The Study – Ovarian Cancer

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Ovarian cancer is one of the deadliest cancer but with a lower incidence rate as compared to other cancers. It has been estimated that in 2019 itself, about 22,530 women in the United States of America will be diagnosed with ovarian cancer and about 13,980 women will die from ovarian cancer. At present, ovarian cancer ranks 5th in cancer deaths among women accounting for more deaths than any other cancer of the female reproductive system. The risk of a woman developing an ovarian cancer is about 1 in 108. Older women are very much prone to this cancer and about half the women who are diagnosed with ovarian cancer have been found to be 63 years of age or older. In the United States of America, the overall ovarian cancer incidence has declined by 29% from 1985 (16.6 women per 100,000) to 2014 (11.8 women per 100,000), while mortality rate has declined 33% from 1976 (10.0 per 100,000) to 2015 (6.7 per 100,000). Moreover, currently there is no recommended screening test for ovarian cancer thus very often it goes unnoticed in the earlier stages.

Although in the pursuit to fight ovarian cancer, several studies have been conducted on Annatto based Tocotrienol (Eannatto – DeltaGold) which has been observed to possess anti-cancer activities. One such study,“Delta tocotrienol in recurrent ovarian cancer. A phase II trial”showed that Delta – Tocotrienol(Eannatto – DeltaGold)possesses anti – neoplastic activity as demonstrated in several in vitro and in vivo investigations. The effect has been observed to rely on inhibition of different pathways. It also has anti – angiogenic activity, and an additive effect to bevacizumab can be expected. This study was a phase II trial of bevacizumab combined with Delta – Tocotrienol(Eannatto – DeltaGold) in chemotherapy refractory ovarian cancer. This study also included analysis of circulating ‘tumor specific HOXA9 methylated DNA (HOXA9 meth – ctDNA)’ during treatment. This study included 23 patients and the rate of disease stabilization was at 70% with very low toxicity. The median PFS was 6.9 months and the median OS 10.9 months, which is rather high as compared to the current literature. A division of the patients according to the level of HOXA9 meth-ctDNA after the first cycle of chemotherapy resulted in formation of two groups of patients with different prognoses. Patients with an increasing level of HOXA9 meth-ctDNA had a median PFS and OS of 1.4 and 4.3 months respectively as compared to 7.8 and 12 months in the group with stable or decreasing levels. The combination of bevacizumab andDelta – Tocotrienol(Eannatto – DeltaGold)was found to be quite potent in chemotherapy refractory ovarian cancer. The level of HOXA9 meth-ctDNA after one cycle of chemotherapy was observed to hold important prognostic information.

Most research in the past 50 – 60 years has been focused on Tocopherols and 50% of all the research in last 30 years has been done on Tocotrienols in last 5 years. Half of the Tocotrienol research ever published has been published in last 10 years as shown in Fig. 1. Each day it is becoming increasingly understood that Tocotienols (especially Eannatto – DeltaGold) are the right form of Vitamin E. Well in excess of 100 studies and clinical trials have shown the surprising benefits of Tocotrienols – without any known side effects.
Fig. 1: In the graph, as you can see, R & D on Tocotrienol has increased exponentially over the years in all fields while research on Tocopherols has decreased. Whether it is cancer, Cardiovascular diseases (CVD), Diabetes, Anti – Oxidant activities or others, in all fields research on Tocotrienol has not only gained pace but quant as well.

Study 1 - Delta tocotrienol in recurrent ovarian cancer. A phase II trial.

Even now, recurring ovarian cancer represents a therapeutic challenge. Most ovarian cancer patients will suffer from recurring ovarian cancer within a few years after the primary treatment like chemotherapies and radiation. Bevacizumab has been observed as an integrated part of both 1st and 2nd line treatment of ovarian cancer but still a majority of patients die from ovarian cancer. Tocotrienols are the part of Vitamin E family. Several in vitro and a few in vivo have showed a clear effect on malignant cells with respect to proliferation and invasion. Several mechanisms and effects on different pathways have been suggested among which inhibition of 2 important transcription factors NF – kB and STAT3 – rank high. Delta – Tocotrienol(Eannatto – DeltaGold)is especially active in relation to malignancies. Delta – Tocotrienol(Eannatto – DeltaGold)suppresses the vascular endothelial growth factor (VEGF) and inhibits proliferation of endothelial cells resulting in reduced tube formation. HOXA9 meth – ctDNA has been suggested as a prognostic marker in ovarian cancer. This study has been aimed to investigate the combination of bevacizumab and Delta – Tocotrienol(Eannatto – DeltaGold)in a phase 2 trial of multi – resistant ovarian cancer.

The patients were treated with bevacizumab 10 mg/kg i.v. every 3 weeks. Delta – Tocotrienol(Eannatto – DeltaGold)capsules were given in a continuous treatment in doses of 300 mg orally 3 times a day. Delta – Tocotrienol(Eannatto – DeltaGold)is a special formulation based on a patented method with 90% Delta – Tocotrienoland 10% Gamma –Tocotrienol.

