U.S. patent application number 14/282171 was filed with the patent office on 2014-09-11 for method of cancer diagnosis using the analysis of isotopes.
The applicant listed for this patent is Won Cheol Choi. Invention is credited to Won Cheol Choi.
Application Number | 20140255982 14/282171 |
Document ID | / |
Family ID | 38690083 |
Filed Date | 2014-09-11 |
United States Patent
Application |
20140255982 |
Kind Code |
A1 |
Choi; Won Cheol |
September 11, 2014 |
METHOD OF CANCER DIAGNOSIS USING THE ANALYSIS OF ISOTOPES
Abstract
Disclosed is a method of diagnosing cancer on the basis of the
quantitative analysis of blood or tissue isotopes, for example,
such as .sup.36S or .sup.40K. The method can accurately diagnose
cancer in a patient even when it is too small for current
conventional technology to diagnose.
Inventors: |
Choi; Won Cheol; (Incheon,
KR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Choi; Won Cheol |
Incheon |
|
KR |
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|
Family ID: |
38690083 |
Appl. No.: |
14/282171 |
Filed: |
May 20, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12674425 |
Feb 20, 2010 |
8771976 |
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PCT/KR2007/005088 |
Oct 17, 2007 |
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14282171 |
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Current U.S.
Class: |
435/34 ;
250/282 |
Current CPC
Class: |
G01N 33/57415 20130101;
H01J 49/0027 20130101; C12Q 1/04 20130101; G01N 33/57426 20130101;
G01N 33/84 20130101; G01N 33/57423 20130101; G01N 33/57438
20130101; G01N 33/57484 20130101; G01N 33/49 20130101; A61P 39/06
20180101; G01N 33/57446 20130101 |
Class at
Publication: |
435/34 ;
250/282 |
International
Class: |
G01N 33/574 20060101
G01N033/574; H01J 49/00 20060101 H01J049/00; G01N 33/49 20060101
G01N033/49 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 27, 2007 |
KR |
10-2007-0085873 |
Claims
1. A method of diagnosing cancer in a patient, comprising (a)
measuring the level of isotope .sup.40K in a blood sample or a
tissue sample of the patient by using a double-focus type mass
spectrophotometer; (b) measuring the level of Deuterium .sup.2D or
.sup.18O in a blood sample or a tissue sample of the patient using
a double-focus type mass spectrophotometer; (c) diagnosing cancer
in the patient if (i) .sup.40K is not detected and (ii) if the
level of the .sup.2D or .sup.18O isotope is greater than the level
of a normal standard for the .sup.2D or .sup.18O isotope.
2. The method according to claim 1, wherein the method comprises
measuring the level of deuterium .sup.2D in a blood sample or a
tissue sample of the patient and diagnosing cancer in the patient
if more than 1.2 times increased level of .sup.2D is detected in
the blood sample or tissue sample of the patient compared to a
normal standard for .sup.2D isotope, or the method comprises
measuring the level of .sup.18O in a blood sample or a tissue
sample of the patient and diagnosing cancer in the patient if more
than 1.4 times increased level of .sup.18O is detected in the blood
sample or tissue sample of the patient compared to a normal
standard for .sup.18O isotope.
3. The method according to claim 1, wherein the method further
comprises measuring the level of at least one from the group
consisting of sulfur isotopes, magnesium isotopes, silicon
isotopes, calcium isotopes and iron isotopes in a blood sample or a
tissue sample of the patient and diagnosing cancer in the patient
if an increased level of at least one from the group consisting of
sulfur isotopes, magnesium isotopes, silicon isotopes, calcium
isotopes and iron isotopes is detected in the blood sample or
tissue sample of the patient compared to a normal standard for the
isotope.
4. The method according to claim 3, wherein the method comprises
measuring the level of sulfur isotope .sup.33S or .sup.34S in a
blood sample or a tissue sample of the patient and diagnosing
cancer in the patient if more than 1.3 times increased level of
.sup.33S or .sup.34S is detected in the blood sample or tissue
sample of the patient compared to a normal standard for .sup.33S or
.sup.34S.
