• BMB Reports
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• 제53권10호
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• pp.533-538
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• 2020

Notch signaling has been identified as a critical pathway in gastric cancer (GC) progression and metastasis, and inhibition of Delta-like ligand 4 (DLL4), a Notch ligand, is suggested as a potent therapeutic approach for GC. Expression of both DLL4 and vascular endothelial growth factor receptor 2 (VEGFR2) was similar in the malignant tissues of GC patients. We focused on vascular endothelial growth factor (VEGF), a known angiogenesis regulator and activator of DLL4. Here, we used ABL001, a DLL4/VEGF bispecific therapeutic antibody, and investigated its therapeutic effect in GC. Treatment with human DLL4 therapeutic antibody (anti-hDLL4) or ABL001 slightly reduced GC cell growth in monolayer culture; however, they significantly inhibited cell growth in 3D-culture, suggesting a reduction in the cancer stem cell population. Treatment with anti-hDLL4 or ABL001 also decreased GC cell migration and invasion. Moreover, the combined treatment of irinotecan with anti-hDLL4 or ABL001 showed synergistic antitumor activity. Both combination treatments further reduced cell growth in 3D-culture as well as cell invasion. Interestingly, the combination treatment of ABL001 with irinotecan synergistically reduced the GC burden in both xenograft and orthotopic mouse models. Collectively, DLL4 inhibition significantly decreased cell motility and stem-like phenotype and the combination treatment of DLL4/VEGF bispecific therapeutic antibody with irinotecan synergistically reduced the GC burden in mouse models. Our data suggest that ABL001 potentially represents a potent agent in GC therapy. Further biochemical and pre-clinical studies are needed for its application in the clinic.

• Journal of Chest Surgery
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• 제57권1호
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• pp.62-69
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• 2024

Background: Cervical esophageal cancer is a rare malignancy that requires specialized care. While definitive chemoradiation is the standard treatment approach, surgery remains a valuable option for certain patients. This study examined the surgical outcomes of patients with cervical esophageal cancer. Methods: The study involved a retrospective review and analysis of 24 patients with cervical esophageal cancer. These patients underwent surgical resection between September 1994 and December 2018. Results: The mean age of the patients was 61.0±10.2 years, and 22 (91.7%) of them were male. Furthermore, 21 patients (87.5%) had T3 or T4 tumors, and 11 (45.8%) exhibited lymph node metastasis. Gastric pull-up with esophagectomy was performed for 19 patients (79.2%), while 5 (20.8%) underwent free jejunal graft with cervical esophagectomy. The 30-day operative mortality rate was 8.3%. During the follow-up period, complications included leakage at the anastomotic site in 9 cases (37.5%) and graft necrosis of the gastric conduit in 1 case. Progression to oral feeding was achieved in 20 patients (83.3%). Fifteen patients (62.5%) displayed tumor recurrence. The median time from surgery to recurrence was 10.5 months, and the 1-year recurrence rate was 73.3%. The 1-year and 3-year survival rates were 75% and 33.3%, respectively, with a median survival period of 17 months. Conclusion: Patients with cervical esophageal cancer who underwent surgical resection faced unfavorable outcomes and relatively poor survival. The selection of cases and decision to proceed with surgery should be made cautiously, considering the risk of severe complications.

• Preventive Nutrition and Food Science
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• 제11권1호
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• pp.1-5
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• 2006

Conjugated linoleic acid (CLA) is a group of positional and geometric isomers of linoleic acid that have been used to reduce the incidence, growth and metastasis of breast, colon, prostate and gastric cancer in animals. CLA could reduce tumor growth by altering angiogenesis; a process requiring associated angiogenic factors such as vascular endothelial growth factor (VEGF). In this study, we determined whether CLA could modulate the expression of VEGF in murine mammary tumor cells and adipocytes. The c9, t11-CLA isomer reduced VEGF transcripts and protein when mammary tumor cells were stimulated with PMA. That isomer also reduced VEGF expression in un stimulated mouse 3T3-L1 adipocytes. Since VEGF can be regulated by cyclooxygenase-2 (COX-2), we determined whether CLA could alter COX-2 enzyme expression and $PGE_2$ production. The c9, t11-CLA isomer reduced not only COX-2 enzyme expression but also $PGE_2$ production. Thus, c9, t11-CLA could modulate neovascularization by alteration of VEGF expression from mammary tumor cells and adipocytes by reducing COX-2 metabolites.

