Corrective Cancer Care and Stem Cells

8/3/2019 Corrective Cancer Care and Stem Cells

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The Weeks Clinic for Corrective Medicine and Psychiatry 2011

Corrective Cancer Care

and

Cancer Stem Cell Therapy

Bradford S. Weeks, M.D.

www.weeksmd.com [email protected]
http://www.weeksmd.com/mailto:[email protected]:[email protected]://www.weeksmd.com/


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Original Titles

Cancer: Striking the Root

vs.Cancer: Dont Kill the Messenger


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Max Wicha, M.D.Distinguished Professor of Oncology

Director, University of Michigan

Comprehensive Cancer Center

The problem is, when we treat cancer cellswith chemotherapy, the cancer stem cells

are being stimulated to grow too.

When we take mesenchymal stem cells andmix them with tumor cells, the tumors grow

much more quickly in animals.


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Cancer expert tells how

treatment can be problem

Wednesday, February 24, 2010 By Mark Roth, Pittsburgh Post-Gazette

Max Wicha: Hopes cancer treatments can avoid generalchemo altogether and just use targeted therapies againstthe stem cells.

Max Wicha is coming to Pittsburgh today to deliver astartling message. Standard cancer treatments not onlyoften fail to eradicate cancer, but can make it worse.

That argument isn't coming from a fringe proponent of

alternative medicine, but from the founder of theUniversity of Michigan's Comprehensive Cancer Centerand a pioneer in research on why cancers recur andspread to other parts of the body.


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..treatment is a problem (cont.)

The reason breast cancer and other malignancies oftenreturn aggressively after treatment is that when tumorcells die under assault from chemotherapy andradiation, they give off substances that can reactivate

a special set of master cells known as cancer stemcells,Dr. Wicha said in an interview Tuesday.

Dr. Wicha's lab has found that inflammatory moleculessecreted by dying tumor cells can hook up with thestem cells and cause them in effect to come out ofhibernation.


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Adult stem cells exist in most tissues, and go intoaction to repair damage from wounds or infections.

In cancer, they can mutate and no longer obey

normal bodily signals to stop growing, Dr. Wichasaid.

He and other researchers say that even whenchemotherapy and radiation cause tumors to

shrink dramatically, these stem cells can stayalive, living under the radar until they are onceagain spurred into action.


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A recent experimental trial with advanced breastcancer patients at the University of Michigan, BaylorUniversity in Texas and the Dana-Farber CancerInstitute at Harvard University used standardchemotherapy along with a substance designed toblock one of the biochemical pathways of stemcells.

The approach killed off more than 90 percent ofthe cancer stem cells, Dr. Wicha said, andresearchers now hope to expand the treatment to amuch larger group of patients.


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Ultimately, he hopes cancer treatments can avoidgeneral chemo altogether, with its debilitating sideeffects, and just use targeted therapies against thestem cells.

There is still a long road ahead, he said, and "my feelingis, to really knock these stem cells out, we're probablygoing to have to use multiple inhibitors.

You Tube http://weeksmd.com/?p=5014 and

http://wn.com/professor_max_wicha__breast_cancer_stem_cell_regulation
http://weeksmd.com/?p=5014http://wn.com/professor_max_wicha__breast_cancer_stem_cell_regulationhttp://wn.com/professor_max_wicha__breast_cancer_stem_cell_regulationhttp://wn.com/professor_max_wicha__breast_cancer_stem_cell_regulationhttp://wn.com/professor_max_wicha__breast_cancer_stem_cell_regulationhttp://weeksmd.com/?p=5014


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The Public retraction

Cancer patients, follow recommended care!

An article published by the Post-Gazette

claimed that our research suggests cancer treatments"not only often fail to eradicate cancer, but canmake it worse" This statement has beenmisinterpreted by patients currently receivingradiation or chemotherapy treatments. I have been

contacted by both my own patients and Pittsburgh-area patients who have questioned whether theyshould continue with their chemotherapy. In fact,these treatments are lifesaving for many patients.


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Brief Review

Know your enemy intimately,

See your target clearly,Set your strategy carefully,

Before you attack wisely.


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Leading Thought:

Is attacking Cancer the Best Strategy?

The ideal strategy whereby one

could win without fighting,accomplish the most by doing the

least, bears the characteristic stamp

of Taoism.- note by Thomas Cleary, translator, of Sun Tzus The Art of War


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Per Prof. Max Wicha, M.D.

