很多版友都對於癌症免疫治療很有興趣,但因為Cincia沒有實戰經驗可以分享,嗚嗚~我還是處於傳統派的治療,不過有外加上營養醫學輔助就是。

不久前認識了卡斯柏,他有把自己在2013年前往日本千葉醫院以免疫療法治療鼻咽癌的經驗分享在他的Blog上,有興趣的版友可以參考看看喔!

點我點我-->進入卡斯柏的Blog

透過卡斯柏也間接知道了艾曼達(Cincia沒有直接接觸喔!),艾曼達未來的公公是肺癌,預計2014年10月前往久留米大學醫院進行免疫療法的治療(她們申請到的是免疫療法人體實驗),卡斯柏也將艾曼達的成功申請經驗分享於版上

艾曼達表示有義務協助台灣病友申請前往久留米醫院進行的免疫療法,由於他未來公公是肺癌,因此主要可以幫到的是肺癌的病友。

有需要的版友可以透過卡斯柏跟她聯繫喔!!

相關文章:

1. 成功前往久留米醫院進行癌症免疫療法的經驗

2. 日本久留米大學醫院免疫治療人體實驗招募資

【結語】

免疫療法在台灣還不盛行,之前詢問台大廖唯昱醫師,他說台大目前也有一些免疫療法的試驗,因為Cincia還是繼續吃標靶藥物,所以這部分廖醫師並沒有多解釋。

想獲知各項藥品試驗計畫,請查詢-->台灣藥品臨床試驗資訊網

以上分享,歡迎各位版友提供更多資訊喔!:)

 

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星希亞的抗癌日誌

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  • peter
  • 【肺癌患者日常照顧 10大原則】:

    1.戒菸及禁二手菸。

    2.改善居家及工作環境之空氣品質。

    3.避免到公共場所,以減少上呼吸道感染的機會。

    4.避免暴露於對呼吸道有刺激性的環境。

    5.舫注意是否有感染或出血的徵象或症狀。

    6.避免接觸有機溶劑,特別是石棉、柏油、電鍍等。

    7.改進烹調習慣、避免高溫烹調、烤炸。

    8.避免攝食過多高脂肪食物。

    9.須有適當的運動,特別是能增加肺活量的運動,如氣功、瑜珈、太極拳等。

    10.肺癌的飲食應攝取天然新鮮的蔬果為主。

    11、如有發燒、寒顫、呼吸速度加快、臉潮紅、牙齦出血、血尿、脈搏速度加快,應立即回院就醫。
  • 感謝Peter分享!!:)

    Cincia 於 2014/10/19 21:14 回覆

  • PETER
  • 1.自從來星希亞部落格發現肺癌的可怕,今年2月底去做底劑量ct發現2顆0.29及0.37結節,雖然後續2次ct追蹤都沒變化,但這裡太多例子如kim部落格,所以不能太放心

    2.目前早上常吃地爪,水煮2個蛋白,生洋蔥,大蒜,少吃糖,每天一杯500cc紅蘿蔔馬鈴薯加水果綜合果汁,避免攝食過多高脂肪,烤炸食物
    3.2天跑1次5-6公里及練太極氣功,爬山,希望明年2月底再去做底劑量ct只是虛驚一埸,但也快50歲了,告訴自己上述吃東西及運動要認真,持之以恆大家共勉之
  • Dear Peter,
    照第二回戰友會顏博士的建議,馬鈴薯不是好物耶!!我們一起調整吧~
    你這麼認真保養身體,明年的檢查一定沒問題,我對你有信心!!:)

    Cincia 於 2014/10/19 21:16 回覆

  • fred
  • 我在去年七月確診為肺腺癌第四期,移轉脊椎, 經過化療4次加放療,穩定控制了半年多,後來追蹤發現肺部有新的不明點出現,醫生建議開刀拿掉,拿出來後來發現只是發炎,今年七月又發現腦轉移,做了全腦放療,10月追蹤發現腦部長出了約3~4公分的囊腫,主治醫生建議追蹤、放射醫生建議開刀、腦神經外科也建議開刀,請問各位朋友或有認識的人有相關的經驗可以給予分享或建議,謝謝!
  • 肺癌家屬
  • To Fred:
    我母親是今年9月確診肺癌轉移腦部,因為已出現手腳不協調症狀,故先於林口長庚處理腦部腫瘤,放療10次後,情況改善很多,腦部腫瘤若長得太大影響生活或出現癲癇都是非常危險的,給您參考。
  • 感謝分享,也希望另堂的狀況可以穩定控制喔!一起與癌細胞和平共處,加油~

    Cincia 於 2014/10/19 07:57 回覆

  • fred
  • 謝謝您的分享,我現雖有腦轉移,現在又出現了一個大囊腫,但幸運的是位置的關系,目前是沒有明顯的症狀,我也做過全腦放療了10次,現在如果要處理只能開腦,所以很難決定
  • 如果沒有明顯症狀的話,我會傾向先不處理,但密切觀察。
    以上個人建議供參考,還是要和醫師多討論再說。^^

    Cincia 於 2014/10/19 21:05 回覆

  • Andrew Chen
  • to Fred, 可以再跟醫師確認是否有立即危險性, 如果可以追蹤, 多久複檢. 另外關於處理方式, 腦部腫瘤還可以用"加馬刀"和"電腦刀"處理, 不過腫瘤不能太大, 但不知囊腫適不適合這種方式.
  • Penny
  • 請問一下您的意見和建議,肺腺癌的病患有適合喝滴雞精嗎?因有人說可以喝補身體,但是又有人說太補對癌細胞不好,不知您的觀點如何?謝謝~
  • 之前化療期間身體虛弱時,我媽也有自製雞精給我喝,對於蛋白質補充應該很好。
    雖然也有人主張吃植物性蛋白就好,但我想雞肉算是白肉,總比喝牛肉湯來的好,這是我的一點想法,給你參考囉!

    Cincia 於 2014/10/20 09:54 回覆

  • fred
  • 謝謝Andrew Chen、Penny 的回覆,現在我和老婆考慮也是傾向先密切追蹤,畢竟開腦的風險沒法預測(雖然我的位置相對安全些)
  • Hi Fred,
    要相信自己會沒事,信念真的很重要,一起加油!!

    Cincia 於 2014/10/23 14:02 回覆

  • fred
  • 謝謝Cincial 的鼓勵, 一起加油; 對了,我已加入fb且得到您的批準,謝謝,另外我還有加您的fb 哦,我fb 用的是中文拼音 chienhao
  • 加囉~

    Cincia 於 2014/10/24 17:49 回覆

  • 悄悄話
  • David
  • Cincia 有沒有聽過Adaptive T cell transfer? 這是我所知最有效的治療方法 把病人的T細胞在體外培養 擴充到幾百億個再打回病人體內 在治療黑色素瘤有很好的效果(45%) 有能擊殺癌細胞種T細胞在淋巴腺和血液裡 不但能縮小腫瘤 也可以阻止腫瘤擴散

    因為T細胞 天性喜歡聚集在肺部和淋巴腺治療肺癌效果 應該更好 人體免疫系統有記憶 療效是長期的不像標靶藥物有突變抗藥性的問題

    以下這段影片 美國安德森治癌中心 Dr. Patrick Hwu 對Adaptive T cell transfer 用在治療黑色素瘤 有很詳細的說明 雖然講的是黑色素瘤 但是對肺癌一樣有效 請仔細觀看 看後一定能讓妳了解 為什麼這是最有效的治療方法

    https://www.youtube.com/watch?v=yGzJzzGj5Jw

    我提出來給Cincia參考Cincia可以找這方面的資訊
    美國安德森治癌中心 MD Anderson cancer center在這方面研究有多年經驗 是全美排名第二的癌症醫院

    他們有許多 clinical trials 網址如下

    http://www.mdanderson.org/patient-and-cancer-information/cancer-information/clinical-trials/clinical-trials-at-md-anderson/index.html

    此外我在卡斯柏的網站 知道日本東京大學也有肺腺癌T細胞療法 建議Cincia考慮試試
  • David
  • Cincia 有沒有聽過Adaptive T cell transfer? 這是很有效的治療方法 把病人的T細胞在體外培養 擴充到幾百億個 訓練T細胞辨識擊殺癌細胞 再打回病人體內 在治療黑色素瘤有很好的效果(45%) 能擊殺癌細胞種T細胞在淋巴腺和血液裡 不但能縮小腫瘤 也可以阻止腫瘤擴散

    目前研究都在致力於提高治療效果
    癌細胞很狡猾 有些癌細胞在其外膜有anti-PD1的突出體 能夠躲避T細胞擊殺
    這方面已有幾種藥品上市 Keytruda (from Merk) Opdivo (from BMS) 可以克服

    另一個問題是T細胞 天性喜歡聚集在肺部和淋巴腺 對一些癌症效果不好
    如果癌細胞在腦部T細胞都聚集在肺部 那麼治療腦癌 皮膚癌效果當然不如治療肺癌的好

    針對這方面 研究人員對T細胞基因加上 一些修改(基改) 讓T細胞能被癌細胞吸引 類似螞蟻被糖吸引

    基改聽起來很可怕 過去也發生T細胞攻擊病人腦的事件 那是因為以前只有加上
    一個探頭 現在都加上兩個不相干的探頭T細胞攻擊自體細胞的機會大大降低

    我個人非常厭惡基改食物 但不得不稱讚基改對癌症治療的貢獻
    人體免疫系統有記憶 療效是長期的不像標靶藥物有突變抗藥性的問題
  • Hi David,
    感謝你提供這麼豐富的資訊給我們參考,e-mail我也有收到,不過還需要一些時間來消化一下內容,太感謝你了。
    ps.感覺你應該是醫學研究相關人員是嘛?不然怎麼會研究這麼透徹。^^

    Cincia 於 2015/02/07 14:31 回覆

  • David
  • 以下這段影片 美國安德森治癌中心 Dr. Patrick Hwu 對Adaptive T cell transfer 用在治療黑色素瘤 有很詳細的說明 雖然講的是黑色素瘤 但是對肺癌一樣有效 請仔細觀看 看後一定能讓妳了解 T細胞療法治療方式

    https://www.youtube.com/watch?v=yGzJzzGj5Jw

    我提出來給Cincia參考Cincia可以找這方面的資訊
    我在卡斯柏的網站 知道日本東京大學也有肺腺癌T細胞療法 Cincia可以找這方面的資訊
  • David
  • 我知道一段影片對Adaptive T cell transfer有很詳細的說明

    有興趣的朋友可以到youtube 網站尋找

    T-cell Adoptive Therapy for Melanoma - Melanoma Education Symposium, Patrick Hwu MD
  • David
  • 美國MD Anderson Cancer Center有許多人體實驗
    可到醫院網站首頁找Browse Clinical Trials
  • David
  • 再接再厲
    美國National Cancer Institute 有12000個正在進行的人體實驗
    網址
    w w w . c a n c e r. g o v / c l I n I c a l t r I a l s
  • David
  • 美國 MD Anderson Cancer Center正在進行的人體實驗
    網址
    w w w . m d a n d e r s o n . o r g
    首頁可以找到clinical trials 連結
  • David
  • 繼續為癌友盡一份心力 翻譯一段從美國NCI介紹T細胞治療的文章
    更多內容在

    w w w . c a n c e r . g o v / c a n c e r t o p i c s / r e s e a r c h - u p d a t e s / 2 0 1 3 / C A R - T - C e l l s

    T細胞療法像是有生命的藥物 從病人取出T細胞 把這些T細胞基因改造
    在T細胞表面生成特殊的感受體
    這些感受體讓T細胞能夠辨識癌細胞表面的抗原
    然後在把這些基因改造的T細胞培養到上百億
    再把這些上百億的T細胞輸入病人體內 這些基因改造T細胞會在病人體內繼續繁殖
    經由植入的感受體辨識和殺死癌細胞

