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Understanding Cervical Cancer

Natural Strategies in Collaborative Cancer Care

Compiled by John G. Connor, M.Ac., L.Ac.

edited by Barbara Connor, M.Ac., L.Ac.

April 6, 2011

 Table of Contents

·        Introduction

·        Natural Strategies in Collaborative Cancer Care

·        Natural Compounds with Specific Application to Cervical Cancer

·        Growth Factors and Genes Involved in Cervical Cancer

·        Examples of Natural Compounds that Protect against Cervical Cancer

·        Comprehensive Cancer Care Consultation

·        References

Introduction

 

Cervical cancer is the second most common malignancy among women worldwide and is highly radioresistant, often resulting in local treatment failure. For locally advanced disease, radiation is combined with low-dose chemotherapy; however, this modality often leads to severe toxicity. (Jawadi et al 2008)

 

Individual studies estimate that as many as 69% of US cancer patients employ some type of complementary and alternative medicine, 76% of patients in a study of Midwestern cancer patients and 95% of radiation oncology patients in another study.  (Wargovich et al 2010)

 

Barbara and I feel that the emerging concept and practice of targeted therapies which have a high specificity toward tumor cells provides a broader therapeutic window with less toxicity than the current chemotherapeutic agents. They are also often useful in combination with cytotoxic chemotherapy or radiation to produce additive or synergistic anticancer activity because their toxicity profiles often do not overlap with traditional cytotoxic chemotherapy. Targeted therapies represent a new and promising approach to cancer therapy, one that is already leading to beneficial clinical effects. There are multiple types of targeted therapies available, including monoclonal antibodies, receptor tyrosine kinase inhibitors, and growth factor receptor inhibitors.

 

The wonderful thing about botanicals and nutritives is that they target many of the same growth factors, receptors and pathways as conventional drugs and chemos but in a gentler and less toxic way thereby allowing for decreased dosages in the more toxic chemos and drugs. One of the characteristics of plants is that they are pleiotrophic, i.e., they exert multiple effects. Therefore botanicals and herbs by their very nature not only enhance the effectiveness of chemos and drugs but they can reduce or eliminate many of their unwanted side effects

 

Cell proliferation, differentiation and apoptosis (programmed cell death) are controlled by a multitude of cell-cell signals.  Loss of this control has devastating consequences. (Ripamonti 2000)  When this control is lost Barbara and I feel that one of the best ways of re-establishing it is by combining natural compounds (herbs, nutrients and diet) along with targeted specific and appropriate conventional medical cancer treatments. 

 

For example, curcumin, a polyphenol extracted from rhizomes of the plant Curcuma longa, is a widely studied chemopreventive agent that was shown to have a low toxicity profile in three human clinical trials. Pretreatment of two cervical carcinoma cell lines, HeLa and SiHa, with curcumin before ionizing radiation (IR) resulted in significant dose-dependent radiosensitization of these cells. (Jawadi et al 2008)

 

Natural Strategies in Collaborative Cancer Care

 

The following is a list of natural strategies we employ and the issues we address in our approach to integrative cancer care:

 

·         Alkalinity and Acidosis in Cancer

·         Angiogenesis Blood Markers

·         Appendix of Cancer Pathways

·         Blood Tests for Cancer-Related Cachexia

·         Blood Tests that Detect Various Polymorphisms that Relate to the Metabolism or Detoxification of Chemotherapy

·         Blood Tests to Assess Hypercoagulation

·         Bone Building Protocol for Bone Related Cancer

·         Cancer and Sugar

·         Chemotherapy and Predictive Bio-markers

·         Copper Reduction Protocol

·         Counteracting Cancer Related Cachexia with Natural Compounds

·         Cytotoxic Herbs & Their Functions

·         Factors that Increase the Risk of Blood Clots and Thrombosis.

