Ancient Chinese medicine could boost cancer therapy

[CFT]

The synergy of TCM herbs and modern chemotherapy:

http://www.newscientist.com/blogs/shortsharpscience/2010/08/ancient-chinese-medicine-could.html


The 1800 year-old recipe, called Huang Qin Tang, consists of a mix of flowers from the Chinese skullcap plant, extract of peonies, liquorice, and the fruit of the buckthorn tree.

The remedy has been used for years to treat stomach upsets and nausea. Now, researchers at start-up pharmaceutical company PhytoCeutica and Yale University School of Medicine, both in Connecticut, have shown that the blend can also aid cancer treatment, reducing diarrhoea and gut damage caused by chemotherapy in colon and rectal cancer patients.

[taai gihk yahn]

ok, it's not "boosting" cancer therapy, it's ameliorating the side-effects of it - big difference;

as far as actual "herbal" cancer therapy, methyl jasmonate (http://en.wikipedia.org/wiki/Methyl_jasmonate) is more along those lines

[CFT]

The mice given PHY906 experienced less toxicity, lost less weight and showed more anti-tumour activity than controls that were given irinotecan alone. PHY906 also encouraged the growth of new intestinal stem cells and prevented inflammation.I guess you're right. Hard to tell really, popular science reporting can be misleading.

[taai gihk yahn]

I guess you're right. Hard to tell really, popular science reporting can be misleading.

lol - maybe next time i'll read the whole thing...

[CFT]

lol - maybe next time i'll read the whole thing...Well I think you did have a valid point. There is a real tangible effect but whether the herbs really boost the chemo drugs themselves ... how do they define these things and does it matter if the effects are beneficial?

[taai gihk yahn]

Well I think you did have a valid point. There is a real tangible effect but whether the herbs really boost the chemo drugs themselves ... how do they define these things and does it matter if the effects are beneficial?

well, if there was an increase in anti-tumor activity, it could be said that it boosted the effects, if not directly, then at least indirectly by improving the function of the organism in general therefore optimizing the function of the chemo; but that can be a judgement call, I suppose;

[mawali]

The study is an example of a false positive in its purest sense.
TCM institutions have used combinations of such mixed medicine but it is of limited value. No doubt we can learn to use less invasive methods but surgical intervention with the best prepared medicines (allopathic or complementary) has the potential to do wonders.

One must also be careful of the herb-drug interactions regardless of how safe the complementary procedures (medicines of various combinations).

[GeneChing]

February, 2016, Vol. 17, Issue 02
From Antiquity to Modernity: Huang Qin Tang at Yale Medical School, Part 1 (http://www.acupuncturetoday.com/mpacms/at/article.php?id=33147)
By Changzhen Gong, PhD

Traditional Chinese medicine is a coherent medical system with several unique characteristics: it originated almost 3,000 years ago; in its area of origin, it has been practiced without interruption since its inception.

Although there is some affinity between traditional Chinese medicine, which is based on ancient Chinese metaphysics, and classic Western medicine, which was based on ancient Greek metaphysics, it is true that at this point in history traditional Chinese medicine is a very different system from modern conventional medicine.
For more than one hundred years, the possibility of "modernizing" traditional Chinese medicine and integrating it with conventional Western medicine has been fiercely debated. China began this integrative process by applying modern scientific research standards to TCM modalities and by practicing both systems of medicine on an equal footing in its hospitals. More recently, researchers in the United States have joined the ongoing effort to reconcile Eastern and Western systems of medicine as exemplified by a study of the classical Chinese herbal formula Huang Qin Tang (Scutellaria Decoction) which was conducted at Yale Medical School.

Huang Qin Tang originated almost 2,000 years ago. It was created and described by Zhang Zhongjing (150 – 219 AD) in his masterpiece, Shang Han Lun: On Cold Damage, written toward the end of the Han Dynasty (202 BC – 220 AD). Fifteen years ago, medical researchers at the Yale School of Medicine began subjecting Zhang Zhongjing's formula to rigorous scientific inquiry and clinical trials as a potential oncology drug. Yale's rigorous investigation of Huang Qin Tang demonstrates that classical Chinese prescriptions can be successfully translated into modern medical practice. Huang Qin Tang went through preclinical trials, phase I clinical studies, phase II clinical studies, and ongoing phase III trials in the treatment of liver cancer, pancreatic cancer and colorectal cancer. Here, we refer to the research effort led by Yung-Chi Cheng at Yale Medical School as the "Yale Project." The Yale Project is comprised of pharmacological research, clinical trials, quality controls, and reflections on the theory and practice of traditional Chinese herbal medicine.