5. The method according to claim 3, wherein the method comprises
measuring the level of .sup.26Mg in a blood sample or a tissue
sample of the patient and diagnosing cancer in the patient if more
than 2.5 times increased level of .sup.26Mg is detected in the
blood sample or tissue sample of the patient compared to a normal
standard for .sup.26Mg.
6. The method according to claim 3, wherein the method comprises
measuring the level of .sup.29Si or .sup.30Si in a blood sample or
a tissue sample of the patient and diagnosing cancer in the patient
if more than 2.4 times increased level of .sup.29Si or .sup.30Si is
detected in the blood sample or tissue sample of the patient
compared to a normal standard for .sup.29Si or .sup.30Si.
7. The method according to claim 3, wherein the method comprises
measuring the level of .sup.57Fe or .sup.58Fe in a blood sample or
a tissue sample of the patient and diagnosing cancer in the patient
if more than 1.6 times increased level of .sup.57Fe or .sup.58Fe is
detected in the blood sample or tissue sample of the patient
compared to a normal standard for .sup.57Fe or .sup.88Fe.
8. The method according to claim 3, wherein the method comprises
measuring the level of at least one of the calcium isotopes
.sup.42Ca, .sup.43Ca, .sup.44Ca, .sup.46Ca and .sup.48Ca in a blood
sample or a tissue sample of the patient and diagnosing cancer in
the patient if more than 2.8 times increased level of at least one
of the calcium isotopes .sup.42Ca, .sup.43Ca, .sup.44Ca, .sup.46Ca
and .sup.48Ca is detected in the blood sample or tissue sample of
the patient compared to a normal standard for the at least one of
the calcium isotopes 42Ca, .sup.43Ca, .sup.44Ca, .sub.46Ca, and
.sup.48Ca.
9. The method according to claim 2, wherein the method further
comprises measuring the level of at least one from the group
consisting of sulfur isotopes, magnesium isotopes, silicon
isotopes, calcium isotopes and iron isotopes in a blood sample or a
tissue sample of the patient and diagnosing cancer in the patient
if an increased level of at least one from the group consisting of
sulfur isotopes, magnesium isotopes, silicon isotopes, calcium
isotopes and iron isotopes is detected in the blood sample or
tissue sample of the patient compared to a normal standard for the
isotope.
10. The method according to claim 1, wherein the levels of
deuterium .sup.2D and .sup.18O are measured and diagnosing cancer
in the patient if the levels of the .sup.2D and .sup.18O isotope
are greater than the level of a normal standard for the .sup.2D and
.sup.18O isotope.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation application under the
provisions of 35 U.S.C. .sctn. 120 of U.S. patent application Ser.
No. 12/674,425 filed Feb. 20, 2010, which is a U.S. national phase
application under the provisions of 35 U.S.C. .sctn. 371 of
International Patent Application No. PCT/KR2007/005088 filed Oct.
17, 2007, which in turn claims priority of Korean Patent
Application No. 10-2007-0085873 filed Aug. 27, 2007.
[0002] The disclosures of such U.S. and international patent
applications and Korean priority patent application are hereby
incorporated herein by reference in their respective entireties,
for all purposes.
TECHNICAL FIELD
[0003] The present invention relates, in general, to cancer
diagnosis and, more particularly, to a method for diagnosing cancer
on the basis of quantitative analysis of isotopes of blood or
tissue samples, which is able to accurately detect cancer even when
it is too small to be detected with conventional technologies.
BACKGROUND ART
[0004] Isotopes are any of several different forms of an element
each having a different atomic mass (mass number). The term
"isotope", coined by British chemist F. Soddy in 1913, comes from
the Greek isos "equal"+topos "place," because despite the different
atomic weights, the various forms of an element occupy the same
place on the periodic table.