Chemotherapy increases numbers of dangerous

cancer stem cells by increasing cytokines like IL-8 so

that cancer stem cell cannot differentiate *, which

cause treatment resistance.

The goal is to combine chemotherapy with adjunctive

therapies which prevent increase of cytokines (like

IL-8) when tumors are attacked with chemotherapy

or radiation (and IPT).

* If they would differentiate, they would become susceptible to chemotherapy again


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What is Cancer?

Cancer is understood to be unregulated cells

proliferating autonomously within the human

beingeither in humoral or tumorous form.

(Query: Are these aggressive or confused cells?)


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What is a Tumor?

A tumor, benign or malignant, is a

proliferation of cells of which, in the case of a

malignant cancer, less than 1% of which aredangerous.


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Interesting Fact

99.1% - 99.6% of the tumor cells are NOTdangerous (aside from steric, obstructive factors).

Similarly, usually less than 1% ofprimary tumor cells cultured in vitro can

give rise to colonies.Diehn, M Therapeutic Implications of the Cancer Stem Cell Hypothesis

Semin Radiat Oncol. 2009 April; 19(2): 7886.


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What metastasizes?

Stem cells!

tumor cells are heterogeneous in their capacity to give riseto tumors upon transplantation or to form colonies in cultureassays. For in vivo tumor transplantation, this is reflected in the

large numbers of tumor cells that must usually be transplanted toform a tumor. For primary human and mouse tumors, this

number often resides in the thousands or millions. (ibid Diehn et al)


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Only stem cells metastasize

Considerable evidence suggests that tumors

contain only a minority of cells which are capable of

regrowing the tumor (ie. tumor stem cells). Since alltumor stem cells must be killed if treatment is to be

successful, the number of stem cells in a tumor can be

expected to be an important determinant of curability.

Hill RP The proportion of stem cells in murine tumors. Int J Radiat Oncol BiolPhys. 1989 Feb;16(2):513-8.


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Normal Tissue Stem Cells resist

Chemotherapy

A large number of the most frequently used therapiesfor cancer induce cell death by inducing DNA damage.

These agents are also toxic to normal stem cells andtheir progeny. Fortunately, normal stem cells haveevolved multiple mechanisms to protect themselvesfrom toxins and genotoxic stress, which make them

relatively resistant to cell killing with cytotoxicagents. (ibid Diehn et al)


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All Stem Cells resist chemotherapy

The apparent similarities between normal tissue stemcells (NTSC) and cancer stem cells (CSC) led to the

hypothesis that CSC may be relatively resistant tocommon chemotherapeutic agents compared to theirmore differentiated non-tumorigenic counterparts and

that improvements in patient outcomes might beachieved by directly targeting CSC . Mounting

evidence suggests that this is the case. (ibid Diehn et al)


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Cancer Stem Cells resist

Chemotherapy

Baker, M Stem cells: Fast and furious.Nature. 2009 Apr 23;458(7241):962-5.


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Cancer stem cells are resistant to chemotherapy

The apparent similarities between normal stem cells and CSCled to the hypothesis that CSC may be relatively resistant tocommon chemotherapeutic agents compared to their more

differentiated non-tumorigenic counterparts and thatimprovements in patient outcomes might be achieved by directlytargeting CSC. Mounting evidence suggests that this is the case.Recent studies have shown that cancer stem cell-like cells

present in some established cell lines and in long-term

xenografts appear to be relatively resistant to cytotoxicchemotherapeutics. (ibid Diehn et al)

Chemotherapy and Radiation is


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Invasive Carcinoma

Chemo-Therapy

RadiationCancer Stem Cell

Normal Cells

Tumor cells

CANCER is spread and

kept alive by

Cancer Stem Cells

Linheng Li and William B. Neaves

Cancer Res 2006; 66: (9). May 1, 2006

Aggressivecancer stem cellssurvive chemo

Chemotherapy and Radiation is

only effective in non-aggressive

cancer cells (tumor cells, not

cancer stem cells).


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and Cancer Stem Cells are

resistant to Radiation Therapy

alsoThus, CSC in some tumors appear to be resistant to

cytotoxic chemotherapies. As is discussed elsewhere in

this issue, CSC in some tumors also appear to beresistant to radiotherapy. These findings suggest the

overcoming CSC resistance mechanisms to cytotoxic

therapies may result in higher cure rates. (ibid Diehn et al)


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Chemotherapy increases Cancer

Stem Cell proliferation

Since it remains to be determined how representativesuch cancer stem cell-like cells are of CSC in primary

tumors, another group analyzed human CD44+ESA+colon cancer stem cells were enriched in

xenografts that had been treated withcyclophosphamide compared to untreated control

tumors.(ibid Diehn et al)


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Invasive Carcinoma

Chemotherapyor Radiation

Cancer Stem Cells

survive

Cancer Stem Cell Normal cellTumor cell (non stemcell)

The worst case scenario(aka the Standard of Care)

Resistence!


