• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1809-1817
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• 2012

Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

• 생명과학회지
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• 제18권6호
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• pp.884-890
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• 2008

본 연구에서는 대두의 대표적인 생리활성 물질인 genistein의 처리에 따른 암세포의 증식억제에서 telomerase 및 COX-2 활성의 변화 연관성을 조사하였다. 이를 위하여 4가지 종류의 암세포주를 사용하였으며, genistein 처리에 의하여 암세포들의 증식억제에서 백혈병 세포인 U937 세포의 감수성이 감장 높게 나타났으며, genistein 처리에 따라 telomere 조절인자들의 발현이 대부분 억제되었으며, telomerase의 활성도 매우 유의적으로 감소되었다. 또한 genistein처리 농도가 증가함에 따라 COX-2의 발현이 전사 및 번역 수준에서 모두 감소되었으며 이에 따른 $PGE_2$의 생성 역시 현저하게 감소되었으나, COX-1의 발현에는 큰 변화가 없었다. 이러한 결과들은 genistein의 항암 활성을 이해하는 귀중한 자료로서 활용될 것으로 생각된다.

• 대한두경부종양학회지
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• 제15권2호
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• pp.162-165
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• 1999

Background and Objectives: Multiple primary tumors of the upper aerodigestive tract are not unusual. We examined head and neck cancer patients to discover the presence of second primary cancer in their upper gastrointestinal tract, using esophagogastroscopy. Materials and Methods: Endoscopic examination of the upper gastrointestinal tract was performed on 51 patients whose head and neck cancers were treated at department of therapeutic radiology from August 1996 to April 1999. Two of all patients had been studied by barium swallowing study. In 51 patients, twenty-four had a primary tumor in the larynx, 8 in the oropharynx, 6 in the nasopharynx, 6 in the oral cavity, 6 in the hypopharynx, and 1 in the nasal cavity. Endoscopically pathologic lesions were biopsied. In control group, endoscopy was performed on 1097 patients who didn't complain any symptoms. Results: Endoscopy showed early malignant lesions in 4 cases(7.7%). Histology of esophageal cancers showed squamous cell carcinoma. Malignant lesions of stomach in 2 cases were histologically identified as adenocarcinoma. Two esophageal cancers occurred in patients whose primary lesions had oropharynx and hypopharynx. Two cases of gastric cancer were also accompanied by oropharynx and hypopharynx. The incidence of second primary cancer was 2 in oropharynx and 2 in hypopharynx. In all cases, second primary cancers were found simultaneously. In control group, 9(0.8%) of 1097 patients were confirmed as early esophageal and gastric cancers. Conclusion: The majority of esophageal and gastric cancer detected by endoscopy were early stage in both head and neck cancer and control group. The incidence of esophageal and gastric cancer of head and neck cancer patients was 10 times as high as that of control group. Although followup period was short, all second primary cancers were detected simultaneously. We would recommend that endoscopic evaluation be included in the workup and followup of all patients with newly diagnosed head and neck cancer.

• 생명과학회지
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• 제27권5호
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• pp.545-552
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• 2017

Julbernardia globiflora는 미옴보 숲에 널리 분포하는 열대 아프리카 나무로, 우울증, 위장장애 등의 치료를 위해 민간요법으로 사용되고 있으나, 항산화능, 항암 활성 등에 대한 연구는 알려진 바가 없다. 따라서 본 연구에서는 J. globiflora 메탄올 추출물(MEJG)을 사용하여 항산화능 및 인체 대장암 세포주인 HT29에 대한 항암 활성에 관하여 분석하였다. 먼저 DPPH radical scavenging activity를 통해 분석한 결과, MEJG의 $IC_{50}$는 $1.23{\mu}g/ml$로 강력한 항산화능을 보유하였음을 확인하였다. 또한 MEJG 농도 의존적으로 HT29 세포의 성장을 억제하였다. MEJG의 HT29 세포 사멸 효과의 기전을 분석하기 위하여 Annexin V 염색과 DAPI 염색을 수행한 결과, 대조군에 비하여 apoptotic 세포 및 apoptotic body가 증가됨을 확인하였다. 또한 apoptosis 관련 단백질들의 발현변화를 분석한 결과, MEJG처리에 의해 사멸수용체인 Fas와 pro-apoptotic 단백질인 Bax의 발현이 증가되었으며, anti-apoptotic 단백질인 Bcl-2의 발현이 감소하였다. 이러한 결과로 cytochrome c가 미토콘드리아에서 세포질로 방출되어 증가되었으며, caspase-3, -8, -9가 활성화되었다. 최종적으로 PARP가 분해되어 apoptosis가 유도되었음을 확인하였다. 이러한 결과들로부터 MEJG는 내인성 및 외인성 경로를 통한 apoptosis 유도에 의하여 HT29 세포의 증식을 억제하는 항암활성을 보유하였음을 확인하였다.

