景德製藥204張藥證1.35億售 健喬信元/ 廠房1.8億售 安成藥業

健喬拚併購 擴大市占 2017-12-04 00:19經濟日報 記者黃文奇／台北報導 健喬併購再啟，擴大產品戰線。健喬信元1日宣布新的併購案，以1.35億元收購景德製藥旗下204張、全數台灣藥證，包含其主力眼科製劑。業界認為，健喬此次納入景德產品線後，將大幅度提升台灣藥品市場競爭力，對未來公司營運將有一定程度的貢獻。健喬表示，景德製藥於2016年營收高達3.6億元，其中，以眼科製劑為主力，約占了營收26%，其次則為抗感染製劑19%、中樞神經製劑15%、腸胃道製劑14%，還含皮膚外用製劑等約占25%，產品布局完整、市場銷售佳且獲利穩健。健喬表示，此次收購案除著眼於布局完整劑型、強化產品組合外，並將整合藥證通路，擴大市場版圖，加乘產品獲利能力，發揮併購綜效。健喬專攻特色學名藥，此次收購看中的便是景德極具市場價值的產品組合，及穩定發展的通路。景德製藥為國內老牌製藥廠，成立於西元1965年，2001年由台泥企業集團旗下之中橡公司接手後，力求轉型，原有業務從原料藥、中藥及西藥製劑成品，積極轉型為生產及行銷新藥、新劑型，並深耕國內市場，旗下主要醫療院所與藥局銷售通路數逾3,000家，布局多元完整。 今年11月初，安成藥業宣布以1.8億元併購景德製藥，健喬表示，安成所併購的是廠房，其他的藥證則由健喬接收，目前已經完成藥證所有權的轉換，下一步將規劃把部分產品線轉到健喬廠房生產，提升營運動能。健喬強調，透過本次併購案，健喬除可新增眼科製劑產品及通路，加速擴大旗下各劑型藥品市場版圖，同時完整布局自身既有產品領域，無縫接軌的產品生產與市場銷售，將可強化健喬營收與獲利的成長潛力。健喬信元1970年成立，旗下擁有鼻噴劑等多個平台，近年來多次併購持續壯大自身產品戰線，前身為信元藥品，2001年與健喬藥品子公司「佩德貿易」合併後變更為現名，為國內極具利基的學名藥廠之一。 健喬於今年9月間，就宣布以1.28億元金額收購健康化學製藥的39.03%剩餘股權，將後者納健喬信元100%子公司，力拚「浣腸類」國內外市占率，該廠主要鎖定「浣腸、軟乳膏」劑型。

安成藥業 發言日期106/12/01 發言時間18:35:22 發言人欒君儀 發言人職稱投資人關係處長 發言人電話02-2657-3350主旨 補充：代子公司景德製藥公告董事會決議處分所持有之藥品許可證暨相關權利以及相關應收帳款債權及存貨 符合條款 第 20款 事實發生日106/12/01 說明1.標的物之名稱及性質（屬特別股者，並應標明特別股約定發行條件，如股息率等）: 藥品許可證暨相關權利以及相關應收帳款債權及存貨 2.事實發生日:106/12/1~106/12/1 3.交易數量、每單位價格及交易總金額: (1)交易單位:不適用。(2)每單位價格:不適用。(3)交易總金額: 338,920,000元(含稅)。4.交易相對人及其與公司之關係（交易相對人如屬自然人，且非公司之 關係人者，得免揭露其姓名）: 健喬信元醫藥生技股份有限公司 5.交易相對人為關係人者，並應公告選定關係人為交易對象之原因及前次移轉之所有人、前次移轉之所有人與公司及交易相對人間相互之關係、前次 移轉日期及移轉金額: 不適用 6.交易標的最近五年內所有權人曾為公司之關係人者，尚應公告關係人之取 得及處分日期、價格及交易當時與公司之關係: 不適用 7.本次係處分債權之相關事項（含處分之債權附隨擔保品種類、處分債權 如有屬對關係人債權者尚需公告關係人名稱及本次處分該關係人之債權 帳面金額: 不適用 8.處分利益（或損失）（取得有價證券者不適用）（原遞延者應列表說明 認列情形）: 預計約新台幣1千3百萬元(此處分利益尚未經會計師查核) 9.交付或付款條件（含付款期間及金額）、契約限制條款及其他重要約定 事項: 依合約條件收款 10.本次交易之決定方式、價格決定之參考依據及決策單位: 董事會決議 11.迄目前為止，累積持有本交易證券（含本次交易）之數量、金額、持股 比例及權利受限情形（如質押情形）:不適用 12.迄目前為止，依「公開發行公司取得或處分資產處理準則」第三條所列之有價證券投資（含本次交易）占公司最近期財務報表中總資產及歸屬 於母公司業主之權益之比例暨最近期財務報表中營運資金數額（註二）: 不適用 13.經紀人及經紀費用: 不適用 14.取得或處分之具體目的或用途: 強化核心業務、提升組織效率並增加經營效益 15.本次交易表示異議董事之意見: 不適用 16.本次交易為關係人交易:否 17.董事會通過日期: 不適用 18.監察人承認或審計委員會同意日期: 不適用 19.本次交易會計師出具非合理性意見:否 20.其他敘明事項: 本案須待子公司景德製藥股份有限公司股東臨時會決議通過後，始得進行交割。

健永(植物新藥) 退出 台灣資本市場 目標美國掛牌

健永將撤興櫃 尋求那斯達克掛牌 發稿時間：2017/12/01 （中央社記者韓婷婷台北1日電）健永今天於櫃買中心召開重大訊息記者會，董事長郭富鳳宣布，決定走向海外市場，已申請終止興櫃股票，目前規劃2018年申請美國藥證，2019年申請那斯達克掛牌。 健永在台灣上櫃市場申請掛牌受挫，今天宣布終止興櫃買賣，擬轉向申請美國那斯達克掛牌，正式終止買賣日期將由櫃買中心另行公告。 郭富鳳表示，健永於2014年登錄興櫃，目前台灣及美國的第三期臨床試驗順利完成，全球專利也陸續完成布局，利於彰顯新藥價值的趨勢下，相信唯有走向更大的世界舞台，才能贏得真正的尊重。郭富鳳表示，目前健永男性前列腺（即攝護腺）增生適應症的新藥已在今年7月開始正式提出台灣藥證申請，美國藥證申請則預計在資料彙整完成後展開，初步預計會在明年度送件申請，另外一項有關預防癌症的新產品，第二期臨床也於2014年11月於衛生福利部食品藥物管理署核准下展開。郭富鳳認為，健永有條件走向海外，主要是已經成功完成台灣及美國共計4個第三期臨床試驗，可以單獨作為第一線處方用藥，也可以與現有藥物併用，具有相當的獨特性；從臨床開發到品質控管CMC都根據美國FDA嚴格要求；第三點則是已具有全球多國「醫療組合物」的專利，未來還會陸續取得更多國家20年的專利保護。郭富鳳表示，健永2014年興櫃掛牌價是128元，目前在外流通股票約有8000多張是不可控的股權，接下來會進行組織重整讓股東權益獲得保障而且會更好，實際詳細配套措施將待股東會時做進一步說明。

微創半髖關節置換手術 術後恢復快、住院天數短

微創正前開髖關節置換手術 勁報 2017/12/03【勁報記者于郁金/連凱斐/臺南報導】年紀高達89歲的田伯伯，因行動不便，在家裡滑了一跤，感覺到右側鼠膝部劇烈疼痛，無法行走，因而到急診就醫；在檢查之後，發現右側股骨頸移位性骨折，需要進行半髖關節置換手術；另一位65歲的薛姓阿嬤不小心被絆倒，摔傷了右手及左側臀部，經檢查發現右手掌骨骨折，及左側股骨頸移位性骨折，無法行走；還有55歲的余姓男子，因業務交際需要，常需飲酒，結果長期酒精習慣，左側股骨頭缺血性壞死，疼痛不堪，而施行全髖人工關節置換手術。新樓醫院骨科楊睿明醫師說：在年事已高的老人家常見合併有骨質疏鬆，跌倒常常是壓垮身體的最後一根稻草。美國骨科醫學會發現只有約2成老人家的髖部骨折病患，可以重回受傷前的活動狀態；多篇研究也顯示髖部骨折的病患接受手術，以增加活動量或是提早下床活動可增加1年內的存活率；近10年來，正前開髖部關節置換微創手術已經成為手術風潮，因為在更小的傷口及更少的組織破壞，依舊可以順利完成手術；拜微創的技術所賜，病人所需要的恢復期也較短，也縮短住院天數及術後的復健療程。在微創手術結束後隔天，田伯伯已經可以利用助行器行走，也可將大腿抬高跨步，完成正常的行走步態；較年輕的薛阿嬤也在2 4小時內可以單手扶助行器行走並抬腿跨步；至於，左股骨頭缺血性壞死的余先生，經全髖人工關節置換術後四小時，就可下床行走。由於微創手術破壞較少的肌肉群，傳統手術後的大腿前側肌肉疼痛大幅下降，復健難度下降，病患下床行走意願也自然大幅提高，進而減少病患臥床時間及比例。楊睿明醫師說明，微創半髖關節置換手術傷口小、組織破壞少、疼痛降低、出血量少、術後恢復快、住院天數短，已經成為新一代關節置換手術的潮流，而全髖關節手術，可以使用微創方式進行，也可以達到較傳統手術更佳的療效。

 

抗體檢測HIV陰性 之 愛滋病Kaposi’s Sarcoma

陽性確診為HIV？大陸首見「陰性」愛滋患者  謝婷婷 2017-12-03  大陸發現首例「陰性」HIV合併卡波西氏肉瘤的愛滋患者。病毒抗體檢測為普遍篩檢HIV的方式之一，結果若是陽性則是感染、反之亦然，這也是絕大多數人判斷的常識。不過，北京協和醫院最近發現了一例抗體檢測為陰性，但經過核酸檢驗後卻是陽性，成為全球首例確診為HIV「陰性」合併卡波西氏肉瘤（KS）的愛滋病患者。 HIV抗體檢測為陰性，卻依然感染了愛滋病。北京協和醫院在最新一期《臨床呼吸雜誌》（Clinical Respiratory Jounal）發表特殊案例。據研究報告指出，2011年一名46歲男性患者因喉嚨痛、咳血、發燒伴隨呼吸困難2個月，經抗體檢測初篩為可疑陽性，但確證為陰性，之後經由醫師判斷為肺部感染，改用抗生素及抗結核治療，病情卻終始沒有起色。最後該男子輾轉到北京協和醫院，從X光片中發現陰影，在進行肺部穿刺後發現造成男子肺部病變的是卡波西氏肉瘤（Kaposi's Sarcoma），此病好發於HIV感染者。該男子在入院後10天才被確診為愛滋病患者，可惜病情已發展到愛滋病末期，此名男子在確診兩週後死亡。北京協和醫院感染內科李太生教授表示，KS是HIV感染者或愛滋病（AIDS）患者最常見症狀之一，也是末期病患主要的病徵。但由於初次篩檢都未顯示陽性反應，於是排除了愛滋可能，表示以一種科學檢測來判斷是否感染HIV，對於某些族群仍是鞭長莫及。 李太生指出，該案肯定HIV核酸檢驗在愛滋病診斷中的重要價值，但他並不建議作為愛滋病常規篩檢的診斷方法。他認為是愛滋母親產下的親生兒、超過3週以上空窗期的檢驗方式，以及臨床表現類似愛滋病的晚期患者，以上3類族群適用核酸檢驗。不過，目前核酸檢驗在大陸仍不普及，只有省級的最高等醫院才有此技術，而且費用比一般檢驗方式更高，建議高風險群族定期篩檢才是保命之道。（謝婷婷/綜合外電報導）

 

握有長庚醫院主導權 掌控集團大金庫

長庚持股逾2800億 難與台塑清楚切割 2017/12/03  長庚醫院爭議不斷，引發外界諸多質疑，儘管台塑集團不斷強調長庚醫院與台塑企業各自獨立運作、互不相干，但攤開兩家公司董監名單可發現，除王家成員，醫院與集團各企業彼此派員進駐董事會，且長庚長期為台塑四寶大股東，持股市值超過2800億元，可說是台塑集團大金庫，兩者在短期內不易清楚切割。