·         Glossary of Chemotherapeutic Drugs

·         Growth Factors and Genes Involved in Cancer

·         How Elevated Glucose and Insulin Promote Cancer

·         Immunotherapy - Activating the Immune System with Natural Compounds

·         Inflammatory Blood Markers

·         Inhibiting Angiogenesis with Natural Compounds

·         Managing the Side Effects of Chemotherapy with Natural Compounds

·         Markers for Assessing Bone Health

·         Natural Aromatase Inhibitors

·         Natural Compounds that Act as Biological Response Modifiers

·         Natural Compounds That Alleviate the Side Effects of Chemobrain

·         Natural Compounds that are Radiation Protective or Synergistic with Radiation Therapy

·         Natural Compounds that Downregulate HPV

·         Natural Compounds that Downregulate IGF and are Insulinotrophic, and Anti-cancer.

·         Natural Compounds that Enhance the Effectiveness of Paclitaxel

·         Natural Compounds that Enhance the Effectiveness of Platinums

·         Natural Compounds that Inhibit Multi Drug Resistance

·         Natural Compounds that Lower Homocysteine

·         Natural Compounds that Protect against Bone Cancer

·         Natural Compounds that Protect against the Side Effects of Doxorubicin

·         Natural Compounds that Reduce the Side Effects of Carboplatin

·         Natural Compounds that Reduce the Side Effects of Paclitaxel

·         Natural Compounds that Reduce the Side Effects of Platinol (Cisplatin)

·         Natural Compounds that Reduce the Side Effects of Platinum Drugs

·         Natural Compounds that Synergize with Doxorubicin (Anthracyclines)

·         Natural Compounds that Target Growth Factors and Genes Involved in Cancer

·         Natural Compounds which Hasten Recovery from Surgery

·         Neuropathy and Cancer Pain Management

·         Nutritional Support for Glutathione and Optimal Liver Detoxification

·         Radiation and Cancer

·         Reducing Inflammation with Natural Compounds

·         Suppressing Hypercoagulation with Natural Compounds

·         Surgery and Cancer

·         Teas and Soups which Alleviate the Side Effects of Chemo and What to Eat During Chemo

·         Tissue Pathology Reports

·         Understanding the Mechanism behind Bone Metastasis

 

Natural Compounds with Specific Application to Cervical Cancer

 

Boron-containing compounds - interfere with the physiology and reproduction of cancer cells. Types of cancers most frequently impacted by Boron-containing compounds include prostate, breast, cervical and lung cancer. Mechanisms involving Boron activity on cancer cells are based on the inhibition of a variety of enzymatic activities, including serine proteases, NAD-dehydrogenases, mRNA splicing and cell division, but also receptor binding mimicry, and the induction of apoptosis. Boron-enriched diets resulted in significant decrease in the risk for prostate and cervical cancer, and decrease in lung cancer in smoking women. Boron-based compounds show promising effects for the chemotherapy of specific forms of cancer, but due to specific benefits should also be included in cancer chemopreventive strategies. (Scorei and Popa 2010)  Boron is found in leafy vegetables, fruits, nuts and grains.

 

Boswellia serrata - This study reports the apoptotic cell death in human cervical cancer HeLa and SiHa cells by a pentacyclic triterpenediol (TPD) from Boswellia serrata. It caused oxidative stress by early generation of nitric oxide and reactive oxygen species that robustly up regulated time-dependent expression of p53 and p21. TPD also decreased the expression of the PI3K/pAkt, ERK1/2, NF-kappaB/Akt signaling cascades. (Bhushan et al 2009)

 

Curcumin - A potential target for preventing and treating cervical cancer is cyclooxygenase-2 (cox-2). Curcumin is an anti-inflammatory agent that is known to have anti-cox-2 activity. There was a statistically significant difference in the expression of COX-2 in adenocarcinoma in comparison to normal (p value=0.01) and squamous cell carcinoma (p value=0.02) tissues. Proteins associated with cancer and cell cycle were significantly altered in cultured cells. Curcumin may have antitumor effect in cervical cancer. (Madden et al 2009)

 

Green tea (EGCG) -Both epigallocatechin gallate and polyphenols E inhibited immortalized cervical epithelial and cancer cell growth. Apoptosis induction and cell cycle changes were observed in a dose-dependent manner. (Zou et al 2010)

