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二氯乙酸鹽可治多種癌症

(2010-04-11 18:42:23) 下一個

二氯乙酸鹽可治多種癌症 (轉貼)

加拿大研究人員一項最新研究顯示,多年來用於治療新陳代謝紊亂症的廉價藥物二氯乙酸鹽可以殺死多種癌細胞。

據最新一期英國《新科學家》雜誌報道,加拿大艾伯塔大學的研究人員用這種藥物對在體外培養的人體各種細胞進行了測試,發現它能殺死肺癌、乳癌和腦癌細胞,但對健康細胞沒有損害。

報道說,研究人員對實驗鼠的試驗也證實了這一結論。研究人員給實驗鼠注射癌細胞,促使其體內生長腫瘤,然後數周給它們喂食加入二氯乙酸鹽的水,結果發現實驗鼠體內的腫瘤明顯縮小了。

迄今,人們一直認為,由於細胞的線粒體遭受無法修複的損壞,癌變細胞利用糖酵解產生乳酸,破壞使細胞聚集在一起的膠原質矩陣,這樣癌變細胞就可以得到釋放,流向人體其他部位,形成新腫瘤。但加拿大研究人員的實驗表明,情況並非不可挽回,因為二氯乙酸鹽能再度喚醒癌細胞中的線粒體,激活細胞凋亡機製,促使癌變細胞死亡。

研究人員說,二氯乙酸鹽對一些病人來說可能會引起疼痛、麻木等問題,但如果它對治療許多癌症都有效果,服用這種藥物所付出的代價也許是值得的。 研究人員計劃下一步用二氯乙酸鹽對癌症病人進行臨床試驗。

二氯乙酸鹽的毒副作用zt

二氯乙酸鹽毒副作用的發生率不高,但對其毒副作用的報道很有一致。在一般治療劑量(12.5~50mg/kg)下,無論是健康誌願者還是不同病因的乳酸酸中毒和心肌或腦缺血患者,均隻有個別出現毒副作用,主要表現為疲倦、鎮靜等。即便有較為嚴重的外周神經係統症狀,停藥後即自行消失,並未發現不可逆的器質性損傷。對大鼠進行的慢性毒性試驗顯示,大劑量二氯乙酸鹽(一日1100 mg/kg),從第4周開始發生神經毒性症狀,表現為運動行為和神經反射異常,以及體重和紅細胞中酮醇轉移活性降低。而這些毒性症狀可通過口服維生素 B1,一日0.6 mg/kg所改善,不影響體重變化。在相同試驗中給予一般治療劑量的二氯乙酸鹽(一日50 mg/kg),無上述毒性症狀發生。中樞神經毒副作用發生的原因可能在於缺乏維生素B1,因為二氯乙酸是丙酮酸脫氫酶複合物和支鏈a酮酸脫氫酶的激動劑,而這兩種酶都依賴於維生素B1,使用二氯乙酸可能增加機體對維生素B1需求,進而造成維生素B1缺乏。所以在二氯乙酸鹽製劑中加入維生素Bl,有助於減少毒副作用的發生,並對毒性症狀有治療作用,由於二氯乙酸鹽抑製其自身的代謝,給藥劑量和時間間隔對其毒副作用的發生可能有重要影響。

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晚期癌症的替代療法 ---DCA

by網友:qiuqiu04

我的嶽父於八年前患有賁門癌, 手術切除後的病理診斷是第三期賁 門癌。計劃中的四個療程的手術後化療,因為毒性反應太大,而未能堅持完成(隻做了兩個療程)。西安醫學院的外科手術醫生預見他隻能生存三年。最後嶽父征求 我的意見,我認為, 西方醫學普遍公認的手術後全計劃療程的化療,它不但摧毀了癌細胞,也同時摧毀了病人自身的抗癌免疫係統(正氣與邪氣都被摧毀),這與中醫的扶正祛邪概念相 左。從我所熟識的許多朋友患者, 老師及同學的病例, 教會裏的癌症患者的許多親身經驗裏, 我認識到,他們很可能是被過度的美式化療打死的。西式的全程化療,其實是得不償失。這樣大劑量長時間的化療至少不是在中國病人的身上試驗出來的。它們是從 白人和黑人患者身上的試驗結果。如果你參考中國科學院院士,北京日壇醫院腫瘤科的科主任孫燕的化療專著,他把西方的化療概念與東方的扶正祛邪的概念結合起 來,形成了適合東方人的手術後的化療方案, 既要摧毀殘餘的癌細胞,又要激活患者的抗癌免疫淋巴係統,就需要中西醫結合。孫燕曾經是我的老師,上世紀八零年在休士頓留學,專攻美式化療。他是國內醫學 界被最先摘冒的右派份子(因為中央領導人需要懂化療的人)。我根據他的不同於洋教條的概念,決定給嶽父嚐試一項替代療法 ---- 免去剩下的二個化療療程, 改為“貞芪扶正膠囊”, 外加《二氯乙酸》, 至今嶽父仍然生存著, 他的壽命已遠遠超越國內手術醫生的預期(八年 vs 三年)。對於《二氯乙酸》,我研究它在三羧酸循環中的作用多年。直到 2008 年, 加拿大阿爾貝塔大學的

