• Title/Summary/Keyword: esophageal cancer

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Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin

  • Seung-On Lee;Sang Hoon Joo;Jin-Young Lee;Ah-Won Kwak;Ki-Taek Kim;Seung-Sik Cho;Goo Yoon;Yung Hyun Choi;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • v.32 no.1
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    • pp.104-114
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    • 2024
  • Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Clinical Studies on Locally Invasive Thyroid Cancer (국소침범한 갑상선암의 임상적 고찰)

  • Kim Young-Min;Lee Chang-Yun;Yang Kyung-Hun;Rho Young-Soo;Park Young-Min;Lim Hyun-Jun
    • Korean Journal of Head & Neck Oncology
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    • v.14 no.2
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    • pp.236-243
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    • 1998
  • Objectives: Local invasion of the thyroid cancer that is invasion of the upper aerodigestive tract, neurovascular structures of the neck and superior mediastinum, is infrequent and comprises of 1-16% of well-differentiated thyroid cancer. However the proximity of the thyroid gland to these structures provides the means for an invasive cancer to gain ready access into theses structures and when invasion occurs, it is the source of significant morbidity and mortality. So locally invasive thyroid cancer should be removed as much as possible, but still much debates have been exist whether the surgical method should be radical or conservative. This study was desinged to evaluate the clinical characteristics and the surgical treatment of the locally invasive thyroid cancer. Material and Methods: At the department of otorhinolaryngology of Hallym university, 10 patients diagnosed as locally invasive thyroid cancer among the 81 patients treated for thyroid cancer between 1991 to 1997 were retrospectively evaluated. Results: Of the 10 patients, 3 patients had histories of previous surgical treatment with or without radiation or radioactive iodine therapy. The site of invasion of thyroid cancer were trachea(7 cases), recurrent laryngeal nerve(5 cases), mediastinal node(5 cases), esophagus(3cases), larynx(3cases), carotid artery(3 cases), pharynx(l case), and other sites(4 cases). The operation techniques included 1 partial laryngectomy and 1 partial cricoid resection, 2 shavings and 3 window resections of the trachea, 1 sleeve resection of the trachea with end-to-end anastomosis and 1 cricotracheoplasty for tracheal invasion, 2 shavings and 1 partial esophagectomies for esophageal invasion, and 1 wall shaving and 2 partial resections with $Gortex^{\circledR}$ tube reconstruction for carotid artery invasion, and so on. Conclusions: These data and review of literature suggest that the surgical method should be perfomed on the basis of individual condition and complete removal of all gross tumor with preservation of vital structures whenever possible will offer a good result.

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Results of Radiotherapy With and Without Chemotherapy for Esophageal Cancers (식도암의 방사선치료 결과 고찰)

  • Kim Sang Bo;Yun Sangs Mo;Ryu Samuel;Park In Kyu
    • Radiation Oncology Journal
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    • v.9 no.2
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    • pp.233-239
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    • 1991
  • This is a retrospective study of 62 patients with unresected squamous cell carcinoma of the esophagus treated by radiotherapy alone (25 patients) or combined chemotherapy and radiotherapy (37 patients). Of these, 14 of 25 patients treated by radiation therapy alone and 25 of 37 patients treated by combined chemotherapy and radiotherapy completed radiotherapy consisting of 55 to 60 Gy in 5 to 6 weeks and were analyzed for local control rate and survival rate. Follow up ranged from 6 days to 58 months. Three ($8\%$) of 39 patients had a complete response, twenty-eight ($72\%$) a partial response and eight ($20\%$) minimal or no response. Overall median survival was 11 months for all stages. The 1 year and 2 year actuarial survival rates were $48.6\%$ and $13\%$ respectively. Age and stage had prognostic significances (p <0.05, p<0.05 respectively). The 1 year survival rate was $70.1\%$ for stage I, $47.6\%$ for stage II, and $28.4\%$ for stage III. The median survival was 19 months for stage I, 11 months for stage II, 6 months for stage III, and 5.5 months for stage III with distant metastases. The 1 year survival rate of patients 55 years and above was $69.6\%$, 54 years and below was $0\%$. There was no significant difference in survival rate between treatment modalities, locations of tumor, and responses of tumor.