 

Histone deacetylase inhibitor (HDACi) pretreatment renders cervical cancer cells sensitive to TNFalpha and TRAIL-induced apoptosis. (Darvas et al 2010)

 

I3C and DIM - These data confirm the proapoptotic action of I3C on transformed cells in vitro, extend the observations to cervical cancer cells and to DIM and show for the first time that dietary I3C results in increased apoptosis in target tissues in vivo. (Chen et al 2001)

 

Silibinin (Milk Thistle) – In this study, silibinin was found to inhibit hypoxia-induced HIF-1alpha accumulation and HIF-1 transcriptional activity in human cervical (HeLa) and hepatoma (Hep3B) cells. (Garcia-Maceira & Mateo 2009)

 

Growth Factors and Genes Involved in Cervical Cancer

 

Examples of Natural Compounds that Protect against

Cervical Cancer

 

COX-2 (Cyclooxygenase-2) - is up-regulated in practically all cancers (75%).  It is induced by phorbol esters, cytokines and growth factors, including TGF-beta-1 and bFGF.  COX-2 is a potent inducer of angiogenesis by inducing angiogenic factors. Most common cancers with altered (amplified) COX-2 expression include: prostate, colon, breast, cervical, brain, gastric, pancreatic, lung, head and neck, kidney and bladder.

 

A potential target for preventing and treating cervical cancer is cyclooxygenase-2 (COX-2). Curcumin is an anti-inflammatory agent that is known to have anti-cox-2 activity. There was a statistically significant difference in the expression of COX-2 in adenocarcinoma in comparison to normal and squamous cell carcinoma tissues. Proteins associated with cancer and cell cycle were significantly altered in cultured cells. Curcumin may have antitumor effect in cervical cancer. (Madden et al 2009)

 

Examples of Natural Compounds that Down-Regulate COX-2:

1.       Panax notoginseng (Son et al 2009)

2.      Parthenolide (Weng et al 2009)

3.       Pterostilbene (Pan et al 2008)

4.       Quercetin (Lee et al 2010) (Turner et al 2009) (Warren et al 2009)

5.       Resveratrol (Kang et al 2009)

HIF-1α – (Hypoxia-inducible factor-1)

HIF-1α -plays a key role in tumor angiogenesis by regulating the expression of angiogenic factors including VEGF.  HIF-1alpha over expression is associated with increased vascularization, drug resistance, and poor diagnosis. The PI3K/Akt/mTOR/p70S6K pathway is implicated in the regulation of HIF-1alpha expression at the translational level. (Jung et al 2010)

Overwhelming evidence indicates hypoxia promotes tumor growth, progression, and resistance to therapies. Recent studies on the hypoxia-inducible factors (HIF), have corroborated further the essential role of hypoxia in tumor growth and progression. Both HIF-1α and HIF-2α are overexpressed frequently in human cancers. (Yoo et al 2011)

Tumour resistance against radiation- and chemo- therapy is facilitated by oxygenation reduction at tumour areas. HIF-1alpha regulated genes are mostly responsible for this type of resistance. (Said et al 2010) Targeting HIF-1 can suppress tumor angiogenesis and improves the effectiveness of other angiogenic targets, chemotherapy and radiation therapy.

Tumor hypoxia is known to activate angiogenesis, anaerobic glycolysis, invasion and metastasis. (Lu et al 2010)

 

In this study, silibinin was found to inhibit hypoxia-induced HIF-1alpha accumulation and HIF-1 transcriptional activity in human cervical (HeLa) and hepatoma (Hep3B) cells. (Garcia-Maceira & Mateo 2009)

Endometrial tumors with the highest HIF-1alpha protein content were ascorbate deficient. Low ascorbate levels were also associated with elevated VEGF, GLUT-1, and BNIP3 protein levels and with increased tumor size, and there was a significant association between low tissue ascorbate levels and increased activation of the HIF-1 pathway. In contrast, tumors with high ascorbate levels had lesser levels of HIF-1 activation. This study shows for the first time a likely in vivo relationship between ascorbate and HIF-1, with low tumor tissue ascorbate levels being associated with high HIF-1 activation and tumor growth. (Kuiper et al 2010)