• Journal of Gastric Cancer
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• 제17권2호
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• 한국식품영양과학회지
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• 제23권2호
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• pp.340-347
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• 1994

원발성 위암환자로 확진받은 환자들의 암조직과 암조직 주위의 정상점막 조직을 대조군으로 사용하여, $TGF-{\alpha}$와 이에 대한 결합력을 갖고 있는 EGF-Receptor에 대한 mRNA를 면역세포화학적 방법과 in situ hybridization방법을 결합하여 규명하였다. 성장한 세포에서 발견되지 않는 $TGF-{\alpha}$가 위암환자의 조직학적으로는 정상적으로 간주되는 위점막 조직에서 발견된 점으로 미루어 $TGF-{\alpha}$가 암의 분화에 적극적으로 개입하고 있다는 증거가 된다. EMB-11 항체를 사용한 면역세포 화학적 방법에 의해 macrophage를 발견하고, macrophage cell에서 $TGF-{\alpha}$와 EGF-R mRNA가 발현됨을 규명할 수 있었다. 또한 단클론 항체를 이용해 EGF-R에 해당하는 단백질을 발견하였다. CEA를 이용한 면역세포화학 실험에서 정상으로 간주되는 위점막 조직에서 암 세포를 규명하였다. 특히, macrophage cell의 활동이 암의 증식과 더불어 증가하고 있다는 점을 관찰할 수 있었다. 위암과 검사 방법으로서 본 실험에서 사용된 면역세포화학적 기법과 in situ hybridization방법을 사용하여 생검을 통한 조직을 대상으로 성장인자에 대한 검사를 함으로써 정확한 위암의 발생과 진행에 대한 판단을 내리는데 이용할 수 있고 실용성이 있다고 사료된다.

• Journal of Gastric Cancer
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• 제8권4호
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• pp.198-203
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• 2008

목적: 다발성 조기위암은 전체 조기위암 중 4.5~11.7%를 차지한다. 본 연구는 다발성 조기위암의 임상병리학적 특징을 조사 분석하여 그 의의를 알아보고 치료방침의 수립에 도움이 되고자 시행하였다. 대상 및 방법: 1994년 1월부터 2004년 12월까지 11년간 연세대학교 의과대학 외과학교실에서 위선암으로 진단받고 근치적 위절제술을 시행한 2,281예의 조기위앙을 대상으로 의무기록을 후향적으로 조사 분석하였다. 결과: 다발성 조기위암은 총 91예(4.0%)였으며 2개의 병변이 81예, 3개가 9예, 4개가 1예였다. 총 102예의 보조병변 중 64예(62.7%)는 크기가 10 mm 이하였으며 83예(81.4%)는 주병변과 같은 부위에 위치하였다. 가장 흔한 조직학적 분류는 분화형으로 52예(57.1%)였다. 점막암은 49예(53.8%)였으며 점막하층암은 42예(46.2%)였고 림프절 전이는 6예(6.6%)에서 발견되었다. 단발성 조기위암과 비교하였 때 전체 생존율에서 통계학적으로 유의한 차이가 없었다. 결론: 다발성 조기위암은 단발성 조기위암과 임상병리학적으로 매우 유사하며 생존율에서도 차이가 없었다. 그러므로 다발성 오기위암의 치료에 있어서 일반적인 조기위암의 치료지침에 준한 방법을 적용할 수 있으며, 조기위암의 수술 전후 잔위에 보조병변을 남기지 않기 위하여 세심한 주의가 필요하다.

• 대한방사성의약품학회지
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• 제5권1호
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• pp.18-25
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• 2019

