Introduction
Cancer Bacteria and HCG
An Unholy
Trinity
Deadly Symbiosis
Potential Adjuvant Therapies
Conclusion
DISCLAIMER: The following hypothesis
does not solely represent our opinion, nor does it represent any treatment
recommendation, implied or otherwise on the part of the Cancer Bacteria Homepage
or its author, Ron Falcone. The following hypothesis and the ideas
presented herein represent a composite, based on our conversations and
interviews with health care practitoners, scientists, and commentators involved
in cancer bacteria research. In this regard, we seek to present a synthesis
of general themes and ideas as culled from many published articles, historical
documents and medical/scientific archives spanning a century. In effect, we at
the Cancer Bacteria Homepage are trying to provide readers, and the general
public, with a synthesis of what we have learned about cancer bacteria
during our many years of researching the subject.
The following
hypothesis and any potential therapies discussed have not
been endorsed by mainstream cancer agencies, and are not
being included here as recommendations or suggestions. It must be
emphasized that any adjuvant, standard, or hypothetical therapies discussed
herein are only mentioned for the sake of discussion, and as
material for further research. They are not meant to serve as the basis for
an actual treatment program. The therapeutic benefits of any therapies discussed
herein is open to intelligent debate, discussion and clinical trial
evaluation.
Ron Falcone
and The Cancer Bacteria Homepage are not in any way responsible
for the choice of therapies adopted by any patient, physician or
health-practitioner whatever similarities might be construed based on
information provided in this website.
The century's old debate as
to whether bacteria are simply opportunistic infections "after the fact" or
whether they can initiate cancer has been a contentious one. As early as the
1920's, Thomas Glover isolated a bacterium which he named "Glover's organism".
Two decades later, Virginia Livingston believed that a single, ubiquitous
pathogen she identified as a Mycobacterium (and which she named
Progenitor cryptocides) was the primary cause of most human cancer. A
handful of others also claimed discovery of a cancer-causing organism which
appeared cameleon like, and seemed to defy one, universal taxonomy. From a
mainstream standpoint, scientists disagreed with Glover and his later
contemporaries, instead arguing that cancer-related pathogens were
simply opportunists, contaminating diseased tissues after the fact. But in
the 1990's, Shy Chung Lo of the Armed Services Institute of
Pathology cultured Mycoplasma fermentans from cancer, injected the
organism into animals, and was then able to induce cancer; in effect, Lo
had established Koch's Postulates, proving that bacteria were indeed able
to directly cause cancer [1].
Other investigators
corroborated Lo's Mycoplasma research. For example, Chan reported
the prevalence of mycoplasmal DNA in ovarian cancer[2]; Schmidhauser
demonstrated that the p37 gene associated with mouse
sarcoma originates from Mycoplasma and that a proportionate
increase in malignant invasiveness was related to such
exposure[3]; Ushio found that Mycoplasma-infected cells have
a higher ability to metastasize in
vivo than non-infected cells[4]; and Bogoch demonstrated that
Mycoplasma secrete a similar polysaccharide used by cancer
antigens to avoid immune-system recognition.
Although mainstream scientists generally disregarded the notion of
a "cancer germ"---even as late as the 1990's---conclusive evidence
now linking H.pylori with stomach cancer has rendered this
position obsolete. In addition, science now appears to be moving toward a
greater acceptance of multiple species of cancer bacteria implicated in
different forms of cancer. For example, Salmonella
typhi, Streptococcus bovis and Chlamydia
penumoniae[5] are being associated with gallbladder,
colorectal, and lung cancer, respectively. And a percursory review of the
scientific literature clearly has shown an exponential increase in cancer
bacteria-based findings, beginning in the early 1990's and
continuing through to the present.
As the evidence continues to accumulate, the long held paradigm of
microbiology that consigns a specific bacterium to a specific infectious disease may not correlate
with the multiple species of bacteria now being associated
with cancer.
Cancer Bacteria and
HCG
Beside
their potential role in oncogenesis, different genera and species of
bacteria have consistently tested positive for the human growth hormone
choriogonadotropin (hCG). While bacterial hCG is a finding that's not been
actively pursued in mainstream laboratories, we feel it represents a major
milestone in the cancer process.