 

Examples of Natural Compounds that Target HIF-1α

  1. EGCG – inhibited the expression of HIF-1 alpha in cervical cancer cells  (Tang et al 2008)
  2. Panax ginseng – gensenoside Rg3 – inhibits the expression of HIF-1 alpha during hypoxia. (Wang et al 2009)
  3. Resveratrol –inhibits HIF-1 alpha in cervical cancer cells. (Tang et al 2007)
  4. Silibinin (Silymarin)/Milk Thistle – inhibits HIF-1 alpha expression in cervical cancer and hepatoma cells (Garcia-Maceira & Mateo 2009)

 

Comprehensive Cancer Care Consultations

 

Barbara & I have been working in the integrative oncology setting for many years and have been collaborating closely with Donald Yance for 6 years.  We are graduates of both his Level One and Level Two Professional Clinical Trainings - Fundamentals of the ETMS (Eclectic Triphasic Medical System) and Advanced Clinical Applications of the ETMS in Cancer Therapies.

 

Our cancer protocols are designed to work synergistically with targeted individualized medical treatment plans and emphasize the practice of healthy medicine aimed at the root source of ill-health.  Our primary focus is to build your immune system, enhance your vitality, and to bring about harmony and balance throughout your body.  The botanicals and nutrients will target a multitude of cancer pathways generally and specifically in each case.

 

Using chemo-sensitivity screening and tumor marker testing we will be identifying what are the most appropriate chemos or drugs to use which will have the greatest impact on the cancer and at the same time have the least negative impact on your health. If you need to undergo chemotherapy or radiation we will provide you with specific protocols to help alleviate the side effects as well as specific protocols to help enhance the effects of the chemos.

 

If you are interested in finding out more about how we work or if you would like to set up a phone consult please phone us at 919-309-7753 or email us at johnandbarbaraconnor@me.com.

 

References

 

  1. Bagchi, Debasis & Harry G. Preuss, Phytopharmaceuticals in Cancer Chemoprevention, CRC Press, Boca Raton, 2005

 

  1. Beckett, Geoffrey, Simon Walker, Peter Rae & Peter Ashby, Lecture Notes – Clinical Biochemistry, 8th edition, Wiley-Blackwell, Oxford,  2010

 

  1. Boik, John, Natural Compounds in Cancer Therapy, Oregon Medical Press, Princeton, MN, 2001

 

  1. Boik, John, Cancer & Natural Medicine, A Textbook of Basic Science and Clinical Research, Oregon Medical Press, Princeton, MN, 1996

 

  1. Chernecky, Cynthia C, and Barbara J. Berger, Laboratory Tests and Diagnostic Procedures, Saunders, St. Louis, 2008

 

  1. Heber, David, Editor-in –Chief, Nutritional Oncology, Second Edition, Academic Press, London, 2006

 

  1. McKenna, Dennis J., PhD,  Kenneth Hones & Kerry Hughes, Botanical Medicines, The Desk Reference for Major Herbal Supplements, Second Edition, The Haworth Herbal Press, New York, 2002

 

  1. Neal, Michael J., Medical Pharmacology at a Glance, Sixth edition, Wiley-Blackwell, Oxford, 2009

 

  1. Stargrove, Mitchell, Jonathan Treasure & Dwight L. McKee, Herb, Nutrient, and Drug Interactions, Mosby Elsevier, St. Louis,  2008

 

  1. Weiss, Rudolf, MD & Volker Fintelmann, MF, Herbal Medicine, Thieme, New York, 2000

 

  1. Yance, Donald, “Donald Yance’s Eclectic Triphasic Medical System (ETMS): An Integrative Wholistic Approach to Treating and Preventing Cancer”, (Monograph) 2010

 

  1. Yance, Donald, Herbal Medicine, Healing & Cancer, Keats Publishing, Lincolnwood (Chicago) IL, 1999

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Copyright © 2011 John G. Connor