    Adoptive cell transfer is like “giving patients a living drug,” continued Dr. Brentjens.
    That’s because ACT’s building blocks are T cells, a type of immune cell collected from the patient’s own blood. After collection, the T cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs). CARs are proteins that allow the T cells to recognize a specific protein (antigen) on tumor cells. These engineered CAR T cells are then grown in the laboratory until they number in the billions. (See the box below.)
    The expanded population of CAR T cells is then infused into the patient. After the infusion, if all goes as planned, the T cells multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill cancer cells that harbor the antigen on their surfaces.
  • David
  • 回Cincia
    我不是醫療工作人員 我在矽谷從事軟體工作
    我爸去年10月檢查出得到黑色素瘤
    我擔心我爸的病 開始研究有關黑色素瘤治療方法
    也因此對T細胞療法有些初步認識
    T細胞和B細胞是人體免疫反應主力
    腫瘤擴張期 一部份癌細胞也會死亡
    在一部份的人身上死亡的癌細胞會激起身體的免疫反應
    然而癌細胞有幾種機制逃避T細胞的攻擊
    最近上市幾種免疫治療藥品就是阻斷癌細胞逃避T細胞的攻擊的機制
    然而只有兩成的人對腫瘤有免疫反應 因此效果不如標靶藥物來的好
    T細胞療法採取完全不一樣的方法
    從病人取出對能摧毀癌細胞的T細胞(tumor infiltrating lymphocytes or TILs)
    把這些T細胞基因改造
    讓T細胞表面生成特殊的感受體
    這些感受體讓T細胞能夠辨識癌細胞表面的抗原
    然後在把這些基因改造的T細胞培養到上百億
    再把這些上百億的T細胞輸入病人體內
    這些基因改造T細胞會在病人體內繼續繁殖
    經由植入的感受體辨識和殺死癌細胞
    經過治療許多病人腫瘤縮小或病情穩定
    而且這免疫反應是相當持久的 不是幾個月 是幾年甚至10年以上
    T細胞療法最大的問題是有此技術的醫院不多
    不像吃藥打針 醫院一個月只能處理幾個病人
    在美國主要是 National Cancer Institute (Maryland), MD Anderson Cancer Center (Taxas), Moffitt Cancer Center (Florida).
    NCI在T細胞療法有10多年經驗 NCI對於非小細胞肺癌人體實驗已經開始 
  • David
  • 需要說明以上關於免疫藥品只有2成療效的敘述
    就像前文說的 癌細胞有幾種機制逃避T細胞的攻擊
    目前已經有藥的機制(pathway)
    1) CTLA-4: Yervoy
    2) PD-1: KeyTruda, Opdivo
    一種藥Yervoy可能只對兩成人有效
    另種藥KeyTruda可能只對兩成人有效
    兩種藥都用對四成人會有效
    不同阻斷機制藥效是可以相加的
    免疫治療藥品藥效是長效的
    因為免疫系統是有記憶的
    CTLA-4和 PL-1機制在許多癌症都有
    所以對不能用標靶藥的人是好消息
    唯一就是太昂貴
  • David
  • 這篇報導說非小細胞癌患者有10-30% 是EGFR possitive 只有3%是ALK possitive.
    對於大部份患者 這幾年都沒新藥 對於這些患者 Keytruda是個好消息

    http://www.pharmaphorum.com/news/mercks-keytruda-gains-breakthrough-status-in-lung-cancer
  • 非小細胞癌患者有10-30% 是EGFR possitive 只有3%是ALK possitive,這數字在東方好像比較高,我看過的數字EGFR應該約50-60%,而ALK是5%左右~

    Cincia 於 2015/02/13 09:53 回覆

  • David
  • 日本的研究發現沒做過化療的癌症病人體內的T細胞B細胞和自然殺手細胞的數量都遠低於健康的人 除了環境污染 身體免疫力低下 是人們罹癌的原因

    Recent progress has been made in understanding the mechanisms of antitumor immune responses, which may further clarify the immune status of cancer patients. In this study, we performed a detailed evaluation of the immunological status of 47 patients with advanced solid cancer, who had received no immunosuppressive treatment, and compared the results with 32 healthy subjects. Flow-cytometry data for peripheral blood were obtained using 19 monoclonal antibodies against various cell surface and intracellular molecules. Absolute numbers of T cells, several T cell subsets, B cells, and NK cells were significantly decreased in patients compared with healthy subjects. The percentage of CD27(+)CD45RA(+) T cells was lower and that of CD27(-)CD45RA(-) T cells was higher in patients compared with controls. Regulatory and type 2 helper T cells were elevated in patients relative to healthy subjects. The percentage of perforin(+) NK cells was significantly lower in patients than in controls. These results suggest a dysfunctional anti-tumor immune response in cancer patients. Furthermore, peripheral blood from 26 of 47 cancer patients was analyzed after adoptive T cell immunotherapy (ATI). ATI increased the number of T cell subsets, but not B and NK cells. The number and percentage of regulatory T cells decreased significantly. These results suggest that ATI can restore impaired and imbalanced T cell immune status.

    http://www.ncbi.nlm.nih.gov/pubmed/24269583
  • David
  • Cincia, 下面這個網頁是很重要的網頁 請加入妳的書籤

    http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/lung-cancer

    這個網頁有美國正在進行中的針對非小細胞免疫治療的臨床實驗
    我會繼續在這裡解釋每一種治療的原理
    Cincia有50個願望 要有健康的身體才能全部達成
    免疫治療可以還給Cincia 健康 達成所有願望和未來的新願望
    希望Cincia 持續注意免疫治療這方面的訊息
    因為免疫系統是人類最終能擊敗癌症的利器
  • David
  • 許多人認為免疫系統根本不會攻擊腫瘤
    如果免疫系統會攻擊腫瘤
    腫瘤沒有機會作大擴散 而應該會逐漸縮小 甚至消失
    的確 要引起免疫反應 腫瘤表面必須具有能被免疫系統識別為外來物的抗原
    多數腫瘤並不會引起免疫反應 因為免疫系統無法辨識它

    Source:
    http://www.microbiologybook.org/mobile/m.immuno-18.htm
  • David
  • 那麼肺腺癌會引起免疫反應嗎?
    觀察最近Keytruda和 Opdivo 針對非小細胞肺癌治療臨床實驗結果
    答案是肯定的 但是有沒有免疫反應 是因人而異
    必竟80歲老人不比30歲年輕人吧
    Keytruda和 Opdivo可以幫助有免疫反應的人縮小甚至清除腫瘤
    下面我會解釋Keytruda和 Opdivo如何運作
  • David
  • 科學家在癌症免疫研究經過許多挫折
    因為科學家對免疫機制如何運作有許多盲點
    針對各類癌症發展出的許多癌症疫苗 証實沒有效果
    直到幾年前 科學家 才瞭解
    在T細胞 表面有幾個接受器是免疫系統用來調節T細胞 的攻擊性的
    請Cincia 參考下面網頁的圖

    http://www.onclive.com/publications/contemporary-oncology/2014/February-2014/Immune-Checkpoint-Blockade-in-Cancer-Inhibiting-CTLA-4-and-PD-1PD-L1-With-Monoclonal-Antibodies

    圖上有 T cell, Tumor cell, Dendritic cell (樹突細胞)
    先稍微解釋一下樹突細胞 樹突細胞是免疫系統的記憶體
    樹突細胞的表面有妳身體曾經見過的疫苗細菌病毒或是腫瘤的抗原
    T細胞經由樹突細胞表面的抗原 瞭解敵人的長像
    T細胞 表面有兩個接受器CD28 和CTLA4
    樹突細胞一旦接上 CD28 (on switch) 可以起動T細胞 進入戰鬥狀態
    樹突細胞一旦接上CTLA4 (off switch) 可以撤銷T細胞的戰鬥狀態
    我之前提到免疫藥Yervoy就是堵住CTLA4 讓T細胞持續戰鬥狀態
    讓腫瘤無法經由樹突細胞來停止對其攻擊
    腫瘤還有另一個方法來 瓦解T細胞的攻擊
    在T細胞 表面還有另一個接受器 PD1 這也是個off switch
    有些腫瘤表面會有PDL1的接受器
    一旦T細胞 靠近腫瘤 馬上會被腫瘤的PDL1黏上 瓦解攻擊
    Keytruda和 Opdivo的運作就是堵住PD1讓腫瘤無法瓦解T細胞攻擊
  • David
  • 相信Cincia現在知道什麼是CTLA4, PD1, PDL1了
    上面請Cincia加入書籤的網頁有許多這類的藥正在做非小細胞肺癌的臨床實驗
    要強調的是有些臨床實驗是可以跟ALK或EGFR標靶藥一起吃的
    目的在測試免疫藥的輔助功效 像是這個

    https://clinicaltrials.gov/ct2/show/NCT01998126

    下次可以問妳的醫師有沒有適合妳的
  • David
  • 下次介紹Adoptive T cell Transfer的非小細胞肺癌的臨床實驗
  • David
  • 禮來達成兩項合作,以研究其癌癥治療藥物與百時時美施貴寶及默沙東抗pd-1治療藥物的合并用藥方案,三家公司于1月13日如此報道稱。“合并治療將會成為解決腫瘤異質性與不可避免耐藥性的關鍵,此次合作可能會開發出最有前景的新型個體化治療藥物方案,”禮來腫瘤部門產品開發及醫療事務高級副總裁gaynor評論稱。

    在一項1/2期試驗中,禮來將研究其試驗性轉化生長因子(tgf)βr1激酶抑制劑與百時美施貴寶opdivo (nivolumab)合并用于晚期膠質母細胞瘤、肝細胞癌及非小細胞肺癌(nsclc)。兩家公司指出,該合作將檢驗一種假說,即pd-1與tgfβ陰性信號共同抑制與抑制其中一條通路相比是否會導致增強的抗腫瘤免疫響應。

    禮來還將進行一項1/2期試驗,用來評價該試驗性重組人igg1單克隆抗體necitumumab與默沙東keytruda (pembrolizumab)合并用于nsclc。此外,禮來將進行一項1/2期研究檢測cyramza (ramucirumab)與keytruda合并用于多種腫瘤。兩項研究均有望于今年開始。

    此外,默沙東將進行一項2期研究以測試keytruda與禮來培美曲塞合并一線用于非鱗狀nsclc,目前該研究正在招募患者。合作的其它條款未披露。

    keytruda成為首款fda批準的pd-1抑制劑,其于去年獲批用于晚期或不可切除的黑色素瘤,默沙東最近披露計劃擬尋求擴大批準這款治療藥物用于egfr突變陰性及alk重排陰性nsclc患者治療。

    與此同時,opdivo被fda加速批準用于不可切除或轉移性黑色素瘤患者治療,適用于不再對其它藥物響應的患者。百時美施貴寶于1月12日表示,在先前有過治療的晚期、鱗狀細胞nsclc患者中進行的一項該藥物與多西他賽對比的3期試驗因達到試驗終點而提前停止。

    Source:
    http://big.sunyet.com/med/a/n864424.html
  • David
  • SMB 公佈了Opdivo (Nivolumab) 治療非小細胞肺癌第一階段臨床實驗結果
    一年存活率42% 兩年存活率24% 對藥物有反應的病人比率(ORR)為17%
    http://news.bms.com/press-release/rd-news/additional-survival-data-nivolumab-investigational-pd-1-immune-checkpoint-inhi
    這些免疫藥品藥效大多長期的 因為免疫系統有記憶
    對有藥物反應的病人 能減少擴散 減少復發 或 延長復發時間
    Anti-PD1, Anti-PDL1, Anti-CTLA4 是目前免疫藥品主流
    有沒有效還是看個人的免疫系統
    一日7蔬果 規律生活 充足睡眠 適當運動 老生常談
    還是有效的防癌抗癌處方
  • David
  • Anti-PD1藥品有沒有效 要看腫瘤細胞表面有沒有PDL1表像
    越多腫瘤細胞有PDL1表像 藥品效果越好
    PDL1表像 多於50%的一組和PDL1表像最少的一組反應差三倍

    Findings from the proof-of-principle (POP) clinical study, presented at the 2014 AACR meeting, showed that advanced NSCLC tumours with strong PD-L1 expression responded better to MK-3475 (Pembrolizumab®) than did tumours with weak or no expression of PD-L1. PD-L1 tumour tissue expression of more than 50 per cent by immunohistochemistry is the most informative cut-off for response to therapy. Strong PD-L1 expression in NSCLC was associated with an MK-3475 (Pembrolizumab®) response rate three times higher than that associated with weakly positive PD-L1 tumours.

    Source: http://lsconnect.thomsonreuters.com/targeted-therapy-nsclc-part-vi-immune-therapy/#sthash.8sTLGIZ2.dpuf

    那麼為什麼腫瘤會有PDL1表像呢?
    其實腫瘤只有在受到免疫系統攻擊時才會有PDL1表像
    PDL1是腫瘤躲避免疫系統攻擊的方法 之一
    如果腫瘤只受到少數零星T細胞的攻擊
    PDL1表像自然會少
  • David
  • Opdivo 治療非小細胞肺癌第三階段臨床實驗傳來好消息
    該實驗證實效果比化療藥品Docetaxel 好的多 而且負作用小
    而提前結束實驗 我預計應該今年能得到美日相關單位准許用於治療非小細胞肺癌
    希望未來免疫藥品能取代化療

    Source:
    http://www.ono.co.jp/eng/news/pdf/sm_cn150115_02.pdf
  • David
  • 在MK-3475(Keytruda) I期臨床試驗,非小細胞肺癌(NSCLC)患者中PD-L1陽性的患者和沒有PD-L1表象的患者相比有顯著更好的結果。在治療6個月後,PD-1陽性的患者的41%的人 沒有疾病進展。患者的腫瘤具有低PD-L1的表達的患者只有17%沒有疾病進展。

    In a phase I trial, non–small-cell lung cancer (NSCLC) patients with tumors that expressed PD-L1 had significantly better outcomes with MK-3475 therapy compared with patients with PD-L1–negative tumors. At 6 months after initiation of treatment, 41% of PD-L1–positive patients had no disease progression compared with 17% of patients whose tumors had low PD-L1 expression.