Michelakis

教授發現它還能在試驗鼠身上有效的縮小肝癌實體的效果, 才引起我對它的另類注意。我對教會的癌症患者和一些晚期癌症朋友建議了采用《二氯乙酸》,從網上幫他們購買到《二氯乙酸》,他們都有體力和精力的明顯改 善,也延長了生命(大於化療醫生的生命預期)。下麵引述其他人的臨床試驗。需要說明的是,任何新生事物都是要麵臨大量的洋教條和執照醫生反對者們的聲音的。我自備了一些《女貞子黃芪扶正膠囊》和《二氯乙酸》,郵寄給國內的嶽父使用。對於那些願意采用此項替代療法來延長晚期癌症患者生命的人, 希望您首先閱讀大量的最新文獻, 自己拿主意。國內有一個《癌症之友》論壇, 主要討論《二氯乙酸》抗癌的經驗交流網站, 網址是 --- http://www.e0575.cn/...&page=e。需要說明的是, 大劑量的《二氯乙酸》可以引起末梢神經炎(四肢有手套襪子型皮膚感覺麻木), 需要加服複合維生素B族, 特別是B1.


Cancer Care » Dichloro Acetic Acid


DCA—my clinical experiences—intravenous and oral uses

By Walter Lemmo, ND, FABNO
When Dr. Michelakis from the University of Alberta published his research showing how a simple vinegar-like chemical could have the ability to kill cancer cells in the laboratory back in October 2008 (and the following media attention he received) some of my more eager patients became enthralled with this potential chemotherapeutic agent and as a consequence so did my learning begin into DCA. Interestingly, the first data I found using DCA & cancer was published by a Dr. Pan from the Campbell Family Institute for Breast Cancer Research in Toronto back in April 2007.

As the name implies, DCA is short for Dichloro Acetic acid or Dichloro Acetate. It has a history in medicine for helping to treat a group of metabolic diseases (i.e. mitochondrial genetic diseases) in children primarily but also in adults for several decades. It has also been more loosely studied in other fields of medicine as well (i.e. exercise, COPD, heart failure, etc.). Because it is a rather simple chemical to make, it is considered a fairly inexpensive medicine. Moreover, because of its simplicity and low cost, most drug companies do not pay much attention to its use because of the more limited money or profit which can be generated as compared to medicines which are patentable or where the intellectual property (IP) can be secured.
I was happy to see the publicity that Dr. Michelakis had managed to stir about DCA and its relationship in cancer care and also exposing some of the politics behind getting non-patentable and lower cost medicines into more main-stream medicine. I even recall seeing Dr. Michelakis on CNN Larry King show on TV. As a consequence of this publicity, whether I wanted my patients to or not, the use of DCA for the treatment of their cancer(s) had become more of a common theme (i.e. it was becoming out of my control). Internet websites were popping up all over the place, selling DCA and providing treatment advice. Since that time, here in Canada and in the United States, DCA has been placed into a prescription category and its use has become more limited and regulated.
What I decided, in order to better help my patients the best I could, was to help those individuals who were interested in using DCA and at the very least monitor and try help avoid any unforeseen danger. When you are more specialized in the area of cancer like myself, you are better able to follow up patients, order the appropriate testing and perform the examinations to make sure that things are moving in the right direction or, conversely, to make suggestions or recommendations if things are going in the wrong direction.
Throughout the years of monitoring my patients with DCA, which included its eventual side-effect in causing numbness in the body (i.e. hands, feet, face, etc.), I had an inclination as to what its more dominant value would be in oncology medicine.
Case No. 1: anaplastic oligodendroglioma (1p/19q chromosome normal)—brain cancer