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The Clinicopathological Characteristics of Adenocarcinoma of the Gastro-esophageal Junction (위식도접합부선암의 임상병리학적 특성)

  • Kim, Han-Su;Jeong, Oh;Park, Young-Kyu;Kim, Dong-Yi;Ryu, Seong-Yeop;Kim, Young-Jin
    • Journal of Gastric Cancer
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    • v.8 no.4
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    • pp.210-216
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    • 2008
  • Purpose: Siewert's classification of adenocarcinoma of the esophagogastric junction (AEG) has been widely adopted, but there is a wide discrepancy of the clinicopathological features of AEG of the Asian patients as compared to that of the Western patients. The aim of this study was to investigate the clinicopathological characteristics of AEG according to the Siewert classification. Materials and Methods: Among the patients who underwent surgery for gastric carcinoma in our institution between May 2004 and February 2008, the AEG patients were selected based on their operation records and the photographs according to Siewert's classification. Results: There were 70 AEG patients (3.9%) among the total of 1,778 patients. There were 3 patients (4.3%) with type I, 30 patients (42.8%) with type II and 37 patients (52.8%) with type III. Curative resection (R0) was achieved in 68 cases (97.1%). No significant differences in gender, stage, Barrett's esophagus and the proximal margin were found between the patients with type II and type III AEG. The patients with type III were younger than the patients with type II (59 vs 64 years, respectively, P=0.049). Well differentiated histology (P=0.045) and the intestinal type (P=0.055) were significantly more frequent in the patients with type II as compared with that in the patients with type III. Conclusion: There was a striking difference of the Asian patients from the Western patients for the incidence of AEG (and especially type I). Some of the differences between type II and type III patients were similar to those of the previous Western studies. A large study is needed to investigate whether these features are typical in the Korean population.

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Concurrent Chemoradiation in Patients with Cancer of the Esophagus (식도암에서의 동시화학방사선요법)

  • Lee Kang Kyoo;Park Kyung Ran;Lee Jong Young;Shin Hyun Soo;Lee Chong In;Chang Woo Ick;Shim Young Hak
    • Radiation Oncology Journal
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    • v.16 no.1
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    • pp.7-16
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    • 1998
  • Purpose : To evaluate survival rate and prognostic factors affecting survival of patients with esophageal cancer treated with concurrent chemoradiation. Materials and Methods : Eligibility included biopsy proven invasive carcinoma of the cervical or thoracic esophagus, confined to esophagus and mediastinum with or without regional lymph node and supraclavicular lymph node, and ECOG Performance status $H_0-H_2$. Patients received radiation therapy with 5940cGy over 7 weeks and chemotherapy, consisted of 5-FU(1000 $mg/m^2/day$ in continuous infusion for 5 days, days 1 to 5 and days 29 to 33) and mitomycin C($8mg/m^2$ intravenous bolus at day 1). After concurrent chemoradiation, maintenance chemotherapy was followed with 5-FU(1000 $mg/m^2/day$ in continuous infusion for 5 days at 9th, 13th, and 17th weeks) and cisplatin($80mg/m^2$ intravenous bolus at the first day of each cycle). Results : From November 1989 to November 1995, 44 patients were entered in this study. After treatment, complete response rate and partial response rate were $59\%$ and $41\%$. Overall 1, 2, and 5-year survivals were $59\%$, $38\%$, and $9.6\%$(median 17 months), Prognostic factors affecting survival were response to treatment and T-stage. Among 26 complete responders, there were 6 local recurrences, 3 distant recurrences, 1 local and distant recurrence, and 2 unknown site recurrences Acute and chronic complication rates with grade 3 or more were $20\%$ and $13.0\%$ and there was no treatment-related mortality. Conclusion : Concurrent chemoradiation, compared with historical control groups that treated with radiation alone, improved median survival and did not significantly increase treatment-related complications. Complete responders had longer survival duration than partial responders. Predominant failure pattern was local failure. So, efforts to improve local control should be proposed.