掌醫院如掌金庫 長庚持有集團股票來自創辦人王永慶及王永在所捐贈，目前長庚主要出任台塑、台化及台塑化各1席董事，至10月底對3家公司持股各為9.44%、18.58%及5.79%，另雖未在南亞出任董事，但持股也高達11.05%，長庚合計持有台塑四寶股票市值超過2800億元，外界認為，握有長庚醫院主導權，就掌控集團大金庫。至於長庚董事名單，包含王瑞慧在內共5席為王家代表、5席為醫師代表及5席社會賢達，社會賢達中有3席由台塑董事長林健男、南亞董事長吳嘉昭及台化副董事長洪福源出任，其餘2席為具有醫師身分的賢達人士。長庚將於近日董事會提出請辭3家公司董事，除現有股權將不行使投票權，也不再加碼關係企業持股，儘管宣示醫院不介入關係企業營運，但要扭轉因爭議重挫的形象，長庚恐還有一段路要走。 財經中心

郭旭崧 副教授 相當教授條件 出任 陽明校長

陽明校長資格爭議 潘文忠：尊重遴委會 2017年12月01日  【記者江禹嬋／台北報導】針對陽明大學選出衛生福利部疾病管制署署長郭旭崧擔任新教長，卻因郭旭崧僅為副教授，不符校長遴選資格而引起爭議。對此，教育部長潘文忠表示，尊重遴選委員會的決定，否認施壓、干預。 陽明大學校方也發布聲明稿澄清，郭旭崧符合「相當教授之教學與學術研究」條件。教育部11月27日發函陽明大學，要求校方補充郭旭崧的資格資料，使郭旭崧無法如期於12月1日上任。 潘文忠接受媒體訪問時提到，因郭旭崧是以兼任講座教授的資格參與遴選，在任用的條件上有特殊性，因此，教育部才會請遴選委員會進一步釐清確認。對於部分立委質疑教育部施壓，潘文忠認為，遴選委員會依專業自主選出校長，沒有誰能施壓、干預。 教育部次長林騰蛟日前受訪時也解釋，教育部認為有必要再請遴選委員會檢附相關佐證資料，遴委會將於近期再召開一次會議。此外，認定候選人資格是遴選委員會的職責，遴委會確認相關資格程序沒有疑義後，報到教育部，教育部就會立即依法聘任。

蘋果布局醫療產業: Apple Watch測心律不整/ 第一款醫療認證 Apple Watch配件: Kardia Band (AliveCor)

蘋果與史丹佛大學合作醫學研究，用Apple Watch隨時偵測心律不整 文/林妍溱 | 2017-12-01發表 Apple Watch的感測器利用每秒閃爍數百次的綠LED光及光電二極體來偵測手腕上的血流。該感測器會蒐集手腕上4點的訊號，配合軟體演算法將心律訊號獨立出來，藉此發現不規則的心律。Apple Watch不再只是單純的消費電子！蘋果周四公佈心臟研究（Heart Study）app，將支援第一個利用Apple Watch蒐集心律不整資料進行的研究。這個app將用於蘋果和史丹佛大學醫學院的一項合作研究。本項研究針對年滿22歲的第一代Apple Watch以上的用戶進行，目前在美國App Store上架。當受試者配戴的Apple Watch偵測到心律不整時，會透過Apple Watch及iPhone通知他們可能有心房纖維顫動（Atrial fibrillation，AFib）的風險，以便進行安排免費的醫師諮詢及進一步心電檢查。心房纖維顫動是中風首要元兇，每年在美國造成近13萬人死亡、75萬人入院，但病患往往事先沒有癥兆。過去必須由醫護人員在受試者身上貼上心電圖（ECG）貼片來蒐集並形成ECG訊號來判斷心律狀態，不過近年愈來愈多消費電子廠商發展出可量測ECG的穿戴裝置，因此蘋果Apple Watch加入也只是時間問題。 Apple Watch的感測器利用每秒閃爍數百次的綠LED光及光電二極體來偵測手腕上的血流。該感測器會蒐集手腕上4點的訊號，配合軟體演算法將心律訊號獨立出來，藉此發現不規則的心律。史丹佛醫學院長Lloyd Minor指出，這項研究將有助於探索Apple Watch心率感測器之類的科技是否能將精準研究拉到更新層次。而配合Apple Watch的消息，美國食品藥物管理署（FDA）也於本周核准穿戴健康管理設備商AliveCor推出的Kardia Band在美上市。售價199美元的Kardia Band是一個整合ECG感測器的Apple Watch腕帶，能在30秒內量測用戶的心電圖並顯示於Apple Watch上，是第一款具備醫療認證的Apple Watch配件。這是蘋果踏入健康照護領域的最新成果。之前，蘋果陸續發表ResearchKit、CareKit，供醫療及健康照護業者分別開發帕金森氏症等研究及用藥或生理資料蒐集的app。蘋果表示，迄今已經有500位多研究人員及超過300萬用戶使用ResearchKit及CareKit平台。

 

台英 專利申請 生物材料寄存 相互承認 !

加快生技業專利布局 台英簽署生物材料寄存MOU 2017年12月03日 00:05 中時 王玉樹 生物科技業的佳音。經濟部智慧財產局訪歐，與英國簽屬「臺英專利程序生物材料寄存相互合作瞭解備忘錄」，是我國生技類第2個專利合作MOU。未來雙方生技業者可將開發疫苗存在本國，相互承認活體效力，方便申請專利，免去現在疫苗要攜往國外，舟車勞頓的成本與風險，有助於我在國生技、醫藥、食品產業的專利布局。智財局說，英國人來台申請發明專利案以生技醫藥類為大宗，並有逐年增加的趨勢，因此智慧局主動與英國智慧財產局接洽此項合作。經過多年努力，繼2015年台日實施生物材料寄存合作計畫後，終於在英國倫敦簽署「台英專利程序上生物材料寄存相互合作瞭解備忘錄」，並於同日起開始實施，再次擴大我國與外國相互承認寄存效力的版圖。智財局官員說明，一般生物科技醫學的研發疫苗，要到國外上市申請專利，必須把活體疫苗帶往國外檢驗與證明。簽署相互寄存備忘錄後，來我國生技業者新疫苗只要提存在我們自己的食品工業研究所冷凍庫內即可，寄存機構會開立「活體證明」，英方須承認效力。反之，英國生技業者到我國申請專利亦然。此寄存合作好處是，生技業者不必舟車勞頓將活體疫苗攜往國外，耗費成本，又增加運送疫苗變異風險。同時省去運輸與繁瑣提存手續，也可增加專利申請速度。 (中時)

 

會跳動的幹細胞 “心臟補丁” (16 cm2) 成功修復老鼠心臟

新型人造肌肉有望給心臟打"補丁"2017-12-03來源：新華網新華社北京12月3日電 美國杜克大學研究人員新開發出一種能給心臟打"補丁"的人造肌肉。這種肌肉的強壯程度和電傳導性很接近健康成人心肌，而且其尺寸足以修復心臟常見損傷。研究人員利用多能幹細胞培育心臟"補丁"，這種幹細胞可以分化成身體中任何種類的細胞，包括心肌細胞和負責為心臟組織提供結構框架的成纖維細胞等。研究人員將這些細胞按特定比例置于凝膠狀物質中，使它們自我組織和生長。雖然培養心肌細胞早已不是新鮮事，但隨著培養尺寸增大，組織性能難以保證，因此早期人造心肌面積很小。通過反復實驗，研究人員找到了恰到好處的細胞配比和培養條件，成功培育出16平方厘米大、有一定厚度的大號"補丁"。動物實驗表明，這些"補丁"植入心臟後能繼續存活，並且運作良好。但為了實現修復人類壞死心肌的目標，研究人員還需讓心臟"補丁"變得更厚，並與原生肌肉完全融合。據介紹，給心臟打"補丁"能夠有效預防心臟衰竭及其並發症。"補丁"被植入壞死心肌後，能長時間保持活躍，為心臟收縮供能，順暢傳導電信號，還能分泌酶和生長因子，幫助修復受損組織。這項研究成果刊登在新一期英國《自然·通訊》網絡版上。

Beating Heart Patch is Large Enough to Repair the Human Heart  NOVEMBER 28, 2017   Beating patch is as strong and electrically active as healthy adult heart  By Ken Kingery  Biomedical engineers at Duke University have created a fully functioning artificial human heart muscle large enough to patch over damage typically seen in patients who have suffered a heart attack. The advance takes a major step toward the end goal of repairing dead heart muscle in human patients. The study appears online in Nature Communications on November 28, 2017. "Right now, virtually all existing therapies are aimed at reducing the symptoms from the damage that's already been done to the heart, but no approaches have been able to replace the muscle that's lost, because once it's dead, it does not grow back on its own," said Ilia Shadrin, a biomedical engineering doctoral student at Duke University and first author on the study. "This is a way that we could replace lost muscle with tissue made outside the body." Unlike some human organs, the heart cannot regenerate itself after a heart attack. The dead muscle is often replaced by scar tissue that can no longer transmit electrical signals or contract, both of which are necessary for smooth and forceful heartbeats. The end result is a disease commonly referred to as heart failure that affects over 12 million patients worldwide. New therapies, such as the one being developed by Shadrin and his advisor Nenad Bursac, professor of biomedical engineering at Duke, are needed to prevent heart failure and its lethal complications. Current clinical trials are testing the tactic of injecting stem cells derived from bone marrow, blood or the heart itself directly into the affected site in an attempt to replenish some of the damaged muscle. While there do seem to be some positive effects from these treatments, their mechanisms are not fully understood. Fewer than one percent of the injected cells survive and remain in the heart, and even fewer become cardiac muscle cells. Heart patches, on the other hand, could conceivably be implanted over the dead muscle and remain active for a long time, providing more strength for contractions and a smooth path for the heart's electrical signals to travel through. These patches also secrete enzymes and growth factors that could help recovery of damaged tissue that hasn't yet died. For this approach to work, however, a heart patch must be large enough to cover the affected tissue. It must also be just as strong and electrically active as the native heart tissue, or else the discrepancy could cause deadly arrhythmias. This is the first human heart patch to meet both criteria. "Creating individual cardiac muscle cells is pretty commonplace, but people have been focused on growing miniature tissues for drug development," said Bursac. "Scaling it up to this size is something that has never been done and it required a lot of engineering ingenuity." The cells for the heart patch are grown from human pluripotent stem cells -- the cells that can become any type of cell in the body. Bursac and Shadrin have successfully made patches using many different lines of human stem cells, including those derived from embryos and those artificially forced or "induced" into their pluripotent state. Various types of heart cells can be grown from these stem cells: cardiomyocytes, the cells responsible for muscle contraction; fibroblasts, the cells that provide structural framework for heart tissue; and endothelial and smooth muscle cells, the cells that form blood vessels. The researchers place these cells at specific ratios into a jelly-like substance where they self-organize and grow into functioning tissue. Finding the right combination of cells, support structures, growth factors, nutrients and culture conditions to grow large, fully functional patches of human heart tissue has taken the team years of work. Every container and procedure had to be sized up and engineered from scratch. And the key that brought it all together was a little bit of rocking and swaying. "It turns out that rocking the samples to bathe and splash them to improve nutrient delivery is extremely important," said Shadrin. "We obtained three-to-five times better results with the rocking cultures compared to our static samples." The results improved on the researchers' previous patches, which were one square centimeter and four square centimeters. They successfully scaled up to 16 square centimeters and five to eight cells thick. Tests show that the heart muscle in the patch is fully functional, with electrical, mechanical and structural properties that resemble those of a normal, healthy adult heart. "This is extremely difficult to do, as the larger the tissue that is grown, the harder it is to maintain the same properties throughout it," said Bursac. "Equally challenging has been making the tissues mature to adult strength on a fast timescale of five weeks while achieving properties that typically take years of normal human development." Bursac and Shadrin have already shown that these cardiac patches survive, become vascularized and maintain their function when implanted onto mouse and rat hearts. For a heart patch to ever actually replace the work of dead cardiac muscle in human patients, however, it would need to be much thicker than the tissue grown in this study. And for patches to be grown that thick, they need to be vascularized so that cells on the interior can receive enough oxygen and nutrients. Even then, researchers would have to figure out how to fully integrate the heart patch with the existing muscle. "Full integration like that is really important, not just to improve the heart's mechanical pumping, but to ensure the smooth spread of electrical waves and minimize the risk of arrhythmias," said Shadrin. "We are actively working on that, as are others, but for now, we are thrilled to have the 'size matters' part figured out," added Bursac. The research is part of a seven-year, $8.6 million grant from the National Institutes of Health. With the large heart patches in hand, the Bursac team is collaborating with researchers at the University of Alabama at Birmingham to develop procedures to successfully integrate the patch onto the hearts of pigs. Another affiliated team of researchers at the University of Wisconsin-Madison is working to develop improved stem cells for creating the main cell types that compose these heart patches, in the hopes of minimizing an immune response to the delivery of the engineered tissues. This research was supported by Foundation Leducq and the National Institutes of Health (R01HL104326, R01HL12652, UG3TR002142, U01HL134764, 5T32GM007171, F30HL122079).

