標靶抗糖酵解治療對乳癌有用


  【24drs.com】對於乳癌治療,併用兩種新策略—代謝治療與影像導引—比目前的手術切除腫瘤更有效。
  
  約翰霍普金斯大學醫學院血管與介入放射科主任、放射科、外科與腫瘤科教授Jeff H. Geschwind醫師在介入放射科協會第36屆年會中發表研究結果,新治療策略運用腫瘤代謝與介入放射科在微創治療策略中的豐富經驗。
  
  Geschwind醫師等人使用一種微創超音波導引、腫瘤內治療策略,將抗糖酵解製劑-3-溴丙酮酸(3-BrPA)直接注入老鼠的乳房腫瘤;這個策略直接使3-BrPA以最大化方式到達腫瘤,並使健康組織曝露於3-BrPA的程度最小化;治療組和對照組老鼠之間,腫瘤大小的差異相當顯著。使用5 mmol/L 3-BrPA治療的組別,治療第6天即可見療效(治療組256 mm3、對照組1809 mm3;P< .05);使用1.75 mmol/L 3-BrPA治療的組別中,在第12天見到療效(治療組1160 mm3、對照組4188 mm3;P< .05)。
  
  Geschwind醫師還提及,研究團隊為了確認對乳癌細胞的半抑制濃度,研究設計設定為200 mol/L,以體外劑量相關之三磷酸腺苷值為計算依據,開始的濃度則為50 mol/L的3-BrPA;當使用傷口轉移分析檢測時,使用100 mol/L的3-BrPA治療則乳癌細胞穿透率比未治療的對照組細胞降低達70%。
  
  約有八分之一婦女會有乳癌診斷,乳癌是美國婦女癌症死亡率第二高,提高癌症警覺度和落實篩檢計畫使得診斷時為早期腫瘤的比率增加;不幸的是,有相當多病患在化療或放射線治療的初步反應後卻是治療失敗。
  
  大部分的癌症細胞會抑制產能之酵解路徑的上調,Geschwind醫師解釋,癌細胞有一個獨特尋找足夠葡萄糖來滿足需求的方式,正常細胞和癌細胞、及其葡萄糖需求之間有很大的差異,這也是可以進行標靶治療的地方。
  
  治療目標是針對癌細胞生長過程,並在2至4次注射之間凍結癌細胞轉移過程;藉由降低基質金屬蛋白酵素-2(MMP)和MMP-9的表現與活性而達到此目標,這些酵素是腫瘤細胞轉移和侵犯所必須。
  
  芝加哥西北大學放射科、研究副主席、生醫工程與放射科教授Reed A. Omary醫師表示,如果這個治療可以成功地運用到病患,將會有重大影響,因為乳癌對婦女影響相當廣泛;乳癌治療選項持續進展,當介入放射科使用影像導引治療身體其他部位(大部分用在肝臟)腫瘤時,Geschwind醫師的新研究將這種局部治療的觀念拓展到乳癌。
  
  全身性方式給予3-BrPA治療時會引起副作用,以標靶方式給藥時,產生的副作用較少。
  
  雖然Geschwind醫師等人的研究目前僅處於動物研究階段,但在以色列曾依特別許可使用於治療兩個病患,結果看來是有效的。Geschwind醫師指出,我們有諸多進步,但是,我們必須提出新藥研發申請,他預期這也可運用到肝癌。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6568&x_classno=0&x_chkdelpoint=Y
  

Targeted Antiglycolytic Therapy Promising in Breast Cancer

By Lara C. Pullen, PhD
Medscape Medical News

July 8, 2011 (Chicago, Illinois) — The combination of 2 innovative strategies — metabolic therapy and imaging guidance — is more effective than the current treatments of surgical resection or tumor removal in the treatment of breast cancer.