The first investigator to discover a bacteria-hCG link was Virginia
Livingston in 1974[6]. Her findings were
corroborated by Cohen and Strampp two years later[7]. In1987, Acevedo also
found HCG but in a majority of different bacterial species isolated
from cancer patients, including Streptococcus faecalis, Staphylococcus
haemolyticus and Staphylococcus epidermidis as well as
gram-negative diptherioids[8].
Acevedo's
findings contradicted Livingston's
claim of an "ubiquitous" or universal cancer bacterium---and this, in turn, was
presented as proof against Livingston's bacterial theory in a report issued by
the American Cancer Society (ACS) in 1990[9]. It will be noted, the ACS based
its negative conclusions on the fact that different bacterial species could
secrete hCG, and also on an inability to isolate Livingston' s
specific bacterium, Progenitor cryptocides. However it should also
be noted that the ACS did not disprove whether or not Livingston's
cultures were actually oncogenic. Fundamentally, Acevedo did agree with
Livingston's premise that cancer-associated bacteria have "revertant"
forms, lack true cell walls, are filter passing (able to simulate
viruses) and also intermittently acid fast---characteristics considered by
some to implicate the controversial phenomenon known as
"pleomorphism".
In additional studies,
Acevedo also found evidence of hCG in all cancer cell lines he examined,
regardless of their origin[10]. These studies offer compelling proof
that hCG is a common cancer marker found in many, or possibly most
types of cancer, and its presence is significantly higher in
disease tissues than in normal ones[11].
Bacteria,
Cancer and HCG: An Unholy
Trinity
We hypothesize that the relationship between bacteria, cancer and hCG
has vast implications both in our understanding of the century's old riddle of
how cancer tissues evade host immunity, and equally important, in the potential
realm of therapeutic intervention. The discovery of hCG as a
viable tumor marker may now solve a riddle which has baffled scientists for
more than a century---i.e., how cancer cells grow unchecked with little, or no
immune system resistance.
When cells become malignant,
their surfaces change and become charged with carbohydrate residues. One of
these residues---a simple sugar known as an oligosaccharide---combines with
another sugar, sialic acid, a key molecule of hCG. Sialic acid, in turn,
appears to protect the cancer cell from host immunity because it is a negatively
charged molecule; immune system cells are also negatively charged[12]. In
effect, HCG creates an "electric shield" (i.e., like poles repel)
which appears to have evolved as an ingenious survival mechanism, not only
for tumors, but for human life itself. In the latter case, HCG plays a significant role in protecting the developing human
embryo from host immunity, just as it does with cancer. Without this effect, the
mother's immunity would seek and destroy the fetus[13],[14]---a partly foreign
protein in the uterus comprised of both friendly (host) and foreign (DNA)
from the mother and father. Other insidious roles of HCG in cancer are tumor
angiogenesis (formation of blood networks for malignant tissues), promotion of
tumor invasiveness, and nourishment of tumors.
Are human cancers
quasi-manifestations of fetal life gone berserk, but expressing the same
intention to live and grow? The parallels are indeed striking. For example, the
primary manufacturers of fetal hCG are specialized placental cells called
trophoblasts, whereas in cancer, the exact source of hCG is not clearly
understood. Several possibilities include genes coded to produce hCG, or
bacteria interfacing with cancer cells through DNA transfer, or via what has
been described as a "plasmid vector". It may be that cancer bacteria serve
as the biologic equivalents of trophoblasts in some capacity, but the
latter arising via the evolution of human life and the former, as
an adaptative mechanism of evolution.
In the final analysis,
cancer shares many similarities with fetal life and it is here that the ultimate
solution to this disease may lie. Indeed, this idea has gained support among
leading scientists working in the fields of genetics and
immunobiology.