CITATION: "Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues," Ilya Y. Shadrin, Brian W. Allen, Ying Qian, Christopher P. Jackman, Aaron L. Carlson, Mark E. Juhas, and Nenad Bursac. Nature Communications,  2017. DOI: 10.1038/s41467-017-01946-x

歐洲EMA核准8個幹細胞產品/ 3個已下架（MACI/ Provenge/ Chondrocelect）

發展幹細胞產業鏈 接軌國際 2017-12-04 00:19經濟日報 陳菀均  上（11）月16日美國食品藥物管理局（FDA）為了鼓勵創新，刺激產業發展新型細胞療法，FDA局長Scott Gottlieb親自對再生醫學發表聲明指出，新型細胞療法這個領域的相關技術，雖然尚處於發展初期，但未來對患者將可能是最具有改善效果治療。 FDA對待細胞療法態度的轉變，與哈佛大學知名生物學家George Q. Daley醫師的看法遙相呼應，Daley說若20世紀是藥物治療的時代，那21世紀將會是細胞治療時代。近年來，細胞治療史無前例連續四年獲得諾貝爾醫學獎肯定，其創新與重要性，不言可喻。美國International Stem Cell公司剛於上月公布，運用胚胎幹細胞所分化之神經幹細胞，進行帕金森氏症治療的臨床試驗結果，顯示整體患者失能時間大幅降低24%，且所有患者情緒及認知能力皆獲得明顯改善。無獨有偶，自然(Nature)期刊也發表了一名因遺傳疾病而喪失大部分皮膚的敘利亞難民，在接受幹細胞治療後成功重建其整個皮膚。而近期，在科學轉譯醫學雜誌所發表的研究更發現，只要5%的血液幹細胞即能重生整個免疫系統。成果豐碩、潛力可期。 幹細胞治療屬於再生醫療的一環，1968年Richard A. Gatti醫師首次利用骨髓移植造血幹細胞以治療先天性免疫缺陷症，此後幹細胞更被廣泛運用於更多樣的血液疾病治療。其機制主要是因為幹細胞可自我更新及分化出各種特定細胞，以達到治療各種疾病的目的。幹細胞主要可分成成體幹細胞、胚胎幹細胞及誘導性多功能幹細胞等三種。傳統研究大多運用成體幹細胞進行細胞修復，在心臟衰竭或心肌梗塞的病人給予幹細胞治療將可改善心臟功能，減少心肌梗塞範圍，而中樞神經系統疾病幹細胞也被認為是阿茲海默症以及帕金森氏症的治療希望。 目前幹細胞相關概念股在美國納斯達克市值已高達300億美元。權威研究機構Technavio於今年9月發布之研究報告說，由於幹細胞存儲技術之進步、捐贈者的成長、再加上相關自動化細胞處理設備及細胞治療產品之成長，全球幹細胞治療市場於2017年至2021年期間將有高達23.27%的年均複合成長率，潛在市場規模超過千億美元。 不過，幹細胞治療技術的標準化，仍有待克服。歐洲醫藥品管理局(EMA)所核准的八個幹細胞治療產品，其中有三個產品（MACI、Provenge及Chondrocelect）分別在近幾年陸續下市，深究其原因皆由於產品製造所產生的問題。這顯示幹細胞產品的生產製造與品質監測，將嚴重影響幹細胞治療的成功商化可能性。上個月中國幹細胞生物學分會也緊跟美國FDA，發布中國第一個《幹細胞通用要求》，《要求》主要是為了將幹細胞相關各操作細項標準化以利於未來幹細胞研究及產業的發展。中國對於幹細胞產業發展的決心與成果，令人敬重。 目前歐洲，日本，韓國以及加拿大皆有幹細胞相關產品，其中由加拿大Osiris Therapeutics公司所開發之Prochymal，更是第一個被FDA所核准的幹細胞治療商品，主要用於治療第一型糖尿病患者。台灣針對細胞治療，雖於2014年及2015年，衛生福利部就分別公告了《人類細胞治療產品臨床試驗申請作業與審查基準》、《人類細胞治療產品查驗登記審查基準》及《人類細胞治療產品捐贈者合適性判定基準》。且去年有條件開放免疫細胞治療，針對無藥可醫的癌症末期患者，即俗稱的恩慈條款。今年7月又公告了《細胞及基因治療產品管理法草案》，且明定細胞治療產品臨床試驗申請需有試驗送件前諮詢。然而對於幹細胞生產卻仍無一通用標準，目前台灣所有幹細胞相關產品都仍在臨床試驗階段，其試驗數已占細胞治療總數的34%。在面對如此發展快速的技術與國際激烈的競爭，以及美中兩國皆在此時發布相關規範下，台灣法規面更應該加緊腳步跟上國際的脈動，盡快提出符合國際標準之規範以帶動國內幹細胞產業鏈的發展。（作者是鑽石生技投資分析室分析師）

(南開大學 陳悅教授) BE-43547類天然產物 低氧殺 胰臟癌幹細胞

抗胰臟癌 南開大學科研邁大步 2017年12月04日 04:10 旺報 資料來源：今晚報（江珊） 記者近日從南開大學獲悉，該校藥物化學生物學國家重點實驗室、藥學院陳悅教授團隊首次實現了抗癌天然產物BE-43547A2的高效化學全合成，並實驗證明了該化合物可選擇性殺滅胰臟癌幹細胞，具有藥物開發潛力。介紹該工作的論文近日發表在國際著名學術刊物上，被國際相關領域評價為「讓人類對胰臟癌的挑戰邁出了非常重要的一大步」。

扮演關鍵角色 大量文獻報導，胰臟癌幹細胞在胰臟癌的耐藥轉移過程中扮演關鍵角色。「雖然胰臟癌幹細胞在胰臟癌細胞中所占比例很低（約1%），但其致癌能力很強，有時能夠達到普通胰臟癌細胞的1000倍以上。和其他癌症幹細胞一樣，胰臟癌幹細胞因其極強的耐藥性很難被殺滅。」陳悅說，目前科學界發現的能夠選擇性殺滅胰臟癌幹細胞的天然產物很少，且選擇性不高。

復發機率下降 既有研究表明，癌細胞在「壞死」的過程中會形成一個低氧環境，這種低氧環境直接導致藥物作用能力大幅下降，而BE-43547類天然產物恰恰在低氧環境中表現出更強的「殺傷力」。基於此，陳悅團隊通過分子合成得到BE-43547A2純品，經過測試，發現其能夠降低胰臟癌細胞中幹細胞含量的功能。這也意味著BE-43547A2能夠使胰臟癌復發機率下降，具有藥物開發的潛力。 (旺報)

 

中研院Extrachromosomal telomere repeat DNA誘發抗癌反應: IFNβ production

中研院免疫機制新發現 癌症治療新契機 發稿時間：2017/11/28（中央社記者余曉涵台北28日電）中研院分生所助研究員陳律佑率領研究團隊發現，在癌細胞生成過程中，人體的「染色體外端粒DNA」會誘發細胞後天免疫反應，進而抑制常見於骨癌、兒童腦瘤等的ALT癌細胞成長。中央研究院今天舉行「發現癌細胞迴避免疫系統關鍵機制，有助發展癌症免疫治療」記者會。會中中研院分子生物研究所助研究員陳律佑表示，癌細胞可以分為兩大類，一種是有「端粒酶」的癌細胞，另一種則為沒有「端粒酶」的替代性延長端粒（ALT）癌細胞。陳律佑說，ALT癌細胞占所有腫瘤的10%至15%，尤其常見於兒童腦瘤、軟組織瘤及骨癌等癌症上面。他指出，這類型的癌症細胞中會充滿「染色體外端粒DNA」（簡稱ECTR），正常狀態中ECTR會活化細胞內負責偵測游離DNA的機制，進而釋放出抑制病毒的干擾素，而癌細胞中卻因為沒有啟動活化機制釋放干擾素，導致癌細胞增生。陳律佑表示，研究發現癌細胞中的ECTR沒有啟動活化機制釋放干擾素的原因是「STING蛋白」受到抑制；研究中也發現ALT癌細胞中功能缺失的「組蛋白H3.3」也是協助釋放干擾素的角色之一。陳律佑說，若可以同時修復STING蛋白跟組蛋白H3.3，就有機會恢復ECTR啟動活化機制釋放出干擾素的功能，抑制癌細胞，為癌症治療帶來新契機。陳律佑也認為，近期美國食品藥物管理局核可的溶瘤病毒免疫療法，可以應用在ALT癌症的治療，趁著免疫系統失能，以毒攻毒。中研院指出，此研究成果論文已經在11月6日發表於「自然-結構與分子生物學」（Nature Structural and Molecular Biology）期刊。1061128

Extrachromosomal telomere repeat DNA is linked to ALT development via cGAS-STING DNA sensing pathway/ Nature Structural & Molecular Biology, 06 November 2017  Extrachromosomal telomere repeat (ECTR) DNA is unique to cancer cells that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, but the role of ECTRs in ALT development remains elusive. We found that induction of ECTRs in normal human fibroblasts activated the cGAS-STING-TBK1-IRF3 signaling axis to trigger IFNβ production and a type I interferon response, resulting in cell-proliferation defects. In contrast, ALT cancer cells are commonly defective in sensing cytosolic DNA. We found that STING expression was inhibited in ALT cancer cell lines and transformed ALT cells. Notably, the ALT suppressors histone H3.3 and the ATRX–Daxx histone chaperone complex were also required to activate the DNA-sensing pathway. Collectively, our data suggest that the loss of the cGAS-STING pathway may be required to evade ECTR-induced anti-proliferation effects and permit ALT development, and this requirement may be exploited for treatments specific to cancers utilizing the ALT pathway.