    Source: http://www.cancernetwork.com/aacr-2014/pd-l1-expression-mk-3475-treated-lung-cancer-correlates-better-outcomes#sthash.S6Cyogb0.dpuf
  • David
  • 修正第29號留言:
    > 多數腫瘤並不會引起免疫反應 因為免疫系統無法辨識它
    最近才學到 正常人體細胞會把細胞內的蛋白質碎片經由MHC1呈現在細胞膜表面
    細胞內的許多蛋白質碎片 也都會呈現在細胞膜表面 供免疫系統辨識
    癌細胞是正常細胞突變 也會把突變的蛋白質碎片呈現在細胞膜表面
    供免疫系統辨識
    免疫系統就是透過這些細胞膜表面的蛋白質碎片辨識這細胞是否正常
    一旦T細胞 發現不正常的蛋白質 會開起一連串的免疫反應
    複製繁衍增生自己 到成千上萬
    一部份後代會成為 記憶型T細胞 一部份後代會成為 毒殺型T細胞
    不論是記憶型T細胞 或是毒殺型T細胞 都有專一性
    毒殺型T細胞 只會攻擊 那些表面有不正常的蛋白質的細胞
    免疫系統是你我身體裡的主力軍隊
    這是場免疫系統與癌症腫瘤的戰爭
    請愛惜你的免疫系統 不到必要不用化療
    一些臨床實驗已經證實
    在NSCLC免疫藥比化療藥有效
    免疫系統如果有效壓制癌症 可以防堵癌症擴散 效果是長期的
    免疫藥修復你的免疫系統 讓免疫系統能與腫瘤作戰
    在未來免疫藥應該是第一線用藥品
    而不是在被化療藥殘害後才用
  • David
  • 我把免疫系統講的那麼神 到底真的假的?
    如果免疫系統可以辨識 腫瘤癌細胞 也能鏟除癌細胞 那麼人為什麼還會得癌?
    很明顯的 癌細胞躲過免疫系統的監視 才會作大
    科學家已經知道癌細胞有幾種方法躲過免疫系統的監視
    PD1 PDL1是其中之一
    癌細胞所長的位置 在 較少白血球巡邏的地方也有關
    病人自己本身因為生活習慣 (睡眠不足 不吃蔬果 常外食 煙酒 工作壓力大) 造成免疫力低下
    年紀越大 免疫力也會差
    除了生活要健康外 要盡量避開生活裡所有已知的致癌物
    例如 香煙 汽機車廢氣 PAH (燒烤的煙 ) 燒香紙錢產生的煙 廚房油煙 空氣污染(PM2.5 微粒) 蔬菜水果裡的農藥 丙烯酰胺(薯條雞排) 雜環銨(烤焦的肉) 亞硝酸鹽(香腸) 甲醛 肉類水產裡的重金屬如汞鉻鉛 三聚氰胺 等等
    我常在想如果自己出身在兩百年前的台灣
    那時代沒有那麼多污染 出門看不到車子 空氣是乾淨的 土地沒有被工廠廢水污染
    海裡河裡的魚沒有重金屬污染
    我大概很少聽到癌症 也不用擔心得到癌症
  • David
  • 找到這篇2015 2月Opdivo 肺癌臨床實驗的報導
    這篇不再是一些統計數字 而是一位老太太的故事
    看到這篇報導 我是蠻開心的 因為我對這些Anti-PD1 藥有很高的期盼
    Barbara Marder 73歲 三年前右肺發現肺癌 醫師切除一部份右肺並給予化療
    一年後癌症復發 這次是在她的左肺有許多腫瘤
    她的醫師Dr. Julie Brahmer 建議她參加Opdivo 肺癌臨床實驗
    在用Opdivo幾週後Barbara 的腫瘤開始完全消失
    Marder 開始Opdivo治療後一年 還是沒有腫瘤的蹤影
    免疫系統有記憶力(via Memory T cell)
    沒有人知道這記憶力能持續多久
    (我知道最早用Yervoy治癒黑色素瘤的一個女子 已經10年沒有復發
    我希望Anti-PD1藥效果也能同樣持久)

    Source:
    http://www.npr.org/blogs/health/2015/02/09/373292216/harnessing-the-immune-system-to-fight-cancer
  • David
  • 最新消息 3/4/2015: FDA 允許Opdivo 用於非小細胞肺癌鱗狀細胞癌治療

    Opdivo’s efficacy to treat squamous NSCLC was established in a randomized trial of 272 participants, of whom 135 received Opdivo and 137 received docetaxel. The trial was designed to measure the amount of time participants lived after starting treatment (overall survival). On average, participants who received Opdivo lived 3.2 months longer than those participants who received docetaxel.

    The safety and efficacy of Opdivo to treat squamous NSCLC was supported by a single-arm trial of 117 participants who had progressed after receiving a platinum-based therapy and at least one additional systemic regimen. The study was designed to measure objective response rate (ORR), or the percentage of participants who experienced partial shrinkage or complete disappearance of the tumor. Results showed 15 percent of participants experienced ORR, of whom 59 percent had response durations of six months or longer.

    Source: FDA
    http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm436534.htm
  • David
  • 這則新聞說明Opdivo能取代化療
    效果比化療藥品Docetaxel 好 而且負作用小
    化療摧殘病人的免疫系統 只能延長病人生命幾個月
    免疫系統是人存活的必要條件
    千萬不要讓你的醫生傷害你的免疫系統

    參與實驗的117位病人 都被化療摧殘過
    還有15%的反應
    前面有提過 如果腫瘤有PD-L1表象 對Opdivo的反應是3倍42%
  • David
  • 免疫系統淺介
    我過去兩個月研讀了許多關於免疫系統的書
    有了些基本概念 漸漸的一些醫學論文也開始能看的懂了
    免疫系統真是個亞馬遜叢林 什麼奇怪的細胞都有
    這些細胞聯合起來日夜不停的守護著你
    你應該感謝他們
    也許你該花點時間瞭解他們的功能
    免疫細胞 分為兩大類 先天性免疫系統(innate immunity)
    先天性免疫系統主要由白血球裡的 巨噬細胞 樹突細胞 和自然殺手細胞所構成
    這些細胞的作用在於識別和消滅可能導致感染的病原體(細菌 病毒 癌細胞)
    這些細胞在吞噬消化病原體後 會將病原體的氨基酸片段經由MHC 2受體表現在細胞膜上
    這就是所謂的抗原 這是激起後序免疫反應的重要步驟
    先天性免疫沒有專一性 只要是外來物質 一律先吞再說
    第二類叫適應性免疫系統 (adaptive immunity)
    適應性免疫系統主要由B細胞 T細胞構成
    當前面那些巨噬細胞 和樹突細胞回到淋巴結時 他們帶回病原體的氨基酸片(抗原)
    如果某一個T細胞 表面的氨基酸片段能接合帶回的抗原 再加上B細胞也帶回同樣的抗原
    顯示病原體入侵 這個T細胞 開始被激活 開始大量繁衍自己 繁衍兩類T細胞
    一種是記憶型T細胞 一種是殺手型T細胞
    記憶型T細胞 的功用在於記得抗原 日後再碰到 同類的病原體會馬上反應
    記憶型T細胞 是免疫療法長效性的原因
    即使記憶型T細胞自然凋亡 它的後代也記得敵人的長像
    記憶型T細胞也是使用免疫療法癌症不容易復發的原因(除非癌細胞突變)
    殺手型T細胞 能分泌酵素溶解病原體(腫瘤)的細胞膜
    殺手型T細胞有專一性 只會攻擊有抗原的目標 (細菌 被病毒入侵的細胞 腫瘤)
    因為它有專一性 近年來成為科學家對抗腫瘤的首選

    待續
  • 感謝David兄提供的資訊,Cincia最近有認真在研究免疫療法的資訊,到時候也可以整理整理跟大家分享~

    Cincia 於 2015/03/31 12:53 回覆

  • David
  • 這是篇參與Opdivo黑色素瘤臨床實驗的病患的經歷

    My Nivo (Opdivo) trial - first dose - 4 years ago 12/29/2010 - thoughts...

    回頭看過去4年是多麼奇怪的!。好像是昨天。這似乎是很久以前的事。抗PD1的藥物是一個未知數。只有極少數的患者在幾個研究用了Anti-PD1藥品。ipilimumab(Yervoy)或是BRAF抑製劑都未獲得FDA的批准。默克的產品Keytruda並不存在。驚訝的是我還活著。我簡直不能相信我在那6個月辦到了隔週工作看病的行程:週一,週二,週三工作12小時工作 週四開車到Atlanta飛往Tempa。租車和晚餐。在La Quinta旅館休息。週五黎明跳上車趕往Moffitt醫院實驗室,見醫生,打針,輸藥。像瘋了一樣開回機場。飛往亞特蘭大。再開兩小時車回Chattanooga。週一繼續上班。我後來發現,許多在像我在臨床實驗的人在治療過程中沒有工作。不過許多人在用Keytruda Yervoy仍然繁忙的生活。剩下的兩年中,只需要每12週去Tempa和輸藥。這似乎像一個休假!在這2年半我錯過了3個工作日內。還有那些誰說我是瘋了 我該休更多假的.....但是這不是我的個性。我是如此幸運。幸運的是能參加臨床實驗。幸運的是能夠有足夠錢參加臨床實驗。幸運地得到大家的支持。

    這是很難說什麼我以為會發生什麼事。我真的沒有想到太多。當然,不像今天這麼多的各種板面,聊天室和論壇所談論的 我不認為Opdivo能治癒我的病。不要誤會我的意思。我很感激有這個選項。腦腫瘤,肺腫瘤,扁桃體腫瘤,另一個大腦快速連續地冒出腫瘤讓我清楚地知道,我迫切需要打破這種循環。我唯一的選擇是IL2或干擾素,我不知道我的未來是什麼。但是同樣沒有任何人知道我的未來是什麼。我只是擔心那些似乎很肯定的是抗PD1的藥物將是他們個人的解脫時,30-40%的有效率告訴我們,有一大部份的人會感到失望。

    花了一輩子的閱讀研究報告,案例分析...這是超現實的經驗 閱讀一個你知道指的是你自己的經驗。 “33名患者參加10例復發患者中,有5名死於轉移性黑色素瘤。三名接受手術後呈現無病狀態54星期 一名病人自然消退......並一直無病3年以上。另一個的復發病人還活著,並在用dabrafenib加trametinib積極治療。“

    我對報告和結果的想法:

    副作用:
    “Nivolumab用疫苗的耐受性良好” 耐受性好?嗯....根什麼相比呢?沿著山間小徑徒步旅行的輕鬆的一天,洗熱水澡,一本好書,一個舒適的壁爐和美味的晚餐?毫無疑問,許多人經歷困難得多治療。儘管如此Nivolumab注射部位反應,疲勞,皮疹,瘙癢,噁心,腹瀉和關節痛是常見的。低鉀血症(低血鉀...的東西,可危及生命),腸炎,結腸炎,垂體和甲狀腺炎人肯定是一些參與實驗的人的症狀。有1例1級pneumonititis。不知道那是誰?也許我的,也許不是。這是很奇怪有那些誰沒有黑色素瘤,也從來沒有得到可憐的那些疫苗或採取反PD1甚至有一次,確定彼此的體驗質量。

    腦轉移:
    “10名患者切除了腦轉移腫瘤。”嗯......這是不完全準確。我的不是“切除”,它是通過電腦刀“切除”的。不能確定其他人是怎樣切除的。這10名病人只有2例有復發。一個轉移到肺。另一個顯然有顯著的中央神經疾病,雖然研究人員那時候沒有意識到,儘管這樣的損失,這是一個非常顯著的成果 因為黑色素瘤腦轉移,沒有治療我們的生命只有6個月左右。

    放射治療:
    “放射治療被給予18例前或手術包括九名與切除腦轉移後。”這項研究並沒有推測,所有我能做的是...但隨著越來越多的研究著眼於回顧性數據和新的研究專門研究輻射結合IPI,抗PD1和BRAF抑製劑......我不得不相信這一組合對我們有正面的幫助。

    PD-L1的
    研究人員希望找到檢測腫瘤的生物標誌,可以告訴我們哪些患者會對哪種藥物有反應。 PD-L1的是其中的一個。我們有28我們的腫瘤進行測試。我仍然不知道我的有沒有PD-L1表象。但是,在我們的研究中,“有這個患者人群 PD-L1和無復發生存期之間沒有顯著的關聯,雖然目前還朝著那些腫瘤是PD-L1陽性更好的RFS無統計學顯著的趨勢......”對於什麼是值得。我懷疑測試PD-L1表象是不是很好的生物標誌,還有更多的關於這方面的研究。

    無復發生存期:
    “回顧性研究顯示 在IV期黑色素瘤患者的12個月的中位 總生存期的中位數是12個月。”然而,我們這些參與實驗的人已經表現出了“令人印象深刻的無復發生存... 47.1個月
    ”對於我來說,我現在:
    診斷出黑色素瘤136個月
    黑色素瘤第四階段黑色素瘤56個月
    開始Opdivo 48個月
    我的最後一次輸入Opdivo 18個月

    這是一個奇妙的旅程。
    以下是對其他參與實驗的人 說的
    讓我們用愛迎接2015年!