Dr. Robert Weinberg, the
first discoverer of a cancer gene and now an MIT professor of biology
stated:
It's now increasingly apparent that one mechanism, quite possibly the
dominant mechanism, involves the ability by the cancer cell to resurrect early
embryonic behavioral programs...This movement in the embryo is superficially
similar to metastasis. The way cancer cells acquire this embryonic trait of
being able to move throughout the organism depends on their ability to resurrect
these early embryonic behavioral programs, which they do through their ability
to induce the expression of early embryonic transcription factors [proteins that
control the expression of a large number of genes]. In this case, these
transcription factors control groups of genes that, when turned on, allow the
cancer cells to move, to become invasive, to resist programmed cell death (which
otherwise threatens their existence once they leave the primary tumor), and even
to release degradative enzymes that break down the [surrounding tissue that]
represents an impediment to the forward march of the cancer
cells[15].
In a similar vein, Italian
researchers wrote in the journal Immunobiology:
The model that most resembles the behavior of tumor cells in terms of
growth, infiltration and suppression of the immune system of the environment in
which they live is undoubtedly that of the embryonic cell. The fetus behaves
like an allogenic transplant within the mother's body, using every means it has
to escape from and defend itself against the mother's immune system. The
majority of these mechanisms are the same as those found in tumor cells
(including)...antigenic loss and induction of apoptosis in infiltrating
lymphocytes...A careful and comparative study of key mechanisms capable of
triggering tolerance or cytotoxicity in both embryonic and tumor cells could
prove immensely valuable in designing new strategies for anti-tumor
immunotherapy[16].
Deadly
Symbiosis: An Additional Role for Cancer
Bacteria
Bacteria may play another
critical role in neoplasia beyond their possible involvement in disease
causation and hCG synthesis. In 2004, Dr. D.H. Robinson
reported that cancer bacteria were capable of acquiring eukaryote-like
qualities in what he has termed "prokaryote to eukaryote transformation".
Through a process involving "vertical DNA transfer," transformed bacteria are
able to "self-organize" into structured tissues and to form vascular networks.
(Such self-organizing structures are not, insists Robinson, "biofilms")[17]. The
symbiotic coupling of eukaryotically transformed bacterial tissues with cancer
might help provide the latter with tumoral blood supply and assist
in such factors as immunosupression and metastasis (See
an abstract of Robinson's work, here).
POTENTIAL
ADJUVANT THERAPIES
If cancer, co-existing
bacteria, and the common denominator hCG form a three-tiered foundation in tumor
formation, would addressing this "cancer trinity" via adjuvant strategies that
neutralize their effects be a logical starting point for
therapy?
Might a vaccine to fight bacterial infection and another to counteract
hCG antigen on the tumor cell make therapeutic sense and synergistically
augment each others' effectiveness?
Over the past
century, anti-bacterial vaccines have been used and various degrees of
success have been claimed, though serious clinical trials are lacking.
In
what might possibly be considered the first trial of its kind, an
active antibody vaccine manufactured by exposing horse blood to
bacteria cultured from cancer patients was given to
one-hundred pathologically confirmed cases of cancer. Reports of remissions
were made, but the trial was not blinded or randomized, and quality control
is impossible to determine[18]. Two decades later, French
researchers conducted a 3 year trial at the Saint Antoine Hospital in Paris
and reported "superior" results with a Mycobacteria-based vaccine given
to surgically treated, primary lung cancer patients[19].
In 1990, a
clinical trial of Livingston's cancer vaccine (made from
patient-derived bacteria) didn't show benefit for patients suffering
from advanced cancer. However, trial patients who also received
conventional therapy also failed to respond and both sets of patients
deteriorated at equal rates[20]. Barrie Cassileth, the trial coordinator,
concluded that the ".....study...involved only patients with diagnoses and
stages of disease for which there is no effective conventional treatment.
Therefore, the results cannot be generalized to patients with less advanced
stages of disease or to other treatment regimens." Cassileth also said that
her study group "hypothesized that survival time would not differ between the
two groups on the basis of the assumption that the unproved remedy would be no
more effective with end-stage disease than conventional care, itself largely
ineffective"[21]. Interestingly, BCG vaccine---which is currently in
use as an approved cancer treatment and derived from the same genus of
bacteria that figured so prominently in Livingston's therapy---was also used
during the Cassileth study. BCG is now used to treat bladder
cancer; it has also shown statistical benefit in the treatment of
colon cancer[22].