 

(溫熱化療42～43℃) 阮綜合醫院 引進 全自動腹腔溫暖灌注儀 (病人存活率差距1倍)

溫熱療法 腹膜癌末治療新選擇 【大紀元2017年11月27日訊】（大紀元記者李晴玳台灣高雄報導）衛福部公布國人十大死因，癌症35年蟬聯榜首，而消化道腫瘤如胃癌、大腸癌等，皆排名十大癌症之列，其中大腸癌發生率更連續9年居冠。究其原因，概由老化、飲食等多重因子長期影響所致。當今，促進國人健康福祉，防癌、抗癌蔚然成為全民健康保衛戰。現年54歲的黃女士，因便秘赴醫就診，經大腸鏡檢出腫塊，切片後確診罹患大腸癌，並有肝臟及腹膜轉移。醫師為她切除癌灶，並施作暫時性人工造口，以便後續治療。對於未來，她別無懸念，勇敢迎向抗癌路。現代人聞癌色變，然而消化道癌症，初期幾無任何症狀，可一旦出現病症，都已進入晚期，其中約有1-2成會出現腹膜轉移。在台灣，當胃腸癌症腹膜轉移（癌細胞在腹腔內擴散），輒被判定為癌症末期，平均存活率約半年。多數腫瘤科醫師因為手術預後不佳，僅建議安寧緩和治療。根據臨床研究分析，消化道癌症的轉移擴散路徑，可藉由三個方式：血液轉移、淋巴轉移與腹膜轉移。一般傳統化療，主要針對血液及淋巴轉移；至於腹膜轉移，療效仍然有限。過去台灣醫界，凡在手術中看到腸胃癌症出現腹膜轉移，率做緩和手術，並建議全身化療或安寧照護。

手術結合熱療 腹膜癌化治療的新選擇 而今，經過20多年醫療技術的研究發展，消化道癌的治療出現了新選擇！國際醫學專家發現，腹膜是腸胃癌轉移的主要去處，若在腹膜癌化（擴散）早期，施以「腫瘤減積切除手術」及「術中腹腔溫熱化療」，可達到不錯的效果。根據日本Satoshi Murata的臨床驗證，7年存活率可達到81％。而只做手術者則僅37.8％，兩者差距1倍。所謂「減積手術」，是指切除一切肉眼可見的腫瘤組織，包括原發腫瘤與腹腔轉移腫瘤，其範圍視腫瘤侵犯的程度而定。「溫熱化療」，則於腫瘤切除後，再以42～43℃的化學藥劑灌洗，毒殺腹腔內殘留的腫瘤細胞。其原理，是利用癌細胞的低耐熱特性，先以高溫破壞癌細胞膜，再讓化學藥物長趨直入，殺死癌細胞。 溫熱治療，全名為「高溫腹腔化療灌洗術」（HIPEC），是當前治療腹膜癌化最有效的方法。其熱療效應如同救火，先以電鋸割開鐵門，再用勁流灌救；高溫與高濃度的化學藥物如同強勁的水注，可以直驅細胞質或細胞核內，一舉殲滅火源。 其實，溫熱治療的概念，早在1980年代既由John Spratt提出，後因機器迅速地疊代進步，將溫熱治療由學理導向臨床，至近5～10年始獲長足進展。在過去，這種套裝式的積極療法，已是腹膜假性黏液瘤、腹膜間皮瘤的標準治療模式。今（2017）年，美國國家癌症資訊網(NCCN)更予以肯定，用來治療大腸癌，同具療效。「腫瘤減積手術」與「腹腔溫熱化療」的開發，顛覆了腫瘤醫學界的傳統醫療模式，為患者帶來了新希望。根據法國的研究報告指出，大腸癌引發的腹膜癌化，只做手術和手術加熱療，五年存活率的差異是13%比上51%。針對胃癌腹膜轉移患者，法國醫師Glehen、日本醫師Yonemura等醫療團隊的臨床應用，也提出了令人鼓舞的結果：其5年存活率為23-27％的長期存活，中位生存期為15-15.5 個月。這些結果證明肉眼下完全腫瘤切除，增加了腹腔溫熱化療的功效。

精良儀器及技術是最佳醫療服務保障 50多歲的謝先生經常腹痛，到阮綜合醫院就診，電腦斷層掃描查無異狀，但胃鏡檢查卻發現胃壁滿布腫瘤，經過近19小時的腫瘤減積手術後（包括全胃切除、淋巴廓清、以及大範圍的腹腔腫瘤切除等），隨即施予腹腔溫熱化療，後續並接受全身性化療。患者手術距今已半年多，不但活得開心，連進食都很順利。 為提升醫療服務品質，阮綜合醫院斥資數百萬元，引進同時通過美國FDA，歐盟CE認證的「全自動腹腔溫暖灌注儀」，並成立跨科別醫療團隊，專責執行手術及熱療。為精進醫療技術，阮綜合溫熱治療中心主任洪國禎，兩年來並自費百萬元赴國外進修。洪國禎表示，實證醫學雖認可減積手術與腹腔化療，對於治療腹腔擴散的大腸癌與胃癌，優於全身化療，也有助於預防腹膜轉移。惟手術過程中，須使用腹膜剝離術，並合併切除多處臟器組織，時間長且風險高，醫師須具備純熟技術及豐富經驗，方可肩負醫療救治使命，如實嘉惠病患。他指出，整個療程療效，減積手術是核心關鍵，減積手術能否將腫瘤切除乾淨，直接影響到溫熱化療的效果；而腫瘤之成功切除，又取決於醫師的專業技術及腫瘤的嚴重度。純熟的手術、醫療與照護服務，對於術後恢復與病患的存活率，起到至關重要的作用。「醫療行為有其極限性！所有複雜的侵入性治療都帶有風險；經驗的累積，雖然可以降低風險，卻也無法完全免除風險。」他強調，嚴格規範篩選病患，可以減少併發症的發生率，「如何將腹膜癌化早期的病患找出來，積極介入治療，讓他們延長生命」，這是他正待努力的。目前可適用HIPEC緩解症狀治療者，除了胃癌、大腸直腸癌，還包括闌尾癌、卵巢癌、間皮瘤、腹膜假性黏液瘤等腹腔轉移的病患，或是肺癌、肋膜間質癌、乳癌引起之胸腔積水。 責任編輯：杜文卿

杏國 正電荷微脂體paclitaxel (EndoTAG(R)-1) 美國專利核准:9827196

杏國新藥 發言日期106/11/28 發言時間14:28:25 發言人蘇慕寰 發言人職稱總經理 發言人電話(02)2764-0826 主旨 本公司SB05_(EndoTAG-1)抗腫瘤新藥經美國專利商標局 核准相關專利；專利名稱：帶正電荷微脂體製劑的投藥方法。符合條款 第51款 事實發生日106/11/28 說明1.事實發生日:106/11/28 2.公司名稱:杏國新藥股份有限公司 3.與公司關係(請輸入本公司或子公司):本公司 4.相互持股比例:不適用 5.傳播媒體名稱:不適用 6.報導內容:無 7.發生緣由: 本公司SB05_(EndoTAG-1)抗腫瘤新藥經美國專利商標局核准相關專利；專利名稱：帶正電荷微脂體製劑的投藥方法 專利證書號：「9827196」。8.因應措施:無 9.其他應敘明事項:無

Method of administering a cationic liposomal preparation Dec 4, 2015 - SynCore Biotechnology Co., Ltd. The present invention relates to the use of pharmaceutical preparations comprising paclitaxel for administration to a human patient in need thereof. SynCore Biotechnology Co., Ltd. Treatment of Triple Receptor Negative Breast Cancer