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Deubiquitinase Otubain 1 as a Cancer Therapeutic Target (암 치료 표적으로써 OTUB1)

  • Kim, Dong Eun;Woo, Seon Min;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.30 no.5
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    • pp.483-490
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    • 2020
  • The ubiquitin system uses ligases and deubiquitinases (DUBs) to regulate ubiquitin position on protein substrates and is involved in many biological processes which determine stability, activity, and interaction of the target substrate. DUBs are classified in six groups according to catalytic domain, namely ubiquitin-specific proteases (USPs); ubiquitin C-terminal hydrolases (UCHs); ovarian tumor proteases (OTUs); Machado Joseph Disease proteases (MJDs); motif interacting with Ub (MIU)-containing novel DUB family (MINDY); and Jab1/MPN/MOV34 metalloenzymes (JAMMs). Otubain 1 (OTUB1) is a DUB in the OTU family which possesses both canonical and non-canonical activity and can regulate multiple cellular signaling pathways. In this review, we describe the function of OTUB1 through regulation of its canonical and non-canonical activities in multiple specifically cancer-associated pathways. The canonical activity of OTUB1 inhibits protein ubiquitination by cleaving Lys48 linkages while its non-canonical activity prevents ubiquitin transfer onto target proteins through binding to E2-conjugating enzymes, resulting in the induction of protein deubiquitination. OTUB1 can therefore canonically and non-canonically promote tumor cell proliferation, invasion, and drug resistance through regulating FOXM1, ERα, KRAS, p53, and mTORC1. Moreover, clinical research has demonstrated that OTUB1 overexpresses with high metastasis in many tumor types including breast, ovarian, esophageal squamous, and glioma. Therefore, OTUB1 has been suggested as a diagnosis marker and potential therapeutic target for oncotherapy.

Treatment of Stomach Cancer Involving Esophagogastric Junction (식도-위 경계부위를 침범한 위암의 치료)

  • 이종목;백희종;박종호;임수빈;조재일
    • Journal of Chest Surgery
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    • v.34 no.12
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    • pp.930-936
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    • 2001
  • Background: The origin site of carcinoma invading esophagogastric junction is variable. It may arise from squamous cell carcinoma of low esophagus, adenocarcinoma arising from Barrett's esophagus, adenocarcinoma of gastric cardia, or extension from proximal stomach cancer. In Korea, the majority of adenocarcinoma invading esophago-gastric junction seems to arise from proximal gastric carcinoma. Material and Method: We reviewed the data of surgically-resected gastric adenocarcinoma involving esophagogastric junction in KCCH between 1988 and 1999. Result: There were 212 cases. Male to female ratio was 156 to 56. Age distribution was between 22 and 78. Variable surgical approaches including median laparotomy, laparotomy with left or right thoracotomy, left thoracotomy, and thoracoabdominal approach were used. Postoperative pathologic stages were : Stage IA-7, IB-11, Ⅱ-25, ⅢA-73, ⅢB-34, and Ⅳ-57. Curative resection was performed in 199 patients, and total gastrectomy was performed in 200 patients. There were 77.4%(164 cases) with esophageal involvement, 74.1%(157 cases) with tumor involvement in the abdominal LN, and 8%(17 cases) with mediastinal LN metastasis. Operative mortality was 3.3%, and over-all 5 year survival rate was 35%. Conclusion: There are various surgical approaches and many things to consider for surgical resection, thoracic and abdominal approach may need for obtain proper resection margin and adequate lymph node dissection in stomach cancer invading esophagogastric junction.

