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NABIL HABIB INSTITUTE
LebanusCedra
Again… the Lebanese cedars
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APPENDIX
1.
2.
3.
4.
5.
6.
INTRODUCTION
MAIN CHARACTERISTICS
FORMULA OF LEBANUS CEDRA HYDROXYSTEROL AND MODE OF ACTION
WHO ARE WE?
ASCO ABSTRACT
Multidisciplinary Mediterranean Oncology Forum (MMOF/ESMO)
ABSTRACT
7. DOCUMENTATION OF MMOF ABSTRACT
8. IMAGES OF PATIENTS RECEIVING LEBANUS CEDRA
9. PATENT CERTIFICATE AND CREDIT LETTERS FROM ALL OVER THE WORLD
10. BIBLIOGRAPHY
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1. INTRODUCTION
WHAT IS “LEBANUS CEDRA” ?
“LEBANUS CEDRA”
Is a cholesterol derivative (hydroxysterol). It is, to our knowledge, the only anticancer chemical with…
Absolutely no side-effects
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2. MAIN CHARACTERISTICS
drug
 Many experiments performed in animal models have shown a remarkable antitumor activity on animal and human cancer cell-lines.
 No acute or chronic toxicity have been found in animals treated with 1000 x
the doses used in humans.
 Hundreds of patients have been treated since 10 years and no side-effect have
been observed with this drug.
 Its mode of action is original creating new avenues in the domain of cancer
research.
 It is active in patients resistant and refractory to standard chemotherapies.
 Its mode of action is very fast; some tumors have been shown to regress within
few days.
 Besides its anti-tumor activity, “Lebanus Cedra” has shown also a very rapid
palliative effect in many patients, even in those who did not show a reduction
of tumor size according to standard evaluation criteria for response to therapy.
 No interaction has been observed with other drugs and it seems (although we
do not have a definitive proof of that), to promote the action of other anticancer drugs.
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3.
FORMULA of LEBANUS CEDRA and Mode of ACTION
(24-ethyl-cholestane- 3β, 5α, 6α-triol)
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Mode of Action andAntineoplastic Activity:
We believe that formula (I) compounds both inhibit the activity of HMG-CoA reductase,
and competitively bind receptors involved in exogeneous colesterol adsorption.
Inhibition of HMG-CoA reductase occurs in both normal cells and neoplastic cells;
however, neoplastic cells are additionnally rendered unable to adsorb exogeneous
cholesterol following administration of formula (I) compound. This selectivity for
neoplastic cells occurs for two reasons. First, tumors are poorly vascularized, which
leads to a reduced supply of available exogeneous cholesterol. Second, the reduced
vascularization additionnally leads to hypoxia, thereby increasing the concentration of
anaerobic metabolic products, pyruvic acid and carbon dioxide. Further, poor
vascularization decreases the rate of carbon dioxideremoval from the tumor tissue.
Increased levels of carbon dioxide, in turn, leads to increased levels of carbonic acid,
the formation of which is catalyzed by carbonic anhydrase. These factors reduce the
pH of the environnment surrounding the cells from a pH of 7.3-7.4, found in normal
cells to pH 6.4-6.8.
The lower pH environnment in neoplastic cells causes the administered formula (I), e.g
., 24-ethyl-cholestane- 3β, 5α,6α-triol, to migrate towards intercellular interstitial acidic
fluid, and also increases the affinity of 24-ethyl-cholestane- 3β, 5α,6α-triol for the
cholesterol receptors. This increased affinity, in combination with the reduced
cholesterol concentration present in the fluid surrounding tumor cells, leads to specific,
irreversible binding of the compound to the receptor. In the case of 24-ethylcholestane- 3β, 5α, 6α-triol, binding is mediated by the three highly hydrophilic
hydroxyl groups interacting with carbonyl groups of the receptor. The position s3β, 5α,
6αhydroxides further provoke distortion of the membrane layers, and the ethyl group at position
24 plays the role of a “check valve”, fixing the hydrophobic tail between the two lipid layers.
In addition to binding the receptors directly, 24-ethyl-cholestane- 3β, 5α, 6α-triol alters the
three-dimensional structure of remaining unbound cholesterol receptors through
distortion of the lipid bi-layer. This alteration is sufficient to prevent adsorption of
cholesterol molecules. This distortion of the lipid bi-layer has other effects as well. The
permeability and the fluidity of the bi-layer membrane are also reduced, thus
decreasing passive, mediated and active diffusion across the membrane. This
alteration can further decrease the nutritional level of tumor cells.
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4.
WHO ARE WE?
Doctor Nabil Habib is a PhD in chemical Engineer teaching at the Lebanese University. He has a
prestigious curriculum and has achieved great and patented inventions in different fields of
the industry and public health. He trained in France and has performed collaborative
researches with scientists in the USSR as well as in the USA.
He launched his research on anti-cancer drugs fifteen years ago. He created his own medical