Description CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of co-pending U.S. patent application Ser. No. 11/919,700, filed Oct. 31, 2007 entitled "Method of Administering a Cationic Liposomal Preparation," which is a U.S. National Phase Application of International Application No. PCT/EP2006/004185, filed May 4, 2006, which claims the benefit of European Patent Application No. 05 009 847.4 filed May 4, 2005, all of which are expressly incorporated herein by reference in their entirety. The present invention relates to the use of pharmaceutical preparations comprising paclitaxel for administration to a human patient in need thereof. The use of antimitotic drugs, such as taxanes, as therapeutic agents for human patients suffering from diseases which are connected with enhanced mitosis are well known in the art. Paclitaxel has a unique mechanism of action and a broad spectrum of antiproliferative activity because paclitaxel binds to microtubules and promotes tubulin polymerisation and stabilizes the assembled microtubules. As a result, paclitaxel blocks the cell cycle at prophase resulting in an accumulation of cells in the G2/M phase. Unfortunately, paclitaxel has extreme low solubility in water, which makes it difficult to provide a suitable dosage form. Currently, paclitaxel is formulated and administered in a vehicle containing Cremophor EL (a polyethoxylated castor oil) and ethanol in a 50:50 (vol/vol) ratio. This solution is diluted 1:10 in saline before being administered to humans. However, various severe side reactions, such as hypersensitivity and hypertensive reactions, nephrotoxicity and neurotoxicity, for example, have been reported in patients due to Cremophor EL formulation. Further, even though paclitaxel (among other antitumor drugs) is a potent, well-established standard antitumor drug ({Rowinsky, 1995 1}, {Awada, 2002 2}, {Seidman, 2003 3}, {Romanini, 2003 4}), drug-unresponsive tumors and metastases are observed frequently in cancer patients ({Blom, 1996 5}, {Modi, 2002 6}, {Ozols, 2003 7}). Genetically instable, rapidly dividing tumor cells gain the capacity to overcome the growth inhibitory effect of a selected anti-cancer drug ({Vogelstein, 1988 8}, {Kerbel, 1991 9}). This capacity is usually not limited to a single drug (first line treatment) but extends to other drugs which are used after development of the first resistance. Hence, this phenomenon is called multi drug resistance (MDR). As the number of available and approved anti-neoplastic drugs is very limited for many cancer types, many patients succumb since their cancer tissues express MDR-related genes. The obvious problem, therefore, is to find methods and means to kill drug-resistant tumors, especially drug resistant cells, which are already resistant against the respective drug. A number of approaches were taken to deal with the above mentioned problems. The conventional strategy is to increase doses up to the maximal tolerated dose (MTD) and attempt to eradicate all tumor cells as quickly and completely as possible ({Schünemann, 1999 10}, {Heidemann,1997 11}). It is obvious that this strategy causes severe side effects and can not be extended to longer periods. Therefore, this treatment schedule consists of cycles of one short treatment period (usually 1 day-1 week) at MTD and a treatment-free interval of several weeks (usually 3-4 weeks), to allow the patient to recover from the obligatory side effects ({Schünemann, 1999 10}, {Heidemann, 1997 11}, {Romanini, 2003 4}). In many instances, tumor growth can also restart during these drug-free periods. Most importantly, this approach fails in many patients where tumor cells develop a high level of resistance which enables them to accommodate with drug concentrations at the MTD. The patients become therapy refractory. The most common solution is to start treatment with a second drug (second line treatment) ({Blom, 1996 5}, {Awada, 2002 2}, {Seidman, 2003 3}, {Heinemann, 2003 12}, {Thigpen, 2003 13}). In the best case, the second line treatment is successful and tumor response is documented. A common experience however is that tumors only respond for a certain time leading to a temporary regression of the tumor. After that, tumors become also resistant to the second drug. It is possible to start treatment with a third drug (third line treatment). However, tumors may become also resistant to the third drug. Continuing with this strategy leads to development of multi drug resistant tumors which are finally refractory to all available anti-cancer drugs ({Blom, 1996 5}, {Seidman, 2003 3}, {Thigpen, 2003 13}). Another possibility is to treat patients immediately with a combination of 2 or more drugs ({Heinemann, 2003 12}, {Kuenen, 2002 14}, {Sledge, 2003 15}, {Ozols, 2003 7}, {Reck, 2003 17}, {Romanini, 2003 4}). This strategy can be more successful as it decreases the likelihood for development of a double drug resistance. However, this strategy needs to explore time and cost intensively suitable drug combinations. A second disadvantage is that the side effects may also increase ({Kuenen, 2002 14}, {Ozols, 2003 7}). The therapeutic window concomitantly becomes small and the toxic effects may overlay the envisioned therapeutic benefit. Also in this case, multi drug resistance may develop and the therapy becomes ineffective ({Zimpfer-Rechner, 2003 18}, {Sledge, 2003 15}, {Sledge, 2003 16}, {Ozols, 2003 7}). The consequence of the negative experiences with such traditional treatment strategies is to develop more and more new drugs to extend the above described treatment options. Obviously, it is a very time and cost intensive race for more potent drugs which will eventually lead in many cases to therapy refractory tumors. In recent years, this recognition has led to a new approach to circumvent tumor resistance. It is based on the assumption that the MDR is caused by overexpression of enzymes which enable cells to expel chemotherapeutic drugs. The most famous member of this category of enzymes is called p-glycoprotein (p-gp). It is located in the cytoplasmic membrane and exports in an ATP-driven way ({Nobmann, 2001 19}, {Thomas, 2003 20}) compounds like paclitaxel or doxorubicin ({Harker, 1985 21}, {Fenner, 2002 22}, {Kiesewetter, 2003 23}). This notion led to the development of p-gp inhibitors which are meant to reverse p-gp mediated drug resistance. Hence the term chemosensitizers was coined for this class of molecules. One of the first examples tested was verapamil. Clinical studies, however, revealed unsatisfactory results, possibly due to low specific activity ({Thomas, 2003 20}, {Kohler, 2003 24}). The further research led to a second generation of compounds which again were found not to be clinically applicable ({Leonard, 2002 25}, {Thomas, 2003 20}). Today a few substances of the third generation, one known as tariquidar, are in clinical trials ({Agrawal, 2003 26}, {Callies, 2003 27}). The usefulness and broad applicability of these compounds is, however, still unclear ({Leonard, 2002 25}, {Thomas, 2003 20}). Even though much improved in comparison to first generation chemosensitizers, third generation compounds also cause side effects and may have unforeseen consequences for the whole body. Extensive clinical testing is needed and it is so far uncertain if such approaches can become general practice in the future ({Leonard, 2002 25}, {Thomas, 2003 20}). Different delivery systems have been used to enhance the effect of paclitaxel and/or reduce toxicity. Liposomes are one of many carriers that have been developed to enhance aqueous solubility and thus efficiency, combined with less toxicity. U.S. Pat. Nos. 5,648,090, 5,424,073 and 6,146,659 (Rahman et al.) provide a liposomal encapsulated paclitaxel for a method for treating cancer in mammals. These patents disclose a method of administering to the host a pharmaceutical composition of a therapeutically effective amount of liposomes which include a liposome forming material, cardiolipin, and an agent such as paclitaxel, or an antineoplastic derivative of paclitaxel, or a mixture thereof, with a pharmaceutically acceptable excipient. In U.S. Pat. No. 6,146,659, a method of administering a taxane to a patient is provided by administering taxane over a period of less than an hour in an amount from about 75 to 300 mg/m2, wherein the taxane is liposomally encapsulated. The liposomes disclosed therein are negatively charged. Since the disclosure of McDonald et al., U.S. Pat. No. 5,837,283, it is known that positively charged liposomes specifically target angiogenic endothelial cells. Strieth et al., 2004, Int. J. Cancer 110, 117-124 describe experiments in Syrian Golden hamsters using paclitaxel in cationic liposomes. The animals were treated with liposomal paclitaxel in a dose schedule three times a week. The problem underlying the present invention was to provide an improved method of administering paclitaxel to a subject in need thereof in a therapeutically effective amount without severe side effects. The treatment schedule should minimize the time spent in clinical treatment for infusions while maintaining optimal treatment results. The solution to the above problem is achieved by providing the embodiments characterized in the claims. A first aspect relates to the use of a cationic liposomal preparation comprising at least one cationic lipid from about 30 mole % to about 99.9 mole %, paclitaxel in an amount of at least about 0.1 mole % and at least one neutral and/or anionic lipid from about 0 mole % to about 70 mole % for the manufacture of a pharmaceutical composition for administration (i) once in a week, (ii) twice in a week or (iii) a combination of (i) and (ii), wherein the monthly dose is about 0.1 mg/kg bw to about 20 mg/kg bw. The combination (iii) of a once weekly administration (i) and a twice weekly administration (ii) is a weekly or biweekly alternating schedule. Surprisingly, it was found in contrast to postulated anti-angiogenic neovascular targeting schedules, which favour daily dosing or multiple weekly dosing (Strieth et al. 2004, Int. J. Cancer 110, 117-124), that cationic liposomal preparations comprising a taxane, particularly paclitaxel are even more efficient in treating cancer even in a weekly or biweekly dosing schedule. It was unexpectedly found that a continuous application of cationic liposomal paclitaxel once or twice a week at a low dose over a longer period of time, such as e.g. for several weeks, preferably at least seven weeks, is equally or even more effective than frequent applications of 3-5 times a week at a low dose over a shorter time period, e.g. of about four weeks interrupted by pause intervals of a week or several days. Furthermore, it was unexpectedly found that a continuous application of cationic liposomal paclitaxel once or twice a week at a low dose over a longer period of time, e.g. of about several weeks or months, preferably of at least about seven weeks, is equally or even more effective than a once a week high dose application interrupted by pause intervals over a shorter period of time, e.g. of about four weeks. Liposomal preparations comprising paclitaxel as disclosed herein can be used in combination therapy with a further active agent. A twice weekly application schedule was found to be especially suitable in combination therapy with a further active agent, particularly with gemcitabine. Furthermore, the twice weekly schedule was found to be particularly suitable for combination therapy of liposomal paclitaxel, especially cationic liposomal paclitaxel (EndoTAG-1) in combination with gemcitabine in the treatment of pancreatic cancer, adenocarcinoma of the pancreas. General advantages of the administration of liposomal paclitaxel are: high amounts of the active ingredient selective targeting improved efficacy lower side effects compared to traditional chemotherapy or to a preparation of neutral or anionic liposomes reduction of disease related pain improvement of quality of life stabilization of body weight during treatment synergistic effects with traditional therapy regimes Particular advantages of an once or twice weekly dosing schedule are as follows: less physical burden for the patient due to longer recovery times fewer hospitalization events the administration over a longer time frame of several weeks or months, preferably of at least seven weeks, is equally or even more efficatious than frequent applications over a shorter period of time The advantages of the once or twice weekly dosing schedule result in an improved quality of life for the patient. The present pharmaceutical composition can be administered at a monthly dose of about 0.25 mg up to about 100 mg, particularly up to about 60 mg of liposomal paclitaxel/kg body weight (bw) of a patient, preferably of about 0.5 mg up to about 30 mg of liposomal paclitaxel/kg bw and more preferably of about 1.0 mg up to about 15 mg of liposomal paclitaxel/kg bw. In a preferred embodiment the monthly dose ranges from between about 1 mg/kg bw to about 15 mg/kg, or about 0.5 mg/kg bw to about 7.5 mg/kg bw, about 2.2 mg/kg bw to about 12.3 mg/kg bw, about 1.1 to about 6.2 mg/kg bw, about 2.2 mg/kg bw to about 9 mg/kg bw, about 1.1 mg/kg bw to about 4.5 mg/kg bw, about 4.5 mg/kg bw to about 12.5 mg/kg bw or most preferably about 2.3 mg/kg bw to about 6.3 mg/kg bw. A single unit dose ranges from between about 0.01 mg/kg bw to about 100 mg/kg bw, preferably between about 0.2 mg/kg bw to about 60 mg/kg bw, or is more preferably about 0.28 mg/kg bw, about 1.13 mg/kg bw or most preferably about 1.88 mg/kg bw. In a preferred embodiment of the present invention the pharmaceutical composition is administered at a single unit dose ranging from about 0.01 to about 10 mg/kg bw, particularly about 0.05 to about 5 mg liposomal paclitaxel per kg of body weight. Preferably, a single dose is about 0.1 mg/kg bw to about 2.5 mg/kg bw, about 0.05 mg/kg bw to about 1.25 mg/kg bw, about 0.25 mg/kg bw to about 1.54 mg/kg bw, about 0.14 mg/kg bw to about 0.75 mg/kg bw, about 0.56 mg/kg bw to about 1.88 mg/kg bw, about 0.29 mg/kg bw to about 0.94 mg/kg bw, about 0.28 mg/kg bw to about 1.13 mg/kg bw or most preferably about 0.14 mg/kg bw to about 0.57 mg/kg bw. In a further preferred embodiment, the suitable dose of liposomal paclitaxel for application to a human patient is in an amount of about 0.01 to 2.5, preferably 0.02 to 1.88, and more preferably 0.25 to 1.88 mg/kg bw, particularly 1.54 mg/kg bw once a day and about 0.01 to 10, preferably 0.02 to 5.0 and more preferably 0.25 to 3.8 mg/kg bw, particularly 3.76 mg/kg bw per week. For applications in human medicine, the present pharmaceutical composition may be administered at a monthly dose of preferably about 40 mg/m2 up to about 3700 mg/m2, particularly up to about 1022 mg/m2 human body surface (bs), more preferably up to about 584 mg/m2 bs, even more preferably up to about 480 mg/m2 bs, and most preferably up to about 352 mg/m2 bs. In a preferred embodiment the present pharmaceutical composition is administered at a monthly dose of about 40 mg/m2 bs up to about 584 mg/m2 bs and more preferably of about 176 mg/m2 bs up to about 352 mg/m2 bs. On an average, a human patient has a body surface of about 1.84 m2. Thus, for an average person of 70 kg body weight and 172 cm height, preferred values for monthly doses, single doses etc. which have been indicated above in mg/kg body weight (bw) may be converted for human applications to corresponding values of in mg/m2 human body surface (bs) by multiplication with a species-specific factor according to known methods. The dose scheme can range from a plurality of times daily to a plurality of times during a month period, each of said times being separated by an interval of between days or weeks. The total treatment period is preferably at least one month. The pharmaceutical composition is also suitable for a long-term administration for at least 3 months, for at least 4 months, for at least 6 months or for at least 12 months and up to 6 months, up to 12 months, up to 18 months, up to 24 months or even longer. In a preferred embodiment the duration of the administration of the once or twice weekly dosing schedule is several weeks, preferably at least seven weeks. Even in prolonged treatment schedules, the drug resistances or detrimental side-effects like alopecia, nephropathy are rarely observed. Further, usually no premedication like corticosteroids or anti-histamines is required. The continued administration of lower doses once or twice weekly is at least as effective as the administration of a single high dose or frequent low dose administration interrupted by pause intervals. During the treatment interval the dose units and the dose intervals may remain constant. On the other hand, the dose units may be increased during the treatment interval, e.g. beginning with a starting dose and escalating in one or several steps to a consolidation dose, which may be 2, 3, 4 or even more times higher than the starting dose. Additionally or alternatively, the treatment interval between single doses may be altered, e.g. decreased or increased during the treatment period. The term "about" as used in the present specification describes a deviation from the given value of up to plus or minus 5%. The term "liposomal preparation" and "liposomes" are used synonymously throughout the present application. The liposomal preparation may be a component of a "pharmaceutical composition" and may be administered together with physiologically acceptable carriers such as a buffer. The term "liposomal paclitaxel" or "lipid complexed paclitaxel" refers to a liposomal preparation comprising paclitaxel encapsulated within liposomes. A specific liposomal paclitaxel formulation is EndoTAG®-1. EndoTAG®-1, sometimes also referred to as MBT-0206, is a liposomal preparation with a molar ratio of 50:47:3 mole % of DOTAP, DOPC and paclitaxel. EndoTAG®-1 is a registered trademark in Germany. The unit "mg/kg bw" refers to mg of liposomal paclitaxel per kg body weight. The unit "mg/m2 bs" or just "mg/m2" refers to mg liposomal paclitaxel per m2 human body surface (bs). Thus, the dose calculation refers only to the mass of the paclitaxel portion, not the lipid portion. The term "angiogenesis associated disease" or "angiogenic disease" refers to a disease which is dominated by the pathological growth of capillary blood vessels (Folkmann, J. and Klagsbrun, M. 1987, Angiogenic Factors. Science 235, 442-446). Examples of such a disease are e.g. diabetic retinopathy, chronic inflammatory diseases, rheumatoid arthritis, inflammation, dermatitis, psoriasis, stomach ulcers, tumor diseases such as hematogenous and solid tumors. The term "chemosensitizer" refers to a substance or drug, which makes it easier for chemotherapy to affect, particularly kill cancer cells. In a preferred embodiment, the cationic liposomal preparation of the present invention comprises at least one cationic lipid from about 30 mole % to about 99.9 mole %, preferably to about 98 mole % cationic lipid, paclitaxel in an amount of at least about 0.1 mole %, preferably of at least about 2 mole %; and at least one neutral and/or anionic lipid from about 0 mole % to