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Chemotherapy increases cancer

stem cell number and virulence

Enrichment was documented both as anincreased percentage of cancer stem cells as

measured by flow cytometry and as highertumor forming capacity in limiting dilution

assays.

Li X, Lewis MT, Huang J, et al. Intrinsic resistance of tumorigenic breastcancer cells to chemotherapy.J Natl Cancer Inst. 2008;100:6729.


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Primum Non Nocere

Chemotherapy and Radiation

make Cancer worse.

Prof. Max Wicha, M.D. Director U. MichiganComprehensive Cancer Center


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Cytokines which inhibit Stem Cell Differentiation are increased by

doxorubicin in H460 tumor cells, In vitro

Int J Cancer, 2009, NIH-PA


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CHEMOTHERAPY INCREASE CYTOKINES IN

TUMORS

Levina et al.

Chemotherape

utic drugs and

human tumor

cells cytokine

network.Int J

Cancer. 2008


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New Directions in Cancer

Treatment

Recent insights into tumor biology.indicate that in manycancers only a subset of malignant cells has the potential to

proliferate indefinitely and therefore to give rise to macroscopic

metastases or to cause tumor recurrence after treatment

It is this subset of cells, often called cancer stem cells(CSC), that needs to be targeted and eliminated in order to

achieve cures, since the remaining cancer cells (called non-

tumorigenic cells) are destined to stop dividing or to die. (ibidDiehl et al)


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New Directions in Cancer

Treatment (cont.)

The CSC hypothesis suggests that agents

targeting these cells should ultimately lead to

improved outcomesfor cancer patients.

http://cirmresearch.blogspot.com/2011/04/shifting-balance-of-stem-cell-renewal.html
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Going Forward

Assessing the efficacy of such treatments will require the adventof new approaches to assessing CSC frequency and viability

within tumors. Furthermore, classic mechanisms of treatment

resistance, such as clonal selection and the tumormicroenvironment, will continue to present obstacles forachieving cure. It is therefore likely that combinations of

cytotoxic, biologic, and CSC-directed therapies will ultimatelyallow the largest possible improvements in patient outcomes.


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We need a targeted therapy

One vexing dilemma in the nascent field ofCSC-based therapeutics is the high similarity

between CSC and normal tissue stem cells,which complicates the second aforementioned

goal of CSC-directed therapyavoiding normalstem cell toxicity. (ibid Diehn et al)


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Certainty in Clinical Practice

I stand firmly upon the

shifting sands ofclinical science.

Dr. Weeks disclaimer to patients, the state medical board andesteemed colleagues (and his mother).


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IPT is better than conventional Rx

Those wicked creatures yet do look well-

favored, when others are more wicked; not

being the worst stands in some rank of praise

Ill go with thee: thy fifty yet doth double five

and twenty, and thou art twice her love

Lear, speaking to daughter Goneril when insulted by daughter Regan - Act 2 scene 1


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But.

IPT, being chemotherapy (albeit low dose andtargeted kinder and gentler) nevertheless still

worsening cancer prognosis since it still kills ONLYcancer tumor cells (not the cancer stem cells):

the resulting IL-8 SOS signal still goes out to musterreinforcements from the mesenchymal stem cells whichincrease the number and virulence of cancer stem cells.


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RX: IPT with Adjuvant Therapies

Stem cell re education

Adjunctive therapies along with IPT to entice

cancer stem cells to differentiate and become

normal tissue stem cells or normal tissue cells.


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The Cordelia Effect

Current Approach:

Killing the Messenger (Cut, Burn, Poison)

Better Approach:

Bring the cancer stem cells back in line becausere-differentiation is better than death.


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The Cordelia Effect (cont.)

The goal of the Cordelia Effect (Corrective

Cancer Care) is to control the variables

including the local tumor environment so as toshift the cancer stem cells metabolism away

from proliferation and towards differentiation, in

order to decrease tumor size, growth andvirulence.


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The Cordelia Effect

(examples of Corrective Cancer Care)

1) Proteolytic Enzyme Therapy (pancreatic enzymes)

2) MEBO (moist exposed burn ointment)

3) Anti-inflammatory agents (tumeric, etc.)