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Current Status and Future Perspective of PET (PET 이용 현황 및 전망)

  • Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.1
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    • pp.1-7
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    • 2002
  • Positron Emission Tomography (PET) is a nuclear medicine imaging modality that consists of systemic administration to a subject of a radiopharmaceutical labeled with a positron-emitting radionuclide. Following administration, its distribution in the organ or structure under study can be assessed as a function of time and space by (1) defecting the annihilation radiation resulting from the interaction of the positrons with matter, and (2) reconstructing the distribution of the radioactivity from a series of that used in computed tomography (CT). The nuclides most generally exhibit chemical properties that render them particularly desirable in physiological studies. The radionuclides most widely used in PET are F-18, C-11, O-15 and N-13. Regarding to the number of the current PET Centers worldwide (based on ICP data), more than 300 PET Centers were in operation in 2000. The use of PET technology grew rapidly compared to that in 1992 and 1996, particularly in the USA, which demonstrates a three-fold rise in PET installations. In 2001, 194 PET Centers were operating in the USA. In 1994, two clinical and research-oriented PET Centers at Seoul National University Hospital and Samsung Medical Center, was established as the first dedicated PET and Cyclotron machines in Korea, followed by two more PET facilities at the Korea Cancer Center Hospital, Ajou Medical Center, Yonsei University Medical Center, National Cancer Center and established their PET Center. Catholic Medical School and Pusan National University Hospital have finalized a plan to install PET machine in 2002, which results in total of nine PET Centers in Korea. Considering annual trends of PET application in four major PET centers in Korea in Asan Medical Center recent six years (from 1995 to 2000), a total of 11,564 patients have been studied every year and the number of PET studies has shown steep growth year upon year. We had 1,020 PET patients in 1995. This number increased to 1,196, 1,756, 2,379, 3,015 and 4,414 in 1996,1997,1998,1999 and 2000, respectively. The application in cardiac disorders is minimal, and among various neuropsychiatric diseases, patients with epilepsy or dementia can benefit from PET studios. Recently, we investigated brain mapping and neuroreceptor works. PET is not a key application for evaluation of the cardiac patients in Korea because of the relatively low incidence of cardiac disease and less costly procedures such as SPECT can now be performed. The changes in the application of PET studios indicate that, initially, brain PET occupied almost 60% in 1995, followed by a gradual decrease in brain application. However, overall PET use in the diagnosis and management of patients with cancer was up to 63% in 2000. The current medicare coverage policy in the USA is very important because reimbursement policy is critical for the promotion of PET. In May 1995, the Health Care Financing Administration (HCFA) began covering the PET perfusion study using Rubidium-82, evaluation of a solitary pulmonary nodule and pathologically proven non-small cell lung cancer. As of July 1999, Medicare's coverage policy expanded to include additional indications: evaluation of recurrent colorectal cancer with a rising CEA level, staging of lymphoma and detection of recurrent or metastatic melanoma. In December of 2001, National Coverage decided to expand Medicare reimbursement for broad use in 6 cancers: lung, colorecctal, lymphoma, melanoma, head and neck, and esophageal cancers; for determining revascularization in heart diseases; and for identifying epilepsy patients. In addition, PET coverage is expected to further expand to diseases affecting women, such as breast, ovarian, uterine and vaginal cancers as well as diseases like prostate cancer and Alzheimer's disease.

Comparison of Stereotactic Radiosurgery and Whole Brain Radiotherapy in Patients with Four or More Brain Metastases (4개 이상의 다발성 전이성 뇌종양의 정위적 방사선수술과 전뇌 방사선조사의 비교)