about 70 mole % and is used for manufacturing a pharmaceutical composition for simultaneous, separate, or sequential combination therapy with a jointly effective dose of at least one further active agent and/or heat and/or radiation and/or cryotherapy. In a further preferred embodiment, the liposomal preparation comprises paclitaxel in an amount of about 0.1 mole %, particularly of about 2 mole %, to about 8 mole %, preferably in an amount of about 0.5 mole %, particularly of about 2 mole %, to about 5 mole %, more preferably in an amount of about 1 mole % to about 4 mole % and most preferably in an amount of about 2.5 mole % to about 3.5 mole %. The cationic liposomal preparation of the present invention comprises substantially no paclitaxel crystals. The liposomal preparation of the present invention is a cationic liposomal preparation which comprises cationic lipids in an amount of about 30 mole % to about 99.9 mole %, particularly to about 70 mole %, preferably from about 40 mole % to about 60 mole % and most preferably from about 45 mole %, to about 55 mole %. The liposomal preparation is characterized by having a positive zeta potential in about 0.05 M KCI solution at about pH 7.5 at room temperature. The preferred cationic lipids of the liposomal preparation have a positive net charge and are N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium salts, e.g. the methylsulfate (DOTAP). Other useful lipids for the present invention may include: DDAB, dimethyldioctadecyl ammonium bromide; 1,2-diacyloxy-3-trimethylammonium propanes, (including but not limited to: dioleoyl, dimyristoyl, dilauroyl, dipalmitoyl and distearoyl; also two different acyl chain can be linked to the glycerol backbone); N-[1-(2,3-dioloyloxy)propyl]-N,N-dimethyl amine (DODAP); 1,2-diacyloxy-3-dimethylammonium propanes, (including but not limited to: dioleoyl, dimyristoyl, dilauroyl, dipalmitoyl and distearoyl; also two different acyl chain can be linked to the glycerol backbone); N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA); 1,2-dialkyloxy-3-dimethylammonium propanes, (including but not limited to: dioleyl, dimyristyl, dilauryl, dipalmityl and distearyl; also two different alkyl chain can be linked to the glycerol backbone); dioctadecylamidoglycylspermine (DOGS); 3β-[N-(N′,N′-dimethylamino-ethane)carbamoyl]cholesterol (DC-Chol); 2,3-dioleoyloxy-N-(2-(sperminecarboxamido)-ethyl)-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA); β-alanyl cholesterol; cetyl trimethyl ammonium bromide (CTAB); diC14-amidine; N-tert-butyl-N′-tetradecyl-3-tetradecylamino-propionamidine; 14Dea2; N-(alpha-trimethylammonioacetyl)didodecyl-D-glutamate chloride (TMAG); O,O′-ditetradecanoyl-N-(trimethylammonio-acetyl)diethanolamine chloride; 1,3-dioleoyloxy-2-(6-carboxy-spermyl)-propylamide (DOSPER); N,N,N′,N′-tetramethyl-N,N′-bis(2-hydroxylethyl)-2,3-dioleoyloxy-1,4-butanediammonium iodide; 1-[2-(acyloxy)ethyl]2-alkyl (alkenyl)-3-(2-hydroxyethyl)-imidazolinium chloride derivatives as described by Solodin et al. (1995) Biochem. 43:13537-13544, such as 1-[2-(9(Z)-octadecenoyloxy)ethyl]-2-(8(Z)-heptadecenyl-3-(2-hydroxyethyl) imidazolinium chloride (DOTIM), 1-[2-(hexadecanoyloxy)ethyl]-2-pentadecyl-3-(2-hydroxyethyl)imidazolinium chloride (DPTIM), 2,3-dialkyloxypropyl quaternary ammonium compound derivatives, containing a hydroxyalkyl moiety on the quaternary amine, as described e.g. by Felgner et al. [Felgner et al. J. Biol. Chem. 1994, 269, 2550-2561] such as: 1,2-dioleoyl-3-dimethyl-hydroxyethyl ammonium bromide (DORI), 1,2-dioleyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide (DORIE), 1,2-dioleyloxypropyl-3-dimethyl-hydroxypropyl ammonium bromide (DORIE-HP), 1,2-dioleyloxypropyl-3-dimethyl-hydroxybutyl ammonium bromide (DORIE-HB), 1,2-dioleyloxypropyl-3-dimethyl-hydroxypentyl ammonium bromide (DORIE-Hpe), 1,2-dimyristyloxypropyl-3-dimethyl-hydroxylethyl ammonium bromide (DMRIE), 1,2-dipalmityloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide (DPRIE), 1,2-disteryloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide (DSRIE); cationic esters of acyl carnitines as reported by Santaniello et al. [U.S. Pat. No. 5,498,633]; cationic triesters of phosphatidylcholine, i.e. 1,2-diacyl-sn-glycerol-3-ethylphosphocholines, where the hydrocarbon chains can be saturated or unsaturated and branched or non-branched with a chain length from C12 to C24, the two acyl chains being not necessarily identical. In a further preferred embodiment, the liposomal preparation optionally comprises at least one neutral and/or anionic lipid. Neutral lipids are lipids which have a neutral net charge. Anionic lipids or amphiphiles are molecules which have a negative net charge. These can be selected from sterols or lipids such as cholesterol, phospholipids, lysolipids, lysophospholipids, sphingolipids or pegylated lipids with a neutral or negative net change. Useful neutral and anionic lipids thereby include: phosphatidylserine, phosphatidylglycerol, phosphatidylinositol (not limited to a specific sugar), fatty acids, sterols, containing a carboxylic acid group for example, cholesterol, 1,2-diacyl-sn-glycero-3-phosphoethanolamine, including, but not limited to, DOPE, 1,2-diacyl-glycero-3-phosphocholines and sphingomyelin. The fatty acids linked to the glycerol backbone are not limited to a specific length or number of double bonds. Phospholipids may also have two different fatty acids. Preferably the further lipids are in the liquid crystalline state at room temperature and they are miscible (i.e. a uniform phase can be formed and no phase separation or domain formation occurs) with the used cationic lipid, in the ratio as they are applied. In a preferred embodiment the neutral lipid is DOPC. In a further preferred embodiment, the liposomal preparation comprises optionally neutral and/or anionic lipids, preferably DOPC in an amount of about 30 mole % to about 70 mole %, preferably from about 40 mole % to about 60 mole % and more preferably from about 45 mole % to about 55 mole %. It is a further object of the present invention that the cationic liposomal preparation which is used therein can be dehydrated, stored for extended periods of time while dehydrated, and then rehydrated when and where it is to be used, without losing a substantial portion of its contents during the dehydration, storage and rehydration processes. To achieve the latter, one or more protective agents, such as cryoprotectants, may be present. Thus, the inventive cationic liposome preparation preferably comprises a cryoprotectant, wherein the cryoprotectant is selected from a sugar or an alcohol or a combination thereof. Preferably, the cryoprotectant is selected from trehalose, maltose, sucrose, glucose, lactose, dextran, mannitol or sorbitol. In a further preferred embodiment, the liposomal preparation comprises trehalose in the range of about 5% (m/v) to about 15% (m/v) with respect to the total volume of the preparation. The formulation of the cationic liposomes of the present invention may vary. In a preferred embodiment the molar ratio is 50:47:3 mole % of DOTAP, DOPC and paclitaxel. This formulation is also designated MBT-0206 or EndoTAG-1. Liposomes of various sizes are useful in the present invention. In a preferred embodiment of the present invention cationic liposomes have an average particle diameter from about 25 nm to about 500 nm, preferably from about 50 to about 500 nm, more preferably from about 100 nm to about 300 nm. The present liposome compositions can be administered systemically, preferably intravenously. In a preferred embodiment, the liposomal composition is administered via intravenous infusion. The initial infusion rate may be about 0.5 ml/min. The rate may be stepwise, e.g. every 10 min, or continuously increased, until it reaches a maximum infusion rate of e.g. about 1.5 ml/min. The cationic liposomes of the present invention may be used to treat any form of a condition associated with increased angiogenesis, such as cancer. The pharmaceutical composition of the present invention is particularly advantageous in treating tumors in human patients such as bladder cancer, breast cancer, colorectal cancer, endometrial cancer, leukaemia, lung cancer, lymphoma, melanoma, non-small-cell lung cancer, ovarian cancer, prostate cancer and to childhood cancers such as brain stem glioma, cerebellar astrocytoma, cerebral astrocytoma, ependymoma, Ewing's sarcoma/family of tumors, germ cell tumor, extracranial, Hodgkin's disease, leukaemia, acute lymphoblastic, leukaemia, acute myeloid, liver cancer, medulloblastoma, neuroblastoma, non-Hodgkin's lymphoma, osteosarcoma/malignant fibrous histiocytoma of bone, retinoblastoma, rhabdomyosarcoma, soft tissue sarcoma, supratentorial primitive neuroectodermal and pineal tumors, unusual childhood cancers, visual pathway and hypothalamic glioma, Wilms' Tumor and other childhood kidney tumors and to less common cancers including acute lymphocytic leukaemia, adult acute myeloid leukaemia, adult non-Hodgkin's lymphoma, brain tumor, cervical cancer, childhood cancers, childhood sarcoma, chronic lymphocytic leukaemia, chronic myeloid leukaemia, esophageal cancer, hairy cell leukaemia, kidney cancer, liver cancer, multiple myeloma, neuroblastoma, oral cancer, pancreatic cancer, primary central nervous system lymphoma, skin cancer, small-cell lung cancer, head & neck cancer, gall bladder and bile duct cancer, stomach cancer, gastrointestinal cancer, Kaposi's sarcoma, urothelial cell carcinoma, thyroid gland carcinoma, testicular carcinoma, vaginal cancer, angiosarcoma, soft tissue sarcoma, mesothelioma and hepatocellular carcinoma. Particularly, the cancer may be a mestastasing cancer and/or a standard (chemo)therapy-resistant cancer. Administration of the composition of the invention may slow or stop disease progression, or may lead to a partial or complete remission. Further conditions may be wound healing or an inflammatory disease or a chronic inflammatory disease such as rheumatoid arthritis, dermatitis, endometriosis or psoriasis. The cationic liposomal preparations of the invention are particularly suitable for the treatment of cancer as indicated above, especially pancreatic cancer, inoperable pancreatic cancer, gastro-intestinal cancer, cancer of the liver, lung cancer, colorectal or gastric cancer, breast cancer, prostate cancer and melanoma, either as a monotherapy or a combination therapy with further treatment therapies, e.g. further active agents as indicated below in detail, especially with chemotherapeutic agents, e.g. DNA/RNA antimetabolites such as gemcitabine. Another preferred embodiment is the treatment of prostate cancer as monotherapy or in combination with at least one further active agent, particularly EndoTAG®-1 in combination with Prednisolon. Generally, the cationic liposomal preparations of the invention may be administered as a first line treatment or as a second or third line treatment as a monotherapy, meaning the liposomal preparation comprising paclitaxel alone, or as a combination therapy, meaning the liposomal preparation comprising paclitaxel together with at least one further active agent such as gemcitabine. The gold standard for the treatment of pancreatic cancer is gemcitabine) (Gemzar®. The standard protocol according to the product information and publications such as Cantore. et al., 2004, J Chemother. 16(6): 589-94, and which is applied herein, is gemcitabine at a single dose of 1000 mg/m2 bs applied over a time period of seven weeks once a week. Thus, it is a preferred embodiment of the present invention to treat prostate cancer or pancreatic cancer or liver cancer in a monotherapy. In an especially preferred embodiment cationic liposomal paclitaxel is administered as monotherapy using a twice weekly dosing schedule for a period of time of several weeks, preferably for at least seven weeks, for the treatment of cancer. A twice weekly administration of lipid complexed paclitaxel (EndoTAG®-1) can be performed at different dose levels in patients with measurable locally advanced cancer such as pancreatic cancer, adenocarcinoma of the pancreas. Various single doses can be used for said treatment, preferably: Cationic liposomal paclitaxel (EndoTAG®-1) low dose: 11 mg/m2 (=0.28 mg/kg body weight) lipid complexed paclitaxel Cationic liposomal paclitaxel (EndoTAG®-1) medium dose: 22 mg/m2 (=0.56 mg/kg body weight) lipid complexed paclitaxel Cationic liposomal paclitaxel (EndoTAG®-1) high dose: 44 mg/m2 (=1.13 mg/kg body weight) lipid complexed paclitaxel Cationic liposomal paclitaxel (EndoTAG®-1) higher dose: 60 mg/m2 (=1.54 mg/kg body weight) lipid complexed paclitaxel Patients therein receive infusions over a time period of at least seven weeks in twice weekly applications of EndoTAG®-1 (days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39, 43, and 46). One complete cycle of this new regimen therefore comprises at least fourteen applications of EndoTAG®-1, which then consists of at least seven weeks. In another preferred embodiment cationic liposomal paclitaxel is administered in combination therapy with a further active agent for the treatment of cancer. In an especially preferred embodiment cationic liposomal paclitaxel is administered in combination with a further active agent for the treatment of pancreatic cancer, adenocarcinoma of the pancreas. In another especially preferred embodiment, cationic liposomal paclitaxel is administered in combination with a further active agent for the treatment of prostate or liver cancer, particularly hepatocellular carcinoma. In a most preferred embodiment cationic liposomal paclitaxel is administered in combination with gemcitabine for the treatment of pancreatic cancer using a twice weekly dosing schedule over a time frame of several weeks, preferably at least seven weeks. In such a most preferred embodiment a 1st line combination treatment with weekly infusions of gemcitabine and twice weekly administration of liposomal paclitaxel (e.g. EndoTAG®-1) can be performed at various dose levels in patients with measurable locally advanced cancer such as pancreatic cancer, adenocarcinoma of the pancreas. For the treatment of cancer such as pancreatic cancer, e.g. adenocarcinoma of the pancreas, using 1st line combination treatment with weekly infusions of gemcitabine and twice weekly administration of EndoTAG®-1, various single doses can be used, preferably: Gemcitabine+EndoTAG®-1 (low dose: 11 mg/m2 lipid complexed paclitaxel) Gemcitabine+EndoTAG®-1 (medium dose: 22 mg/m2 (=0.56 mg/kg body weight) lipid complexed paclitaxel Gemcitabine+EndoTAG®-1 (high dose: 44 mg/m2 (=1.13 mg/kg body weight) lipid complexed paclitaxel) Gemcitabine+EndoTAG®-1 (higher dose: 60 mg/m2 (=1.54 mg/kg body weight) lipid complexed paclitaxel) In a preferred embodiment patients receive a standardized chemotherapy regime, preferably gemcitabine, in combination with EndoTAG®-1 infusions over a time period of at least seven weeks. The treatment schedule preferably consists of a weekly gemcitabine treatment (days 4, 11, 18, 25, 32, 39, and 46) which is combined with a total of at least fourteen twice weekly applications of EndoTAG®-1 (days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39, 43, and 46). One complete cycle of this new regimen therefore comprises at least seven applications of gemcitabine and at least fourteen applications of EndoTAG®-1, which then consists of at least seven weeks. The further active agent for combination therapy is selected from a cytotoxic or cytostatic substance such as an anti-tumor or an anti-endothelial cell active substance, a chemotherapeutic agent or an immunological active substance, a compound that reduces or eliminates hypersensitivity reactions or a chemosensitizer. In a preferred embodiment, the liposomal composition is administered prior to the further active agent. In a preferred embodiment, the active agent is selected from antineoplastic agents, especially antimitotic agents like paclitaxel, alkylating agents, especially platinum containing compounds like cisplatin, carboplatin, DNA topoisomerase inhibiting agents like camptothecin or doxorubicin, RNA/DNA antimetabolites, especially 5-fluorouracil or gemcitabine and/or other compounds having antitumor activity such as a statin, a depsipeptide, thalidomide, other agents interacting with microtubuli such as discodermolide, laulimalide, isolaulimalide, eleutherobin, Sarcodictyin A and B. Especially preferred are combination therapies with cisplatin or carboplatin, with 5-fluorouracil or with gemcitabine. In a further preferred embodiment, the compound that reduces or eliminates hypersensitivity reactions is selected from the group comprising (but not limited to) steroids, antihistamines, H2 receptor antagonists, and combinations thereof in a sufficient amount to prevent fatal anaphylactic reactions. In an even more preferred embodiment the compound is selected from the group comprising Ranitidine, Dexamethasone, Diphenhydramine, Famotidine, Hydrocortisone, Clemastine, Cimetidine, Prednisolone, Prednison, Chlorpheniramine, Chiorphenamine, Dimethindene maleate, Indomethazine and Promethazine or any derivative thereof. In a further preferred embodiment, the chemosensitizer is selected from the group comprising (but not limited to) cell cycle modulators, substances that revert a drug resistance like verapamil, vasoactive substances like anti-hypertensive drugs, substances that modify the charge-related interaction of cationic liposomes with blood components like protamine. Preferably, the further active agent is present in a non-liposomal formulation. In another aspect of the present invention said liposomal preparation comprises a taxane, preferably paclitaxel or docetaxel or a derivative thereof in an amount of about 0.1 to about 20 mol %, preferably in an amount of about 0.5 mole % to about 10 mole %, more preferably in an amount of about 1 mole % to about 5 mole % and most preferably in an amount of about 2 mole % to about 4 mole %. It is another preferred embodiment of the invention that the cationic liposomal paclitaxel is administered in combination with a transarterial chemoembolization (TACE) therapy, percutaneous ethanol injection (PEI), radiofrequency thermal ablation (RFA) therapy, microwave thermal ablation and/or laser-induced thermotherapy (LITT) for the treatment of hepatocellular carcinomas. Transarterial chemoembolization can comprise the administration of gelfoam particles, gelatine sponges, starch, polyvinyl alcohol, ethanol, collagen, cytotoxic agents (e.g. mitomycin, doxorubicin, epirubicin, cisplatin) or iodized oil (Lididol). In a more preferred embodiment, cationic liposomal paclitaxel is administered e.g. once a week in combination with a transarterial chemoembolization (TACE). It should be noted that all preferred embodiments discussed for one or several aspects of the invention also relate to all other aspects. This particularly refers to the amount and type of cationic lipid, the amount and type of neutral and/or anionic lipid, the amount and type of a taxane agent, the amount and type of a further active agent, particularly for combination therapy, and the type of disorder to be treated. 