A Classical Prescription

Scutellaria Decoction (Huang Qin Tang) is a combination of four herbs: Scutellaria baicalensis (Huang Qin), Glycyrrhiza uralensis (Gan Cao), Paeonia lactiflora (Bai Shao), and Ziziphus jujuba (Da Zao). Shang Han Lun: On Cold Damage, Line 172 says, "When, in a greater yang/lesser yang combination disease, spontaneous diarrhea is manifested, Huang Qin Tang is prescribed."1 Zhang Zhongjing goes on to state that Huang Qin Tang is prescribed for lesser yang pathogenic heat distressing yang brightness, with symptoms of diarrhea, abdominal pain, and scorching heat in the anus.1 Since the third century, Huang Qin Tang has been documented to treat common gastrointestinal distress and its concomitant symptoms of fever, headache, extreme thirst, nausea, vomiting, diarrhea, abdominal spasms, and subcardiac distention. In the 17th and 18th centuries, the application was broadened to include the treatment of warm-pathogen diseases. Seventeenth-century physician Zhang Lu observed that Huang Qin Tang basically treats "spring and summer warm pathogen heat where fever develops from within (i.e., without marked exterior symptoms like chills at the onset)."2 Later, Ye Tianshi, a great physician of the Warm Febrile Disease school, extended Zhang Lu's theory and practice to the treatment of lurking pathogens. In his text, Differentiating Lurking Pathogens and Externally-Contracted Diseases During Three Seasons, Ye Tianshi stated: "Cold that attacks the body in winter lurks in the kidneys, transforms into heat, and manifests in the gallbladder in the spring. Huang Qin Tang is prescribed for this condition to clear heat with bitter and cold herbs."3

continued next post

[GeneChing]

Clinical Trials

For any new medicine or invasive medical device to be approved for use in the United States, it must be subjected a series of clinical trials which have been mandated and standardized by the U.S. Food and Drug Administration (FDA). The first is a preclinical trial, which is a laboratory test on animal subjects. Preclinical trials are conducted with the objective of gathering sufficient evidence to justify a clinical trial using human subjects. After a medicine or device is tested in the lab or on animals, it enters a phase I clinical trial with humans.

Phase I clinical trials are typically conducted on a small number of human subjects to see if an experimental medication or treatment is safe, and to determine the optimum dosage and administration of the drug. If the medication or treatment appears safe after analyzing the results of the phase I clinical trial, it may then enter a phase II trial, a study performed to determine the efficacy of the treatment. If the medication or treatment is deemed safe in a phase I trial and effective in a phase II trial, it will then enter a phase III clinical trial.

Phase III clinical trials are much larger, and are conducted to see if the medication or treatment is not only safe and effective, but works better or has fewer side effects than treatments currently available. Phase IV clinical trials are conducted to determine if a medication or treatment is safe over time, or to see if the medication or treatment can be used in other circumstances. Phase IV clinical trials are done after a treatment has gone through phase I, II and III clinical trials, and has already been approved by the FDA.

Here, I will be referencing pharmaceutical agents according to the identification tags assigned to them by the FDA. The pharmaceutical form of Huang Qin Tang is called PHY9064. We will frequently refer to the following chemotherapeutic agents: CPT-11 (Irinotecan), 5-FU (5-fluorouracil), LV (Leucovorin), Oxaliplatin, Capecitabine, VP-16 (Etoposide), L-OddC, Gemcitabine, Sorafenib and Sunitinib. CPT-11, LV and Oxaliplatin are chemotherapeutic agents used to treat colorectal cancer. Capecitabine is a chemotherapeutic agent for colorectal and liver cancer. VP-16 is a chemotherapeutic agent for lung cancer. L-OddC and Gemcitabine are chemotherapeutic agents for pancreatic cancer. Sorafenib and Sunitinib are chemotherapeutic agents for renal and liver cancer. 5-FU is a chemotherapeutic agent for colorectal and pancreatic cancer.

In a preclinical trial,5 an in vivo study using a mice model showed that PHY906 protected against the weight loss associated with CPT-11 treatment. The study also showed that mice were able to tolerate otherwise-lethal doses of CPT-11 in the presence of PHY906. The treatment using the combination of PHY906 and CPT-11 showed significantly improved antitumor activity and overall survival rate compared with CPT-11 alone. A combination of PHY906 with CPT-11, 5-FU, and LV also resulted in at least additive antitumor activity, with no increased host toxicity.

