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From the Townsend Letter
August / September 2017

Angiostop (Sea Cucumber Extract) Inhibits Multiple Cancer Targets and Addresses Many Limitations of Cancer Therapies
by Tsu-Tsair Chi, NMD, PhD
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Part 1, 2, 3

Blocking Multiple RTKs for Better Cancer Management
Blocking multiple RTKs has been shown to better fully suppress cancer. This is because most cancer processes like angiogenesis, proliferation, invasion, metastasis, and apoptosis are not associated with only one but multiple RTKs. For instance, VEGFr is a very important target, involved in all of the cancer processes. It is the RTK mainly responsible for new blood vessel growth from tumors. If not inhibited, more blood vessels can proliferate from the tumor, continually feeding its growth. Many of the targeted drugs have VEGFr as the primary target; however, blocking VEGFr alone may not be enough to fully suppress cancer. Cancer cells express multiple RTKs at the same time. For example, breast, prostate, lung, colorectal, ovarian, brain, and pancreatic cancer express all five RTKs.
One disadvantage of available cancer therapies is the limited number of RTK targets. This may only lead to partial suppression and could explain poor patient prognosis and/or recurrence. For instance, let us look at this breast cancer case report.

F. Akbarpour, MD, from California, has an 81-year-old female patient with breast cancer. She had a mastectomy but the cancer recurred as angiosarcoma in the breast. She was given Sutent (25 mg/day) with no apparent effect. The dose was doubled, but still there were no results. Then Dr. Akbarpour reduced the Sutent dose and added Angiostop. After about four months, the angiosarcoma cleared.

Sutent is a targeted drug that inhibits VEGFr and PDGFr, but it does not inhibit EGFr, FGFr, and IGFr. This explains why Sutent had limited effect even after doubling the dose. It was only after adding Angiostop that the desired results were achieved. Similar results were seen in the following case:

R. Abraham, MD, from California, has a male patient in his 60s with kidney cancer. He took Sutent, which reduced his tumor to only 2 cm. Then he added Angiostop and Revivin. After approximately four months, the tumor reduced to one cm. After a year, the tumor cleared.

Again, kidney cancer expresses all five RTKs. The addition of Angiostop provided a synergistic effect with Sutent, leading to better prognosis.
Another example is a lung cancer patient who took Tarceva, an EGFr inhibitor drug and the best targeted drug for lung cancer, along with Angiostop, Myomin, and other cancer supplements, Revivin, Asparagus Extract, and Reishi Spore Extract. Lung cancer is also related to high estrogen so in the following case, Myomin, a natural aromatase reducer, was also recommended.14

Antoine E., a 60-year-old male from Florida, was diagnosed with primary pulmonary adenocarcinoma in his lung in 2010 at age 53. Surgery removed the mass. However, within two years, the cancer recurred and spread from his left lung to his right lung and chest cavity. The large mass in his chest cavity was increasing at a rapid rate. At that time, it had grown to the size of a grapefruit and considered inoperable Stage 4 adenocarcinoma. He was given three to six months to live. He underwent chemotherapy. In April 2012, he added Angiostop, Revivin, Reishi Spore Extract, Asparagus Extract, Myomin and OxyPower. He also took Tarceva. In December 2013, his PET scan revealed no tumor. He continues to take the supplements and Tarceva and is determined to be cancer free. In his words, his oncologist told him, "I am their only patient on Tarceva living that long. Tarceva is only good for nine months before patients acquire drug resistance."
Dino F. is a 51-year-old male from Florida who started weekly testosterone injections and the HCG diet. His testosterone was 350 and PSA was 3.0. After a year, his testosterone shot up to 1400 and his PSA to 5.9. He was then diagnosed with prostate cancer. He took Angiostop, Myomin, Revivin and other supplements for one-and-a-half years. At age 51, his PSA has reduced to 2.8, and he also lost 78 lbs (
see Table 2).

Table 2. Reduction of PSA and Weight in Prostate Cancer Patient

In the case above, this patient may well have a microscopic prostate tumor already and testosterone therapy may have been the trigger for the growth, causing the increase in PSA level. Taking Angiostop definitely helped reduce growth, as evidenced by the decrease in PSA. Since prostate cancer is an estrogen-responsive condition, Myomin also contributed to the reduction.

Angiostop Induces Cancer Apoptosis
When cells are no longer needed by the body, they die a natural death in a process called apoptosis. Cancer cells, however, have a defective apoptosis mechanism that allows them to be immortal, accumulate, and eventually form a tumor. Research from the last few years has revealed that sea cucumber activates caspases and proteins that induce apoptosis and it also inhibits proteins that block apoptosis.
Caspases are a member of the cysteine-aspartic acid protease family and are the primary regulators of cancer apoptosis or cell death. In cancer cells, missing or deficient caspases can give them immortality and make them resistant to cancer drugs. Either activating or inhibiting these caspases is an important cancer therapy mechanism.

Studies demonstrate that Angiostop activates not only Caspase 3, but also Caspase 7, 8, and 9, enabling it to more effectively induce apoptosis (Illustrated as ovals in Figure 2).15-18
In addition, Angiostop also acts on other types of proteins that affect the apoptosis process. Cancer thrives when there are more proteins that block apoptosis than proteins that promote apoptosis. Angiostop has been shown to tip this balance in favor of apoptosis: it inhibited proteins that block apoptosis, such as Bcl-2 and survivin, while promoting pro-apoptotic proteins like Bax and BAD.15,18-20

Other Mechanisms
Angiostop has other mechanisms that are worth mentioning.