One of the first patients where I suggested the use of DCA was in a 39 year old woman who was diagnosed with a type of brain tumor known as an Anaplastic oligodendroglioma. She received surgery to get as much of the tumor the surgeon could (some was left behind) followed by radiation and the oral chemo pill known as Temozolomide which she continues to this day. The patient was stable for over a year receiving a comprehensive naturopathic oncology treatment alongside her standard oncology care. The patient thrived throughout. What was more unique about this patient versus others, however, is that even though her brain tumor was stable and she could be this way for many, many years as several of my patients have demonstrated, she had a goal of wanting the tumor completely gone! It was during this process (and eventual push) where DCA had come into question and her desire would become a greater reality.
I had noticed that DCA caused numbness in the hands & feet as a common side-effect which for me implied that the medicine managed to penetrate into the nervous system and possibly the brain and have an effect there. Based on these observations and gaining a better comfort with DCA, together, we decided to incorporate DCA into her protocol and see how things would go. However, in this case, while most patients were using DCA orally (in pill or powder form), I used an intravenous form that I used in helping out another patient with advanced ovarian cancer. To my knowledge, there was nobody else using DCA intravenously for the treatment of cancer anywhere and this was the first way on how I began using it. There is data using DCA by injection for non-cancer related medical conditions in research papers (i.e. COPD, exercise, congestive heart failure) which gave me some security about its potential use and safety for patients.
During the very first injection, the patient with brain cancer began to experience a “tingling” sensation in the area of the tumor site on her head. I had never seen this before in my years of specializing in cancer. I had initial concerns whether this was a good effect or a negative effect (which I later learned was OK). Together we continued a protocol of DCA twice weekly combined with low doses of vitamin C and B-vitamins mixed into the intravenous bag to theoretically help with any potential nervous system side-effects. Moreover, throughout, the patient also continued on the oral Temozolomide chemotherapy (there was no negative interaction). We had noticed that as time progressed, the tingling sensation in her head subsided and we were not certain what this had meant. The next MRI scan revealed again a stable image, and in the following several months, another MRI scan of the brain indicated the tumor was either dead or inactive. This observation was a wonderful outcome! Was this due to the combination of DCA and chemotherapy, DCA or the chemotherapy agent alone? Typically in this kind of brain tumor subtype, chemotherapy is considered not as effective and survival is poorer as compared to those with more favourable genetics (i.e. 1p/19q chromosome deletion). It has now been over 3 years and the patient continues to do extremely well. She looks fantastic, she is energetic, and she has also wed to her long-time love. She receives DCA intravenously every 1-2 months as part of a maintenance plan, along with the chemotherapy pill Temozolomide, and a naturopathic cancer care program.
Case No. 2: NSCLC—brain metastasis

In another case, a 49 year old, non-smoker woman with a history of lung cancer better demonstrated the value of DCA and its effects on the body & brain. This patient was initially diagnosed with stage III lung cancer in 2006 and managed to respond amazingly well along with an extremely devoted Acupuncturist (i.e. Gerard Tan in Vancouver), an integrated cancer care approach, and the oral chemo-agent Tarceva for over 2 years. She had no signs of tumors throughout this period which was impressive in itself when you compare to the standard conventional statistics oncologists tell you. She too thrived during this time without any complications other than a rash which was a positive sign of the Tarceva. Unfortunately, following this golden time she presented with a low grade headache that was eventually determined to be a tumor in her brain in July 2008 (i.e. leptomeningial carcinomatosis and frontal lobe areas). She received radiation which did not appear to be helpful and she later received a surgical stent in her brain to help drain the fluid that tended to accumulate there from the cancer. Chemotherapy was no longer an option. When I eventually saw her in my office, both her hearing and vision was quite poor (damaged) as a side-effect of the radiation treatment, and she had lost a fair deal of weight. I personally felt that her time left with us was going to be very short (i.e. weeks)—I was wrong. The patient, like the previous, had a continued desire to live and she placed the pressure on me to help figure out a solution—For the second time. After a series of attempts in recommending treatment ideas, I introduced the possibility of DCA. I shared with the patient’s husband my personal views about using DCA and its potential to target cancers in the brain and nervous system. Consequently, together with the patient’s husband, I suggested for the patient to take DCA orally mixed in juice. In addition, the Acupuncturist Gerard Tan continued to provide treatments which included home visits by this time (which helped tremendously). I received a phone call a few days later from her devote husband after beginning DCA that he noticed his wife’s cognition was much improved. Weeks continued and so did the improvement. Eventually, a CT scan of the brain was ordered in December (3 months later) which showed the tumors had shrunk and the brain was stable (i.e. a response to leptomeningeal carcinomatosis is truly noteworthy since there is not much out there especially in this kind of scenario)! Interestingly though, the cancer in her lungs was growing and so it appeared to confirm my intuition about DCA’s predominant role for helping from the “neck up” and not so much from the “neck down”. What was good, however, is because the brain was not the primary problem anymore, this opened up chemotherapy options once again (she was also seeing a progressive medical oncologist which helped). She continued with DCA alongside for another 6 months which she later stopped. Three months later a repeat CT scan was ordered showing the brain continued to be stable even though the DCA had stopped but, unfortunately, not the lungs. After a long battle, the patient eventually passed away from her lung cancer disease about 1.5 years after the cancer had spread to the brain—a statistical wonder. I recall the oncologist telling the family that she would be deceased by Christmas 2008, ironically this turned out close to be true—but rather the year was incorrect (i.e. the following Christmas 2009). Interestingly, the brain was not the problematic area throughout this period even though DCA was stopped for 6 months prior to her passing.
Case No. 3: ATRT Grade IV – brain cancer