center (Nabil Habib’s Institute) 10 years ago and with the collaboration of a team of physicians
and medical oncologists, is helping desperate cases of terminal cancer patients trying to
improve their quality of life and fight their cancer without causing any side effect with his new
and revolutionary molecule e.g Hydroxysterol alias “Lebanus Cedra” .
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5.
ASCO Abstract
ASCO Home
Meetings
Abstracts
2009 ASCO Annual Meeting
Antitumor activity of a new cholesterol derivative
(24-ethyl-cholestane- 3β, 5α, 6α-triol) in solid
tumors.
Developmental Therapeutics: Cytotoxic Chemotherapy
Meeting:
2009 ASCO Annual Meeting
Abstract No:e13541
Citation: J Clin. Oncol. 27, 2009 (suppl; abstr e13541)
Author(s):
N. Habib, H. Daaboul, G. Hajj, A. Jabbour, N. Kassem; Bitar Hospital, Beirut, Lebanon
Abstract:
Oxysterols are oxygenated derivatives of cholesterol. They have nuclear receptors and
have been shown to pass cell membranes and the blood-brain barrier at a faster rate
than cholesterol itself. In addition, oxysterols have been ascribed a number of important
roles in connection with cholesterol turnover, atherosclerosis, apoptosis, and necrosis.
Oxysterols have been shown to have antitumor effects on experimental models. These
compounds however may be toxic and to our knowledge, although some derivatives
have been tested in animals, none have reached the clinical level. 24-ethyl-cholestane3β, 5α, 6α-triol is a new oxysterol developed in our lab. An oral form of this compound
has been tested in mice and rats and has shown neither acute nor chronic toxicity. It has
also been tested on animal tumor models and on human cancer xenografts. The results
of these tests were very promising showing an anti-tumor activity on a panel of tumor
cell lines. Our experiments on humans have shown no toxicity for this drug. Many
patients with a variety of solid tumors all of whom have received many lines of
chemotherapy and considered refractory to any conventional therapy have received this
new drug. We observed in most of these patients a rapid and dramatic improvement in
their quality of life and a fast pain control. Some patients could stop taking high doses
of opioids within 1 or 2 days. A high rate of clinical benefit has also been observed in a
variety of solid tumors including lung, breast, pancreatic, ovarian and uterine cancers,
associated in some cases with a sharp decrease in tumor markers. Some patients with
brain tumors (glioblastomas) have also responded to this therapy.
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6.
MMOF/ESMOABSTRACT
An Oxysterol (24-ethyl-cholestane- 3β, 5α, 6α-triol) with high antitumor activity
against a variety of sarcomas.
N. Habib; G. Hajj. H. Daaboul. R. Khalifeh and A. Jabbour; Bitar Hospital. Sabtieh.Sadd El Baouchrieh.
LEBANON
Oxygenated derivatives of cholesterol, oxysterols, have different physicochemical properties
acting on cell membranes. Agents belonging to this class of compounds have been found to
induce apoptosis and to harbor antitumor activity demonstrated in vitro and in vivo. 24-ethylcholestane- 3β, 5α, and 6α-triol are a new oxysterol developed in our lab. Unlike other
derivatives, it is, to our knowledge, the first tested in the clinic. We have previously reported
encouraging and rapid results observed in patients suffering from a variety of solid tumors with
an improvement of their quality-of- life and without side- effects. We have treated six patients
suffering from different types of sarcomas on a compassionate basis because we did not have
any ongoing trial in sarcomas. Furthermore most of these patients would not have been eligible
for a clinical trial because of their bad performance-status. Three patients were suffering from
carcinosarcomas one from angiosarcoma, one from osteosarcoma and one from Ewing sarcoma.
Most of them were pretreated with chemotherapy and radiotherapy and most of them were in a
bad clinical condition. All the patients were females with ages ranging from 21 to 82 (median
age 55y). None of these 6 patients experienced any side-effect despite the fact that one of them
was taking a mild chemotherapy in association with oxysterol. This patient was excluded from
the evaluation of the response to therapy. Among the 5 patients evaluable for response, we
observed 4 complete responses (one of them confirmed by PET scan) and one progressive
disease. The complete responses were observed in one osteosarcoma, one Ewing sarcoma, one
angiosarcoma and one carcinosarcoma. As with our previous experience with this drug, no
clinical or biological side-effect was observed and symptom control was achieved rapidly in
most patients. We believe that this new compound deserves to be tested in a phase II trial
setting in patients suffering from sarcomas.
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7.
DOCUMENTATION of PATIENTS in the MMOF Abstract
Summary of Case Reports
 Case No 1: G.J.
This is the case of a 70 YO female patient with a history of diabetes and hypertension.
In Nov 2010, she was diagnosed with a carcinosarcoma of the uterus. She did not receive any therapy until
end of December 2010. At that time a new work-up showed a pelvic tumor measuring 14 cm and a right