4) Fermented Soy products (Haelan 951)


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Proteolytics Enzymes


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MEBO

Moist Exposed Burn Ointment

Create a healthy environment which allows

nutrition, detoxification and differentiation for

cancer stem cells wherein cancer can not persist.

Therapy in concordance with the human beings

powerful momentum towards health.


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Tumors are wounds, that do

not heal. Every cancer

medication should improve

wound healing.- Rudolph Virchow, 1865

Today we know thatcytokines (inflammation)

inhibit cell differentiation

and wound healing.
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Anti-Inflammatory Agents

Goal: To interrupt the IL-8 cytokine SOS and allowdifferentiation of cancer stem cells

Reprotaxin -CXCR1 receptor blocker- (Wicha)Oxygen (hypoxemia stimulates CSCs)

Tumeric

MEBO

Fermented Soy
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Anti-Inflammatory Agents in

Corrective Cancer Care
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CANCER STEM CELLS AND FERMENTED SOY

1) Soy decreases cytokines (including IL-8)Handayani, R Soy Isoflavones Alter Expression of Genes Associated with

Cancer Progression, Including Interleukin-8, in Androgen-Independent PC-3

Human Prostate Cancer Cells1 J. Nutr. 136:75-82, January 2006

2) Fermented soy promotes cell differentiation
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Basis-Werte

NachEinnahme

Serum TNF-a(pg/ml)

-5 0 5 10 15 20 25 Zeit (Wochen)

0

10

20

30

40

50

Isoflavone

(125/Tag)

Isoflavones reduce cytokines in the blood

Ursula Jacobet al , 2009

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ERalpha vs. ERbeta

Prostate cancer growth depends, in its earlier stages, onandrogens and is usually pharmacologically modulated withandrogen blockade. However, androgen-ablation therapy maygenerate androgen-independent prostate cancer, oftencharacterized by an increased invasiveness.

We have shown that the dihydrotestosterone metabolite 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), a steroid whichdoes not bind androgen receptors, but efficiently binds theestrogen receptor beta (ERbeta), exerts a potent inhibition of

prostate cancer cell migration through the activation of theERbeta signaling.
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Fermented Soy increases ER Gene Expression
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Fermented Soy increases ER- Gene Expression

in dissiminated Tumor Cells

ER-Gen Expression

Fold increaseSingle cases

300

200

100

0 Time

(Month)

0 1,5 3

Patient consumed Isoflavones regularly Patients with high GLEASON Factor

(High Malignicy)

facher Anstieg

Ursula Jacob et al , 2009

Soy Increases Anti tumor Factor p21 p53
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Prostate Ca Breast Ca

Ovary Ca

Soy Increases Anti-tumor Factor p21, p53

In Circulating Tumor Cells

Re

l.Gen-Expressionvon

ZellzyklusInhibitorp

21

Single Cases Single Cases

Single Cases

untreated

With fermented soy

Ursula Jacob et al , 2009

Cachexia in Cancer Patients
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Cachexia in Cancer Patients

Rohr et al, Hormone

Molecular

Biology and

Clinical Investigation

2010

N= 164 N= 78

%

Chemotherapy

+ fermented soyChemotherapy

+ Placebo

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In leukemic Children increases

a) transplant efficiency and

b) reduces hospital stay of

children

Hospital Stay of Children

4 month with

Conventionaltransplantation

1 1/2 month

if treated with

fermented soy

Haematopoeises (Cell Differentiation)

Bone Marrow Transplant in Children

Dramatic increase of

Cell differentiation

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GENE EXPRESSION IN CIRCULATING TUMOR

CELLS WITH FERMENTED SOY

Rohr et al. Horm Mol Biol Clin Invest 2010;3(2):391409

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Anti-Angiogenesis

Stabilizing blood capillaries in cancer patients is the newgoal in severe diseases.

Adiol (and/or Fermented Soy) inhibits stem cell

metastastasis by this anti-inflammatory mechanism.

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Fermented Soy is structurally and

functionally similar to the

hormone ADIOL

Pregnancy

Prevents Miscarriage

Trauma

Severe Stress

In Soldiers like PTSD

Fermented Soy transforms Resistant Cancer Stem Cells
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Chemotherapy

Cancer Stem Cell Normal CellTumor Cells (non stem cell)

Fermented Soy transforms Resistant Cancer Stem Cells

into differentiated cancer cells which can then be

treated with Chemo or Radiation therapy.