One of the youngest patients to have received DCA is a 21 month old infant with a diagnosis of Atypical Teratoid Rhabdoid Tumor (ATRT) Grade IV in April 2010. This type of brain cancer is extremely rare and aggressive. Because there have been so few cases of this disease (i.e. 5-7 cases across Canada), the conventional treatments & options are more experimental (i.e. like DCA) and the outcomes thus far have been quite poor. As a consequence of this, the parents decided to try less harmful treatment approaches first and if there were signs of disease progression, changing the game plan would be in order. One of the recommendations I suggested was the use of DCA amongst other things. While I’ve never used it in a paediatric setting, I knew it would be easy to take (mix in juice), it appeared safe, and I suspected that the potential positives outweighed the potential negatives (which I knew from adults the negative effects were reversible). Keep in mind that the primary use of DCA originated in children with metabolic diseases for several decades. Along with a naturopathic oncology program, we very cautiously began the use of DCA. At first, the medical oncologist has hesitant on the idea. As months passed and the infant did not show any signs of disease progression, the oncologist’s views began to change in a much more positive direction. Eventually, he began refilling the prescription of DCA for the family personally. On September, 2010, an MRI was ordered which revealed that the brain tumor had grown again. As you can imagine, this was a tremendous disappointment for everyone. However, the medical oncologist had felt that there was, in fact, a positive benefit. He suspected that the grow rate of the tumor had actually slowed down (i.e. instead of doubling every 15 days, it doubled every 30 days). Because the child was taking more than DCA as a treatment, we do not know which of the recommendations could help account for this effect. However, I hope that this can serve as an example for future parents and oncologists, to consider incorporating DCA, perhaps in higher doses, (and other naturopathic approaches) alongside other standards of care so that a better response can be ultimately attained for future children.
Patients often ask how DCA targets or impacts cancer in the body. It appears that a large part of how DCA works to kill cancer cells is by affecting their mitochondria function which is the “battery” center. DCA may interfere in the way the cancer cells use energy leaving them somehow more vulnerable. This effect is a newer way of targeting cancer cells from a metabolic point of view which stems from some very old research by Dr. Otto Warburg (i.e. the noble prize winner in 1931). Basically, he had shown that cancer cells use sugar to grow (i.e. the Warburg-Effect) and so by interfering in that metabolic energy process could potentially disrupt more sensitive growing cancers. There is also a recent study in a colon cancer cell line showing when the oxygen environment is normal, the cancer cells dies with DCA (i.e. apoptosis). However, it was also observed that when the environment is low in oxygen (i.e. hypoxic) DCA appeared to be more protective for the cancer which implies some caution, and that oxygen or oxidative mechanisms may also be involved in how it selectively kills cancer.
What are the concerning side-effects or toxicity concerns with using DCA? We have to first remember that DCA is considered an environmental hazardous chemical of which chronic use has been shown in mice to be damaging to the liver and induce cancer growth. Ironically, the DCA doses used in animal toxicology experiments are very similar to those used clinically or as a medicine for the chronic or acute treatment of metabolic or cardiovascular diseases. So for patients who are considering long-term use of DCA, and especially in those who are using DCA for reducing their cancer recurrence risks (i.e. long-term users), this may be something to consider.
The more common side-effect which I see in practice is numbness & tingling symptoms. In my experience, this effect has been reversible upon discontinuation and we have patients who have been using DCA for over 2 years. We have not seen any point of concern thus far. Older patients may be more sensitive to these side-effects than younger patients. In unmonitored patients, there has been a recent published case where DCA caused very bad numbness and severe brain irritation (i.e. encephalopathy) in a patient with metastatic melanoma after using DCA for only 1 month (1200mg/day) along with high doses of vitamin A (150,000 IU/day) and it took over 8 months for the person to recover which involved physical therapy. I have not personally seen this. A personal communication with the author of this reported revealed that the patient had lived for over 3 years with this metastatic disease which, by conventional standards, is considered extremely impressive (i.e. above average). Nonetheless, it is strongly advised that patients need to be medically monitored while using DCA!