suprarenal metastasis measuring 7cm and a lung nodule measuring 1.5 cm.
She started her treatment with Lebanus Cedra on the 31 st of Dec 2010. A new work-up performed on the 16th
of June 2011 shows a clearance of the pelvic mass and the suprarenal cystic mass is stable.
 Case No 2: H.M.H.
This is the case of a 22 YO female Iraqi patient with no past medical history.
In Dec 2006, she was diagnosed with a Ewing sarcoma of the right radius. She is treated with chemotherapy in
India and with radiotherapy in Iran, followed by chemotherapy for a total of 12 courses.
In 2008, a PET scan performed in India shows a right axillary adenopathy. She is operated in Iraq but
unfortunately she has a new recurrence few months after. This axillary recurrence will be irradiated again in
India in 2009
In May 2010, a PET scan shows a large recurrence in the right axillary area. The patient refuses to undergo a
new chemotherapy. She started her treatment with Lebanus Cedra in June 2010.
A new PET scan performed on the 8th of Nov 2010 shows a complete remission
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 Case No 3 : N. N.
This is a 59 YO female patient with no past medical history.
In 2009, she is diagnosed with a poorly diff. carcinosarcoma of the uterus which is operated. She receives post
op radiotherapy but in March 2011, she develops lung metastases
She receives one course of combination chemotherapy (carboplatin and doxorubicin) but experiences a severe
hematological and systemic toxicity.
On the 8th of April 2011, she starts a treatment with Lebanus Cedra associated with a new chemotherapy with
low doses of carboplatin and docetaxel. She is currently in good partial response.
 Case No 4: L.H.
This 52 YO female patient has no past medical history
In 2008, she is diagnosed with a poorly diff. thoracic carcinosarcoma which is operated and the patient
receives post-op irradiation to the chest.
In 2010, she develops a local recurrence and receives chemotherapy with gemcitabine and docetaxel without
any success.
From March to July 2011 she receives a treatment with Lebanus Cedra but unfortunately a work-up shows a
progressive disease
 Case No 5 : R.M.
This 21 YO female patient with no past medical history is diagnosed in August 2008 with an osteosarcoma of
the maxillary sinus. She refuses standard therapy and is treated with herbs without success
On the 19th of October 2000, she presents with a huge endo-buccal mass responsible of deglutition and
respiratory problems. She is cachectic, dehydrated and asthenic. She starts a treatment with Lebanus Cedra.
Few days after, her swallowing difficulties improve and her oral tumor starts to melt and to disintegrate. Her
general condition improves also very quickly.
A CT scan and a bone scan performed 3 months after show a complete remission
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Case No 6:M.B.
This 82 YO female patient has a history of right breast cancer operated and irradiated.
In May 2007, she is operated for a well differentiated (probably radio-induced) angiosarcoma of the right
breast with skin invasion.
In August 2008, she presents with lung metastases and severe dyspnea. She starts her treatment with Lebanus
Cedra and one year after, she is in complete remission
Summary of Patients‘Characteristics and Response
Patient
Age
Type of
sarcoma
Response
G.J
70
Carcinosarcoma CR
H. H
22
Ewing Sarcoma
N. N
59
Carcinosarcoma PR
L. H
52
Carcinosarcoma PD
R .M
21
Osteosarcoma
CR
M. B
82
Angiosarcoma
CR
CR
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+chemo
8. IMAGES OF PATIENTS’ RESPONSE TO LEBANUS CEDRA
PATIENT WITH EWING SARCOMA
PET scan BEFORE TREATMENT
PET scan AFTER TREATMENT
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ANGIOSARCOMA OF THE LUNG
Before treatment
After treatment
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T
SQUAMOUS-CELL CARCINOMA OF THE LUNG
CHEST X-RAY BEFORE TREATMENT
CHEST X-RAY AFTER TREATMENT
CT-SCAN BEFORE THERAPY
CT-SCAN AFTER THERAPY
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PATIENT WITH POORLY DIFFERENTIATED
ADENOCARCINOMA OF THE LUNG
CT-SCAN BEFORE THERAPY
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CT-SCAN AFTER THERAPY
PATIENT WITH LARGE-CELL CARCINOMA OF THE LUNG
WITH LIVER METASTASES
CHEST CT-SCAN BEFORE THERAPY
CHEST CT-SCAN AFTER THERAPY
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CT SCAN OF LIVER
BEFORE THERAPY
AFTER THERAPY
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BREAST CANCER AND BONE METASTASES
BONE SCAN BEFORE THERAPY
BONE SCAN AFTER THERAPY
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SQUAMOUS-CELL CARCINOMA OF THE TONGUE
PET scan before treatment
After treatment
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BREAST CANCER WITH BRAIN METASTASES
Brain metastases before treatment
Brain metastases after treatment
Another case of Brain Metastases from a Breast Cancer
Before treatment
After treatment
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9. PATENT CERTIFICATE and CREDIT LETTERS
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CREDIT LETTERS
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10.
BIBLIOGRAPHY:

Antitumor activity of a new cholesterol derivative (24-ethyl-cholestane- 3β, 5α,6α-triol) in solid tumors.
Habib N;Daaboul H; Hajj G; Jabbour A;Kassem N; ASCO Abstract No: e13541
Citation: J ClinOncol 27, 2009 (suppl; abstr e13541)
Bitar Hospital, Beirut, Lebanon

Natural products reveal cancer cell dependence on Oxysterol-binding proteins.
Nature Chemical Biology 7, 639-647 (2011) doi: 10. 1038/nchembio.625
Burgett AWG; Poulsen TB; Wangkanont K; Anderson R; Kikuchi C

Oxysterols: friends, foes, or just fellow passengers?
ArteriosclerThrombVasc Biol. 2002; 22(5):734-42 (ISSN: 1524-4636)
Björkhem I; Diczfalusy U
Division of Clinical Chemistry, KarolinskaInstitutet, Huddinge University Hospital, Huddinge,
[email protected]

On the efficacy and safety of combination Ezetimibe plus statin therapy .
ClinLipidology. 2010; 5 (5) 655-684, Future Edicine
Toth PP; Catapano A; Tomassini

Synthesis and anticancer evaluation of certain indolo[2,3-b]quinoline derivatives.
Bioorg Med Chem. 2004; 12(24):6539-46 (ISSN: 0968-0896)
Chen YL; Hung HM; Lu CM; Li KC; Tzeng CC
Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical

Structures of biologically active oxysterols determine their differential effects on phospholipid membranes.
Biochemistry. 2006; 45(35):10747-58 (ISSN: 0006-2960)
Massey JB; Pownall HJ
Section of Atherosclerosis and Lipoprotein Research, Department of Medicine, Baylor College of
Medicine, One Baylor Plaza, Houston, Texas 77030, USA. [email protected]

Analysis of oxysterols by electrospray tandem mass spectrometry
J Am Soc Mass Spectrom. 2006; 17(3):341-62 (ISSN: 1044-0305)Griffiths WJ; Wang Y; Alvelius G;
Liu S; Bodin K; Sjövall J
Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London,
London, United Kingdom.

Role of oxysterol structure on the microdomain-induced microsolubilization of phospholipid membranes
by apolipoprotein A-I.
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Biochemistry. 2005; 44(43):14376-84 (ISSN: 0006-2960)
Massey JB; Pownall HJ
Section of Atheroscler Steroids. 2003; 68(3):221-33 (ISSN: 0039-128X)
Adiposis and Lipoprotein Research, Department of Medicine, Baylor College of Medicine, One Baylor
Plaza, Houston, Texas 77030, USA. [email protected]

Chromatographic behavior of oxygenated derivatives of cholesterol.
Steroids. 2003; 68(3):221-33 (ISSN: 0039-128X)
Shan H; Pang J; Li S; Chiang TB; Wilson WK; Schroepfer GJ
Department of Biochemistry and Cell Biology, Rice University, MS 140, 6100 Main Street, Houston, TX
77005-1892, USA.

Cytotoxic properties of a phosphoglycoconjugated derivative of 7 beta-hydroxycholesterol upon normal
and tumor cells in culture.
AnticancerRes. 1997; 17(4A):2621-6 (ISSN: 0250-7005)
Hyun JW; Weltin D; Holl V; Marchal J; Dufour P; Luu B; Bischoff P
Laboratorie de Chimie Organique des Substances Naturelles, ULP associé CNRS, Strasbourg, France.

Metabolism of new anticancer oxysterol derivatives in rats.
Anticancer Res. 1993; 13(4):953-8 (ISSN: 0250-7005)
Moog C; Frank N; Luu B; Bertram B
Institute of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
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