Jeff H. Geschwind, MD, FSIR, professor of radiology, surgery, and oncology and director of vascular and interventional radiology at Johns Hopkins University School of Medicine in Baltimore, Maryland, presented the results of a study here at the Society of Interventional Radiology 36th Annual Scientific Meeting. The novel treatment strategy exploits tumor metabolism and leverages the interventional radiology's vast experience in minimally invasive treatment strategies.

Dr. Geschwind and colleagues used a minimally invasive ultrasound-guided intratumoral treatment strategy to deliver the antiglycolytic agent 3-bromopyruvate (3-BrPA) directly to breast tumors in mice. The strategy maximized 3-BrPA delivery to the tumor and minimized the exposure of healthy tissue to the 3-BrPA. The result was a statistically significant difference in tumor volume between treated and control mice. In the group treated with 5 mmol/L 3-BrPA, results were seen on day 6 of treatment (256 vs 1809 mm3 in the control group; P < .05); in the group treated with 1.75 mmol/L 3-BrPA, results were seen on day 12 (1160 vs 4188 mm3; P < .05).

Dr. Geschwind also presented data describing the research team's work to determine the half maximal inhibitory concentration of the breast cancer cell line used in the study (200 μmol/L). They characterized an in vitro dose-dependent decrease in adenosine triphosphate levels, starting at a concentration of 50 μmol/L of 3-BrPA. When tested using a wound-migration assay, the penetration of breast cancer cells treated with 100 μmol/L of 3-BrPA decreased by 70%, compared with untreated control cells.

One in 8 women is diagnosed with breast cancer during her life, and breast cancer is the second leading cause of cancer death in women in the United States. Increased cancer awareness and the implementation of screening programs have resulted in an increased proportion of early-stage carcinomas at the time of diagnosis. Unfortunately, a significant number of patients experience treatment failure after an initial response to chemotherapy or radiation.

Most cancer cells exhibit upregulation of the energy-producing glycolytic pathway. Dr. Geschwind explained to Medscape Medical News that "cancer cells have a unique way of finding enough glucose to satisfy their needs. There is a big dichotomy between normal cells and cancer cells and their needs for glucose. This is something that can be targeted."

The goal of therapy is to treat the process of cancer growth and to freeze the process of cancer metastases with 2 to 4 injections. It appears to do this by decreasing the expression and activity of matrix metalloproteinases (MMP)-2 and MMP-9, which are required for the migration and invasion of tumor cells.

Reed A. Omary, MD, MS, professor of radiology and biomedical engineering and vice chair of research in the Department of Radiology at Northwestern University in Chicago, Illinois, discussed the research with Medscape Medical News. "If this therapy can be successfully translated to patients, it could have a significant impact, as breast cancer affects so many women. Treatment options for breast cancer continue to evolve. While interventional radiologists have used imaging guidance to treat tumors elsewhere in the body (most commonly in the liver), Dr. Geschwind's innovative research expands this concept of local therapy to breast cancer."

When administered systematically, 3-BrPA therapy causes adverse effects. As targeted therapy, it appears to result in few adverse effects.

Although the research by Dr. Geschwind's team has thus far been performed primarily in animals, the protocol has been used to treat a couple of patients in Israel on a compassionate-use basis. The results were promising. Dr. Geschwind notes: "We have made a lot of progress, but we have to make an Investigational New Drug Application." He anticipates that this application will target liver cancer.

Dr. Geschwind reports serving as a consultant to Biosphere Medical, Biocompatibles, Bayer HealthCare, Guerbet, and MDS Nordion. Dr. Omary has disclosed no relevant financial relationships.

Society of Interventional Radiology (SIR) 36th Annual Scientific Meeting: Abstract 8. Presented March 29, 2011.

    
相關報導
芳香酶抑制劑:對治療癌症有幫助,但有心臟風險?
2016/12/28 上午 09:56:32
針灸可以舒緩乳癌引起的熱潮紅
2015/9/15 上午 11:09:59
乳房X光攝影發現乳癌:對年長婦女有幫助
2014/8/13 上午 10:29:47

上一頁
   1   2   3   4   5   6   7   8   9   10  




回上一頁