Another more common side-effect when DCA is used orally, because of the vinegar-like properties, it may irritate the stomach and especially in those who are sensitive already. It may be advised that in interested patients, that a stomach protective medicine be used alongside DCA.
In mainstream literature there have been 5 cases in patients with brain tumors (i.e. Glioblastoma) where 3 patients appeared to respond on MRI scan and 4/5 were stable after 15 months. DCA was used alongside their conventional treatment program. There is also a recent case report of a patient with Non-Hodgkin’s Lymphoma Stage IV who has gone into remission after beginning DCA alone. There are other medical centers, like myself, who have yet to publish some of their positive findings in journals (which I will to do in the near future).
According to new research from Dr. Michelakis in Alberta, it was shown that approximately a 3 month period of time was needed before DCA can be detected in the blood when used orally. Perhaps it better accumulates in tissues and the cerebral spinal fluid, which is not common or more difficult to test. I suspect that an initial loading dose may be needed followed by a maintenance oral dose in most patients to attain an optimal therapeutic effect. The intravenous route may be an ideal means for patients who are able do this followed by an oral maintenance dosing program (i.e. the same has been observed with the use of vitamin C oral vs intravenous)
I suspect the ideal situation for most using DCA is combined together with chemotherapy/radiation protocols as they may better enhance each other. I know that most oncologists warn patients about negative interaction concerns especially when dealing with experimental agents like DCA, but there are creative ways of cycling situations (i.e. breaks in between) for those that are worried and want to do both. There has been some more recent test-tube research showing that DCA is OK with Temozolomide but not with cisplatinum and doxorubicin, however, in another paper it synergized or worked well with cisplatinum and topotecan. There is not enough data either for or against the use of DCA with chemotherapy agents (just like most drugs), so it does become a person’s individual choice. Like my patient with brain cancer who has taken DCA together with her chemo, her choice has translated to an above average response so far.
In conclusion, in my experiences and personal views, DCA appears to have a better affinity for targeting cancers in the brain & nervous system for some reason (whether it started or spread there) and it also appears to work quickly when the conditions are right which is why a whole-person approach to cancer is important. In patients with cancers which have tendencies for spreading to the brain and central nervous system (i.e. advanced lung, melanoma, kidney, and breast cancers) DCA may also have potential for acting as a preventative or protective agent as well? To my knowledge only radiation is used in this capacity.
Because DCA is a prescriptive item in Canada and the US, people who are interested in its use need to be evaluated by a licensed healthcare professional and preferably by one who has cancer care experience. In addition, we have been exploring the use of DCA by intravenous injection and it may hold an added key in helping patients in more acute situations, where time is critical to achieve a quicker therapeutic effect.
References
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  • Michelakis ED et al. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. British J Cancer 2008;99:7:989-94
  • Michelakis ED et al. Metabolic modulation of glioblastoma with dichloroacetate. Sci Transl Med 2010; 2:31:31ra34
  • Barshop BA, et al. Chronic treatment of mitochondrial disease patients with dichloroacetate. Mol Genet Metab 2004; 83:1-2:138-49
  • Mercken EM et al. Dichloroacetate modulates the oxidative stress and inflammatory response to exercise in COPD. Chest 2009; 136:3:744-51
  • Papandreou I, et al. Anti-cancer drugs that target metabolism, is dichloroacetate the new paradigm? Int J Cancer 2010 Oct 18
  • Brandsma D et al. Severe encephalopathy and polyneuropathy induced by Dichloroacetate. J Neurol July 15 2010
  • Heshe D, et al. Dichloroacetate metabolically targeted therapy defeats cytotoxicity of standard anticancer drugs. Cancer Chemother Pharmacol 2010 May 26
  • Stockwin LH, et al. Sodium dichloroacetate selectively targets cells with defects in the mitochondrial etc. Int J Cancer 2010; 127:11:2510-9
  • Cao W et al. Dichloroacetate (DCA) sensitizes both wild-type and over expressing Bcl-2 prostate cancer cells in vitro to radiation. Prostate 2008; 68:11:1223-31
  • Shahrzad S et al. Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia. Cancer Lett. 2010; 297:1:75-83
  • Flavin DF. Non-Hodgkin's Lymphoma Reversal with Dichloroacetate. J Oncol 2010 Sep 16; Epub:pii: 414726.
  • Stacpoole PW. et al. Clinical pharmacology and toxicology of dichloroacetate. Environ Health Perspect 1998; 106 Suppl 4:989-94

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