• 대한암한의학회지
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• 제19권1호
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• pp.33-41
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• 2014

This report is aimed to investigate the effect of Integrative Medicine Therapy (IMT) in treating metastasized ovary and endometrial cancer. A 51-year-old woman who was diagnosed double primary ovarian and endometrial cancer in 2009. The patient was treated with Laparoscopic Assisted Vaginal Hysterectomy (LAVH), Bilateral Salpingo Oophorectomy (BSO) Pelvic Lymph Node Dissection (PLND), adjuvant chemotherapy till Sep. in 2013. But metastases to Rt. External Iliac artery, Aortocaval area Lymph Nodes, Liver(caudate lobe), Rt. Buttock subcutaneous area, Lt. Gastric Area Lymph Nodes were found. Finally, the patient decided to be treated by IMT including Abnoba Viscum, Vitamin C, herbal medication and pharmacopuncture combined with chemotherapy. The efficacy was evaluated with Positron Emission Tomography and Computed Tomography (PET-CT) and Abdomen Computed Tomography (CT). The metastatic tumor in liver was disappeared and Rt. external iliac artery, aortocaval area Lymph Nodes, Rt. buttock subcutaneous area were also decreased after 6 months treatment. These results suggest that IMT may have a potential role for metastatic cancer.

• 대한수의학회지
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• 제37권3호
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• pp.547-554
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• 1997

Galectin-3 is known as an animal ${\beta}$-galactoside-binding lectin charicterized with S-type carbohydrate recognition domain. It plays a role in growth, adherence and movement of cells. It is, also, related to the cell transformation and metastasis of tumor cells. In this study, we have expressed and purified recombinant human galectin-3 (rHgalectin-3) using E coli system and asialofetuin affinity chromatography for the future development of monoclonal antibody to Hgalectin-3, which is suggested as the tumor marker for the gastric and thyroid gland cancers. Expressed protein was confirmed as the Hgalectin-3 by immunoblot with cross-reactive murine monoclonal antibody. Lectin activity and specificity of purified protein were, also, confirmed by the competitive inhibition with galectin-3 specific carbohydrate, lactose. Like physiological galectin-3, lectin activity of the molecule was not changed in nonreduced condition. Dimer formation, furthermore, was observed at high concentration of the protein even in the reduced condition, which is well known in physiological galectin-3. These results showed purified rHgalectin-3 has the same activity and molecular nature compared to the physiological galectin-3.

• Journal of Gastric Cancer
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• 제5권3호
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• pp.174-179
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• 2005

배경: 대부분의 악성종양에 있어 그 치료성적을 평가하는 가장 유용한 방법으로 가장 많이 사용되는 매개변수는 전체 5년 생존율이다. 그러나 근치적 절제술이 시행된 위암환자에 있어 재발의 대부분은 수술 후 3년 이내에 일어나므로 3년 무병 생존이 5년 전체 생존의 의미를 대치할 수 있는가를 알아보고자 한다. 대상 및 방법: 근치적 위절제술을 받고 추적이 가능한 656예에서 생존 함수로 산출한 각각의 생존확률을 이용한 단순 회귀분석에서 3년 무병 생존이 5년 전체 생존을 대치할 수 있는지를 파악하였다. 결과: 추적 기간동안 175예에서 재발이 확인되었고, 재발시기별 누적빈도는 수술 후 1년이 81예(46%), 3년이 156예(89%), 5년이 170예(97%)였다. 3년 무병 생존확률과 5년 전체 생존확률 사이의 회귀 분석결과 상관성은 r=0.87, 설명력은 $R^2=0.76$, 회귀 방정식은 5년 전체 생존확률=0.18+($0.80{\times}3$년 무병 생존확률)을 나타냈다. 복막파종, 혈행성 전이, 국소 재발의 경우 상관성과 설명력은 각각 $r=0.89\;(R^2=0.80),\;r=0.88\;(R^2=0.78),\;r=0.86\;(R^2=0.73)$으로 모두 높은 상관관계가 있음을 나타냈다. 결론: 위암환자의 근치적 위절제술 후 3년 무병 생존 확률은 5년 전체 생존확률에 대한 높은 상관성 및 설명력을 보였다. 위암의 치료성적을 평가하는 방법으로 5년 전체 생존 대신에 3년 무병 생존을 이용한다면 기간을 단축(2년)하여 평가하고 결론을 얻고 또한 보고할 수 있는 이득이 있겠다.

• Journal of Gastric Cancer
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• 제8권4호
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• pp.189-197
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• 2008