The study included 23 patients from March 2015 to Jan 2018. It was observed that most patients were diagnosed with stage 3 disease, and serious histopathology was found to be the dominating type. The median number of prior chemotherapy regimens was 4.0. All patients were platinum resistant and more than half of them had previously received bevazicumb with progression on treatment. It was also observed that all patients but one were in good performance status. The median number of treatment cycles was 6 with 20% of the patients treated for more than 12 months.

Why Tocotrienol?

  • Antioxidants, especially Tocotrienol was observed to exhibit anti-cancer activity against ovarian cancer cells cells by lowering inflammation and oxidative stress as shown in Fig. 2.
Fig. 2: In the study conducted by Dr. Qureshi, he saw that at 250 mg of Tocotrienols, the endogenous anti-oxidant, TAS (represented with grey colour) increased, while the C-reactive protein (CRP) dropped by 40%, oxidized fat (MDA) dropped by 34% and Total Anti-oxidant increased by 22%.
  • Angiogenesis which is the process of formation of blood vessels in cancer cells like in your ovarian cancer promotes cancer cell death to a very great extent. Studies have also demonstrated that Delta-Tocotrienol hindered hypoxia-induced VEGF and IL-8 overexpression and by lowering HIF-1 alpha, thus consequently inhibiting angiogenesis in cancer cells.
Fig. 3: In a study, it was observed in mice cells, that Delta - Tocotrienol inhibited the formation of blood vessels in cancer cells (Anti – Angiogenesis) while Tocopherol completely failed on such grounds. Delta-Tocotrienol was also observed to induce apoptosis in the mice cancer cells.
  • Apoptosis is the programmed cell death which leads to the death of cancer cells. According to the study, Tocotrienol was found to induce apoptosis in ovarian cancer cells in vitro and in vivo by downregulating NF-kB and its regulated gene products.
  • Paraptosisis a type of programmed cell death distinct from apoptosis which features cytoplasmic vacuolation independent of Caspase activation and inhibition, and lack of apoptotic morphology. According to the research, it was observed that Delta-Tocotrienol induced paraptosis-like cell death in ovarian cancer cells.
  • Cell Proliferation is the process by which cancer cells copy their DNA and divide into two cancer cellsduring mitosis and rapidly multiply into more cancer cells. It was observed that Delta-Tocotrienol inhibited ovarian cancer cell proliferation, induce cancer cell death and prevented cell cancer invasion.
  • Cancer stem cell death has been observed by the action of Tocotrienols especially Delta – Tocotrienols (DeltaGold – Eannatto). Even after chemotherapies, radiation and surgeries, there are stem cells of those cancerous tissues left revolving in your body which can lead to your cancer coming back. Henceforth, their death is very necessary and Tocotrienols have been observed to kill cancer stem cells.
Fig. 4: About 1% of cancer cells are Cancer Stem Cells (CSC) which keep circulating in your body even after nailing the cancer through chemo. It has been observed that Gamma – Tocotrienol and Delta – Tocotrienol, both specifically target CSC.

  • Tumor nutrition can also be obstructed by Tocotrienol as they may well work on dual antitumor mechanisms that include the removal of the vital nutrient to tumor lifeline.

Dosage

  • Under the study, 900 mg/day of Tocotrienols were used to treat ovarian cancer cells and no adverse effects were observed and the death of breast cancer cells was witnessed.
  • Substances that complement Tocotrienol for cancer include Vitamins C, D, Selenium, B complex.

Why Tocotrienol and Not Tocopherol?

  • Tocopherol, the enemy of Tocotrienol: Tocopherol has been observed to attenuate lung cancer inhibition, inhibits absorption, reduces adipose storage, and compromises cholesterol and triglyceride reduction. Tocopherol hinders the functioning of Tocotrienol and even when they are consumed simultaneously, Tocopherol obstructs all the functions of Tocotrienol.
  • Tocopherol, the antagonist in liver cancer treatment:It has been observed thatTocopherolnot only interferedwith the functioning of Tocotrienol but also showed harmful effects during the treatment.
  • Tocotrienol, the protector of State: Tocotrienol has more mobility than Tocopherol due to its small structure so it can cover a larger area targeting more number of ovarian cancer cells.
  • Small structure and less molecular weight: The higher anti-oxidant activity of Tocotrienols is due to their small structure and less molecular weight which assist in their integration of the cell, unlike Tocopherols.
  • Absorption: As compared to Tocopherols, Tocotrienols absorb better in the body and Tocopherols have been observed to prevent absorption of Tocotrienols. 
Fig. 5: The 2nd pie chart represents Palm Tocotrienol rich fraction with 32% Alpha – Tocopherol which was given to people and when the Alpha – Tocopherol was removed then it was represented by the 1st pie chart with 0.3% Alpha – Tocopherol which was then given to people. In the graph, the hollow bar represents the Tocotrienol with Tocopherol which reduced the concentrations of Alpha, Gamma and Delta Tocotrienol in the body but when Tocopherol was removed from the dosage (Solid grey bars in graph), the concentrations of Alpha, Gamma and Delta – Tocotrienol significantly increased.

References



Note:
1.       To read studies in detail, follow the references and links given.
2.       The dosages given must not be taken as the advice of a medical practitioner. Consult your physician for the optimum dosage to be consumed.



Location: Surrey, BC V3W 1H9, Canada

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