• Title/Summary/Keyword: Cancer, Pancreatic

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Chronicles of EGFR Tyrosine Kinase Inhibitors: Targeting EGFR C797S Containing Triple Mutations

  • Duggirala, Krishna Babu;Lee, Yujin;Lee, Kwangho
    • Biomolecules & Therapeutics
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    • v.30 no.1
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    • pp.19-27
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    • 2022
  • Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wild-type EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and third-generation EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

Regulation of BNIP3 in Normal and Cancer Cells

  • Lee, Hayyoung;Paik, Sang-Gi
    • Molecules and Cells
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    • v.21 no.1
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    • pp.1-6
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    • 2006
  • Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a mitochondrial pro-apoptotic protein that has a single Bcl-2 homology 3 (BH3) domain and a COOH-terminal transmembrane (TM) domain. Although it belongs to the Bcl-2 family and can heterodimerize with Bcl-2, its pro-apoptotic activity is distinct from those of other members of the Bcl-2 family. For example, cell death mediated by BNIP3 is independent of caspases and shows several characteristics of necrosis. Furthermore, the TM domain, but not the BH3 domain, is required for dimerization, mitochondrial targeting and pro-apoptotic activity. BNIP3 plays an important role in hypoxia-induced death of normal and malignant cells. Its expression is markedly increased in the hypoxic regions of some solid tumors and appears to be regulated by hypoxia-inducible factor (HIF), which binds to a site on the BNIP3 promoter. Silencing, followed by methylation, of the BNIP3 gene occurs in a significant proportion of cancer cases, especially in pancreatic cancers. BNIP3 also has a role in the death of cardiac myocytes in ischemia. Further studies of BNIP3 should provide insight into hypoxic cell death and may contribute to improved treatment of cancers and cardiovascular diseases.

Total Gastrectomy with Distal Pancreatico-splenectomy for Treating Locally Advanced Gastric Cancer (진행 위암에서의 위 전절제술에 동반된 원위부 췌-비장 절제)

  • Lee, Sung-Ho;Kim, Wook;Song, Kyo-Young;Kim, Jin-Jo;Chin, Hyung-Min;Park, Jo-Hyun;Jeon, Hae-Myung;Park, Seung-Man;Ahn, Chang-Jun;Lee, Jun-Hyun
    • Journal of Gastric Cancer
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    • v.7 no.2
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    • pp.74-81
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    • 2007
  • Purpose: Routine pancreatico-splenectomy with total gastrectomy should no longer be considered as the standard surgical procedure for gastric cancer because of the lack of proven surgical benefit for survival. The aim of this study is to evaluate the clinicopathologic factors and the survival of patients with locally advanced gastric cancer and they had undergone combined pancreatico-splenectomy with a curative intent. Material and Methods: We retrospectively reviewed a total of 118 patients who had undergone total gastrectomy with distal pancreatico-splenectomy from 1990 to 2001. The patients were divided into 2 groups: 90 patients who were free from cancer invasion (group I), and 28 patients with histologically proven cancer invasion into the pancreas (group II). The various clinicopathologic factors that were presumed to influence survival and the survival rates were analyzed. Results: The rate of pathological pancreatic invasion was 23.7%. The tumor stage, depth of invasion, pancreas invasion, lymph node metastasis, lymph node ratio, curability and the hepatic and peritoneal metastasis were statistically significance on univariate analysis. Among these factors, the tumor stage, lymph node ratio and curability were found to be independent prognostic factor on multivariate analysis. The 5-years survival rates were 36.2% for group I and 13.9% for group II. The morbidity rate was 22.1%, and this included pancreatic fistula (5.1%), intra-abdominal abscess (4.2%) and bleeding (4.2%). The overall mortality rate was 0.8%. Conclusion: Combined distal pancreatico-splenectomy with total gastrectomy with a curative intent was selectively indicated for those patients with visible tumor invasion to the pancreas, a difficult complete lymph node dissection around the distal pancreas and spleen, and no evidence of liver metastasis or peritoneal dissemination.

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Changes of Serum soluble ICAM-1 levels in Patients with Lung Cancer (폐암 환자에서 혈청 soluble ICAM-1농도의 변화)

  • Yoo, Wan Hee;Lee, Yong Chul;Rhee, Yang Keun
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.527-535
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    • 1996
  • Background : Cell adhesion molecules knave been Implicated In the various stages of tumor progression and metastasis. ICAM-1 plays a important roles in cell-cell interactions in inflammatory and immune response of several diseases. Recently, elevated levels of sICAM-1 in circulation was reported as association with liver metastasis in gastric, Colonic, gall bladder and pancreatic cancer, with reduced survival in malignant melanoma. This study was performed to measure the sICAM-1 in patients with lung cancer and to evaluate the relations between staging of lung cancer and level of sICAM-1. Methods : Serum sICAM-1 was measured in 36 patients with lung cancer according to the pathologic types and clinical staging before therapy and in 8 controls with ICAM-1 ELISA kit. Results : Serum sICAM-1 levels were elevated in patients with lung cancer except small cell type. Also progression and metastasis of lung cancer associated with elevation of sICAM-1 levels. Conclusion : These results suggest that higher levels of serum ICAM-1 reflect the progression and metastasis of lung cancer and it may be used as a marker with diagnostic and prognostic significance.