[0005] Generally, the chemical properties of an element depend on
the number of protons, that is, the atomic number. Isotopes of an
element have nuclei having the same number of protons (the same
atomic number) but different numbers of neutrons. Therefore,
isotopes have different mass numbers, which indicate the total
number of nucleons-the number of protons plus neutrons. For
example, oxygen occurs in nature as three different isotopes, each
with 8 protons. The most common isotope is .sup.16O (8 protons, 8
neutrons), which constitutes more than 99% of all oxygen atoms on
earth. There is also the rare isotope .sup.18O (10 neutrons) and
the even rarer isotope .sup.17O (9 neutrons). Nitrogen exists as
two stable isotopes, .sup.14N and .sup.18N, in nature. Naturally
occurring uranium is composed of three major isotopes, uranium-238,
uranium-235, and uranium-234.
[0006] Because there are the same numbers of electrons as protons
in an element, isotopes of an element are identical in the number
of electrons. Approximately 90 elements exist in nature, and there
are as many as about 300 naturally occurring isotopes, with an
average of 3 isotopes per element. In fact, tin (Sn) is the element
with the greatest number of stable isotopes (ten), and cadmium has
the second highest number of isotopes (eight) while there are
elements that exist as only one isotope in nature, such as
beryllium, fluorine, sodium and bismuth.
[0007] There is no general rule for relationship between a
naturally occurring element and the number of stable isotopes
thereof. However, it has been observed that most of the elements
that have odd atomic numbers each have two or fewer isotopes,
whereas individual elements with even atomic numbers have
relatively many isotopes. A naturally occurring element is a
mixture of isotopes with almost the same ratios therebetween or
thereamong in any sample of the earth. In general, the atomic
weight of an element is the average of the atomic masses of all the
chemical element's isotopes as found in a particular environment,
weighted by isotopic abundance. The reason why a majority of atomic
weights are not integers or near-integers but decimals is that most
elements are assemblages of isotopes. For a short-hand designation
of different isotopes (also called nuclides), the mass number
(number of nucleons) is written in the right position or in the
upper left corner of the chemical symbol, like oxygen-16, .sup.16O,
nitrogen-14 .sup.14N, uranium-235 .sup.228U, etc. Particularly as
for hydrogen isotopes, specific names are given thereto, such as
protium for H-1, deuterium for H-2, and tritium for H-3.
[0008] Recent studies have showed that the oxygen isotope .sup.18O
is toxic to organisms. Deuterium .sup.2H in the form of D.sub.2O
was found to have 92% inhibitory activity against microorganisms
and to kill rats at a rate of 99.5% within 5 days.
[0009] High prevalence rates of cancer are reported in radioactive
contamination area, implying that persons excessively exposed to
radioactive radiation may increase in isotope level in their bodies
and may be liable to affliction with cancer.
[0010] Leading to the present invention, intensive and thorough
research into the treatment and diagnosis of cancer, conducted by
the present inventor, resulted in the finding that cancer can be
caused with a change in blood isotope level and that the incidence
and kind of cancer can be diagnosed through the quantitative
analysis of blood or tissue isotopes.
DISCLOSURE
Technical Problem
[0011] The present invention pertains to cancer diagnosis through
the analysis of blood or tissues for isotope content.
[0012] It is difficult for even up-to-date scientific technology to
accurately diagnose tumors less than 1 mm in size. However, blood
analysis according to the present invention can provide a basis or
criteria with which accurate diagnosis can be achieved for the
incidence and kind of cancer in an early stage, thus giving rise to
an increase in the probability of successful cancer treatment.
Therefore, it is an object of the present invention to provide a
method of diagnosing cancer by analyzing blood or tissue isotope
levels and comparing them with those of normal persons.
Technical Solution
[0013] In order to accomplish the above object, the present
invention provides a method of diagnosing cancer, comprising
measuring levels of isotopes of an element in a blood sample or a
tissue sample.
[0014] In accordance with a modification thereof, the element is
selected from a group consisting of hydrogen, oxygen, magnesium,
calcium, potassium, sulfur, chloride, silicon, iron, copper, and
combinations thereof.
