Why did we choose Pancreatic Cancer ?
First, both these cancers often do not cause any obvious symptoms so the victims do not know something serious is wrong. This means that both cancers are diagnosed relatively late, which limits treatment options.
Second, the tumor cells in both ovarian and pancreatic cancers usually become resistant to the drugs chosen for treatment. This means that the tumors may be reduced in the first stage of therapy, but when the cancer cells become resistant to the toxic effect of the drugs, they keep growing even in the presence of the drugs.
As a result of these shared problems, the prognosis for patients with ovarian or pancreatic cancer is bleak so there is a compelling need for innovative treatments for ovarian and pancreatic cancer including an urgent need for agents that overcome the chemo-resistance characteristic of these tumors.
Following the successful research at Columbia University Medical Center with prostate cancer, The Beljanski Foundation decided to extend its research program to focus on ovarian and pancreatic cancers.
Our interests matched those of Dr. Jeanne Drisko and Dr. Qi Chen in the Department of Pharmacology, Toxicology and Therapeutics at Kansas University Medical Center.
Dr. Chen used cell-based assays to show that the Pao pereira (formerly known as PB-100) and Rauwolfia vomitoria extracts (provided by Natural Source International, Ltd) inhibited the growth of multiple ovarian and pancreatic cancer cell lines, including cells that are resistant to chemo drugs. Dr. Chen went on to show that the Pao Pereira or the Rauwolfia vomitoria extracts combined with either Carboplatin (ovarian) or Gemcitabine (pancreatic) worked especially well even against drug resistant ovarian and pancreatic cancer cells. The extracts have anti-cancer activities of their own, but also appear to overcome drug resistance.
The results of the animal studies conducted at KUMC were impressive.
The Pao pereira and Rauwolfia vomitoria extracts reduced ovarian and pancreatic tumor size by themselves, but also worked to enhance the activity of the chemo drugs. For example, in the case of ovarian cancer, “Pao pereira alone suppressed tumor growth by 79%… when Pao pereira was combined with Carboplatin, tumor inhibition reached 97%.”
The results indicate that Pao pereira and Rauwolfia vomitoria hold therapeutic promise for pancreatic as well as ovarian cancer.
More dangerous, or malignant, tumors form when the cancer cells migrate to other parts of the body through the blood or lymph systems. When a tumor successfully spreads to other parts of the body and grows, invading and destroying other healthy tissues, it is said to have metastasized. This process itself is calledmetastasis, and the result is a more serious condition that is very difficult to treat.
In the United States each year, over 30,000 people are diagnosed with pancreatic cancer. Europe sees more than 60,000 diagnoses each year. Because pancreatic cancer is usually diagnosed late into its development, the five-year survival rate after diagnosis is less than 5%.
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- Milestone in Cancer Stem Cell Research
New research just published in Integrative Cancer Therapies shows that the Pao pereira plant extract inhibits pancreatic cancer stem cells. This dramatic result means that the extract will be useful for preventing cancer recurrence.
Everyone knows that cancer treatments are not cancer cures. Chemotherapy treatments kill cancer cells and shrink tumors, but the cancer often comes back. Cancer stem cells (CSCs) are the culprit because they are resistant to anti-cancer drugs, they can metastasize and form new tumors. CSCs make up a small fraction of the cells in a tumor that survive after the majority of primary cancer cells are killed by anti-cancer drugs. The CSCs persist, spread and restart tumor growth.
CSCs are also referred to as cancer stem-like cells because they share the capacity for self-proliferation with normal stem cells that are involved in the renewal and repair of tissues, but unlike normal stem cells, CSCs are cancerous and drug resistant.
In vitro experiments show Pao pereira reducing the number of pancreatic CSCs (see figure below).
As the amount of Pao pereira is increased, the number of pancreatic cancer stem cells (spheroids) decrease dramatically. In additional cell-based studies, the Pao pereira extract also specifically reduced the pancreatic cancer stem cell population.
In vivo experiments showed that Pao pereira inhibited the capacity of pancreatic CSCs to form tumors – the defining characteristic of CSCs – and significantly reduce the volume of tumors that did form (see figure below).
At day 6 (Figure A), tumor formation rate in the control group reached 80%, while in Pao-treated group it was only 10%. At day 20, when the treatment stopped, all mice in control group were bearing tumors on both flanks (100% tumor formation), while the Pao-treated group only had 30% tumor formation. Growth of the formed tumors was also inhibited by Pao pereira treatment compared with the control group (Figure B). A long-term inhibitory effect in tumor growth was observed after treatment had stopped. Pao pereira works by lowering the signals that trigger the pancreatic cancer stem-like cell properties that lead to cancer recurrence.
The researchers at Kansas University Medical Center concluded that Pao pereira holds great promise as a novel treatment for targeting pancreatic CSCs, an essential component of treatments that will lead to real cancer cures.
- Publication on Rauwolfia Vomitoria Extract against Pancreatic Cancer
March 2014 – 'Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Gemcitabine Effects Against Pancreatic Cancer'
by Jun Yu, PhD and Qi Chen, PhD
Integrative Cancer Therapy. 2014 Apr 24;13(3):217-225.
The fourth publication from the scientific collaboration between the Beljanski Foundation and Kansas University Medical Center has been released. It shows, in vitro and in vivo, the effectiveness of Rauwolfia vomitoria (the extract prepared according to Dr. Mirko Beljanski's proprietary process) on pancreatic cancer cells. This publication also confirms – if confirmation were needed – the non-toxicity of Rauwolfia ('Rau'), on healthy cells, its selective effect against cancer cells, and its excellent synergistic action with Gemcitabine chemotherapy. This study, conducted with extracts provided by Natural Source International, Ltd. is now available on The Beljanski Foundation website.