Another preclinical study5 assessed whether PHY906 would reduce the injury to intestinal tissue which results from irradiation of the abdomen. Post-radiation intestinal damage includes marked blunting and loss of villi, crypt hyperplasia and irregular crypt morphology. This trial demonstrated that PHY906 decreased toxicity from fractionated abdominal irradiation. PHY906 did not affect the radiation-induced outcome of weight loss, but did result in more rapid post-radiation recovery. The study concluded that PHY906 decreased the toxicity of abdominal irradiation while not protecting tumors, and thereby increased the therapeutic ratio. Based on these preclinical trials, the Yale Project moved forward with phase I and phase II studies of PHY906.

A phase I multicenter, double-blind, randomized, placebo-controlled, dose escalation, cross-over study6,7 was conducted to determine the efficacy of PHY906 as a modulator of the regimen of CPT-11, 5-FU, and LV (IFL) in the first-line treatment of patients with advanced colorectal cancer. This study investigated the safety and tolerability of PHY906 as it was administered concomitantly with the IFL regimen. The clinical trial showed that the administration of PHY906 did not alter the pharmacokinetics of CPT-11, 5-FU, or the CPT-11 metabolite SN-38.

In a phase I/II study8, the combination of PHY906 and capecitabine resulted in lower rates of drug-related toxicities, and this combination was generally well tolerated. The occurrence of nausea and emesis from the PHY906/capecitabine combination was lower than that from capecitabine alone. This study indicated that administering PHY906 and capecitabine in combination provided a survival benefit and had a tolerable safety profile in advanced hepatocellular carcinoma patients. Because of the poor prognosis of hepatocellular carcinoma patients and the 100% tumor progression rate seen with sorafenib therapy, the PHY906/capecitabine combination promises to provide an additional opportunity to stabilize the disease for relatively longer periods of time.

A Phase I study9,10 on patients with advanced pancreatic and gastrointestinal malignancies was designed to determine the maximum tolerated dose (MTD) of capecitabine when it was given in combination with PHY906. The patients were given increasing dosages of Capecitabine until they began to exhibit dose-limiting toxicities (DLTs). Results of the study showed that PHY906 reduced some of capecitabine's common side effects in patients, such as diarrhea, thus enabling an increase in the therapeutic index of capecitabine in those patients. This study concluded that PHY906 in combination with capecitabine resulted in an improved disease control rate for patients with advanced pancreatic and gastrointestinal malignancies. Because of these results, it was felt that a phase II study was warranted to assess the clinical activity and tolerability of the PHY906/capecitabine combination in patients with gemcitabine-refractory pancreatic cancer.

A phase II study11 was subsequently conducted, exploring the efficacy of the PHY906/capecitabine combination in the treatment of patients with advanced pancreatic cancer who had previously been ineffectively treated with gemcitabine-based regimens. Results of the phase II study demonstrated that administering a PHY906/capecitabine combination to patients with advanced pancreatic carcinoma provided a safe and feasible salvage therapy after the failure of gemcitabine treatment. This was the first phase II trial conducted on human subjects which investigated the PHY906/capecitabine combination as a second-line therapy in patients with advanced pancreatic cancer. It confirmed preclinical studies in which PHY906 demonstrated synergistic anti-tumor activity when administered in combination with capecitabine.

References:

Mitchell C, Ye F, Wiseman N. Shang Han Lun: On Cold Damage, Paradigm Publications, 1999.
Zhang L. Complete Book of Medicine by Zhang Lu, China Chinese Medicine Press, 1998.
Ye TS. Complete Book of Medicine by Ye Tianshi, China Chinese Medicine Press, 2004.
Liu SH, Cheng YC. Old formula, new Rx: the journey of PHY906 as cancer adjuvant therapy. J Ethnopharmacol. 2012 Apr 10;140(3):614-23.
Rockwell S, Grove TA, Liu Y, Cheng YC, Higgins SA, Booth CJ. Preclinical Studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as a Potential Adjunct to Radiation Therapy. Int J Radiat Biol. 2013 Jan;89(1):16-25.
Farrell MP, Kummar S. Phase I/IIA randomized study of PHY906, a novel herbal agent, as a modulator of chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer. 2003 Feb;2(4):253-6.
Kummar S, Copur MS, Rose M, Wadler S, Stephenson J, O'Rourke M, Brenckman W, Tilton R, Liu SH, Jiang Z, Su T, Cheng YC, Chu E. A phase I study of the chinese herbal medicine PHY906 as a modulator of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer. 2011 Jun; 10(2):85-96.
Yen Y, So S, Rose M, Saif MW, Chu E, Liu SH, Foo A, Jiang Z, Su T, Cheng YC. Phase I/II study of PHY906/capecitabine in advanced hepatocellular carcinoma. Anticancer Res. 2009 Oct;29(10):4083-92.
Saif, M., Li, J., Lamb, L., et al. Phase II study of PHY906 plus capecitabine (CAP) in pts with gemcitabine-refractory pancreatic cancer (PC) and measurement of cytokines. Journal of Clinical Oncology 2010 (28) (suppl; abstr e14540).
Saif, M.W., Lansigan, F., Ruta, S., et al. Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies? Phytomedicine 2010 (17) (3–4), 161–169.
Saif MW, Li J, Lamb L, Kaley K, Elligers K, Jiang Z, Bussom S, Liu SH, Cheng YC. First-in-human phase II trial of the botanical formulation PHY906 with capecitabine as second-line therapy in patients with advanced pancreatic cancer. Cancer Chemother Pharmacol. 2014 Feb;73(2):373-80.
Dr. Changzhen Gong is the president of the American Academy of Acupuncture and Oriental Medicine (AAAOM) located in Roseville, Minnesota. AAAOM offers a Master's degree and a doctoral program in acupuncture and Oriental medicine. AAAOM can be researched at (651) 631-0204.

Perhaps a better thread title would be "Huang Qin Tang" :rolleyes:

[herb ox]

From NPR this morning
http://www.npr.org/sections/health-shots/2014/01/18/261055778/western-scientists-look-to-chinese-medicine-for-fresh-leads



Western Scientists Look To Chinese Medicine For Fresh Leads
Updated January 22, 20148:08 AM ET Published January 18, 20142:56 PM ET
Alan Yu


In the quest for new treatments, U.S. researchers are looking to traditional Chinese medicines, some of the oldest remedies in the world.

A recent discovery resulted in a better treatment for a type of leukemia that strikes about 1 in 250,000 people in the U.S. Another study found a potential new painkiller in China's medicine chest. Other researchers are studying a traditional medicinal plant called "thunder god vine" for its anti-cancer properties.

The approach has already had some success. The Chinese herbal medicine artemisinin, for instance, has gone on to become the most potent anti-malarial drug available.

Not all the leads have panned out, of course. But the old field has shown enough potential to keep interest high.

A better leukemia treatment drawn from an ancient medicine should give us hope for developing anti-cancer drugs, says Dr. Samuel Waxman, a co-author of the report and professor of medicine and cancer specialist at Mount Sinai Hospital. "It gives a lot of optimism of seeking other types of cancer medicines in the Chinese pharmacopedia, which many people are looking into," Waxman says.

The treatment uses arsenic trioxide, which has traditionally been used in Chinese medicine. The U.S. Food and Drug Administration approved arsenic trioxide (sold as Trisenox here) as a treatment in 2000, and later research showed that patients who received standard chemotherapy followed by arsenic trioxide did better than patients who just received standard chemotherapy.

But a big clinical test recently found that the drug, in combination with all-trans retinoic acid — another drug commonly used to treat acute promyelocytic leukemia (APL) — turned out to be more effective than the usual chemotherapy.

That results means arsenic trioxide should become the new standard for patients that can use it, says Dr. Richard Stone, director of the adult acute leukemia program at the Dana-Farber Cancer Institute.

"So this was a cure for leukemia without chemotherapy, really for the first time in a large randomized trial," says Stone. "We've got a patient in the hospital right now who's receiving that very therapy."

He says there are still side effects from the new regimen affecting the skin and heart, but for most people they're less of a problem than the hair loss, vomiting and diarrhea that can come with chemotherapy.

The arsenic trioxide treatment was developed by a Chinese doctor working in northern China during the Cultural Revolution, according to Mount Sinai's Waxman. This doctor couldn't use much Western medicine, so to treat his APL patients, he started giving them arsenic trioxide intravenously. He kept a journal for 10 years and noticed that it worked remarkably well. He eventually published his findings in 2001 with other collaborators.