    Source:
    http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/12/my-nivo-opdivo-trial-first-dose-4-years.html
  • 看完了,感謝David持續分享,

    Cincia 於 2015/04/01 14:24 回覆

  • David
  • 這是篇參與Opdivo黑色素瘤臨床實驗的病患的經歷
    回頭看過去4年是多麼奇怪的!。好像是昨天。這似乎是很久以前的事。抗PD1的藥物是一個未知數。只有極少數的患者在幾個研究用了Anti-PD1藥品。ipilimumab(Yervoy)或是BRAF抑製劑都未獲得FDA的批准。默克的產品Keytruda並不存在。令人驚訝的是我還活著。我簡直不能相信我在那6個月辦到了隔週工作看病的行程:週一,週二,週三工作12小時工作 週四開車到Atlanta飛往Tempa。租車和晚餐。在La Quinta旅館休息。週五黎明跳上車趕往Moffitt醫院實驗室,見醫生,打針,輸藥。像瘋了一樣開回機場。飛往亞特蘭大。再開兩小時車回Chattanooga。週一繼續上班。我後來發現,許多在像我在臨床實驗的人在治療過程中沒有工作。不過許多人在用Keytruda Yervoy仍然繁忙的生活。剩下的兩年中,只需要每12週去Tempa和輸藥。這似乎像一個休假!在這2年半我錯過了3個工作日內。還有那些誰說我是瘋了 我該休更多假的.....但是這不是我的個性。我是如此幸運。幸運的是能參加臨床實驗。幸運的是能夠有足夠錢參加臨床實驗。幸運地得到大家的支持。

    這是很難說什麼我以為會發生什麼事。我真的沒有想到太多。當然,不像今天這麼多的各種板面,聊天室和論壇所談論的 我不認為Opdivo能治癒我的病。不要誤會我的意思。我很感激有這個選項。腦轉移,肺轉移,扁桃體轉移,另一個大腦快速連續地冒出腫瘤讓我清楚地知道,我迫切需要打破這種循環。我唯一的選擇是IL2或干擾素,我不知道我的未來是什麼。但是同樣沒有任何人知道我的未來是什麼。我只是擔心那些似乎很肯定抗PD1的藥物將是他們個人的解脫時,30-40%的有效率告訴我們,有一大部份的人會感到失望。

    花了一輩子的閱讀研究報告,案例分析...這是超現實的經驗 閱讀一個你知道指的是你自己的經驗。 “33名患者參加10例復發患者中,有5名死於轉移性黑色素瘤。三名接受手術後呈現無病狀態54星期 一名病人自然消退......並一直無病3年以上。另一個的復發病人還活著,並在用dabrafenib加trametinib積極治療。“


  • David
  • 我對報告和結果的想法:

    副作用:
    “Nivolumab用疫苗的耐受性良好” 耐受性好?嗯....根什麼相比呢?沿著山間小徑徒步旅行的輕鬆的一天,洗熱水澡,一本好書,一個舒適的壁爐和美味的晚餐?毫無疑問,許多人經歷困難得多治療。儘管如此Nivolumab注射部位反應,疲勞,皮疹,瘙癢,噁心,腹瀉和關節痛是常見的。低鉀血症(低血鉀...的東西,可危及生命),腸炎,結腸炎,垂體和甲狀腺炎人肯定是一些參與實驗的人的症狀。有1例1級pneumonititis。不知道那是誰?也許我的,也許不是。這是很奇怪有那些誰沒有黑色素瘤,也從來沒有得到可憐的那些疫苗或採取反PD1甚至有一次,確定彼此的體驗質量。

    腦轉移:
    “10名患者切除了腦轉移腫瘤。”嗯......這是不完全準確。我的不是“切除”,它是通過電腦刀“切除”的。不能確定其他人是怎樣切除的。這10名病人只有2例有復發。一個轉移到肺。另一個顯然有顯著的中央神經疾病,雖然研究人員那時候沒有意識到,儘管這樣的損失,這是一個非常顯著的成果 因為黑色素瘤腦轉移,沒有治療我們的生命只有6個月左右。

    放射治療:
    “放射治療被給予18例前或手術包括九名與切除腦轉移後。”這項研究並沒有推測,所有我能做的是...但隨著越來越多的研究著眼於回顧性數據和新的研究專門研究輻射結合IPI,抗PD1和BRAF抑製劑......我不得不相信這一組合對我們有正面的幫助。

    PD-L1的
    研究人員希望找到檢測腫瘤的生物標誌,可以告訴我們哪些患者會對哪種藥物有反應。 PD-L1的是其中的一個。我們有28我們的腫瘤進行測試。我仍然不知道我的有沒有PD-L1表象。但是,在我們的研究中,“有這個患者人群 PD-L1和無復發生存期之間沒有顯著的關聯,雖然目前還朝著那些腫瘤是PD-L1陽性更好的RFS無統計學顯著的趨勢......”對於什麼是值得。我懷疑測試PD-L1表象是不是很好的生物標誌,還有更多的關於這方面的研究。

    無復發生存期:
    “回顧性研究顯示 在IV期黑色素瘤患者的12個月的中位 總生存期的中位數是12個月。”然而,我們這些參與實驗的人已經表現出了“令人印象深刻的無復發生存... 47.1個月
    ”對於我來說,我現在:
    診斷出黑色素瘤136個月
    黑色素瘤第四階段黑色素瘤56個月
    開始Opdivo 48個月
    我的最後一次輸入Opdivo 18個月

    這是一個奇妙的旅程。
    以下是對其他參與實驗的人 說的
    讓我們用愛迎接2015年!

    http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/12/my-nivo-opdivo-trial-first-dose-4-years.html
  • David
  • 免疫監視(1)

    免疫功能與腫瘤的發生、發展有密切關係。
    Ehrlich免疫監視的理論最早在1909年提出 近 幾十年來的許多實驗證實免疫監視的存在
    舉個例子 一項老鼠實驗給10隻 有先天缺乏免疫功能的老鼠注射癌細胞 10隻全部長出腫瘤
    同樣的10隻 在健康的老鼠注射癌細胞 只有2隻長出腫瘤
    另一個例子 早年器官移植的人 需長期吃降低免疫力的藥來避免排斥 許多人後來得到癌症
    雖然免疫監視的確存在 但腫瘤仍能在人體生長、轉移、復發,這顯示腫瘤具有逃避免疫攻擊的能力。

    下面我會免疫監視的3個階段: 1)癌細胞免疫系統被消滅 2)免疫與腫瘤平衡 3)腫瘤逃脫免疫監視

    Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265921/
  • David
  • 免疫系統淺介 (2)

    很特別的是每個T細胞表面的受體 都不一樣
    T細胞表面的受體 可以有千億種變化
    受體的功能是什麼呢? 受體讓來自 循環 神經 內分泌 免疫系統
    或是臨近的細胞發出的訊息能傳到細胞內 起動細胞一連串後續反應
    前面提到的和樹突細胞表面的抗原 和一個T細胞 表面的受體結合
    會激活這個T細胞 起動免疫反應
    也就是說T細胞 表面的受體讓T細胞可以辨認抗原(包括腫瘤表面的抗原)
    T細胞表面的受體 有千億種 也就是讓免疫系統能辨認千億種抗原
    這是免疫系統有適應性的原因 能對從未見過的病毒 細菌 癌細胞產生免疫反應
    T細胞 是由骨隨產生 新生的T細胞進入胸腺受訓和繼續演化
    T細胞 在胸腺演化成T Helper cell (CD4 T cell)
    和 Cytotoxic毒殺型 T cell (CD8 T cell)
    胸腺功能在訓練T細胞認識自體細胞 避免T細胞離開胸腺後攻擊自體器官
    造成自體免疫疾病如紅斑性狼瘡 類風濕性關節炎
    大約90%的T細胞 會在這個階段被胸腺鏟除
    只有少數T細胞能完成訓練 離開胸腺執行任務
    T Helper cell (CD4 T cell)是免疫系統 的警報器
    一旦被激活 會分泌介白素促進被激活 B細胞 不斷分裂 生產抗體
    AIDS 就是HIV病毒攻擊T Helper cell削弱免疫系統
    許多AIDS病患最後死於病毒細菌感染
    免疫系統對人的重要性可想而知

    待續
  • David
  • 免疫監視是個重要話題 特別是腫瘤如何逃避免疫系統的監視
    只有當人類了解腫瘤如何逃避免疫系統的監視
    才能設計藥品協助免疫系統辨識消滅腫瘤
    像PD1 CTL4 抑制劑的發明 開啟癌症治療的新時代
    即使是末期全身轉移 也有例子用PD1 CTL4 抑制劑後腫瘤完全消失
    我最近在讀這方面的醫學資訊 希望能提供正資訊
  • David
  • 大概沒人在看這版吧 非常安靜
  • 很多人都有看David提供的資訊,真的很謝謝你的熱心呢!我想大家需要一點時間消化吸收啦!^^

    Cincia 於 2015/05/12 20:19 回覆

  • jl4552ms62
  • 不會沒人看阿!像我一有空一定都會上來看看(雖然只是個過客)
    很感謝David搜集一些有關免疫的資料給大家分享,也可時常提醒大家免疫的重要性及未來治愈癌症的方針,這些訊息也可帶給一些戰友正面思考及希望,不是嗎?
  • 感謝版友的回應,這樣David兄應該可以知道他收集的資訊幫助了不少人,真的很感謝~

    Cincia 於 2015/05/20 10:34 回覆

  • Gary YC LIN
  • 很感謝 David 搜集一些有關免疫的資料給大家分享 +1

    To David, 這就是網路的特性,潛水的人居多啦! 其實你po的文章,大家還是有在看的。 你何時回台灣啊?? 大家可以找星希亞一起出來吃個飯,認識一下喔! ^_^
  • David
  • 感謝Cincia j14552ms62 和Gary 的回應 也謝謝你們的關注
    我覺得我還是把關於免疫療法的資訊PO在這版
    方便病友版友查詢

    Gary 我有機會回台 一定會跟你們聯繫
  • 真的很感謝David,
    可惜免疫療法對肺腺癌的有效率只有30%,遠低於標靶的60-70%,不過當沒有標靶可吃的時候,免疫30%看起來也很高了,好矛盾的心理啊!

    Cincia 於 2015/05/15 18:26 回覆

  • David
  • 固體腫瘤會形成微環境不利於免疫系統攻擊
    Mayo Clinic研究人員試驗用探針伸進腫瘤 把腫瘤瞬間冷凍
    造成大量的癌細胞死亡
    在自然回溫的過程中 死亡的癌細胞 會釋放出細胞內不正常的蛋白質
    (生魚片壽司也是用負20度冷凍和自然回溫來殺寄生蟲卵)
    我在免疫系統淺有說明過 樹突細胞和巨噬細胞會吞下這些不正常的蛋白質
    並把這些蛋白質的片段呈現在它的細胞膜 讓T細胞 B細胞辨認
    激起後序免疫反應
    醫界已經知道 CTLA4抑制劑 要有效 病人本身對腫瘤已經有免疫反應
    CTLA4抑制劑主要功用在延續病人本身已經有免疫反應
    Mayo Clinic 用冰凍法激發免疫反應 然後給病人CTLA4抑制劑
    讓免疫反應持續 效果值得期待

    Source:
    https://www.mskcc.org/blog/new-immunotherapy-approach-breast-shows-promise
  • David
  • 淺談腫瘤逃避免疫監視的機制

    Source: http://annonc.oxfordjournals.org/content/23/suppl_8/viii6.full

    Studies of cancer–immune system interactions have revealed that every known innate and adaptive immune effector mechanism participates in tumour recognition and control [5]. The first few transformed cells are detected by NK cells through their encounter with specific ligands on tumour cells. This leads to the destruction of some transformed cells and the uptake and processing of their fragments by macrophages and dendritic cells. In turn, these macrophages and dendritic cells are activated to secrete many inflammatory cytokines and present tumour cell-derived molecules to T- and B cells. Activation of T- and B cells leads to the production of additional cytokines that further promote activation of innate immunity and support the expansion and production of tumour-specific T cells and antibodies, respectively. The full power of the adaptive immune system leads to the elimination of remaining tumour cells and, importantly, to the generation of immune memory to specific tumour components that will serve to prevent tumour recurrence.