2-Nitroimidazole derivatives have been reported to accumulate in hypoxic tissue. We prepared a novel $^{99m}Tc-MAG_3$-2-nitroimidazole and evaluated the feasibility for hypoxia imaging agent. $Bz-MAG_3$-2-nitroimidazole was synthesized by direct coupling of $Bz-MAG_3$ and 2-nitroimidazole using dicyclohexylcarbodiimide. $Bz-MAG_3$-2-nitroimidazole was labeled with $^{99m}Tc$ in the presence of tartaric acid and $SnCl_2-2H_2O$ at $100^{\circ}C$ for 30 min. And the reaction mixture was purified by $C_{18}$ Sep-pak cartridge. The labeling efficiency and the radiochemical purity were checked by ITLC-SG/acetonitrile. The tumor was grown in balb/c mice for 8~13 days after the subcutaneous injection of tumor cells, CT-26 (murine colon adenocarcinoma cell). Biodistribution study and tumor autoradiography were performed in the xenografted mice after i.v injection of 74 kBq/0.1 mL and 19 MBq/0.1 mL of $^{99m}Tc-MAG_3$-2-nitroimidazole, respectively. In vivo images of $^{99m}Tc-MAG_3$-2-nitroimidazole in tumor bearing mice were obtained 1.5 hr post injection. The labeling efficiency was $45{\pm}20%$ and the radiochemical purity after purification was over 95%. Paper electrophoresis confirmed negative charge of $^{99m}Tc-MAG_3$-2-nitroimidazole. $^{99m}Tc-MAG_3$-2-nitroimidazole was very stable at room temperature and its protein binding was 53%. The $^{99m}Tc-MAG_3$-2-nitroimidazole exhibited high uptake in the liver, stomach and intestine. In biodistribution study using tumor bearing mice, the uptakes (% ID/g) of the tumor were $0.5{\pm}0.1$, $0.4{\pm}0.0$, $0.2{\pm}0.1$ and $0.1{\pm}0.1$ at 5, 15, 30 min and 4 hrs. Tumor/muscle ratio were $1.4{\pm}0.1$, $2.2{\pm}0.83$, $3.0{\pm}0.9$, and 3.7 (n=2) for 5, 15, 30 min and 4 hrs. The uptake in hypoxic area was found higher than in non-hypoxic area of tumor tissue by autoradiography. In vivo images showed the relatively faint uptake to the hypoxic tumor region. $^{99m}Tc-MAG_3$-2-nitroimidazole was successfully synthesized and found feasible for imaging hypoxia.

• Journal of Gastric Cancer
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• 제21권2호
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• pp.169-178
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• 2021

Purpose: The aim of this study was to investigate the oncologic safety and identify potential candidates for proximal gastrectomy (PG) in upper third advanced gastric cancer (AGC) and esophagogastric junction (EGJ) cancers. Materials and Methods: Among 5,665 patients who underwent gastrectomy for gastric adenocarcinoma between January 2011 and December 2017, 327 patients who underwent total gastrectomy with standard lymph node (LN) dissection for upper third AGC and Siewert type II EGJ cancers were enrolled. We analyzed the correlation between the metastatic rates of distal LNs (No. 4d, 5, 6, and 12a) around the lower part of the stomach and the clinicopathological characteristics. We identified subgroups with no metastasis to the distal LNs. Results: The metastatic rate of distal LNs in proximal AGC and Siewert type II EGJ cancers was 7.0% (23 of 327 patients). On multivariate analysis, pathological T stage (P=0.001), tumor size (P=0.043), and middle third invasion (P=0.003) were significantly associated with distal LN metastases. Pathological 'T2 stage' (n=88), or 'T3 stage with ≤5 cm tumor size' (n=87) showed no metastasis in distal LNs, regardless of middle third invasion. Pathological T3 stage with tumor size > 5 cm (n=61) and T4 stage (n=91) had metastasis in the distal LNs. Conclusions: In the upper third AGC and Siewert type II EGJ cancer, pathological T2 and small-sized T3 stage groups are possible candidates for PG in cases without distal LN metastasis. Further validation studies are required for clinical application.

• Journal of Gastric Cancer
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• 제22권4호
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• pp.381-394
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• 2022

Purpose: Gastric neoplasia is a common manifestation of familial adenomatous polyposis (FAP). This study aimed to elucidate the clinical characteristics, endoscopic features including fundic gland polyposis (FGPsis), and treatment outcomes of gastric neoplasms (GNs) in patients with FAP. Materials and Methods: A total of 35 patients diagnosed with FAP, including nine patients from four pedigrees who underwent esophagogastroduodenoscopy (EGD), were investigated regarding patient characteristics, GN morphology, and treatment outcomes. Results: Twenty-one patients (60.0%) had 38 GNs; 33 (86.8%) and 5 (13.2%) were histologically diagnosed with adenocarcinoma and adenoma, respectively. There were no specific patient characteristics related to GNs.Nodule-type GNs were more prevalent in patients with FGP than without (52.2% vs. 0.0%, P=0.002) in the upper body of the stomach. Conversely, depressed-type GNs were fewer in patients with FGPsis than in those without (13.0% vs. 73.3%, P<0.001). Slightly elevated-type GNs were observed in both groups (34.8% vs. 20.0%, P=0.538). Even within pedigrees, the background gastric mucosa and types of GNs varied. In total, 24 GNs were treated with endoscopic submucosal dissection (ESD) and eight with endoscopic mucosal resection (EMR). EMR was selected for GNs with FGPsis because of the technical difficulty of ESD, resulting in a lower en bloc resection rate (62.5% vs. 100%, P=0.014). Conclusions: Our study indicates the necessity of routine EGD surveillance in patients diagnosed with FAP. Notably, the morphology and location of GNs differed between patients with and without FGPsis. Endoscopic treatment and outcomes require more attention in cases of FGPsis.