FIG. 1: Cationic liposomal paclitaxel (EndoTAG®-1) in twice weekly dosing schedule. Schematic of the dose schedule for twice weekly application of liposomal paclitaxel. Cationic liposomal paclitaxel (EndoTAG®-1) is applied twice weekly (days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39, 43, and 46) in three different doses: (low dose: 11 mg/m2 lipid complexed paclitaxel); (medium dose: 22 mg/m2 lipid complexed paclitaxel); (high dose: 44 mg/m2 lipid complexed paclitaxel).  

FIG. 2: Cationic liposomal paclitaxel (EndoTAG®-1) in a pancreatic cancer study. Schematic of the dose schedule for twice weekly application of liposomal paclitaxel in combination with gemcitabine (Gemzar®) once weekly. The control group of patients receives 1: gemcitabine monotherapy. The other patients receive gemcitabine in combination with cationic liposomal paclitaxel (EndoTAG®-1) at three doses: 2: gemcitabine+EndoTAG®-1 (low dose: 11 mg/m2 lipid complexed paclitaxel); 3: gemcitabine+EndoTAG®-1 (medium dose: 22 mg/m2 lipid complexed paclitaxel); 4: gemcitabine+EndoTAG®-1 (high dose: 44 mg/m2 lipid complexed paclitaxel). Gemcitabine is applied at a dose of 1000 mg/m2 body surface once a week (Mon; =days 4, 11, 18, 25, 32, 39, and 46). Cationic liposomal paclitaxel (EndoTAG®-1) is applied twice weekly (days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39, 43, and 46). The following examples should be illustrative only but are not meant to be limiting to the scope of the invention. Other generic and specific configurations will be apparent to those skilled in the art. 

Example 1 Human Therapy Treatment Protocol This example is concerned with human treatment protocols using the formulations disclosed. Treatment will be of use preventing and/or treating various human diseases and disorders associated with enhanced angiogenic activity. It is considered to be particularly useful in anti-tumor therapy, for example, in treating patients with solid tumors and hematological malignancies or in therapy against a variety of chronic inflammatory diseases such as rheumatoid arthritis or psoriasis. A feature of the invention is that several classes of diseases and/or abnormalities may be treated by directly targeting angiogenic epithelial cells without directly targeting the tissue or cells involved in the abnormality, e.g. by inhibiting angiogenesis the blood supply to a tumor is cut off and the tumor is killed without directly targeting the tumor cells in any manner. Other classes of diseases and/or abnormalities may be treated by directly targeting angiogenic endothelial cells and by directly targeting the tissue or cells involved in the abnormality. In another application, drug resistant cells such as drug resistant cancer cells or highly proliferative synoviocytes in rheumatoid arthritis can be affected directly. The various elements of conducting a clinical trial, including patient treatment and monitoring, will be known to those skilled in the art in light of the present disclosure. For regulatory approval purposes, it is contemplated that patients chosen for a study are either anti-neoplastic treatment naive or would have failed to respond to at least one course of conventional therapy and would have objectively measurable disease as determined by physical examination, laboratory techniques, or radiographic procedures. Such patients would also have no history of clinically relevant cardiac or renal disease and any chemotherapy should be stopped at least 2 weeks before entry into the study. Prior to application, the formulation can be reconstituted in an aqueous solution in the event that the formulation was freeze dried. As outlined above, the required application volume is calculated from the patient's body weight and the dose schedule. The disclosed formulations may be administered over a short to medium infusion time. The infusion given at any dose level should be dependent upon the toxicity achieved after each. Thus, if Grade II toxicity was reached after any single infusion, or at a particular period of time for a steady rate infusion, further doses should be withheld or the steady rate infusion stopped unless toxicity improved. Increasing doses should be administered to groups of patients until approximately 60% of patients showed unacceptable Grade III or IV toxicity in any category. Doses that are ⅔ of this value would be defined as the safe dose. Physical examination, tumor measurements and laboratory tests should, of course, be performed before treatment and at intervals of about 3-4 weeks later. Laboratory tests should include complete blood cell counts, serum creatinine, creatine kinase, electrolytes, urea, nitrogen, SGOT, bilirubin, albumin and total serum protein. Clinical responses may be defined by acceptable measure or changes in laboratory values e.g. tumor markers. For example, a complete response may be defined by the disappearance of all measurable disease for at least a month, whereas a partial response may be defined by a 50% or greater reduction. All of the compositions and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that variations may be applied to the composition, methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims. Some variation in dosage will necessarily occur depending on the condition of the subject being treated. The person responsible for administration will, in any event, determine the appropriate dose for the individual subject. Moreover, for human administration, preparations should meet sterility, pyrogenicity, general safety and purity standards as required by the FDA Office of Biologics standards. The present invention includes a method of delivery of a pharmaceutically effective amount of the inventive formulation of an active agent to a target site such as an angiogenic vascular target site of a subject in need thereof. A "subject in need thereof" refers to a mammal, e. g. a human. The route of administration preferably comprises peritoneal or parenteral administration. For use with the present invention the "pharmacologically effective amount" of a compound administered to a subject in need thereof will vary depending on a wide range of factors. The amount of the compound will depend upon the size, age, sex, weight, and condition of the patient, as well as the potency of the substance being administered. Having indicated that there is considerable variability in terms of dosing, it is believed that those skilled in the art can, using the present disclosure, readily determine appropriate dosing by first administering extremely small amounts and incrementally increasing the dose until the desired results are obtained. Although the amount of the dose will vary greatly based on factors as described above, in general, the present invention makes it possible to administer substantially smaller amounts of any substance as compared with delivery systems which only target the pathologic tissue, e. g. target the tumor cells themselves.  

Example 2 Twice Weekly Administration Protocol for Cationic Liposomal Paclitaxel (FIG. 1) Indication: Pancreatic Cancer; adenocarcinoma of the pancreas Study Design: A controlled, -three armed, randomized, open label clinical phase II trial 1st line treatment with twice weekly administration of lipid complexed paclitaxel (EndoTAG®-1) in three dose levels compared with gemcitabine monotherapy in patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas is performed. The four treatment arms consist of (see FIG. 1): Arm 1: Gemcitabine monotherapy (control group): 1000 mg/m2 (=25.67 mg/kg body weight) Arm 2: EndoTAG®-1 (low dose: 11 mg/m2 (=0.28 mg/kg body weight) lipid complexed paclitaxel) Arm 3: EndoTAG®-1 (medium dose: 22 mg/m2(=0.56 mg/kg body weight) lipid complexed paclitaxel) Arm 4: EndoTAG®-1 (high dose: 44 mg/m2 (=1.13 mg/kg body weight) lipid complexed paclitaxel) Patients with advanced and/or metastatic adenocarcinoma of the pancreas that are considered unresectable are eligible to enter the study after signing informed consent and having undergone baseline evaluation. Those patients meeting study eligibility criteria will either receive a standardized chemotherapy regime (i.e. gemcitabine) as a monotherapy or EndoTAG®-1 infusions. Seven weekly applications of gemcitabine will be administered in arm 1 (gemcitabine monotherapy control arm without EndoTAG®-1). In arms 2, 3 and 4 seven weeks of fourteen twice weekly applications of EndoTAG®-1 (days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39, 43, and 46) are performed. In summary, one complete cycle of this new regimen comprises fourteen applications of EndoTAG®-1, which then consists of seven weeks (arms 2, 3, and 4).  