[0015] In accordance with another modification thereof, the method
is based on an increase in the level of deuterium (.sup.CH) by 10%
or higher compared to a normal standard.
[0016] In accordance with a further modification, the method is
based on an increase in the level of .sup.18O by 10% or higher,
compared to a normal standard.
[0017] In accordance with still a further modification, the method
is based on an increase in the level of a heavy isotope of the
element compared to a normal standard.
[0018] In accordance with still another modification, the method is
based on the depletion of .sup.40K and/or .sup.36S from the
sample.
Advantageous Effects
[0019] Featuring the quantitative analysis of blood or tissue
isotopes, the present invention can accurately diagnose cancer even
when it is too small for current conventional technology to
diagnose. Hence, the present invention can make a great
contribution to the treatment of cancer and provide an opportunity
for cancer patients to recover from the disease and lead a healthy
life. It is well known that when cancer is diagnosed in its early
stage, it can be cured at a high success rate. However, diagnosis
methods that can detect even small cancers with certainty have not
been developed yet. The present invention, which overcomes the
limitation of the prior art methods, can detect cancer in the early
stage thereof and thus allow cancer to be successfully cured.
Best Mode
[0020] Prior to entry into the detailed description of the present
invention, it should be noted that a description of well-known
functions or constitutions in conjunction with the present
invention will be omitted in order to make the gist of the present
invention unambiguous.
[0021] In the present invention, distilled water, mineral water,
electrolysed water, and blood and tissues from healthy persons and
cancer patients are qualitatively and quantitatively analyzed for
isotopes. An example of an instrument for use in the isotope
analysis includes EMAL-2 (Energy Mass Analyzer), which is a
double-focus type mass spectrophotometer. Individual ions are used
as laser sources for atomic ionization and vaporization.
[0022] A standard sample is used to correct the analysis results.
In this regard, 10 elements, including magnesium, silicon, sulfur,
chloride, potassium, calcium, chrome, iron, copper, hydrogen, and
oxygen, are employed and analyzed for compositions in various
samples. Stable isotopes analyzed in the present invention have
mass numbers 24, 25 and 26 for the element magnesium, mass numbers
28, 29 and 30 for the element silicon, mass numbers 32, 33, 34 and
36 for the element sulfur, mass numbers 35 and 37 for the element
chloride, mass numbers 39, 40 and 41 for the element potassium,
mass numbers 40, 42, 43, 44, 46 and 48 for the element calcium,
mass numbers 50, 52, 53 and 54 for the element chrome, mass numbers
54, 56, 57 and 58 for the element iron, and mass numbers 63 and 65
for the element copper. Prior to isotope analysis, all samples
except for water are dried at 360.degree. C. for 1 hour in a vacuum
oven.
[0023] SMOW (Standard Mean Ocean Water), which serves as a
reference standard for comparing hydrogen and oxygen isotope
ratios, mostly in water samples, is also used in the present
invention. The isotope composition of oxygen and hydrogen in a
sample is expressed as per mil (% thousand) differences relative to
SMOW. 4-5 ml of water is reacted with uranium at 800.degree. C. in
a vacuum of 10.sup.-5-10.sup.-6 mmHg to generate hydrogen atoms for
use in the measurement.
[0024] An instrument suitable for analyzing the isotope
compositions of hydrogen includes a Varian GD 150 isotope ratio
mass spectrometer while the isotope compositions of oxygen in water
and in gas phase samples are analyzed using an Electron
spectrometer (Sumi, Ukraine). These spectrometers can detect very
small changes in the isotope compositions of individual elements
and analyze samples and a standard simultaneously. The mass
spectrometer is equipped with 2 or 3 ion collectors and can measure
2-3 ion currents at the same time and analyze the relationship
therebetween. The isotope compositions of elements in blood samples
are analyzed using EMAL-2.
MODE FOR INVENTION
[0025] A better understanding of the present invention may be
obtained through the following examples which are set forth to
illustrate, but are not to be construed as the limit of the present
invention.