"That was one of the first examples of a targeted treatment in all of cancer," Waxman says.

Other researchers are also studying triptolide, a natural product of a traditional Chinese medicinal plant called lei gong teng or "thunder god vine" as a possible anti-cancer drug. The product was effective against cancer in animal models and scientists in the West are now studying exactly how it works, says Jun Liu, one of the researchers and a professor of pharmacology and molecular sciences at Johns Hopkins University.

"Traditional medicine will always remain a useful source of new drugs. The question is, to what extent?" Liu says. "Drug discovery and development is a very lengthy and costly process and there are always failures."

Research into Chinese medicine is no different. Cancer reseachers at the University of Minnesota recently started an early clinical trial to study a drug that was developed from triptolide for treating pancreatic cancer, says Edward Greeno, associate professor of medicine at the University of Minnesota. He points out it took millions of dollars just to get to this point.

"It's easy to think, and normal to think, that if people are using it already then it shouldn't require a lot to develop it into a useful product. The problem is that our standard for what is safe and effective is very high, appropriately," Greeno says. "It looks like a pretty straight path but what you don't see are all the false starts and wrong turns that we make along the way."

Studying Chinese medicine for new treatments has had its share of wrong turns. Western scientists previously looked into treatments for the prevention of dementia, eczema, and bacteria that cause most types of stomach ulcers, but concluded they weren't particularly effective.

But the failures don't mean we should give up, says Brian Berman, a professor of medicine at the University of Maryland who served as the principal investigator of two Chinese medicine research initiatives funded by the National Institutes of Health.

Chinese medicine is one lead to consider, especially for chronic diseases that have yet to be cured. "The advantage you have when you look at some of the Chinese medicine therapies is that by and large, they are safe, as long as what you're getting doesn't have added ingredients," Berman says. "We need to look at what other cultures have to offer and then we need to put them through a scientifically rigorous test."

[GeneChing]

This was just published in Science Advances and has got a lot of attention in the TCM newsfeed. Here's the original abstract, from the source.


A specialized flavone biosynthetic pathway has evolved in the medicinal plant, Scutellaria baicalensis (http://www.express.co.uk/life-style/health/659308/Plant-Chinese-ancient-medicine-help-cancer-liver-disease-study-research)

Qing Zhao1,2,3,4, Yang Zhang2,*, Gang Wang3, Lionel Hill2, Jing-Ke Weng5, Xiao-Ya Chen1,4,6, Hongwei Xue1,4 and Cathie Martin2,4,†
+ Author Affiliations
↵†Corresponding author. E-mail: cathie.martin@jic.ac.uk
↵* Present address: School of Life Science, Sichuan University, Chengdu, Sichuan 610065, China.

Science Advances 08 Apr 2016:
Vol. 2, no. 4, e1501780
DOI: 10.1126/sciadv.1501780

Abstract

Wogonin and baicalein are bioactive flavones in the popular Chinese herbal remedy Huang-Qin (Scutellaria baicalensis Georgi). These specialized flavones lack a 4′-hydroxyl group on the B ring (4′-deoxyflavones) and induce apoptosis in a wide spectrum of human tumor cells in vitro and inhibit tumor growth in vivo in different mouse tumor models. Root-specific flavones (RSFs) from Scutellaria have a variety of reported additional beneficial effects including antioxidant and antiviral properties. We describe the characterization of a new pathway for the synthesis of these compounds, in which pinocembrin (a 4′-deoxyflavanone) serves as a key intermediate. Although two genes encoding flavone synthase II (FNSII) are expressed in the roots of S. baicalensis, FNSII-1 has broad specificity for flavanones as substrates, whereas FNSII-2 is specific for pinocembrin. FNSII-2 is responsible for the synthesis of 4′-deoxyRSFs, such as chrysin and wogonin, wogonoside, baicalein, and baicalin, which are synthesized from chrysin. A gene encoding a cinnamic acid–specific coenzyme A ligase (SbCLL-7), which is highly expressed in roots, is required for the synthesis of RSFs by FNSII-2, as demonstrated by gene silencing. A specific isoform of chalcone synthase (SbCHS-2) that is highly expressed in roots producing RSFs is also required for the synthesis of chrysin. Our studies reveal a recently evolved pathway for biosynthesis of specific, bioactive 4′-deoxyflavones in the roots of S. baicalensis.