations of adenomatous polyposis coli (APC), which occur in 90% of human CRCs. The increases in these proteins by APC loss synergistically promote tumorigenesis. Therefore, we tested KYA1797K, a recently identified small molecule that degrades both ${\beta}$-catenin and Ras via $GSK3{\beta}$ activation, and its capability to suppress the cetuximab resistance of KRAS-mutated CRC cells. KYA1797K suppressed the growth of tumor xenografts induced by CRC cells as well as tumor organoids derived from CRC patients having both APC and KRAS mutations. Lowering the levels of both ${\beta}$-catenin and RAS as well as EGFR via targeting the $Wnt/{\beta}$-catenin pathway is a therapeutic strategy for controlling CRC and other types of cancer with aberrantly activated the $Wnt/{\beta}$-catenin and EGFR-RAS pathways, including those with resistance to EGFR-targeting drugs attributed to KRAS mutations.

Inhibition of Proinflammatory Cytokine-induced Invasiveness of HT-29 Cells by Chitosan Oligosaccharide

  • Nam, Kyung-Soo;Kim, Mee-Kyung;Shon, Yun-Hee
    • Journal of Microbiology and Biotechnology
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    • 제17권12호
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    • pp.2042-2045
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    • 2007
  • The effect of chitosan oligosaccharide (COS, 1 kDa${\gamma}$, 10 ng/ml IL-$1{\alpha}$, and 25 ng/ml TNF-${\alpha}$) in HT-29 cells. Inducible nitric oxide synthase (iNOS) expression induced by these cytokines was inhibited by COS. COS pretreatment inhibited the invasiveness of cytokines-treated HT-29 cells through Matrigel-coated membrane in a dose-dependent manner. COS also inhibited cytokines-induced matrix metalloproteinase (MMP)-2 activity. This study shows that proinflammatory cytokines induce NO production, iNOS expression, and invasiveness of human colorectal adenocarcinoma HT-29 cells. COS pretreatment inhibited cytokines-mediated NO production, iNOS expression, and invasiveness of HT-29 cells. These results provide sufficient information for the further development of COS as an antitumor metastatic agent for the treatment of colon cancer.

Creatine Kinase (CK)-MB-to-Total-CK Ratio: a Laboratory Indicator for Primary Cancer Screening

  • Chang, Chih-Chun;Liou, Ching-Biau;Su, Ming-Jang;Lee, Yi-Chen;Liang, Chai-Ting;Ho, Jung-Li;Tsai, Huang-Wen;Yen, Tzung-Hai;Chu, Fang-Yeh
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6599-6603
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    • 2015
  • Background: For the determination of creatine kinase (CK)-MB, the immunoinhibition method is utilized most commonly. However, the estimated CK-MB activity may be influenced by the presence of CK isoenzymes in some conditions like cancer. Thus, a CK-MB-to-total-CK ratio more than 1.0 could be found in such a situation. The study aimed to explore the relationship of cancer to high CK-MB-to-total-CK ratio. Materials and Methods: From January 2011 to December 2014, laboratory data on all CK-MB and total CK test requests were extracted at Far Eastern Memorial Hospital (88,415 requests). Patients with a CK-MB-to-total-CK ratio more than 1.0 were registered in this study. Clinical data including tumor location, tumor TNM stage and metastatic status were also collected. Results: A total of 846 patients were identified with a CK-MB-to-total-CK ratio more than 1.0. Of these, 339 (40.1%) were diagnosed with malignancies. The mean CK-MB-to-total-CK ratio was significantly higher in malignancy than in non-malignancy ($1.35{\pm}0.28$ vs $1.25{\pm}0.23$, p<0.001) groups. The most frequent malignancy with a CK-MB-to-total-CK ratio more than 1.0 was colorectal cancer ($1.42{\pm}0.28$, 16.5%, n=56), followed by lung cancer ($1.38{\pm}0.24$, 15.9%, n=54) and hepatocellular carcinoma (14.5%, n=49). Higher CK-MB-to-total-CK ratios in hematological malignancies ($1.44{\pm}0.41$)were also noted. Additionally, the CK-MB-to-total-CK ratio was markedly higher in advanced stage malignancy than in early stage ($1.37{\pm}0.26$ vs. $1.29{\pm}0.31$, p=0.014) and significantly higher in liver metastasis than in non-liver metastasis ($1.48{\pm}0.30$ vs. $1.30{\pm}0.21$, p<0.001). Conclusions: The CK-MB-to-total-CK ratio is an easily available indicator and could be clinically utilized as a primary screening tool for cancer. Higher ratio of CK-MB-to-total-CK was specifically associated with certain malignancies, like colorectal cancer, lung cancer and hepatocellular carcinoma, as well as some cancer-associated status factors such as advanced stage and liver metastasis.