Example 3 Combination Therapy of Cationic Liposomal Paclitaxel (EndoTAG®-1) Twice Weekly in Combination with Gemcitabine Once Weekly (FIG. 2) Study No. Indication CT4001 Pancreatic Cancer; adenocarcinoma of the pancreas Study Design CT 4001: A controlled, -four armed, randomized, open label clinical phase II trial 1st line combination treatment with weekly infusions of gemcitabine and twice weekly administration of lipid complexed paclitaxel (EndoTAG®-1) in three single dose levels compared with gemcitabine monotherapy in patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas is performed. The four treatment arms consist of (see FIG. 2): Arm 1: Gemcitabine monotherapy (control group): 1000 mg/m2 (=25.67 mg/kg body weight) Arm 2: Gemcitabine+EndoTAG®-1 (low dose: 11 mg/m2 (=0.28 mg/kg body weight) lipid complexed paclitaxel) Arm 3: Gemcitabine+EndoTAG®-1 (medium dose: 22 mg/m2 (=0.56 mg/kg body weight) lipid complexed paclitaxel) Arm 4: Gemcitabine EndoTAG®-1 (high dose: 44 mg/m2 (=1.13 mg/kg body weight) lipid complexed paclitaxel) Patients with advanced and/or metastatic adenocarcinoma of the pancreas that are considered unresectable are eligible to enter the study after signing informed consent and having undergone baseline evaluation. Those patients meeting study eligibility criteria will either receive a standardized chemotherapy regime (i.e. gemcitabine) as a monotherapy or gemcitabine preceded by EndoTAG®-1 infusions. Seven weekly applications of gemcitabine will be administered in arm 1 (gemcitabine monotherapy control arm without EndoTAG®-1). In arms 2, 3, and 4 seven weeks of gemcitabine treatment (days 4, 11, 18, 25, 32, 39, and 46) will be combined with a total of fourteen twice weekly applications of EndoTAG®-1 (days 1, 4, 8, 11, 15, 18, 22, 25, 29, 32, 36, 39, 43, and 46). In summary, one complete cycle of this new regimen comprises seven applications of gemcitabine (all arms) and fourteen applications of EndoTAG®-1, which then consists of seven weeks (arms 2, 3, and 4). Conclusion Treatments with high doses of EndoTAG®-1 can be replaced by using low doses at a higher frequency. There is a correlation between treatment density (no. of treatments per week) and treatment efficacy. The optimised dosing regimen potentially reduces toxic side effects caused by high dose treatments and reduces physical burden of the patient, which leads to an improved quality of life.  

Example 4 Treatment of Liver Cancer (Hepatocellular Carcinoma) Study Design: A controlled, two-armed, randomized, open label clinical phase II trial, comparing TACE therapy only to TACE (transarterial chemoembolization) therapy combined with once weekly administration of lipid complexed paclitaxel (EndoTAG®-1) is performed. The two treatment arms consist of: Arm 1: TACE therapy alone (control group); Arm 2: TACE therapy in combination with once weekly EndoTAG®-1 (44 mg/m2 lipid complexed paclitaxel). Patients with irresectable histological/cytological proven hepatocellular carcinoma (HCC) who have shown responsiveness to TACE therapy are eligible to enter the study after signing informed consent and having undergone baseline evaluation. Those patients meeting study elegibility criteria are randomized and either receive TACE therapy or TACE therapy in combination with a once a week administration of 44 mg/m2 EndoTAG®-1, an interim analysis determining progression or response based on DCE-MRI and MRI scans is performed. Progression-free-survival (PFS) is determined as the primary efficacy parameter in the study.

Claims 1. A method of treating a human subject suffering from cancer comprising administering to the human subject a pharmaceutical composition comprising a cationic liposomal formulation comprising: wherein the cationic liposomal formulation has a positive zeta potential in about 0.05 M KCI solution at about pH 7.5 at room temperature, wherein the composition is administered at a schedule of: wherein the pharmaceutical composition is administered at a dose of paclitaxel from about 0.05 mg/kg to about 1.88 mg/kg body weight (bw) of the subject, wherein a total monthly dose of paclitaxel administered is from about 0.1 mg/kg to about 15 mg/kg bw of the subject, and wherein the cancer is pancreatic cancer, liver cancer, prostate cancer, breast cancer, lung cancer, gastrointestinal cancer, or melanoma. at least one cationic lipid from about 30 mole % to about 99.9 mole %, paclitaxel in an amount of at least about 0.1 mole %, and optionally a neutral and/or anionic lipid, (i) once a week, (ii) twice a week, or (iii) a combination of (i) and (ii), 2. The method of claim 1, wherein the pharmaceutical composition is administered at a dose of paclitaxel from about 0.25 mg/kg to about 1.54 mg/kg bw of the subject, about 0.25 mg/kg to about 1.25 mg/kg bw of the subject, about 0.25 to about 1.13 mg/kg bw of the subject, about 0.28 to about 1.13 mg/kg bw of the subject, about 0.28 to about 0.94 mg/kg bw of the subject, or about 0.28 mg/kg bw to about 0.75 mg/kg bw of the subject. 3. The method of claim 1, wherein the pharmaceutical composition is administered at a dose of paclitaxel of about 0.28 mg/kg bw of the subject, about 0.56 mg/kg bw of the subject, about 1.13 mg/kg bw of the subject, or about 1.54 mg/kg bw of the subject. 4. The method of claim 1, wherein the total monthly dose is from about 1 mg/kg to about 15 mg/kg bw of the subject, about 0.5 mg/kg to about 7.5 mg/kg bw of the subject, about 1.1 mg/kg to about 6.2 mg/kg bw of the subject, about 1.1 mg/kg to about 4.5 mg/kg bw of the subject, about 2.2 mg/kg to about 6.2 mg/kg bw of the subject, or about 2.2 mg/kg to about 4.5 mg/kg bw of the subject. 5. The method of claim 1, wherein the pharmaceutical composition is administered at a schedule of once a week. 6. The method of claim 1, wherein the method further comprises administering to the human subject at least one further active agent and/or heat and/or radiation and/or cryotherapy. 7. The method of claim 6, wherein the pharmaceutical composition and the at least one further active agent and/or heat and/or radiation and/or cryotherapy are administered simultaneously, separately, or sequentially. 8. The method of claim 6, wherein the further active agent is a chemotherapeutic agent. 9. The method of claim 6, wherein the further active agent is an alkylating agent, a DNA topoisomerase inhibiting agent, a RNA/DNA antimetabolite, an anti-endothelial cell active agent, an anti-tumor active agent, an immunological active agent, or a chemosensitizer. 10. The method of claim 9, wherein the immunological active agent is a compound that reduces or eliminates a hypersensitivity reaction. 11. The method of claim 10, wherein the compound that reduces or eliminates a hypersensitivity reaction is ranitidine, dexamethasone, diphenhydramine, famotidine, hydrocortisone, clemastine, cimetidine, prednisolone, chlorphenamine, dimethindene maleate, or promethazine. 12. The method of claim 9, wherein the chemosensitizer is a cell cycle modulator, a substance that reverts drug resistance, and a vasoactive substance. 13. The method of claim 1, wherein the cationic liposomal formulation comprises paclitaxel in an amount of about 2 mole % to about 8 mole %. 14. The method of claim 13, wherein the cationic liposomal formulation comprises paclitaxel in an amount of about 2.5 mole % to about 3.5 mole %. 15. The method of claim 1, wherein the cationic liposomal formulation comprises 50:47:3 mole % of DOTAP, DOPC, and paclitaxel. 16. The method of claim 1, wherein the cationic liposomal formulation comprises liposomes having an average particle diameter from about 25 nm to about 500 nm, or about 100 nm to about 300 nm. 17. The method of claim 1, wherein the pharmaceutical composition is administered systemically. 18. The method of claim 7, wherein the further active agent is cisplatin, carboplatin, camptothecin, doxorubicin, 5-flurouracil, gemcitabine, thalidomide, discodermolide, laulimalide, isolaulimalide, eleutherobin, sarcodictyin A, or sarcodictyin B. 19. The method of claim 1, wherein the cationic lipid is selected from the group consisting of N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethyl ammonium salt (DOTAP); dimethyldioctadecyl ammonium bromide (DDAB); 1,2-diacyloxy-3-trimethylammonium propane N-[1-(2,3-dioloyloxy)propyl]-N, N-dimethyl amine (DODAP); 1,2-diacyloxy-3-dimethylammonium propane; N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA); 1,2-dialkyloxy-3-dimethylammonium propane; dioctadecylamidoglycylspermine (DOGS); 3β-[N-(N′,N′-dimethylamino-ethane)carbamoyl]cholesterol (DC-Chol); 2,3-dioleoyloxy-N-(2-(sperminecarboxamido)-ethyl)-N, N-dimethyl-1-propanaminium trifluoroacetate (DOSPA); β-alanyl cholesterol; cetyl trimethyl ammonium bromide (CTAB); diC14-amidine; N-tert-butyl-N′-tetradecyl-3-tetradecylamino-propionamidine; 14Dea2; N-(alpha-trimethylammonioacetyl)didodecyl-D-glutamate chloride (TMAG); O,O′-ditetradecanoyl-N-(trimethylammonioacetyl)diethanolamine chloride; 1,3-dioleoyloxy-2-(6-carboxy-spermyl)-propylamide (DOSPER); N,N,N′,N′-tetramethyl-N,N′-bis(2-hydroxylethyl)-2,3-dioleoyloxy-1,4-butanediammonium iodide; 1-[2-(acyloxy)ethyl]-alkyl (alkenyl)-3-(2-hydroxyethyl)-imidazolinium chloride; 1,2-dioleoyl-3-dimethyl-hydroxyethylammonium bromide (DORI); 1,2-dioleyloxypropyl-3-dimethylhydroxyethylammonium bromide (DORIE); 1,2-dioleyloxypropyl-3-dimethylhydroxypropylammonium bromide (DORIE-HP); 1,2-dioleyloxypropy-3-dimethylhydroxybutylammonium bromide (DORIE-HS); 1,2-dioleyloxypropyl-3-dimethylhydroxypentylammonium bromide (DORIE-Hpe); 1,2-dimyristyloxypropyl-3-dimethylhydroxylethylammonium bromide (DMRIE); 1,2-dipalmityloxypropyl-3-dimethylhydroxyethylammonium bromide (DPRIE); 1,2-disteryloxypropyl-3-dimethylhydroxyethylammonium bromide (DSRIE); and 1,2-diacyl-sn-glycerol-3-ethylphosphocholine. 20. The method of claim 19, wherein the 1-[2-(acyloxy)ethyl]2-alkyl (alkenyl)-3-(2-hydroxyethyl)-imidazolinium chloride is 1-[2-(9(Z)-octadecenoyloxy)ethyl]-2-(8(Z)-heptadecenyl-3-(2-hydroxyethyl)-imidazoliniumchloride (DOTIM) or 1[2-(hexadecanoyloxy)ethyl]-2-pentadecyl-3-(2-hydroxyethyl)imidazolinium chloride (DPTIM). 21. The method of claim 1, wherein the neutral lipid is selected from the group consisting of cholesterol, phospholipid, lysolipid, sphingolipid, and pegylated lipid with a neutral charge. 22. The method of claim 21, wherein the neutral lipid is lysophospholipid. 23. The method of claim 1, wherein the neutral lipid is selected from the group consisting of 1,2-diacyl-sn-glycero-3-phosphoethanolamine, 1,2-diacyl-sn-glycero-3-phosphocholine, and sphingomyelin. 24. The method of claim 23, wherein 1,2-diacyl-sn-glycero-3-phosphoethanolamine is 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). 25. The method of claim 23, wherein 1,2-diacyl-sn-glycero-3-phosphocholine is 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). 26. The method of claim 1, wherein the cationic liposomal formulation comprises DOTAP, DOPC, and paclitaxel. 27. The method of claim 1, wherein the cationic liposomal formulation further comprises an anionic lipid in an amount of 30 mole % to 55 mole %. 28. The method of claim 9, wherein the RNA/DNA antimetabolite is 5-fluorouracil or gemcitabine. 29. The method of claim 17, wherein the pharmaceutical composition is administered intravenously. 30. The method of claim 1, wherein the pharmaceutical composition is administered for at least one month, at least seven weeks, at least three months, at least four months, at least six months, at least twelve months, or at least 24 months. 31. The method of claim 30, wherein the pharmaceutical composition is administered for up to six months, up to twelve months, up to eighteen months, or up to 24 months.