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Non-Steroid Anti-Inflammatory Agents for Management of Cold Sweating in Advanced Cancer Patients (식은 땀을 호소하는 진행성 암 환자에서 비스테로이드성 항염증 제제를 이용한 치료)

  • Choi, Hye Jung;Song, Haa-Na;Kang, Jung Hun
    • Journal of Hospice and Palliative Care
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    • v.19 no.4
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    • pp.331-334
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    • 2016
  • Purpose: Advanced cancer may accompany cold sweat as paraneoplastic symptom. Few studies have been performed on the efficacy of non-steroid anti-inflammatory drug (NSAID) in advanced cancer patients who sweated without fever. Methods: To select study participants, medical records were retrospectively reviewed for patients who satisfied the following criteria: 1) incurable, advanced solid cancer; 2) Cold sweating of 4 or higher on the numeric rating scale (NRS) 4; 3) No evidence of infection or hypoglycemia; 4) No newly started opioid or anti-hormonal agents within one month; 5) NSAID prescription for the management of cold sweating and 6) Documented NRS information before and after NSAID administration. Results: A total of 13 patients were selected after excluding four patients due to lack of NRS information or fever. The mean age was 59 years old (range: 50~71), and nine patients (69%) were male. Bile duct cancer was the most common primary tumor followed by pancreatic cancer, gastric cancer and prostate cancer. The mean NRS of cold sweating dropped from baseline 6.5 (min-max: 4~10) to 1.9 at the follow-up assessment (min-max: 0~5). The mean follow-up period was 9.1 days (range: 2~30 days) from NSAID treatment to assessment. Conclusion: NSAID was effective medication for management of sweating without fever in patients with advanced cancer.

Celiac Plexus Neurolysis for the Treatment of Patients with Terminal Cancer at a Tertiary University Hospital in Korea

  • Byeon, Gyeong-Jo;Park, Ju Yeon;Choi, Yun-Mi;Ri, Hyun-Su;Yoon, Ji-Uk;Choi, Eun-Ji
    • Journal of Hospice and Palliative Care
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    • v.23 no.1
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    • pp.5-10
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    • 2020
  • Purpose: The aim of this study was to investigate celiac plexus neurolysis (CPN) for the treatment of cancerous upper abdominal pain in a tertiary university hospital in Korea. Methods: At the tertiary university hospital in Korea, electronic medical records of cancer patients who underwent CPN and died in the hospital from November 2009 to June 2018 were retrospectively analyzed. Results: The total number of subjects was 51. The 17 patients were from the Department of Gastroenterology (33.0%), followed by 11 patients from the Department of Hemato-oncology (21.6%), 11 patients from the Department of Anesthesia and Pain Medicine (21.6%), 9 patients from the Department of General Surgery (17.6%). The diagnosis was pancreatic cancer in 15 patients (29.4%), stomach cancer in 8 patients (15.7%), hepatobiliary cancer in 20 patients (39.2%), colon cancer in 1 patient (2.0%), esophageal cancer in 2 patient (3.9%) and intra-abdominal metastasis in 5 patients (9.8%). The mean survival time after the surgery was 66.4±55.0 days. The pain intensity before and 1 week after the procedure significantly decreased, but the amounts of opioids consumed before and 1 week after the procedure were not statistically significant. Side effects occurred after the procedure including temporary localized pain in 24 patients (47.0%), hypotension in 12 (23.5%), and diarrhea in 6 (11.8%). Conclusion: CPN is an effective and safe procedure for reducing upper abdominal pain caused by cancer, and it is necessary to perform CPN within the appropriate time by establishing a system of interdepartmental cooperation.

Correlation Between Pancreatic Cancer Incidence and Lifestyle Modification in Urban Residents (도심지역 주민들의 건강생활습관과 췌장암 발생과의 연관성)

  • Lee, Seong-Ran
    • Proceedings of the KAIS Fall Conference
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    • 2009.12a
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    • pp.759-763
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    • 2009
  • 본 연구의 목적은 도심지역 주민들의 건강생활습관과 췌장암과의 연관성을 파악하는데 있다. 이를 위해 2008년 6월 20일부터 7월 20일까지 종합병원에 내원한 췌장암 환자군 51명, 대조군 116명을 대상으로 설문 및 면접조사를 실시하였다. 연구결과 첫째, 음주량이 증가함에 따라 췌장암발생 위험은 유의하게 증가되었다(P<0.05). 둘째, 췌장암 발생위험에 대한 식사속도, 자극성 음식선호여부, 뜨거운 음료선호여부, 채식선호 정도 등은 환자군과 대조군간에 유의한 차이를 보이지 않았으나 교육수준이 낮을수록 수입이 낮을수록 도시보다는 농 어촌에 거주할수록 췌장암 발생위험도가 유의하게 증가함을 보였다(P<0.01). 셋째, 췌장암 발생에 대한 흡연과 음주의 상협효과 결과 흡연과 음주를 동시에 이용하였을 때 췌장암 발생위험도는 흡연 또는 음주만 이용할 때보다 상협적인 증가를 보였으며 통계적으로 유의하였다(P<0.05). 이상에서 볼 때 췌장암 진단을 위한 정기적인 검사가 보편화되지 않고 대상자의 판단에 의해서만 실시되고 있는 국내 상황을 고려할 때 본 연구에서 유의하게 나타난 위험요인들을 기초로 췌장암 위험 사정 도구의 개발이 필요하다.