    長期的研究發現所有參與先天性免疫和適應性免疫的免疫細胞都參與腫瘤辨識和管理
    自然殺手細胞可能最先遇上突變的細胞 根據突變的細胞膜上的不正常的受體 判定這細胞不正常 進而消滅它
    樹突細胞和巨噬細胞遇上突變細胞的遺骸 會把它吃掉 並把突變的細胞內的蛋白質的碎片表現在細胞膜上
    這時樹突細胞和巨噬細胞會分泌介白素 吸引T細胞 和B細胞 引發適應性免疫反應T細胞和B細胞
    開始大量繁衍 生產抗體和毒殺型T細胞 繁衍的T細胞 和B細胞會分泌更多不同的介白素 進一步激起免疫反應
    最終導致癌細胞被鏟除 更重要的是記憶型T細胞 會記得癌細胞的樣子 可以預防癌症復發

    Instead of defining immunosurveillance as the process by which cancer is recognised and eliminated and a diagnosis of cancer to represent the failure of this process, it is now recognised that in different individuals and with different cancers, the process can have at least three different but related outcomes: elimination, equilibrium, and escape

    與其說免疫監視是免疫系統辨識和鏟除癌細胞的過程 而癌症的發生是免疫監視的失敗
    現代醫界認為不同的癌症發生在不同的人身上 有3種不同的結果: 1) 腫瘤被免疫系統殲滅
    2) 腫瘤與免疫系統保持平衡狀態 3) 腫瘤逃出免疫系統監視

    A highly immunogenic tumour in a highly immunocompetent individual will result in optimal stimulation of the innate immune system leading to the production of highly immunostimulatory cytokines, acute inflammation, activation of a large number of T- and B cells, and prompt elimination of the arising tumour.

    辨識度高的癌細胞在一個免疫力強的人身上會激起自體免疫反應導致癌細胞被免疫系統鏟除

    With a less immunocompetent individual and/or less immunogenic tumour, however, there might not be a complete elimination leading to the survival of some cancer cells that nevertheless remain under immunosurveillance. Over a prolonged period of time, the slow growth of the tumour would be accompanied by repeated activation of the immune system and elimination of some tumour cells, followed by further cycles of tumour regrowth and immune-mediated destruction. This period, when the tumour is present but not yet a clinical disease, is known as equilibrium.

    辨識度低的腫瘤或是一個免疫力低的人身上新生成的癌細胞一部份被免疫系統鏟除
    但免疫系統無法鏟除所有癌細胞 這時腫瘤已經成型 但還不是癌症
    腫瘤還是在免疫系統的控制中 這是所謂的平衡狀態

    The equilibrium phase could be life-long, thus mimicking elimination, or be disturbed by changes in the tumour that allow it to avoid immunosurveillance or changes in the immune system that weaken its capacity for tumour surveillance. Either change ultimately leads to tumour escape

    這平衡狀態可能維持相當久的時間 最後可能因為人的免疫力下降下
    (熬夜 飲食不當 工作壓力 離婚 喪偶 吃類固醇藥物等等)或是腫瘤發生突變 而使腫瘤逃出免疫系統監視 產生癌症
  • David
  • 淺談腫瘤逃避免疫監視的機制 (2)

    Source: http://annonc.oxfordjournals.org/content/23/suppl_8/viii6.full

    In many cancers, however, malignant progression is accompanied by profound immune suppression that interferes with an effective antitumour response and tumour elimination. Initially, most of the escape from immunosurveillance was ascribed to changes in the tumour cells themselves (loss of tumour antigens, loss of human leukocyte antigen molecules, loss of sensitivity to complement, or T cell or natural killer (NK) cell lysis), making them a poor target of an immune attack.

    在許多癌症進展過程中伴隨著令人難以理解的免疫系統被壓制的現象
    起初的想法是腫瘤產生突變 失去了可以辨識的抗原 失去了承現抗原的MHC 或者對T細胞或自然殺手細胞 分泌的溶解細胞膜的酵素不再有反應 (即T細胞或自然殺手細胞沒辦法溶解它的細胞膜進而消滅它)

    However, it has become clear that the suppression comes from the ability of tumours to subvert normal immune regulation to their advantage. The tumour microenvironment can prevent the expansion of tumour antigen-specific helper and cytotoxic T cells and instead promote the production of proinflammatory cytokines and other factors, leading to the accumulation of suppressive cell populations that inhibit instead of promote immunity. The best described are regulatory T cells and myeloid-derived suppressor cells.

    後來的研究人員漸漸清楚 腫瘤是利用正常的免疫機制來壓抑免疫系統
    腫瘤微環境能分泌介白素引起慢性發炎吸引 抑制型T細胞和MDSC細胞的聚集
    抑制毒殺型T細胞 和T helper細胞繁衍

    Source: http://www.nature.com/cmi/journal/v10/n3/full/cmi201310a.html

    Some tumors protect themselves by establishing an immune-privileged environment. For example, they can produce immunosuppressive cytokines IL-10 and transforming growth factor-β (TGF-β) to suppress the adaptive antitumor immune response, or skew the immune response toward a Th2 response with significantly less antitumor capacity.2,3,4

    一些腫瘤會分泌抑制免疫系統的介白素像IL-10或TGF-β讓免疫反應趨向於抑制的方向

    Some tumors alter their expressions of IL-6, IL-10, vascular epithelial growth factor or granulocyte monocyte-colony stimulating factor (GM-CSF), impairing DC functions via inactivation or suppressing maturation.5 In some cases, induced regulatory T cells suppress tumor-specific CD4+ and CD8+ T-cell responses.6

    一些腫瘤會改變介白素像IL-6, IL-10,GM-CSF 阻礙樹突細胞的功能
    抑制型T細胞 (regulatory T cells) 會壓抑毒殺型T細胞 (CD8+) 輔助型T細胞 (CD4+) 的功能

    Tumor cells also minimally express or shed tumor-associated antigens, shed the ligands of NK cell-activating receptor such as the NKG2D ligands UL16-binding protein 2, major histocompatibility complex (MHC) class I chain-related molecules A and B molecules (MICA/MICB) or alter MHC-I and costimulatory molecule expression to evade the immune responses.7,8,9

    一些腫瘤會突變失去原有的抗原 失去可辨識的配體 (ligand) 或MHC來蒙蔽免疫系統

    Malignant cells may also actively eliminate immune cells by activation-induced cell death or Fas ligand (FasL) expression.10,11 In addition, primary cancer treatments like chemotherapy and ionizing radiation can compromise antitumor immune responses by their immunosuppressive side effects

    一些腫瘤甚至會引發免疫細胞的凋亡機制 殺死免疫細胞
    另外化療和放療都會傷害免疫系統
  • Jason
  • 新光醫院腫瘤治療科的熱治療是去年8月向衛福部申請,以實驗名義從日本引進,之前我在該院做螺旋刀治療時,有遇到幾位癌友(大多是頭頸癌及肺癌,放化療搭配熱治療),其表示使用熱治療的癌友還不多。
  • David
  • What have we learned from cancer immunotherapy in the last 3 years? (1)

    Given the numerous immune checkpoints that exist, combining immuno-oncology agents that target different checkpoint pathways is also an attractive therapeutic approach. Tumours exploit these pathways to turn off the immune response in different ways, either by decreasing T-cell proliferation or inactivating T cells at the tumour site [77]. For example, by inhibiting CTLA-4, ipilimumab promotes T-cell proliferation, increasing the number of activated T cells that can migrate to attack the tumour; conversely, anti-PD1 agents such as nivolumab counteract tumour defences specifically within the tumour microenvironment, reactivating T-cell activity and inducing tumour cell death [9,11]. The complementary roles of these two pathways in regulating adaptive immunity are supported by preclinical models in which simultaneous administration of anti-CTLA-4 and anti-PD1 antibodies resulted in enhanced antitumour activity compared with single agent treatments [78,79]. In a phase 1 combination study of ipilimumab and nivolumab in patients with advanced melanoma, 40% of patients treated with the concurrent combination regimen had objective responses and the 1-year OS rate was 82%; notably, responses with the combination were both rapid and deep [80,81]. This combination is being further evaluated versus ipilimumab or nivolumab monotherapy in a phase 3, randomised trial. Accumulating preclinical and clinical data also support the use of other investigational immunotherapy combinations such as nivolumab plus anti-LAG3 and ipilimumab plus GM-CSF [82,83].

    http://www.translational-medicine.com/content/12/1/141
  • David
  • Phase III Study Finds Initial Nivolumab-Based Treatment Halts Melanoma Progression

    ASCO Perspective
    ASCO Expert Steven O’Day, MD
    “Immunotherapy drugs have already revolutionized melanoma treatment, and now we’re seeing how they might be even more powerful when they’re combined. But the results also warrant caution – the nivolumab and ipilimumab combination used in this study came with greater side effects, which might offset its benefits for some patients. Physicians and patients will need to weigh these considerations carefully.”

    A randomized phase III trial indicates that initial therapy with nivolumab alone or in combination with ipilimumab is significantly more effective than ipilimumab alone. Nivolumab alone more than doubled the average time to disease progression, compared to ipilimumab (6.9 months vs. 2.9 months), and the benefit was even greater when ipilimumab and nivolumab were combined (11.5 months). The response rates were also substantially higher in patients receiving the combination therapy (57.6%) and nivolumab (43.7%) alone, as compared to ipilimumab (19%).

    “We’re very encouraged that the initial observations about the efficacy of this combination held up in this large phase III trial,” said lead study author Jedd Wolchok, MD, PhD, Chief of Melanoma and Immunotherapeutics Service at Memorial Sloan Kettering Cancer Center in New York, NY. “Our study also suggests that patients with a specific tumor marker appear to benefit the most from the combination treatment, whereas other patients may do just as well with nivolumab alone. This will help doctors provide important insight for patients on which treatment is right for them.”

    Nivolumab and ipilimumab are monoclonal antibodies that block two different immune checkpoints ─ PD-1 and CTLA-4, respectively. Both treatments, commonly referred to as checkpoint inhibitors, essentially boost the immune system’s ability to fight cancer.

    Prior research has shown that immune checkpoint inhibitors can improve survival for patients with melanoma and lung cancer. Both ipilimumab and nivolumab are FDA-approved for use as single agents in patients with unresectable (cannot be removed by surgery) or metastatic (advanced) melanoma that no longer responds to other drugs.

    This study randomly assigned 945 patients with previously untreated, advanced melanoma to receive ipilimumab, nivolumab, or the combination of the two. After a follow-up period of at least nine months, the median progression-free survival was 2.9 months for ipilimumab, 6.9 months for nivolumab, and 11.5 months for the combination. The differences between the combination and ipilimumab groups, and nivolumab and ipilimumab groups were statistically significant.

    The response rates for the combination, nivolumab, and ipilimumab groups were 57.6%, 43.7%, and 19%, respectively. The average reductions in tumor burden (depth of response) were 52% with the combination and 34% with nivolumab alone. In contrast, patients who received ipilimumab alone experienced a 5% increase in tumor burden.

    As expected, the rate of serious drug-related side effects was the highest in the combination group (55%), and 36% of patients in this group had to stop the therapy due to side effects. Dr. Wolchok remarked that prior studies have shown that many patients who stop immunotherapy early still continue to do well.

    This prolonged benefit is explained by the fact that immunotherapy works by activating the immune system rather than targeting the tumor directly. It is not yet clear how long patients need to be treated to fully activate the immune system, and the minimal duration of therapy probably varies from patient to patient.

    Quality of life data were collected on the study, and the analysis of those results will be reported at a later time.