  • Inhibiting the Topoisomerase 2-alpha enzyme – Angiostop is able to attack cancer at the DNA level by inhibiting the topoisomerase 2-alpha enzyme. But unlike topoisomerase 2-alpha inhibitor chemotherapy drugs, like Adriamycin or Vincristine, Angiostop does not have toxic effects.21
  • Activating the Tumor Suppressor, PTEN – In about 70% of prostate cancer patients, the tumor suppressor PTEN (Phosphatase and tensin homolog) is missing so cell proliferation occurs. PTEN is also deficient in breast, lung, brain, kidney, pancreatic, and endometrial cancer. Angiostop has been shown to activate PTEN (illustrated as a hexagon in Figure 2), blocking cell proliferation and other related processes.15
  • Antagonizing Prostaglandin E2 (PGE2) Receptors – A 2012 National Institutes of Health (NIH)-grant supported study at the University of Maryland Greenebaum Cancer Center found sea cucumber to reduce the risk of metastasis by antagonizing Prostaglandin E2 (PGE2) receptors, EP2 and EP4 (illustrated as diamonds in Figure 2).22 This leads to reduced tumor growth and metastasis.

Angiostop's multiple mechanisms are illustrated in Figure 2. In the tyrosine kinase pathway (illustrated as rectangles in Figure 2), Angiostop blocks important RTKs such as VEGFr, EGFr, FGFr, PDGFr, IGFr, Akt, ERK, FAK and paxillin. Therefore, it can affect gene regulation and reduce cell proliferation, migration, and angiogenesis. Furthermore, its activation of several caspases and other apoptosis factors like Cytochrome C, BAD and Bax (seen as ovals in Figure 2), makes it effective in inducing cancer apoptosis. Through the PGE2 pathway, it antagonizes the receptors EP2 and EP4 (seen as diamonds in the figure) to block tumor growth and metastasis. Finally, it activates the tumor suppressor PTEN (seen as a hexagon in Figure 2) that is missing in many types of cancer. Activation of PTEN can also contribute towards caspase activation and apoptosis through Akt signaling.

Case Analysis: Triple Negative Breast Cancer Case
F. Mercado, MD, from Sanoviv Medical Institute, has a 52-year-old female patient with Grade 3 ER negative, PR negative and HER2 negative (triple negative) invasive ductal carcinoma in her right breast. She had a lumpectomy in September 2016 and was recommended full dose chemotherapy; however, she opted for natural therapies and took Angiostop and Revivin immediately after her lumpectomy. Her Circulating Tumor Cells (CTCs) level then was 9.4 cells/7.5ml (see Table 3). By January 2017, her CTC was zero. All other cancer markers, CEA, CA 15-3 and CA 27-29, are normal.

Table 3. Circulating Tumor Cancer Cells Reduced in Triple Negative Cancer Patient

This patient's favorable response to Angiostop and Revivin are explained by her RGCC genetic testing results, which assessed her risk using certain cancer markers. Her results showed that she is at high risk for angiogenesis-related markers, VEGFr, FGFr and PDGFr (see Table 4). Indeed, Angiostop inhibits these markers. Her proliferation-related marker EGFr is at 50%, which puts her at high risk. Again, this RTK is inhibited by Angiostop. Furthermore, she was at high risk for certain markers that target the cell cycle rate. Revivin, another supplement she is taking, targets the G1 to S phase of the cell cycle, thereby interrupting uncontrolled cell replication. Her assessment results indicated that her hormone receptors are normal, which is expected of triple negative breast cancer cases. If her hormone receptors were positive, Myomin, a natural aromatase reducer, would have been recommended.

Table 4: RGCC Assessment of Results for Triple Negative Breast Cancer Patient Category Mechanism Clinical Risk Markers Results Outcome

All these assessment results serve to illustrate that, because Angiostop and Revivin address many facets of her cancer, especially the markers for which she is at high risk, she then achieved favorable results (i.e., reduction of CTC).

Core BioticCase Analysis: Leiomyosarcoma Patient
RGCC results can be a useful tool in assessing a patient's potential response to therapeutics, especially Angiostop. We demonstrate it in the following case. A 44-year-old female patient had a chemosensitivity RGCC test after surgery and chemotherapy. Her CTC was still above normal at 7.6 cells/7.5 ml even after conventional treatment. Her RGCC results (see Table 5) provide clues as to which other therapies might be effective for her. Assessment of her results shows that there are many markers that Angiostop can address. For instance, she tested high risk for the angiogenesis and proliferation markers, VEGFr, FGFr, PDGFr, EGFr and IGF-r1. Angiostop inhibits all of these markers. Additionally, Angiostop promotes the pro-apoptotic marker, Bax, and inhibits the anti-apoptotic marker, Bcl-2, both of which were high risk on this patient's results. The tumor suppressor gene, PTEN, is also promoted by Angiostop. So, based on the assessment, Angiostop would be a good candidate therapy for this patient because it can potentially suppress multiple cancer pathways for which she is at high risk.

Table 5: RGCC Assessment of Results for Leiomyosarcoma Patient Category Mechanism Clinical Risk Markers Results Outcome

Part 1, 2, 3

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