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Resistant Starch (저항전분)

  • 신말식
    • Korean Journal of Human Ecology
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    • v.2 no.2
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    • pp.29-38
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    • 1999
  • 저항전분(RS)은 건강한 사람의 소장에서 소화되지 않는 전분이나 전분질 식품의 부분이다. 저항전분은 4가지 형태로 구분하는데 RS 1은 물리적으로 효소와 만나지 않는 부분, RS 2는 생전분으로 감자, 바나나와 고아밀로오스 옥수수전분, RS 3는 노화된 전분 그리고 RS 4는 화학적으로 변성시킨 전분이다. RS 함량은 열에 안정한 $\alpha$ -아밀라아제나 pancreatin, pancreatic $\alpha$ -아밀라아제와 미생물에서 분리된 아밀라아제 등을 이용한 몇 가지 방법에 의해 분석되고 있다. RS는 대장에서 미생물에 의해 발효되어 단쇄지방산을 생성하는데 특히 부티릭산이 생성된다. 아세트산이나 프로피온산은 간의 대사에 영향을 주며 부티릭산은 항 종양(항 대장암) 특성이 있다. RS는 소화가 되지 않아 저열량원이므로 당뇨병 환자나 운동에 의한 혈당 조절이 필요할 때 조절능력을 갖는다. RS가 건강에 중요한 인자임이 알려지면, 건강을 위해 매일 섭취량의 증가를 권장해야 할 것이다.

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A Study on the Comparison of One Step Method and Two Step Method to Improve Reporting of CA 19-9 Results (CA 19-9 결과보고 개선을 위한 One step 방식과 Two step 방식의 비교에 관한 연구)

  • Jae-Seok An;Ji-Na Kim;Kwang-Seo Park;Eun-Bit Joo;Sang-Hyuk Yoon;Yoon-Cheol Kim
    • The Korean Journal of Nuclear Medicine Technology
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    • v.28 no.1
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    • pp.81-87
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    • 2024
  • Purpose: CA 19-9 is the most widely used tumor marker for the diagnosis of digestive system tumor, especially pancreatic and biliary tract cancer. This study was conducted to improve the result value near reference range by comparing the reagents of CA 19-9 one step method and two step method. In addition, it was intended to establish a standard for selecting reagents. Material and Methods: 120 patients who visited the National Cancer Center in 2023 were selected as subjects for this study. The reagents used in the study were CA 19-9 IRMA kits (Shinjin, Korea) and three types of reagents were compared. Two step method reagent that is currently being used (A), one step method reagent (B) and two step method reagent improved by request (C) were compared and regression analysis was performed on their data. And we also performed recovery test, linearity test and hook effect test for each reagent. Result: There were 46 cases of reagent B in which the concentration value was lower than the result measured in reagent A that was previously used, and 77 cases of reagent C. As a result of regression analysis of reagents A, B, and C, the coefficients of determination of reagents A and B, reagents A and C, and reagents B and C were 0.653, 0.577, and 0.875. In the recovery rate test and the linearity test, the results of all reagents were good, and in the hook effect test, reagent B showed a hook effect at a low value. Conclusion: The improved reagent C appears to have been improved based on the concentration value of reagent B, which the manufacturer judged to be more stable at low concentrations. The hook effect in reagent B can be a fatal reason for disqualification when selecting reagents in general patient samples which high-concentration samples appear frequently. The first improved reagent C will be able to be used once it is confirmed that it has more stability for various concentration values.

METASTATIC CARCINOMA OF ORAL CAVITY (구강 및 악골에 생긴 전이 암종)

  • Kim, Chang-Soo;Lee, Jeong-Hoon;Ann, Heui-Yong;Chung, Sang-Chul;Choi, Hong-Sik
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.12 no.1
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    • pp.142-147
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    • 1990
  • Malignant oral tumors occurred in the oral cavity. They were thought to result from the other primary tumors through hematogenous metastasis. Primary tumors were unusually gall bladder tumor and pancreatic tumor. Biopsy was performed and these specimens were similar to those of the primary sites histologically and clinically. Diagnoses were adenocarcinomas metastatic from the primary tumors. They did not reveal the bony changes, only soft tissue masses.

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