    PD-L1 Status May Help Define Optimal Treatment

    The PD-1 protein on immune cells attaches to another protein called PD-L1, which is sometimes found on the surface of some tumor cells. Prior research suggested that patients who had detectable PD-L1 levels in their tumor (PD-L1-positive tumors) typically had better responses to PD-1 therapy.

    In this study, nivolumab alone seemed to be as effective against PD-L1-positive tumors as the combination of nivolumab and ipilimumab. For patients with PD-L1-negative tumors, however, the combination treatment was significantly more beneficial than nivolumab alone.

    This study received funding from Bristol-Myers Squibb.
  • David
  • 什麼是CTLA4 ? 什麼是PD1? 分享一下最新的心得

    人體對腫瘤產生免疫反應要經過一連串過程
    這過程我在”免疫系統淺介”有說明過
    腫瘤在免疫反應發生過程中每一步驟都可能干預
    讓身體對腫瘤無法產生免疫反應
    免疫系統裡負責辨識和擊殺癌細胞的主要成員是T細胞
    T細胞 的表面 有兩個受體 是T細胞的死穴
    一個受體叫做CTLA4
    在正常狀態 抗原呈現細胞(樹突細胞)是起動T細胞 活化的重要推手
    但腫瘤可以經由抗原呈現細胞來結合T細胞表面的CTLA4受體
    讓T細胞 無法活化無法繁衍
    T細胞 無法活化無法繁衍 自然無法對腫瘤產生免疫反應
    T細胞 的表面另一個受體叫做 PD1
    腫瘤可以經由癌細胞表面的PDL1的配體
    來讓已經活化的毒殺型T細胞 失去攻擊力
    平時癌細胞表面是沒有PDL1的配體的
    但是當遭到獨殺型T細胞的攻擊
    癌細胞就會產生PDL1來抵抗T細胞的攻擊
    一旦T細胞PD1被癌細胞的PDL1黏上
    可以讓T細胞失去攻擊力甚至自然凋亡
    CTLA4 抑制劑與PD1抑制劑實際上是人造的蛋白質
    一旦黏上T細胞的CTLA4和PD1 後
    腫瘤將無法再經由這兩個受體阻蒙蔽免疫系統
    這就是為什麼去年唐獎生技獎是搬給發現CTLA4和PD1機制的兩位教授
  • David
  • Cincia 和各位病友 今天我在研究化療放療對免疫系統的影響
    化療放療對免疫系統的確傷害很大 而且看來傷害是長期的
    我會提出數據和說明 妳們的心臟要夠強喔
    先貼原文出處

    Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777669/
  • David
  • #65
    化療放療會傷害骨髓 傷害免疫系統 相信大家都知道
    對免疫系統那些功能有傷害? 多久能復原? 這篇研究有數據
    針對化療 放療 和化療+放療 對病人的免疫功能的影響
    這篇研究在下列4個時間點測量病人的免疫功能的各項指數
    治療前˙ 治療後2個月˙ 治療後6個月 ˙治療後12個月
    結果如下 請看這頁

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2777669/table/T3/

    每項數字是病人免疫功能回復到治療前的百分比
    例如化療CD4 (T helper cell) 在治療後2個月有41%的病人恢復到治療前水準
    但在治療後12個月這數字卻跌到18%
    我特別在提一下 IL2 這介白素是促進T cell繁殖的
    IL2不足會影響活化T cell的數量
    只有6%的病人的IL2有回到正常值
    整體來看 化療 放療 會嚴重影響病人的免疫系統
    傷害是深切而且是長期的
    因為我們還在放療化療當道的世界
    肺癌免疫療法還在臨床實驗階段
    因此我呼籲各位病友
    化療 放療後 把握時間盡快做免疫療法修復你的免疫系統
  • David
  • 各位病友
    這段時間對免疫系統與癌症的探討
    我的感想是正常的免疫系統是無法對抗癌症的
    免疫系統內建許多讓免疫反應結束的方式
    被腫瘤利用
    因此免疫系統會對癌細胞視而不見
    讓癌細胞恣意擴散
    要用免疫系統控制癌症 還是需要藥品或醫療手段介入
    我到 Keytruda 官網首頁看到這個公式 (稍作修改免得為Keytruda做廣告)
    我的免疫系統 + 免疫治療 = 擊敗腫瘤的力量
    免疫治療是防止癌症擴散的必要療法
  • David兄真的很可愛,Keytruda不需要你幫忙做廣告好嗎?應該已經賺翻了,哈哈~
    我也相信免疫療法是可以期待的,需要進步快一點啊~please~

    Cincia 於 2015/06/12 09:42 回覆

  • David
  • #20 除了PD1 CTLA4抑制劑 我很少提到其他的免疫療法
    原因是美國一年有上千個免疫療法臨床實驗
    真正得到FDA Break through status 快速合准上市的也只有 那3種抑制劑
    因為對4期癌症病友 做任何一項免疫治療都是拿生命做賭注
    免疫療法要幾個月才知道有沒有效
    選錯了可能錯過治療時機讓病情惡化
    我真的不希望病友選錯
    所以我很努力的把我知道的寫出來

    Immunotherapy of Cancer: Statement of the problem
    Immunotherapy of cancer must do more than simply present antigen to the immune system
    It must disrupt a pre-existing state of functional tolerance toward tumor antigens

    免疫療法必需要解決的問題 (也是你評估免疫療法的方法)
    免疫療法不能只是把腫瘤的抗原承現給免疫系統 (疫苗 或樹突細胞療法)
    免疫療法一定要破壞病人免疫系統對腫瘤的耐受性 (缺乏免疫反應)

    1) because tolerance cannot be overcome simply by a good antigen and a strong adjuvant (i.e. response are actively suppressed)

    2) because even vaccination or adoptive transfer of pre-activated T cells is still subject to suppression

    原因是
    1) 只是承現抗原 無法克服免疫系統對腫瘤的耐受性
    (因為腫瘤會積極的壓抑免疫反應)

    2) 疫苗 或體外培養未經活化的T cells仍然會受到腫瘤壓抑

    以這樣評估免疫療法 目前也只有PD1 CTLA4抑制劑能破壞腫瘤壓制免疫系統的方式
    讓免疫反應持續下去
  • 之前聽榮總蔡主任的演講,他的意見是主動免疫和被動免疫(PD1 CTLA4抑制劑)能雙管齊下的話效果更可以期待。
    不過這多傷荷包阿~可以的話Cincia真的也很想兩者併用啊!
    之前詢問的結果,台大也有免疫療法試驗計畫,不過得重新切片,Cincia目前切片有難度,so....

    Cincia 於 2015/06/12 09:37 回覆

  • David
  • 卡斯柏在久留米的實驗疫苗傳出令人振奮的好消息
    他的免疫系統對抗原(胜肽)產生很大的反應
    請看
    "久留米醫院免疫治療的初步檢查結果"
  • David兄,
    我都有在follow Caspar的消息,看到的確令人很振奮,我該認真考慮來做免疫了。

    Cincia 於 2015/06/29 10:09 回覆

  • David
  • understanding the function and dysfunction of the immune system in cancer
    1. O. J. Finn*
    + Author Affiliations
    1. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, USA
    1. ↵*Correspondence to: O. J. Finn, Department of Immunology, University of Pittsburgh School of Medicine, E1040 Biomedical Science Tower, Pittsburgh, PA 15261, USA. Tel: +1-412-648-9816; Fax: +1-412-648-7042; E-mail: ojfinnpitt .edu

    Abstract
    The immune system has the greatest potential for the specific destruction of tumours with no toxicity to normal tissue and for long-term memory that can prevent cancer recurrence. The last 30 years of immuno-oncology research have provided solid evidence that tumours are recognised by the immune system and their development can be stopped or controlled long term through a process known as immunosurveillance. Tumour specificity of the immune response resides in the recognition of tumour antigens. Viral proteins in tumours caused by viruses and mutated proteins from oncogenes or other genes, as well as nonmutated but abnormally expressed self proteins found on all tumours, have been shown to be good antigens and good targets for immunosurveillance. In many cancers, however, malignant progression is accompanied by profound immune suppression that interferes with an effective antitumour response and tumour elimination. Initially, most of the escape from immunosurveillance was ascribed to changes in the tumour cells themselves (loss of tumour antigens, loss of human leukocyte antigen molecules, loss of sensitivity to complement, or T cell or natural killer (NK) cell lysis), making them a poor target of an immune attack. However, it has become clear that the suppression comes from the ability of tumours to subvert normal immune regulation to their advantage. The tumour microenvironment can prevent the expansion of tumour antigen-specific helper and cytotoxic T cells and instead promote the production of proinflammatory cytokines and other factors, leading to the accumulation of suppressive cell populations that inhibit instead of promote immunity. The best described are regulatory T cells and myeloid-derived suppressor cells. Great conceptual and technical advances in the field of immuno-oncology over the past 30 years have provided us with the knowledge and techniques to develop novel immunotherapeutic approaches for the treatment of cancer. These include methods that enhance tumour immunity by blocking inhibitory pathways and inhibitory cells in the tumour microenvironment (e.g. antibodies against cytotoxic T-lymphocyte-associated antigen-4, programmed death 1 or its ligand programmed death ligand 1, or low-dose chemotherapy). Of equal importance, they include methods that can enhance the specificity of antitumour immunity by inducing the expansion of T cells and antibodies directed to well-defined tumour antigens (e.g. cancer vaccines, potent adjuvants, immunostimulatory cytokines). Even as monotherapies, these approaches are having a substantial impact on the treatment of some patients with advanced, previously untreatable, malignancies. Most exciting of all, these successes provide a rationale to expect that used in various combinations or earlier in disease, current and future immunotherapies may transform cancer treatment, improving a prognosis for many patients.

    introduction
    Most people, and scientists are no exception, measure the passing of time by acknowledging substantial events from the past and looking towards future accomplishments. Using this ‘Janus’ principle, anniversaries that celebrate substantial events or are reminders of what remains to be done can be used to monitor the progress of scientific research. One reminder of the need for progress was recently marked by the 40th anniversary of the US National Cancer Act, a Senate Bill enacted on 23 December 1971 that strengthened the authority of the National Cancer Institute and provided it with new resources to create the National Cancer Program. The US National Cancer Act was prepared and passed in recognition of the serious problem that this lethal disease was posing with its ever-increasing frequency and apparent incurability. The expectation was that an increased understanding of the basic scientific nature of the cancer would be the best road to finding a cure. The bill also recognised the timeliness of this effort, coinciding both with rapid developments in many scientific disciplines and technological advances that appeared close to allowing the biological complexity of the cancer cell to be resolved.
    Forty years later, despite many brilliant discoveries around the world in fields as diverse as genetics and molecular biology, virology, chemistry, pharmacology and others, cancer continues to elude cures. However, the pace of scientific discovery and technological developments continues to increase and, as a result, the picture of cancer is being redrawn. Immunology, long considered not to be a critical discipline for understanding cancer, has provided important new clues to cancer biology and for the first time, immune-based therapy is a focus for pharmaceutical companies developing anticancer drugs.
    Until recently, investigations into the nature of cancer focused strictly on the cancer cell and on cancer as a genetic disease. This is perfectly illustrated in the widely cited and highly popular paper by Hanahan and Weinberg [1] published in 2000 that, after reviewing a large body of cancer research, proposed six consensus characteristics (hallmarks) that could be used to define a cell as cancerous. The hallmarks comprised the capacity to sustain proliferative signaling, to resist cell death, to induce angiogenesis, to enable replicative immortality, to activate invasion and metastasis, and to avoid growth suppressors.
    A decade later, and with increased emphasis on studying cancer as a systemic disease, there is a new understanding that cancer is not one disease, but many different diseases. Therefore, to understand cancer fully, studies must move their focus from the cancer cell to the host and the microenvironment in which the cancer grows; a very important component of which is the immune system. As a result, a new picture of cancer is emerging and, in 2011, four additional hallmarks were proposed. Two of these highlight the newly recognised dual interaction between cancer and the immune system: first, the ability to avoid immune destruction which results in acute inflammation and cancer elimination, and secondly, the potential for chronic inflammation that promotes tumour growth rather than elimination [2, 3].