Invasive

Carcinoma

Cancer Stem

Cell

Differentiating

Fermented SoyRadiation

MetsPrimary

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Fermented soy transformed circulating cancer stem

cells (in vivo, human) into more differentiated and

therefore more targetable treatable cancer tumor

cells.

This mechanism may be the reason for dramatic

increase in survival we see in clinic.

An example of the Cordelia Effect



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Summary:

Stem Cells and Cancer

1) Cancer mortality is directly related to cancer stem cell

activity (metastatic and proliferative processes)

2) Chemotherapy and radiation do not kill cancer stem cells

3) Chemotherapy and radiation make cancers grow faster andmore virulent

4) Treatment of (people with) cancer requires adjunctive careand not just chemotherapy or radiation

5) Treatment which fails to address the toxicity of cancer stemcells is futile and irresponsible


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Summary:

Stem Cells and Cancer (cont.)

6) IPT, while kinder and gentler, must not begiven unless adjunctive care is taken to minimizecancer stem cell stimulation

7) Adjunctive treatment modalities represent asignificant improvement over traditional IPT.

8) This is a therapeutic message which our patients, aswell as our oncology colleagues, are ready to hear.
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Thank You for your Attention

References / Recources

Inspiration

People to watch in stem cell work

Key Articles re. stem cells and cancer

Epic Poetry

Feel free to email me for further discussion
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The Oath of Paracelsus

This is my Vow: To perfect my medical art and never toswerve from it so long as God grants me my office, andto oppose all false medicines and teachings. Then to lovethe sick, each and all of them, more than if my own body

were at stake. Not to judge superficially, but bysymptoms, nor to administer any medicine withoutunderstanding, nor to collect any money without earningit. Not to trust any apothecary, nor to do any violence to

any child. Not to guess, but to know.Paracelsus

1493 - 1541
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Ode to the Totipotent Hematopoetic (sic)

Stem Cell

My musing on stem cells, circa 1987

Sirens sang from Science rocksand caught my ear, despite the plug

nestled deep of orthodoxwhich churches plant, so proud and smug.

Orphans each adrift we are;homeless, steering course by star.

The winds would change, time was short. The moment asked of me resolve.

So digging deep within my heart, I chose, swung prow, intent to solve

the only question man must ask; the only truly human task

For the rest of the epic poem, see Appendix and http://weeksmd.com/?p=5456

Further Reading on Stem Cell Treatment
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1) Therapeutics formulated to target cancer stem cells: Is it in our future?Stephanie Clayton, Cancer Cell Int. 2011; 11: 7.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073868/

2) Therapeutic Implications of the Cancer Stem Cell Hypothesis Maximilian Diehn,MD/PhD and Michael F. Clarke, MD http://weeksmd.com/?p=5465

3) Eradication of Cancer Cells via Regeneration Xu Rongxiang, M.D.http://en.mebo.com/Achievement/ShowInfo.asp?InfoID=262

4) Haelan

5) Powerpoint on Proteolytic Enzymes Bradford S. Weeks, M.D. Presentation at 2010IPT Conference www.

6) The Enzyme Treatment of Cancer and its Scientific Basis John Beard, D. Sc.1911

7) The Trophoblast and the Origins of Cancer Nicholas Gonzalez, M.D. New SpringPress 2009
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073868/http://weeksmd.com/?p=5465http://en.mebo.com/Achievement/ShowInfo.asp?InfoID=262http://en.mebo.com/Achievement/ShowInfo.asp?InfoID=262http://weeksmd.com/?p=5465http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073868/


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People to Watch

Max Wicha, M.D. (Dir. U. Michigan Cancer Center)

Michael Clark M.D. Dir. Stanford Institute for StemCell & Regenerative Medicine.

Max Diehn M.D. (Oncology radiologist Stanford)

Ursula Jacob, M.D. and Walter Wainright (Haelan)

Xu Rongxaing, M.D. (MEBO)

John Beard, M.D. (deceased) / Nicholas Gonzales,M.D.

Cordelia quotations from King


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Cordelia quotations fromKing

Lear

Time shall unfold what plighted cunning hides;

who covers faults, at last shame them derides.

We are not the first who with best meaning

incurred the worst.

Kent: Vex not his ghost: O, let him pass: he

hates him that would upon the rack of this

tough world stretch him out longer.

Corrective Cancer Care and Stem Cells

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Transcript of Corrective Cancer Care and Stem Cells