For the purpose of this study, pancreatic cancer cells were inoculated into four groups of mice (control group treated with saline solution, mice treated with Gemcitabine alone, mice treated with Rauwolfia alone, and mice with combination treatment of Gemcitabine and Rauwolfia). As the tumors did not respond to Gemcitabine, Rauwolfia at either 20 mg/kg or 50 mg/kg provided observable inhibition in tumor growth. The combination of Gemcitabine + Rauwolfia at both doses also inhibited tumor progression. Notably, there were 2 mice in the Gemcitabine + Rauwolfia 50 mg/kg group that had complete tumor regression, an effect that was not observed in any other treatment group.
Necropsy confirmed the imaging results at the end of the treatment. Gemcitabine at the dose used did not provide any reduction in tumor weight, when Rauwolfia alone decreased tumor weight by 53% at the daily dose of 20 mg/kg, and 46% at the daily dose of 50 mg/kg, compared with saline-treated control. By combining Rauwolfia with Gemcitabine, the decrease in tumor weight was 56% at both Rauwolfia doses. The improvement in tumor inhibition provided by the combination was significant compared with that of Gemcitabine alone.
On assessing tumor metastasis, 12% of mice in the control group (saline-treated) and in the Rauwolfia 20 mg/kg group did not form metastasis, whereas all mice in Gemcitabine group formed metastasis. The percentage of metastasis free mice increased to 40% with both Rau 50 mg/kg treatment and Gemcitabine + Rauwolfia treatment, suggesting that Rauwolfia provided benefit in reducing metastatic potential while Gemcitabine did not.
None of the mice demonstrated observable toxicity associated with the treatments. At the end of the experiments, major organs (kidney, liver, and spleen) were subjected to hematoxylin and eosin staining and histopathological analysis. No tissue damage was detected in the treatment groups, and there were no significant differences between the control group and the treated group. This data demonstrated that Rauwolfia at the dose used, either alone or combined with Gemcitabine, was effective and, at the same time, low in toxicity.
This would open an avenue to reduce toxicity associated with chemotherapy.
Pancreatic cancer is one of the most lethal malignancies with very limited treatment option. In the effort of enhancing the effect of the conventional chemotherapeutic drug gemcitabine against pancreatic cancer, we investigated in vitro and in vivo the anticancer effect of a β-carboline-enriched extract from the plant Rauwolfia vomitoria (Rau), either alone or in combination with gemcitabine, in preclinical pancreatic cancer models. Rau induced apoptosis in pancreatic cancer cells in a concentration-dependent manner, and completely inhibited colony formation of PANC-1 cells in soft agar.
The combination of Rau and gemcitabine had synergistic effect in inhibiting cell growth with dose reduction effect for gemcitabine. In an orthotopic pancreatic cancer mouse model, PANC-1 tumor growth was significantly suppressed by Rau treatment. Metastasis was inhibited by Rau. Adding Rau to gemcitabine treatment reduced tumor burden and metastatic potential in the gemcitabine non-responsive tumor. These data suggest that Rau possesses anti–pancreatic cancer activity and could improve effect of gemcitabine.
- Publication on Pao pereira Extract against Pancreatic Cancer
March 2013 – 'Inhibition of Pancreatic Cancer and Potentiation of Gemcitabine Effects by the Extract of Pao Pereira'
by JUN YU, JEANNE DRISKO and QI CHEN
Oncology Reports' Journal (doi: 10.3892/or.2013.2461)
The scientific team at the University of Kansas Medical Center has just published a new article entitled, 'Inhibition of Pancreatic Cancer and Potentiation of Gemcitabine Effects by the Extract of Pao Pereira' in the 'Oncology Reports' Journal (doi: 10.3892/or.2013.2461).
This scientific paper describes the results of in vitro and in vivo studies demonstrating the anti-cancer effect of the Pao pereira extract, used alone and in combination with gemcitabine (chemotherapy used in most cancer treatments), in multiple cancer cell lines including those of the pancreas resistant to anti-mitotic drugs.
Pre-clinical studies conducted with mice, both in vitro an in vivo, confirm that adding Pao Pereira to the treatment regiment reduced the concentration of Gemcitabine to produce an equitoxic effect on pancreatic cancer cells. The Pao's anti-cancer effect was seen in vivo and in vitro working alone and in conjunction with other chemotherapy treatments. Over the course of the study, the Pao pereira was seen to suppress tumor growth significantly, by up to 72%.
This confirms another study, published just a few years ago, out of Columbia University demonstrating that the two plant extracts, Pao Pereira and Rauwolfia Vomitoria, contain Beta-Carbolines with effective anti-cancer properties which inhibit cancer cell growth, even in those cells resistant to drugs used in chemotherapy. This study, specific to anti-prostate cancer activity, also substantiated that all healthy cells were not negatively affected, thus demonstrating the safety of the plant extracts prepared by the Beljanski method.
With such promising initial results, the research will continue on Pao Pereira to assess its effectiveness on other types of cancerous cells!
Lack of effective therapy is a major problem in the treatment of pancreatic cancer. In the present study, we investigated a natural product, the extract of Pao Pereira (Pao), for its anti-pancreatic cancer effect in vitro and in vivo, either alone or in combination with the first-line chemotherapeutic drug gemcitabine (Gem). Pao induced dose-dependent apoptosis to all five tested pancreatic cancer cell lines. The combination of Pao and Gem had a synergistic effect in the inhibition of cell growth, with combination indices (CIs)