（一）探討KIAA0101基因在人類非小細胞肺癌中所扮演的角色 （二）統合分析長期照護管灌及身體約 束之照護模式

（I）Investigate the le of KIAA0101 gene in human NSCLC. （II）Care model of tube-feeding and physical restraints in long term care system − Mroeta-analysis

藍紹桓(Shao-Huan Lan)

指導教授 ： 吳文俊 ； 林隆堯 ； 蔡明勳

中山醫學大學/醫學院/醫學研究所/博士(2018年)

摘要

為了找尋肺癌的診斷標誌，我們利用大規模分析肺腫瘤及其鄰近正常組織基因的表現差異，發現數個在肺癌中被活化的基因。在本文中以肺癌細胞中於免疫染色法分析有大量表現的KIAA0101基因為本文的研究目標。KIAA0101蛋白最早因會與proliferating cell nuclear antigen（PCNA）結合而被稱為p15PAF（PCNA associate factor）。先前已有研究顯示在癌細胞改變KIAA0101基因的表現會影響細胞的生長能力，但是其生物機轉及臨床上的影響仍是未知的，因此探討KIAA0101如何影響癌細胞增生的機轉及KIAA0101對肺癌病人的影響是必須的。研究中使用定量PCR的方法比較非小細胞肺癌中肺癌組織及其鄰近正常組織中KIAA0101的RNA表現量，結果顯示KIAA0101在肺癌組織中有大量的表現。為了研究KIAA0101在肺癌細胞中大量表現的情況，我們將KIAA0101在H1355肺癌細胞株中大量表現；並在H1299肺癌細胞株中以shRNA的方法將KIAA0101抑制。我們發現轉染並大量表現KIAA0101蛋白的細胞株與控制組相比，其細胞生長速度在細胞實驗及動物試驗中都有顯著的上升。反之，利用shRNA方法抑制KIAA0101表現的細胞株則對細胞生長速度造成顯著的減緩。在流式細胞儀分析shRNA方法抑制KIAA0101表現的細胞株則會發現其細胞週期停滯於G1時期。同時，抑制KIAA0101的表現在細胞實驗及動物實驗中會降低肺癌細胞的生長能力。
由NSCLC病患肺癌組織切片IHC免疫染色及數據分析發現，KIAA0101蛋白質的細胞質與細胞核的高表現量皆會降低NSCLC病患的存活率，但影響的情況不完全相同。在KIAA0101的細胞核表現量，僅對肺癌鱗狀上皮細胞癌的病人存活率有影響，對肺腺癌病患則無影響，在往後的研究中，進一步探討其原因是必要的。
背景：管灌餵食和身體約束情形在台灣長期照護機構很常見，衛生福利部於拓展長期照護相關計畫的同時，也考量到以慈悲/關懷的態度和作法，調整長期照護機構施行管灌餵食和身體約束的照護模式。
目的：統合分析探討長期照護住民管灌餵食和身體約束照護模式。分別為：評估管灌餵食和經口進食對長期照護機構居民營養狀況影響；探討長期照護機構人員施行約束相關教育和諮詢計畫是否有效減少身體約束。
搜尋方針：資料庫The Cochane Library, ProQuest, Pubmed, Airiti Library、CINAHL （EBSCO）、Web of Science （WOS）和Ovid-medline搜尋，涵蓋英語和非英語體系之發表期刊。
選擇標準：研究方法沒有特別限制。研究的對象為機構中的住民，將短期、急重症的對象做排除（不包括得癌、手術後、呼吸器的病人）。期刊內文分別要含有長期照護住民管灌餵食和身體約束照護模式相關的結果。
結論：管灌餵食組的住民其營養生化指標較低。身體質量指標和飲食攝取指標於兩組間沒有顯著差異。長期照護機構人員如有參與約束相關教育和諮詢計畫將有效減少身體約束。