    interactions between the immune system and cancer
    Evidence has been accumulating since the middle of the last century, first from animal models and later from studies in cancer patients, that the immune system can recognise and reject tumours. The goal of tumour immunology has been to understand the components of the immune system that are important for tumour immunosurveillance and tumour rejection to understand how, when, and why they fail in cases of clinical disease. Immunotherapy, which involves strengthening the cancer patient's immune system by improving its ability to recognise the tumour or providing a missing immune effector function, is one treatment approach that holds promise of a life-long cure [4].
    Studies of cancer–immune system interactions have revealed that every known innate and adaptive immune effector mechanism participates in tumour recognition and control [5]. The first few transformed cells are detected by NK cells through their encounter with specific ligands on tumour cells. This leads to the destruction of some transformed cells and the uptake and processing of their fragments by macrophages and dendritic cells. In turn, these macrophages and dendritic cells are activated to secrete many inflammatory cytokines and present tumour cell-derived molecules to T- and B cells. Activation of T- and B cells leads to the production of additional cytokines that further promote activation of innate immunity and support the expansion and production of tumour-specific T cells and antibodies, respectively. The full power of the adaptive immune system leads to the elimination of remaining tumour cells and, importantly, to the generation of immune memory to specific tumour components that will serve to prevent tumour recurrence.
    Effectors of adaptive immunity, such as CD4+ helper T cells, CD8+ cytotoxic T cells, and antibodies, specifically target tumour antigens; i.e. molecules expressed in tumour cells, but not in normal cells. Tumour antigens are normal cellular proteins that are abnormally expressed as a result of genetic mutations, quantitative differences in expression, or differences in posttranslational modifications [5]. In tumour types that have a well-documented viral origin, such as cervical cancer, caused by the human papillomavirus [5], or hepatocellular carcinoma caused by the hepatitis B virus [6], viral proteins can also serve as tumour antigens and targets for antitumour immune response [7].
    The first indication that tumours carried molecules distinct from those on the normal cell of origin was derived from immunising mice with human tumours and selecting antibodies that recognised human tumour cells but not their normal counterparts. The major question was whether some, or all, of these molecules would also be recognised by the human immune system. 2011 was an important anniversary for human tumour immunology, marking 20 years since the publication by van der Bruggen et al. [8] that described the cloning of MAGE-1, a gene that encodes a human melanoma antigen recognised by patient's antitumour T cells. This was not a mutant protein; its recognition by the immune system was due to the fact that it was only expressed by transformed, malignant cells and, with the exception of testicular germ cells, was not expressed in normal adult tissue. Many similar discoveries followed, with each new molecule providing a better understanding of what might be good targets for different forms of cancer immunotherapy. Tumour antigens have been tested as vaccines, as targets for monoclonal antibodies, and as targets for adoptively transferred cytotoxic T cells. There is a wealth of publications from preclinical studies targeting these antigens and results from phase I/II clinical trials. Recently, these studies were critically reviewed and a list of tumour antigens with the largest body of available data compiled [9]. The goal was to encourage faster progress in the design, testing, and approval of immunotherapeutic reagents that incorporate or target the most promising antigens.
    Antitumour immune responses in animal models and cancer patients have contributed to the resurgence of the immunosurveillance theory; albeit one that has been modified to encompass different observed outcomes. Instead of defining immunosurveillance as the process by which cancer is recognised and eliminated and a diagnosis of cancer to represent the failure of this process, it is now recognised that in different individuals and with different cancers, the process can have at least three different but related outcomes: elimination, equilibrium, and escape [10]. A highly immunogenic tumour in a highly immunocompetent individual will result in optimal stimulation of the innate immune system leading to the production of highly immunostimulatory cytokines, acute inflammation, activation of a large number of T- and B cells, and prompt elimination of the arising tumour. With a less immunocompetent individual and/or less immunogenic tumour, however, there might not be a complete elimination leading to the survival of some cancer cells that nevertheless remain under immunosurveillance. Over a prolonged period of time, the slow growth of the tumour would be accompanied by repeated activation of the immune system and elimination of some tumour cells, followed by further cycles of tumour regrowth and immune-mediated destruction. This period, when the tumour is present but not yet a clinical disease, is known as equilibrium. The equilibrium phase could be life-long, thus mimicking elimination, or be disturbed by changes in the tumour that allow it to avoid immunosurveillance or changes in the immune system that weaken its capacity for tumour surveillance. Either change ultimately leads to tumour escape (Figure 1).
    To date, most studies of tumour/immune system interactions have been performed after cancer has been diagnosed, i.e. in the escape phase of immunosurveillance. This particular phase is characterised by an increase in previously unknown immunosuppressive cells, such as regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), immunosuppressive cytokines derived from Treg, MDSC, and tumour cells and poorly functional effector T cells expressing molecules capable of preventing T-cell activation [11–13].

    immunotherapy: old and new
    In the past, immunotherapy was referred to as ‘passive’ (e.g. the infusion of preformed immune effectors, such as antibodies, cytokines, or activated T cells, NK cells, or lymphokine-activated killer cells), presumably acting directly on the tumour and independent of the immune system or ‘active’ (e.g. vaccines), designed to activate and therefore be dependent on the patient's immune system.
    However, with increased understanding of the importance of multiple immune effector mechanisms for tumour elimination and of the immunosuppressive forces that influence these mechanisms in the tumour microenvironment, it has since become clear that both passive and active immunotherapies depend on the patient's immune system for long-term tumour control or complete tumour elimination.
    By directly targeting specific antigens expressed by cancer cells, anticancer monoclonal antibodies are a well-established class of immunotherapeutic agent; more than a dozen of which have been approved by the Food and Drug Administration as standard treatment of several different cancers, including trastuzumab for breast cancer and retuximab for B-cell lymphoma [4]. Although the mechanism of their direct antitumour action has been well studied and is clearly responsible for transient remissions in patients receiving this therapy, cure rates are still very low. The potential of these antibodies is drastically undermined by their administration relatively late in the disease course, when the patient's immune system is largely compromised. Under more optimal conditions, antibody treatment might result not only in the direct cytostatic or cytotoxic effect on the tumour cell, but also in the loading of antibody-bound tumour antigens onto antigen presenting cells (APC) in the tumour microenvironment. The resultant cross-presentation to antitumour T- and B cells could result in additional antibodies to these antigens being produced, and propagation of the immune response at the tumour site would maintain tumour elimination long after the infused monoclonal antibody is gone. Not only would the response change from a monoclonal antibody against a single epitope to a polyclonal response to multiple epitopes, thus avoiding antigen-negative tumour escape, but the effector T-cell response would also generate memory.
    The same scenario could be predicted for adoptively transferred T cells. Unlike antibodies, transferred T cells persist longer and may provide a memory response [14]; however, as long as the memory response is restricted to one clone, or a limited number of clones, then antigen-negative tumours will be able to escape. In addition, cancer vaccines encounter large numbers of immunosuppressive Treg and MDSC in circulation, as well as immunosuppressive cell-derived soluble products that flood the lymph nodes, preventing maturation of APCs and activation of T cells. Even when vaccines are delivered in the context of ex vivo matured and activated dendritic cells, their ability to activate T cells is compromised by the high-level expression of various molecules on T cells that block this process.
    The scenarios proposed above present a rather bleak picture of the potential of immunotherapy to achieve the cure for cancer that has eluded standard therapy [15]. Interestingly, failures of some standard therapies are beginning to be ascribed to their inability to activate the patient's immune system [16]. However, rather than seeing the picture as a deterrent, it should be considered as a road map, providing at least two major directions for new developments in immunotherapy.
    The first direction is to continue using the old classes of immunotherapy that target the cancer directly, but to use them in combination with therapies that target the immune system in the tumour microenvironment, such as cytokines, suppressors of Treg or MDSC activity, or antibodies that modulate T-cell activity. The recently approved antibody, ipilimumab, which acts to sustain cytotoxic T-cell activity by augmenting T-cell activation and proliferation, is one example of such an immunomodulatory agent [17].
    The other direction is to use immunotherapies, both old and new, for preventing cancer in individuals at high risk [18]. Studies of the tumour microenvironment are providing information about immunosurveillance of tumours from early premalignant lesions to more advanced dysplastic lesions to cancer. At each step, tumour-derived and immune system-derived components have a unique composition that will have distinct effects on immunotherapy. Because these premalignant microenvironments are less developed and immunosuppression is less entrenched, it should be easier to modulate towards the elimination of abnormal cells.
    The lessons learnt from past accomplishments suggest that in the future, well-designed immunotherapies, administered at the right stage of tumour progression, have the potential to significantly change the ongoing immune response in the tumour microenvironment from tumour-promoting to tumour-rejecting (Figure 1).


    http://annonc.oxfordjournals.org/content/23/suppl_8/viii6.full
  • David
  • Cincia #70 這篇值得細讀
  • David
  • 本來以為樹突細胞(DC)是促進免疫反應的推手 這週末才驚訝的發現
    原來在腫瘤得以擴散前 腫瘤附近的樹突細胞和巨噬細胞都已被腫瘤收買
    非但不促進免疫反應 反而抑制免疫反應
    一部份的T細胞也被收買成為調節型T細胞(Treg) 抑制免疫反應
    一旦腫瘤收買免疫機制 從此身體裡再也沒有可以阻止它擴散的力量
    所幸Anti PD1 Anti CTLA4藥物已經問市 即使DC被收買也不能抑制T細胞活化

    我深深感覺一種免疫治療是不夠的
    多種免疫治療Anti CTLA4 Anti PD1 DC 療法 IL-2 才能喚醒免疫系統
    或者免疫治療搭配標靶 或電腦刀 或放療


    Dendritic cell switch

    DCs from mice in the early stages of ovarian tumorigenesis were immunocompetent (as measured by their ability to induce expansion of tumour-reactive T cells). Immunocompetence was lost by DCs in advanced tumours, and these DCs could also suppress the T cell expansion that was induced by immunocompetent DCs from early stage tumours.
    How do DCs change to become immunosuppressive? DCs from advanced mouse tumours expressed higher levels of programmed death ligand 1 (PDL1) and had strong arginase activity, both of which are immunosuppressive. High arginase activity was also observed in DCs taken from advanced human ovarian

    Source: http://www.nature.com/nrc/journal/v12/n4/full/nrc3253.html
  • 是阿~上次蔡主任就有提到他認為應該主動免疫搭配被動免疫兩者一起治療效果會最佳,只是單一就已經很貴了,加在一起負擔的起的病患真很少。

    Cincia 於 2015/07/14 09:59 回覆

  • catwalk01
  • David: Thanks for the sharing. Most of people belong to "quiet majority" category. I read most of your post and benefit from there.
  • David
  • #73 catwalk01
    Thank you . I will continue post my latest study on these important topics.
  • David
  • 腫瘤是怎樣抑制免疫系統 跟癌症擴散息息相關
    一旦腫瘤能抑制免疫系統 從此身體裡再也沒有可以阻止它擴散的力量
    所有罹癌的朋友的免疫系統都無法對體內的癌症產生有效免疫反應(進行攻擊清除)
    即使你現在的吃的健康 有充足睡眠 也有運動 不常感冒 有感冒也很快能痊癒
    你的免疫系統的確是運作正常的 能有效清除外來的細菌病毒
    但是你的免疫系統卻任由腫瘤擴散 問題出在哪裡?
    有些醫生說基因突變的癌細胞是屬於自己的基因
    免疫系統認不得它是外來物 所以不會攻擊癌細胞
    我只能說這醫生大概很久沒讀書沒看醫學報告了
    根據Nature突變的癌細胞有上千種能被免疫系統認識的抗原
    也就是說癌細胞有上千種方式激起可以攻擊腫瘤的免疫反應
    但是為什麼免疫系統對腫瘤視而不見呢?
    到這裡我們得先瞭解一下在正常情況下免疫系統是如何運作的
    當癌細胞死亡時 細胞膜裡面的突變不正常的蛋白質外洩
    會被身體的清道夫巨噬細胞 或是免疫系統的哨兵樹突細胞吞噬
    巨噬細胞或樹突細胞消化後會把這些蛋白質片段(抗原)承現在它的細胞膜上
    然後會經由血液淋巴液回到最近的淋巴結把抗原承現給T 細胞和B細胞
    如果某一個T細胞 或B細胞表面的氨基酸能接合樹突細胞或巨噬細胞帶回的抗原
    這個T細胞B細胞 開始被激活 開始大量繁衍自己
    繁衍出兩 類T細胞 一種是 毒殺型T細胞 能夠辨識擊殺有同樣抗原的癌細胞
    另一類T細胞 是輔助型T細胞 它的功能是分泌介質促進B細胞 和T細胞 繁衍
    好啦 如果照著正常運作 免疫系統沒有理由對腫瘤視而不見
    的確 如果是外來的細菌病毒 免疫系統就是照著上述正常運作方式
    激起免疫反應B細胞繁殖大量抗體清除血液裡的外來物
    毒殺型T細胞攻擊被病毒入侵的細胞
    但是癌細胞是身體反叛的細胞 知道如何抑制免疫系統
    實際上腫瘤是利用正常的免疫機制來壓抑免疫系統
    腫瘤微環境能分泌介白素引起慢性發炎吸引 調節型T細胞和MDSC細胞 的聚集
    抑制毒殺型T細胞 和T helper細胞繁衍
    在腫瘤聚集的巨噬細胞或樹突細胞也受到腫瘤微環境的影響
    改變成抑制型的
    抑制型的巨噬細胞或樹突細胞如何抑制免疫反應呢?
    當這些抑制型的巨噬細胞或樹突細胞的表面有PDL1
    (大家應該都知道PDL1是讓T細胞失去攻擊性)
    回到淋巴結把抗原承現給B細胞 和T細胞 辨識時
    一邊承現癌細胞的抗原 一邊用解除已活化的毒殺型T細胞 和輔助型T細胞
    這好像哨兵回報將軍時 一手拿著敵人的畫像 另一手拿刀刺死將軍
    在老鼠實驗 研究人員發現 抑制型巨噬細胞或樹突細胞出現
    伴隨著腫瘤快速擴展
    巨噬細胞或樹突細胞被腫瘤收買後會積極為腫瘤消滅殘存的免疫反應
    從此身體裡再也沒有可以阻止它擴散的力量
    唯有經由多種免疫療法 AntiPD1, AntiCTLA4, DC therapy, T cell therapy, IL2
    配合標靶 電腦刀 破壞腫瘤微環境
    才能扭轉局勢
  • David
  • Today, seven pharmaceutical companies are testing PD-1 drugs on more than two dozen cancers, from bladder to ovarian to bone. Two received FDA approval in the past year.