  • Kim, Cheol-Jin;Baek, Mi-Young;Park, Sung-Kwang;Ahn, Ki-Jung;Cho, Heung-Lae
    • Radiation Oncology Journal
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    • v.27 no.3
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    • pp.163-168
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    • 2009
  • Purpose: This study was a retrospective evaluation of the efficacy of stereotactic radiosurgery (SRS) in patients with >4 metastases to the brain. Materials and Methods: Between January 2004 and December 2006, 68 patients with $\geq$4 multiple brain metastases were included and reviewed retrospectively. Twenty-nine patients received SRS and 39 patients received whole brain radiotherapy (WBRT). Patients with small cell lung cancers and melanomas were excluded. The primary lesions were non-small cell lung cancer (69.0%) and breast cancer (13.8%) in the SRS group and non-small cell lung cancer (64.1%), breast cancer (15.4%), colorectal cancer (12.8%), esophageal cancer (5.1%) in the WBRT group. SRS involved gamma-knife radiosurgery and delivered 10~20 Gy (median, 16 Gy) in a single fraction with a 50% marginal dose. WBRT was delivered daily in 3 Gy fractions, for a total of 30 Gy. After completion of treatment, a follow-up brain MRI or a contrast-enhanced brain CT was reviewed. The overall survival and intracranial progression-free survival were compared in each group. Results: The median follow-up period was 5 months (range, 2~19 months) in the SRS group and 6 months (range, 4~23 months) in the WBRT group. The mean number of metastatic lesions in the SRS and WBRT groups was 6 and 5, respectively. The intracranial progression-free survival and overall survival in the SRS group was 5.1 and 5.6 months, respectively, in comparison to 6.1 and 7.2 months, respectively, in the WBRT group. Conclusion: SRS was less effective than WBRT in the treatment of patients with >4 metastases to the brain.

Hyperfractionation Radiation Therapy in Advanced Head and Neck Cancer (진행된 두경부암에서 다분할 방사선치료)

  • Kim, Jin-Hee;Ye, Ji-Won
    • Radiation Oncology Journal
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    • v.21 no.2
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    • pp.112-117
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    • 2003
  • Purpose: The effects of hypefractionation radiation therapy, such as the failure pattern and survival, on the treatment results in advanced stage head and neck cancer were studied. Materials and Methods: Between September 1990 and October 1998, 24 patients with advanced stage (III, IV) head and neck cancers, were treated using hyperfractionation radiation therapy in the Department of Radiation Oncology at the Keimyung University Dongsan Medical Center. The male to female ratio was 7 : 1, and the age range from 38 to 71 years with the median of 56 years. With regard to the TNM stage, 11 patients were stage III and 13 were stage IV. The sites of primary cancer were the nasopharynx in six, the hypopharynx in 6, the larynx in five, the oropharynx in three, the maxillary sinus in three, and the oral cavity in one patient. The radiotherapy was delivered by 6 MV X-ray, with a fraction size of 1.2 Gy at two fractions a day, with at least 6 hours inter-fractional interval. The mean total radiation doses was 72 Gy, (ranging from 64.4 to 75.8 Gy). Follow-up periods ranged between 3 and 136 months, with the median of 52 months. Results: The overall survival rates at 3 and 5 years in all patients were 66.7$\%$, and 52.4$\%$. The disease-free survival rates at 3 and S years (3YDFS, 5YDFS) in all patients were 66.7$\%$ and 47.6$\%$. The 3YDFS and 5YDFS in stage III patients were 81.8$\%$ and 63.6$\%$, and those in stage IV patients were 53.8$\%$ and 32.3$\%$. Ten patients were alive with no local nor distant failures at the time of analyses. Six patients (25$\%$) died due to distant metastasis and 12.5$\%$ died due to local failure. Distant metastasis was the major cause of failure, but 2 patients died due to unknown failures and 3 of other diseases. The distant metastasis sites were the lung (3 patients), the bone (1 patient), and the liver (2 patients). One patient died of second esophageal cancer. There were no severe late complications, with the exception of 1 osteo-radionecrosis of the mandible 58 months after treatment. Conclusion: Although this study was peformed on small patients group, we considered hypefractionated radiation therapy for the treatment of advanced stage head and neck cancer might improve the disease free survival and decrease the local failure with no increase in late complications despite of the slight Increase in acute complications.