목적: 진행성 위암에서 복막 세포진 검사는 복강 내 미세전이를 진단하는 유용한 방법으로 사용되고 있으나 아직까지 국내외에서 액상세포검사를 사용한 복막 세포진 검사의 의의에 대한 연구가 보고되지 않고 있다. 본 연구는 수술 중 수집된 복막 세척액을 이용한 액상세포($ThinPrep^{(R)}$) 검사의 임상적 의의를 분석하기 위해 시행되었다. 대상 및 방법: 2001년부터 2006년까지 본원에서 위암 진단하에 수술 중 위장막의 침범 또는 노출이 의심되어 복막 세포진 검사를 시행 받은 424예의 진행성 위암 환자들의 임상 병리학적 자료와 세포진 검사 결과를 후향적으로 조사하여 분석하였다. 결과: 복막 세포진 양성은 31%였으며, 복막 세포진 결과는 단변량 및 다변량 분석에서 T 병기, N 병기, P 병기와 밀접한 관계를 보였다. 3년 생존율은 복막 세포진 음성에서 68% 양성에서 26%였으며, 복막전이(P)와 복막 세포진(CY)을 기준으로 분류하였을 때 P0CY0 71%, P0CY1 39%, P1/2/3CY0 39%, 그리고 P1/2/3CY1 11%의 3년 생존율을 보였다. 그리고 단변량 및 다변량 생존분석 결과, 복막 세포진 결과가 성별, T 병기, N 병기, P 병기, 복막 외 원격 전이, 혈청 CEA와 함께 독립적인 예후 인자로 증명되었고, 또한 근치적 절제 군에서 복막 세포진 결과는 복막 재발의 위험 인자임이 밝혀졌다. 결론: 본 연구는 복막 세포진 검사가 복강 내 미세전이를 진단 할 수 있는 신뢰성 높은 진단 방법이며 진행성 위암에서 강력한 예후 인자이며 복막 재발의 위험 인자임을 증명하였다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권4호
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• pp.289-300
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• 2001

Telomerase is a ribonucleoprotein that synthesizes telomere repeats. It has been reported that activation of telomerase was associtated with immortalization, proliferative activity and carcinogenesis. Recently, telomerase activity has been extensively studied in many kinds of malignant tumors for clinical diagnostic and/or prognostic utilities. In neuroblastoma, breast carcinoma, gastric carcinoma, non-small cell lung carcinoma, close relationship has been reported between high telomerase activity and lymph node metastasis, tumor aggressiveness and poor prognosis. The purpose of this study is to investigate the clinical implication of telomerase activity assay as an adjunctive factor in decision-making on neck node management, speedy pre-operative judging on histologic malignancy grading. Thus we performed semi-quantitative assay of telomerase activity using Telomerase PCR ELISA $kit^{(R)}$(Boeringer Manheim, Germany) and evaluated correlation between telomerase activity and tumor size, neck node metastasis, Anneroth malignancy score and influence of pre-operative chemotherapy on its activity in 27 cases of oral squamous cell carcinomas and 18 cases of normal oral epithelium. Also, correlation between telomerase activities and PCNA indices was evaluated. The results were obtained as follows: 1. The telomerase activities were detected in 24 specimens out of 27 oral squamous cell carcinoma specimens (88.9%) and in 5 specimens out of 18 normal oral epithelium specimens (27.8%). The mean value of telomerase activities was $0.9793{\pm}0.3428$ in 24 oral squamous cell carcinoma specimens and $0.4855{\pm}0.1117$ in 5 normal oral epithelium specimens. The positivity rate and mean value of telomerase activities in oral squamous cell carcinoma specimens were significantly higher than those of normal oral epithelium specimens (p<0.05). 2. There was no significant correlation between total Anneroth malignancy score and telomerase activity (p>0.05), but points of mitosis index and depth of invasion were significantly correlated with telomerase activities (p<0.05). 3. The positive immunohistochemical staining for PCNA(proliferating cell nuclear antigen) was observed in 26 specimens out of 27 oral squamous cell carcinoma specimens and mean value of PCNA indices of 26 specimens was $53.67{\pm}26.46$. PCNA indices were significantly correlated with telomerase activities (p<0.05). 4. The mean value of telomerase activities was significantly higher in pathologic T3/T4 group than in T1/T2 group (p<0.01). There was no significant difference of mean value of telomerase activities between pathologic neck node positive group and negative group (p> 0.05). Pre-operative chemotherapy significantly lowered the telomerase activities (p<0.05). The above results suggested telomerase activity could be used as diagnostic marker and adjunctive parameter for judging on histologic malignancy in oral squamous cell carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10267-10272
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• 2015

To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3705-3713
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• 2014

E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis of various cancers by altering gene transcriptional activity of epithelial cells. However, published studies on the association of CDH1 gene polymorphisms and cancer risk remain contradictory, owing to differences in living habits and genetic backgrounds. To derive a more better and comprehensive conclusion, the present meta-analysis was performed including 57 eligible studies of the association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and 3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, -160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with the homozygotes (CC), and the similar result was discovered for the -160A allele in the overall analyses. In the subgroup analyses, obvious elevated risk was found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate cancer, while a decreased colorectal cancer risk was shown with the AA genotype. For the -347 G>GA polymorphism, the GAGA genotype was associated with increased cancer risk in the overall analysis with homozygous and recessive models. In addition, results of subgroup analysis indicated that the elevated risks were observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a decreased risk of cancer was found in heterozygous, dominant and allele models. Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a potential protective factor in gastric cancer and Asian descendants.