    M.D. Anderson specialists in lung cancer are now dropping everything else to focus on immunotherapy, says Heymach, chairman of the hospital's thoracic/head and neck medical oncology department. He's never seen anything like it.

    "More than anything else in lung cancer's history, it's changing the course of what we're doing," he says.
  • David
  • Deciphering and Reversing Tumor Immune Suppression

    Immunity
    Volume 39, Issue 1, 25 July 2013, Pages 61–73

    Generating an anti-tumor immune response is a multi-step process that is executed by effector T cells that can recognize and kill tumor targets. However, tumors employ multiple strategies to attenuate the effectiveness of T-cell-mediated attack. They achieve this by interfering with nearly every step required for effective immunity, from deregulation of antigen-presenting cells to establishment of a physical barrier at the vasculature that prevents homing of effector tumor-rejecting cells and the suppression of effector lymphocytes through the recruitment and activation of immunosuppressive cells such as myeloid-derived suppressor cells, tolerogenic monocytes, and T regulatory cells. Here, we review the ways in which tumors exert immune suppression and highlight the new therapies that seek to reverse this phenomenon and promote anti-tumor immunity. Understanding anti-tumor immunity, and how it becomes disabled by tumors, will ultimately lead to improved immune therapies and prolonged survival of patients.

    Click here for full text
    http://www.sciencedirect.com/science/article/pii/S1074761313002896
  • 訪客
  • 標準治癌免疫療法簡介, 尤其日本衛生部專利認證之新法制作的自體樹狀細胞疫苗,皮內皮下注射, 配合專利新法制作之自體活性NK細胞點滴療法介紹, 優點是
    1. 對任何癌, 對任何程度, 初期到末期, 即使第4期皆有效
    2. 可與各式癌療法, 包括手術, 化療, 放射療, 漢方等療法配合使用
    3. 沒有任何副作用
    4. 可一再施打

    請參閱本網文章及 http://www.abecancer.com/
    あべ腫瘍内科クリニック is great because

    為製作成熟的病患自體樹狀細胞疫苗,目前一般是採用類似血液淨化(apheresis)方式,兩側手臂血管與類似洗腎機的大型機器連結,將全身血液抽到機器內,單次採取足夠的單核球,冷凍保存,此過程需2-3小時,有危險性,尤對癌末病人是一大負擔。阿部醫師以其已獲得日本衛生部專利認證書的名為「多價樹狀細胞疫苗製作法」,是最高效能的癌症免疫療法。只需抽取25cc周邊靜脈血液,以培養後的疫苗,注射投與,經連續6次,每兩週1次的採血及注射,每次皆能不斷提昇樹狀細胞數量及免疫力,不但安全,而且培養的疫苗新鮮,質量皆佳。他以先進專利細胞培養技術,將單核球附加長鏈癌細胞胜肽(peptide),胜肽是人工的癌抗原,製作成為樹狀細胞,再將此培養後的成熟樹狀細胞接種注射到此病人癌附近的皮下淋巴節內,則此樹狀細胞擔任司令官角色,教導病人體內的T淋巴球,認識癌抗原,成為細胞傷害性淋巴球(CTL),對標的細胞,也就是癌細胞集中攻擊。多價的意思是以其專利技術製作的樹狀細胞,可附加5種以上癌症抗原胜肽。以阿部醫師的方法,於第一次注射時,疫苗中的樹狀細胞數每cc即可高達1千萬個以上,有效細胞率97%以上。並以此抽取的血液, 使用獲專利之新法, 制作新活性NK 細胞點滴療法; 阿部醫師由2002年起以其附設研究室,設置與國家級研究機關同水準的細胞培養技術單位(cell processing center,CPC),防止免疫細胞遭受細菌及病毒污染,已獲數項ISO認證。 病人有從韓國、美國及台灣來看診。他也接受國內外合作醫院委託製作疫苗。有任何問題可寫英日或中文, fax:002-81-3-6380-8032去給他本人, 阿部博幸教授會專答, 也可用中文接受診療, 他懂中文
  • 訪客
  • あべ腫瘍内科クリニック 、對於已有復發或轉移者,建議疫苗療法為首選療法。配合
    Opdivo(Nivolumab)是抗PD-1抗體, 目的是強化疫苗的効能、譲疫苗発揮100%効能


    於あべ腫瘍内科クリニック常規使用於任何癌, 作法是以其研究室製作的新樹狀細胞疫苗皮下淋巴內注射及新NK細胞點滴後, 續點滴Opdivo, Opdivo 1 支40mg, 4cc, 分成 5次點滴, 每次隔 3 週 , 每次抽0.8cc, 8 mg, 混入 100 cc 生理食鹽水 , 點滴30分鐘, 唯需配合他的新樹狀細胞疫苗皮下淋巴內注射及新NK細胞點滴、也可増成每次 20 mg
  • 訪客
  • 到2015現在為止、治癌免疫療法已有標準化、多價樹狀細胞疫苗療法皮下注射、配合自體活性NK細胞點滴及抗PD-1抗體Opdivo(Nivolumab)點滴。一点都不複雑。科学進歩只有這様子。
  • 訪客
  • 多價樹狀細胞疫苗療法皮下注射、配合自體活性NK細胞點滴及抗PD-1抗體Opdivo(Nivolumab)點滴, 台湾都無、最近的是日本
  • 訪客
  • 再次向病友說明令人擔心之點, #79 訪客説的阿部教授是執行醫療, 他掛心的是病人能不能被他治好,所以當然選對各該病人最有利的治療方式 , 讓病人能早日康復, 而日本的大學附設醫院在做試驗, 極可能病人被分配到無效組或未知效果組, 那就慘了, 兩者就差在此 、我這様説実話、引起恐慌、只好説対不起。
  • 請問一下有認識的人過去找阿部教授治療的嗎?成效如何呢?
    Cincia想多收集資料看看,不過關於阿部博幸教授資料好少阿!日文網站居多,但有看沒有懂阿!-_-!

    Cincia 於 2015/08/13 17:59 回覆

  • 訪客
  • 我是在某大學醫學中心服務的腫瘤科主任, 剛好今天台風天, 下午病人少一點, 本來都上百的, 我閒著, 瀏覽一下網頁, 突然發現有這個網頁, 很多癌友, 遠赴久留米與千葉, 覺得很好奇, 又發現有一位自稱訪客的,推崇在台灣頂頂大名的日本免疫治癌專家阿部博幸教授, 這位訪客書寫有關癌症免疫及阿部醫師的治療方式簡潔扼要切題, 我想他極可能也是位資深腫瘤醫師, 我再看這位訪客寫的, 我深深的必須呼應強調的是, 就像他說的, 病人當然有自由選擇看病的地方的權利, 但在世界上哪裡都一樣, 醫學中心做的事就是臨床試驗, 久留米與千葉也不會例外, 試驗一定需分組, 有一半當然是被選為無效組, 這是一定的, 那位訪客說明有關阿部醫師治療的方式一點都沒錯, 阿部醫師不是做臨床試驗, 每位病人接受他的治療當然會很有效, 但我所知, 要接受阿部醫師治療, 可能還是得親自去日本找他, 因為這位訪客講的韓國模式在台灣可能還行不通
  • 訪客
  • 既然有位新訪客, 那弊人就用自謙用原訪客吧, 韓國模式需有在台灣的代理商 , 及在台灣的醫師, 代理商拿著醫師抽的病人25cc血, 親送日本到阿部教授處, 以其獲日本厚生省專利認證的新法製作疫苗, 於兩週後, 把製作好的新鮮疫苗, 於24小時內送回台灣讓原抽血醫師為病人施打, 到2015現在為止, 治癌免疫療法已有標準化, 多價樹狀細胞疫苗療法皮下注射、配合自體活性NK細胞點滴及抗PD-1抗體Opdivo(Nivolumab)點滴。一点都不複雑。科学進歩只有這様子。
  • 新訪客
  • 原訪客有反應了, 那我就用新訪客; 治癌免疫標準療法就是, 以樹狀細胞疫苗療法皮下注射, 最好是皮內注射, 配合自體活性NK細胞點滴及抗PD-1抗體Opdivo 點滴, 對於任何癌症之任何stage都一樣, 治癌免疫醫學之目前進歩就只有這様子。阿部博士就是採此標準療法, 而以專利認證的新法製作, 半年前來台灣的醫學會做專題演講時已說過

  • 新訪客
  • 請問原訪客, 您是不是也是腫瘤科醫師, 您說台灣近期不太可能開放癌症免疫療法, 原因我所瞭解的當然是不可能健保給付, 至於不太可能開放我同意就您所說的, 因在台灣社會不太能接受有錢人才能接受這種治療, 另一個原因是怕有非合格醫師亂來, 政治多事之秋, 主管機關多一事不如少一事的心態, 阿部來多做幾次演講或許可以催生吧

  • 訪客
  • 回答新訪客, 弊人不能透露名字, 其實我們應本來就認識, 阿部好像很忙, 今年年底前不太可能再來
  • 新訪客
  • 您與阿部很熟嗎, 我想帶幾位年輕醫師去他CPC參訪學習
  • 訪客
  • 回答新訪客, 您可與他直接聯繫
  • 訪客
  • 請問新訪客, 您覺得在台灣要有代理商那麼困難嗎
  • 新訪客
  • 我不敢回答, 會不會被追蹤, 反正我也不當代理商
  • 新訪客
  • 在學會大家見面公開談吧
  • 訪客
  • 請問新訪客, 上次阿部演講時說免疫療法對復發及轉移最有效, 您認為呢
  • 新訪客
  • 我個人覺得應是手術, 放療, 化療過後, 腫瘤有縮小, 為防復發及轉移時最有效, 阿部說的應是他的經驗, 為凸顯以其新法治療時, 甚至有復發及轉移皆會有效, 不過演講時, 他的數據就顯出他說的沒錯, 也許是他用他最近研發成功的日本衛生部專利認證過的新法, 才那麼有效吧
  • 新訪客
  • 下次他來時應可再看到他的新數據吧
  • 期待有新數據可以分享廣大的癌症戰友參考,謝謝主任。^__^

    Cincia 於 2015/08/10 16:23 回覆

  • 訪客
  • 美女,有高手決戰光明頂了,趕快搬椅子來看。
  • cecilia188
  • 不好意思借星星的版提問,
    請教兩位醫師,如果想找阿部醫師治療,是不是直接透過上面提到的傳真,要傳那些資料,完整病歷嗎,還是可以直接寄去日本,不好意思我沒這方面經驗,還請不吝指教,謝謝您們。
  • 訪客
  • To cecilia188,  傳真 is OK,

    不要完整病歷、手写、要傳: 病名、簡単治療経過、有無接受過免疫治療、最近診察時医師説目前状態 (復発、転移有無)
  • 訪客
  • 有任何問題可寫英日或中文, fax:002-81-3-6380-8032去給他本人, 阿部博幸教授會專答, 也可用中文接受診療, 他懂中文 、不要客気、附上e-mail可能他比較方便
  • cecilia188
  • 醫生很感謝您哦!
    星不好意思。
  • 不會啦!姊決定要嘗試看看嗎?

    Cincia 於 2015/08/10 16:21 回覆

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