| 摘要: | 大腸直腸癌目前是國人發生人數最多的癌症，在2012年全世界約有一百四十萬人診斷出罹患大腸直腸癌而且這些個案大多發生於已開發的國家中。根據世界衛生組織的統計資料，在2015年約有七十七萬四千多人死於大腸直腸癌，這高居十大癌症死因的第三名，台灣目前也是如此，2015年台灣每十萬人口平均約24.2人死於大腸直腸癌(男性約27.4人，女性約21人) 。尤其是現在西風東漸，國人的飲食習慣日漸西化，可想而知未來大腸直腸癌一定會更加威脅國人的健康。本論文主要是報告台灣大腸直腸癌特殊及首次發表的個案及針對台灣大腸直腸癌病患其血管內皮生長因子和其接受器(Vascular endothelial growth factor, VEGF and Vascular endothelial growth factor receptor, VEGFR)來進行同步的分析，希望能找出大腸直腸癌各期別的差異性，另外比對腫瘤細胞復發或轉移時的蛋白質變化及病人的存活時間，期望可以找出大腸直腸癌的危險蛋白及使用抗血管新生藥物的指標及預後的參考。第一章是報告一例79歲男性個案，無家族腫瘤史，主要是因腹痛三個月、胃口不佳及體重減輕而求診，經檢查手術後證實為大腸直腸同時三處發生腫瘤的個案，且首次發表出來。第二章是報告一例82歲男性個案因下腹痛持續數周且併有貧血情況求診，經檢查手術後證實為乙狀結腸癌同時伴有闌尾黏液性囊狀腺瘤的個案，這也是很罕見的病況。第三章則是同步分析台灣大腸直腸癌病患其組織及血液五種血管內皮生長因子和三種血管內皮生長因子接受器的變化，我們發現VEGF-A, -B, -C, -D, placental growth factor (PlGF), VEGFR-1, VEGFR-2和VEGFR-3這八種蛋白在腫瘤組織的量都比非腫瘤組織的部位來得高，同時血液中的量也是比健康人高，且轉移性大腸直腸癌病患在其血液及組織中比非轉移性大腸直腸癌病患有較高的VEGF-A, -B, -C, -D, 和PlGF。另外血液中VEGF統計或組織中VEGF及VEGFR陽性人數來比較，主要和病患年紀、腫瘤位置、腫瘤大小、腫瘤期別及淋巴轉移與否有其關聯性，同時VEGF和其結合之VEGFR也存在著正相關，病患有高量的VEGF和VEGFR其存活率會較短。藉由這些資料可以讓我們來根據台灣大腸直腸癌病患其血管內皮生長因子和其接受器的量來判斷其是否有轉移的可能，有利於癌症預後的判別，並決定出適合以VEGF抑制劑來治療大腸直腸癌的標記。;Colorectal cancer (CRC) is a cancer that starts in the colon or rectum. 1.4 million new cases were diagnosed with CRC over the world in 2012 and more than 50 percent of CRC cases occurred in more developed countries. According to the WHO statistics, about 774,000 people died from the CRC in 2015, and this disease is the third most common cause of death worldwide, including Taiwan. In 2015 in Taiwan, 24.2 in 100,000 people (27.4 in 100,000 men and 21.0 in 100,000 women) died from the CRC. This reflects the big impacts of CRC on a country mortality and human health. The overall objective of this dissertation was thus to report new cases in CRC patients living in Taiwan, as well as evaluating the profiles of the vascular endothelial growth factor (VEGF) family and the VEGF receptors (VEGFR) in patients with CRC.
The first chapter indicated a new CRC case on synchronous triple carcinoma of the colon and rectum from a case of a 79-year-old patient who did not have a family history of cancer but had a 3-month history of abdominal pain associated with anemia, loss of appetite, and body weight loss. This was the first case of synchronous triple carcinoma of the colon and rectum found in Taiwan.
The second chapter showed a new CRC case on synchronous mucinous cystadenoma of the appendix (characterized by a cystic dilatation of the appendicular lumen with stasis of mucus inside it) in an 82-year-old patient who had several weeks’ history of low abdominal pain associated with anemia.
The third chapter showed synchronous changes in tissue and circulating protein levels of all the five VEGFs and all the three VEGFRs from Taiwan patients with colorectal carcinoma. VEGF-A, -B, -C, -D, placental growth factor (PlGF), VEGFR-1, VEGFR-2 and VEGFR-3 were higher in tumor tissues than non-tumor tissues. Besides having higher circulating VEGFs and soluble VEGFRs than healthy subjects, metastatic patients exhibited higher VEGF-A, -B, -C, -D and PlGF proteins in both tumor tissue and serum than non-metastatic patients. Besides serum VEGFs, VEGF-positive or VEGFR-positive cases were mainly associated with the age, tumor site, tumor size, tumor stage and lymph node metastasis. Positive correlations between VEGF and VEGFR reflected their specific relationship. Patients exhibiting high levels of VEGF and VEGFR had a shorter overall survival and a less disease-free survival than those with low levels. These data suggest that particular VEGF and VEGFR family members allow discrimination of metastatic CRC from non-metastatic CRC in the studied Taiwanese population and may be possibly used as a marker for gauging the clinical effect of various treatment on the CRC patients. |