Anti-metastatic mechanism of mountain cultivated wild ginseng in human cancer cell line

  • Jang, S.B.;Lim, C.S.;Jang, J.H.;Kwon, K.R.
    • 대한약침학회지
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    • 제13권1호
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    • pp.37-43
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    • 2010
  • Objective : Ginseng is one of most widely used herbal medicine. Ginseng showed anti-metastasis activities. However, its molecular mechanisms of action are unknown. So we want to report the wild ginseng repress which plays key roles in neoplastic epithelial-mesenchymal transition process. Methods : Treatment of the human colorectal carcinoma LOVO cells and human gastric carcinoma SNU601 cells with the increased concentrations of cultivated wild ginseng extracts resulted in a gradual decrease in the AXIN2 gene expression. Results : Metastasis-suppressor genes, maspin and nm23 was not affected by the treatment of ginseng extracts in LOVO cells. Moreover, the mountain cultivated wild ginseng or mountain wild ginseng are similar in their inhibitory effects on the expression of AXIN2 gene, but are substantially stronger than cultivated ginseng. Conclusion : We described the novel mechanism of wild ginseng-induced anti-metastasis activity by repressing the expression of AXIN2 gene that plays key roles in epithelial-mesenchymal transition process.

Survival of Rectal Cancer in Yazd, Iran

  • Akhavan, Ali;Binesh, Fariba;Soltani, Amin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권12호
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    • pp.4857-4860
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    • 2014
  • Background: Colorectal cancer is common in Iran. However our knowledge about survival of rectal cancer in our province is low. The aim of this study is to evaluate this question. Materials and Methods: Patients with documented pathology of adenocarcinoma of the rectum and rectosigmoid junction referred to our center from September 2004 to September 2012 were enrolled in this study. Metastatic and recurrent patients were excluded. A questionnaire including clinicopathologic parameters, quality and sequence of treatment modalities was filled in for each patient. Patients treated with a combination of surgery, chemotherapy and radiation therapy were divided into standard and non-standard treatment groups, according to the sequence of treatment. Results: One hundred and nineteen patients were evaluated. Mean age was 60.8 year. The median overall survival was 62 months and five year survival was 55%. TNM staging system was not possible due to (Nx) in 21 (17.6%) patients. The others were in stage I, 20 patients (16.8%), II, 35 (29%.5) and III, 43(36.1%). According to our definition only 25 patients (21%) had been treated with standard treatment and 79% had not received it. A five year survival in patients with standard treatment was 85% and in the non-standard group it was 52%.Age, sex, stage and grade of tumor did not show any significant relation to survival. Conclusions: Our study showed a five year survival of rectal cancer in our patients was about 10% lower than the rate which is reported for developed countries. Preoperative concurrent chemoradiation significantly improved local control and even overall survival.

소아 대장에서 발생한 전이성 반지세포암 1예 (A Case of Metastatic Signet Ring Cell Carcinoma of the Colon in a Child)

  • 오대성;한경희;신지연;심정옥;박지숙;양혜란;고재성;신희영;안효섭;박귀원;강경훈;천정은;김우선;서정기
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • 제10권1호
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    • pp.76-80
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    • 2007
  • 소아암에서 장관계 악성 종양 특히, 대장암은 극히 드문 질환이다. 그러나, 대장은 소아 장관계 상피세포암이 가장 호발하는 부위이며, 반지세포암은 성인과는 달리 소아 대장암 중에서 가장 흔한 조직형태 중 하나이다. 국내에서는 소아 대장에서 발생한 반지세포암에 대한 보고는 아직 없었다. 반지세포암은 점액이 세포내에 풍부하고 핵이 한쪽으로 치우쳐 있는 특징적 고리모양의 암 세포가 전체 암 세포의 50% 이상을 차지하는 조직 소견으로 진단된다. 저자들은 복통, 체중감소, 요통, 좌측 대퇴부 통증, 혈변으로 내원한 11세 남아에서 내시경 조직검사 소견으로 확진된 복강내 침습, 혈액 및 림프성 전이가 진행된 소아 대장에서의 전이성반지세포암을 경험하였기에 보고하는 바이다.

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$^{18}F-FDG$ PET/CT 에서 발견된 S상 결장암의 단일 비장 전이 (Isolated Splenic Metastasis of Sigmoid Colon Cancer Detected by $^{18}F-FDG$ PET/CT)

  • 안영실;윤준기;홍선표;최봉회;조철우;윤석남
    • Nuclear Medicine and Molecular Imaging
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    • 제41권3호
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    • pp.263-264
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    • 2007
  • Splenic metastasis from colon carcinoma are rare and usually occur in the presence of disseminated visceral metastasis. The liver is the most common site of metastatic spread from colon cancer. Several hypotheses have attempted to explain the low incidence of splenic metastasis. It should be difficult for colorectal cancer cells to reach the spleen through the portal venous system, in which the blood flow is usually from the spleen to the liver. Reticuloendothelial system or rhythmic contraction of the spleen may squeeze out the tumor in the spleen. The absence of afferent lymphatic to the spleen, phagocytic activity and humoral anticancer substances are considered to be other reason for low incidence of splenic metastasis. We report the case of $^{18}F-FDG$ PET/CT finding in a 70-year-old woman who develop isolated splenic metastasis of sigmoid colon cancer.