Because a variety of bacterial species have
now been associated with cancer, Livingston's adherence to a
Mycobacterium-only based theory was
evidently incorrect. However, her thesis of a microbiologic for
cancer represented a starting point ahead of the science yet to be
accumulated and now, scientists agree that bacteria do, in fact, cause some
forms of the disease.
Beside antibacterials, there have been trials
involving anti-hCG vaccines, and early results have been promising. We
believe these results lend credence to our hypothesis of hCG as a
critical component of the cancer trinity.
In a phase
II trial of patients with extremely extremely poor prognosis pancreatic
cancer, a combination of the anti-hCG vaccine Avicine (Avi
Biopharma) with the cancer drug Gemzar (Eli Lilly) significantly extended
life span beyond that usually attained from Gemzar alone (see anti-HCG trials). Unfortunately, plans to expand
Avi Biopharma's vaccine to Phase III never materialized, despite the
positive reports. Meanwhile, Lilly's drug continues being marketed and
offered as a first line therapy. Presently, two new biotech companies,
CG Therapeutics, and CellDex Therapeutics are now acitvely developing
newer and more potent anti-hCG vaccines, and clinical trial recruitment is
underway. According to a press release issued by CG Therapeutics, they believe
their vaccine to have major potential as a universal treatment for cancer.
They go on to state that "Prior formulations of CG201(anti-HCG
vaccine) showed safety and effectiveness in human Phase 1 and Phase 2
cancer treatment trials. The antibodies stimulated by CG201 blocked hCG's
effects and extended survival in late-stage colorectal and pancreatic cancer
patients" (see Anti-HCG Trials for further information, and
additional links).
Conclusion
In conclusion, there
are now very exciting developments regarding anti-hCG therapies for cancer,
and the concurrent use of anti-bacterial vaccines is an area that may
offer additional potential. We thus close our hypothesis with
a brief summary of such adjuvant immunotherapies based on
the concepts we've presented here and throughout this
website:
AUTOGENOUS VACCINES are prepared from hCG-positive
cultures, procured from individual cancer patients. Because a number
of different bacterial species have been identified in human cancer, utilizing
individual cultures for vaccine preparation has been suggested by several
physicians; they see this as an ideal method of bypassing problems with
bacterial classification as a prerequisite for treatment. Other factors cited as favoring autogenous vaccine
treatments are their relative non-toxicity, and their compatibility
with standard protocols.
ANTIBIOTIC THERAPIES have been used, or suggested,
by health practitioners. If bacteria are an etiology in some
cancers, reduction of bacterial infection may be accomplished via
chemosensitivity testing of multiple antibiotics, with individual
patient cultures. Bicillin, ampicillin and penicillin G have all been used in
this regard. However with recent documentation of mycoplasma as possible factors
in oncogenesis, non-bacteriostatic drugs including the tetracyclines might be
more appropriate, considering the lack of cell walls and resistance to
bacteriostatics by mycoplasma type organisms. The final determination would
depend on the test results gathered for each patient.
ANTI-HCG SPECIFIC
VACCINES would directly target cancer cell
surface antigens, while antibacterial and antibiotic therapies address the
underlying cancer 'infection'. Hypothetically, the 'electric shield' effect
would be neutralized via anti-hCG treatment, exposing cancer cells to attack by
the immune system.
NON-SPECIFIC IMMUNOTHERAPIES have
also been used in the adjuvant setting to help accelerate the body's natural
defenses against cancer. There have been variable reports in the literature
concerning such immunotherapies including several total
remissions. The physician Burton Waisbren MD treated cancer patients
with a four-vaccine regimen consisting of BCG (now approved for use in
bladder cancer), transfer factor, lymphoblastoid lymphocytes and mixed bacterial
vaccine (based on the earlier pioneering work of William Coley). He
has reported cases of cancer remissions in the peer reviewed
literature[23].