關鍵字

KIAA0101 ； 肺癌 ； 管灌餵食 ； 身體約束 ； 統合分析

並列摘要

To isolate novel diagnostic markers ad therapeutic targets for lung cancer, we erstwhile did expression profile analysis of lung cancer cells using a genome-wide cDNA microarray combined with microdissection. Among dozens of trans-activated genes in lung cancer cells, this study focused on KIAA0101 whose overexpression in lung cancer cells was validated by immunohistochemical analysis. KIAA0101 was previously identified as p15PAF (proliferating cell nuclear antigen-associated factor) to bind with with PCNA. Previous studies demonstrated that when modulation of KIAA0101 gene expression in tumor cells will affect cell proliferation; however, its biological mechanism remain unclear. It is necessary to assess biological mechanism of KIAA0101 for tumor cell growth. Lung cancer is the global leading cause of cancer-related death including Taiwan. Quantitative real time PCR were performed to compare KIAA0101 RNA expression level in paired human non-small cell lung cancer (NSCLC) and non-cancerous lung tissues from the same patients. The results demonstrated that KIAA0101 gene largely expressed in tumor site of lung tumor specimens. To investigate the biological significance of KIAA0101 overexpression in lung cancer cells, we overexpress KIAA0101 in H1355 and knocked down KIAA0101 gene expression by short hairpin RNA（shRNA）in H1299 lung cancer cells. Introduction of wild-type KIAA0101 gene into lowly endogenous KIAA0101 expression H1355 cells increased cell proliferation both in viro and in vivo compared with controls. Otherwise knocked down KIAA0101 gene expression by shRNA in H1299 lung cancer cells caused attenuation of their proliferation. FACS was used to analyze the cell cycle after shRNA transfection showed that KIAA0101 downregulated H1299 cells induced G1 cell cycle arrest.
IHC of non-snoll-cell-lung cancer (NSCLC) patients’ lung cancer tissue showed that whatever KIAA0101 express in cytoplasm or cell nuclear, high KIAA0101 expression bring low survival rate to NSCLC patients. But KIAA0101 nuclear expression had no effect on lung adenocarcinoma patients’ survival rate and it decreased squamous cell lung cancer patients’ survival rate only. In future research, investigate the reason of this different phenomenon of KIAA0101 location is needed.
Background：The use of tube feeding for elderly patients in long-term institution who have poor nutritional status is common. Since malnutrition endanger the health has been well documented, we try to explore the nutritional status and feeding route of residents in the long-term care facilities. For this practice are needed to do, because the patient is unable to eat by mouth, or convenience of care, resulting in tube feeding.
Objective：First, according to demographic variables, feeding route and nutritional status indicators, divided into two groups assesment. Second, to investigate the nutritional status indicators cling to use tube feeding or through the hand-feeding. Third, the results of the study as the future long-term care of the nutritional status indicators.
Search methods：The Cochane Library, ProQuest, Pubmed, Airiti Library were searched in December 2012. The authors included English- and non-English-language studies and hand-searched journals.
Selection criteria：The following criteria were used to include published studies in English or Chinese: (1) variables should associated with residents living in long-term care institution’s and nutrition indicators; (2) study selection is not limited; (3) the papers must offer the size of the samples, average、standard difference or other information that can help us analysis the results, like as 95% confidence intervals (CIs); and (4) the participate with living in long-term care institutions.
Studies were excluded if one of the following existed: (1) the design was not comparation group; (2) the outcome was not use continues variables; or (3) there was insufficient information for data extraction.
Conclusions：The residents in tube-feeding group had worser condition in nutritional biochemical parameters. Otherwise, there are no difference in patients’ anthropometric parameter and dietary intake between tube-feeding group and hand feeding group. Caregiver in long term care facilities with restraint related care education programs and consultation generally drcrease physical restraint rate in long term care facility.

並列關鍵字

KIAA0101 ； lung cancer ； tube-feeding ； physical restraint ； Meta-analysis

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