Expression of MiR200a, miR93, Metastasis-related Gene RECK and MMP2/MMP9 in Human Cervical Carcinoma - Relationship with Prognosis

  • Wang, Ling;Wang, Qiang;Li, He-Lian;Han, Li-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권3호
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    • pp.2113-2118
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    • 2013
  • Aim and Background: Cervical cancer remains the third most common cancer in women globally after breast and colorectal cancer. Well-characterized biomarkers are necessary for early diagnosis and to predict metastatic progression and effective therapy. MiRNAs can regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or degradation in tumor cells. The present study was conducted to assess expression of miR93, miR200a, RECK, MMP2, MMP9 in invasive cervical carcinoma, and analyze their clinical significance. Method: A total of 116 patients with invasive cervical carcinoma and 100 patients undergoing hysterectomy for benign lesions were retrospectively examined. Quantitative real-time PCR was performed to determine expression of miR93 and miR200a while RECK, MMP2, MMP9 and MVD were assessed by immunohistochemical staining. Results: Cervical carcinoma patients demonstrated up-regulation of miR-93, miR-200a, MMP2 and MMP9, with down-regulation of RECK as compared to benign lesion tissues. RECK was significantly inversely related to invasion and lymphatic metastasis. The 5-year survival rate for patients with strong RECK expression was significantly higher than that with weakly expressing tumors. Conclusion: MiR-93 and miR-200a are associated with metastasis and invasion of cervical carcinoma. Thus together with RECK they are potential prognostic markers for cervical carcinoma. RECK cooperating with MMP2, MMP9 expression is a significant prognostic factor correlated with long-term survival for patients with invasive cervical carcinoma.

Survival of Brain Metastatic Patients in Yazd, Iran

  • Akhavan, Ali;Binesh, Fariba;Heidari, Samaneh
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권8호
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    • pp.3571-3574
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    • 2014
  • Background: Brain metastasis occurs when cancerous cells come from a known (or sometimes an unknown) primary tumor to the brain and implant and grow there. This event is potentially lethal and causes neurologic symptoms and signs. These patients are treated in order to decrease their neurologic problems, increase quality of life and overall survival. Materials and Methods: In this study we evaluated clinical characteristics of 206 patients with brain metastases referred to our center from 2004 to 2011. Results: The mean age was 53.6 years. The primary tumors were breast cancer (32%), lung cancer (24.8%), lymphoma (4.4%), sarcoma (3.9%), melanoma (2.9%), colorectal cancer (2.4%) and renal cell carcinoma (1.5%). In 16.5% of the patients, brain metastasis was the first presenting symptom and the primary site was unknown. Forty two (20.4%) patients had a single brain metastasis, 18 patients (8.7%) had two or three lesions, 87 (42.2%) patients had more than three lesions. Leptomeningeal involvement was seen in 49 (23.8%) patients. Thirty five (17%) had undergone surgical resection. Whole brain radiation therapy was performed for all of the patients. Overall survival was 10.1 months (95%CI; 8.65-11.63). One and two year survival was 27% and 12% respectively. Conclusions: Overall survival of patients who were treated by combination of surgery and whole brain radiation therapy was significantly better than those who were treated with whole brain radiation therapy only [13.8 vs 9.3 months (p=0.03)]. Age, sex, primary site and the number of brain lesions did not show significant relationships with overall survival.

남자 환자에서 방광암의 유방 전이암: 유방촬영술 및 초음파 영상 소견 (Bladder Cancer Metastasis to the Breast in a Male Patient: Imaging Findings on Mammography and Ultrasonography)

  • 윤인나;차은숙;김정현;이지은;정진
    • 대한영상의학회지
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    • 제83권3호
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    • pp.687-692
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    • 2022
  • 남성 유방암은 드물며 유방암의 약 1%를 차지한다. 유방 외 악성 종양이 남성 유방으로의 전이는 매우 드물다. 남자에서 유방으로 전이되는 가장 흔한 원발성 종양은 전립선암, 폐암, 위암, 대장암, 흑색종 및 육종이다. 남자에서 방광암의 유방으로의 전이 유방암은 드물게 보고되었고, 종괴가 아닌 침윤성 소견의 전이 소견을 보이는 경우는 매우 드물다. 방광암이 유방으로 전이된 59세 남자 환자의 유방촬영술 및 초음파에서의 영상 소견을 보고하고자 한다.