Non-specific immunotherapies might
theoretically confer several advantages. First, their effectiveness
might be potentiated when administered to patients with
hCG-neutralized antigens and bacterial control; second, they have a track record
of safety, are considered mostly non-toxic, and have reportedly
shown efficacy; and finally, they are compatible with standard
treatments when, and if indicated.
REFERENCES
1.
Tsai S, Wear DJ, Shih JW, Lo SC. "Mycoplasmas and oncogenesis: persistent
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2. Chan PJ et al. "Prevalence of
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PCR-ELISA." Gynecol Oncol, 1996 Nov, vol. 63, pp.258-260.
3.
Dudler R, Schmidhauser C. "A mycoplasmal protein influences tumour cell
invasiveness and contact inhibition in vitro." J Cell Sci 1990 Mar;95 (
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4. Ushio S, Iwaki K, et al. "Metastasis-promoting activity
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nucleotide sequence." Microbiol Immunol
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5. Mager DL "Bacteria and
cancer: cause, coincidence or cure? A review". (2006). J Transl Med 4:
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6. Livingston, V. "Some Cultural Properties, Immunological and
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June 1974;36(6):569-82.
7. H Cohen and A Strammp. "Bacterial Synthesis of
Substance Similar to HCG." Proceedings of the Society for Experimental
Biology and Medicine 152, no.3 (July 1976).
8. H. Acevedo, Matias Pardo,
Elizabeth Campbell-Acevedo and Gerald J. Dominigue.
"Human Choriogonadotropin-like Material in Bacteria of Different
Species: Electron Microscopy and Immunocytochemical Studies with Monoclonal and
Polyclonal Antibodies." Journal of
General Microbiology (1987), 133, 783-791.
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pp.1476-1475, 1995 Oct 15.
11. ibid.
12. Suzuki Y,
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(1998) Mar-Apr;35(2):155-70.
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Cameo P,
Srisuparp S, Strakova Z, Fazleabas AT. "Chorionic gonadotropin and uterine
dialogue in the primate." Reprod Biol Endocrinol.
2004; 2:50 (ISSN: 1477-7827).
14.
Kayisli UA, Selam B, Guzeloglu-Kayisli O, Demir R, Arici A. "Human chorionic
gonadotropin contributes to maternal immunotolerance and endometrial apoptosis
by regulating Fas-Fas ligand system." J Immunol. 2003; 171(5):2305-13.
15.
Katherine Bourzac, "How a Tumor Is Like an Embryo," Technology Review,
Tuesday, November 06, 2007.
16. Ridolfi L, Petrini M,
Fiammenghi L, Riccobon A, Ridolfi R. "Human embryo
immune escape mechanisms rediscovered by the tumor." Immunobiology 2009;214(1):61-76.
17.
Douglas
H. Robinson. "Pleomorphic mammalian tumor-derived bacteria self-organize as multicellular mammalian eukaryotic-like organisms: morphogenetic properties
in vitro, possible origins, and possible roles in mammalian
'tumor ecologies.' Medical Hypothesis, 26, April, 2004.
18.
Glover TJ (1930). "The bacteriology of cancer".
Canada Lancet and Practitioner 74: 92–111.
19.
V Djurovic and G Decroix. "Five years of active non-specific immunotherapy with
a transformed mycobacterium in surgically treated primary lung cancers. One to
three years of post-operative follow-up," French Society of Medical
Radiology 59, no.11 (1978):651-54.
20. Cassileth, B., et al.
"Survival and Quality of Life Among Patients Receiving Unproven as Compared with
Conventional Cancer Therapy." New England Journal of Medicine 324
(April 25, 1991): 1180.
21. ibid.
22. van den Eertwegh AJ. "Active specific immunotherapy in colon cancer." Cancer
Res 2005;165:260-7.
23. B.A. Waisbren, "Observations on the Combined Systemic
Administration of MBV, BCG, TF,and LL to Patients with Cancer, 1974-1985," J
of Biol Response Modifiers 6 (1987): 1-19.
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