EXAMPLE 1
Deuterium Level in Blood
[0026] Deuterium content was expressed as ppm relative to protium
content. Listed in Table 1 are the numbers of .sup.2D per 1,000,000
.sup.1H.
TABLE-US-00001 TABLE 1 Blood Samples D/H (in ppm) Normal 126
Stomach Cancer Patient 147 Liver Cancer Patient 147.5 Lung Cancer
Patient 148.2 Breast Cancer Patient 147.6 Leukemia Patient
148.2
[0027] Cancer patients were measured to have a 15.about.20%
increase in the blood level of deuterium, compared to normal
persons.
EXAMPLE 2
.sup.18O Level in Blood
[0028] The oxygen isotope .sup.18O content was expressed as ppm
relative to the oxygen isotope .sup.16O content. Listed in Table 2
are the numbers of .sup.18O per 1,000,000 .sup.16O.
TABLE-US-00002 TABLE 2 Blood Samples .sup.18O/.sup.16O (in ppm)
Normal 1430 Stomach Cancer Patient 1998 Liver Cancer Patient 1995
Lung Cancer Patient 1994 Breast Cancer Patient 1996 Leukemia
Patient 1995.5
[0029] Cancer patients were measured to have an about 35.about.40%
increase in the blood level of .sup.18O, compared to normal
persons.
EXAMPLE 3
Comparison of Levels of Magnesium Isotopes in Blood
[0030] In Table 3, below, the measurements of blood magnesium
isotope content using a mass spectrometer were expressed in
arbitrary units.
TABLE-US-00003 TABLE 3 Blood Samples .sup.24M .sup.25M .sup.26M
Normal 72.1 7.2 9.1 Stomach Cancer Patient 69.5 9.5 23.2 Liver
Cancer Patient 45.2 9.6 45.5 Lung Cancer Patient 55.1 9.5 41.0
Breast Cancer Patient 55.6 15.2 33.2 Leukemia Patient 40.2 8.5
52.6
[0031] The levels of heavy isotopes in the blood were measured to
be significantly increased in cancer patients, compared to normal
persons.
EXAMPLE 4
Comparison of Levels of Silicon Isotopes in Blood
[0032] In Table 4, below, the measurements of blood silicon isotope
content using a mass spectrometer are expressed in arbitrary
units.
TABLE-US-00004 TABLE 4 Blood Samples .sup.28Si .sup.29Si .sup.30Si
Normal 55.2 10.5 2.2 Stomach Cancer Patient 65.3 25.7 8.6 Liver
Cancer Patient 49.9 39.5 12.5 Lung Cancer Patient 59.4 33.4 13.6
Breast Cancer Patient 65.8 30.2 8.6 Leukemia Patient 65.3 25.6
10.5
[0033] The levels of heavy isotopes in the blood were measured to
be significantly increased in cancer patients, compared to normal
persons.
EXAMPLE 5
Comparison of Levels of Iron Isotopes in Blood
[0034] In Table 5, below, the measurements of blood iron isotope
content using a mass spectrometer are expressed in arbitrary
units.
TABLE-US-00005 TABLE 5 Blood Samples .sup.54Fe .sup.56Fe .sup.57Fe
.sup.58Fe Normal 3.2 58 14.1 2.1 Stomach Cancer Patient 3.6 68 25.1
3.3 Liver Cancer Patient 3.7 59 35.2 3.8 Lung Cancer Patient 4.1 63
28.5 3.5 Breast Cancer Patient 4.2 52 32.4 4.2 Leukemia Patient 4.2
60.5 31.5 3.5
[0035] The levels of heavy isotopes in the blood were measured to
be significantly increased in cancer patients, compared to normal
persons.
EXAMPLE 6
Comparison of Levels of Copper Isotopes in Blood
[0036] In Table 6, below, the measurements of blood copper isotope
content using a mass spectrometer are expressed in arbitrary
units.
TABLE-US-00006 TABLE 6 Blood Samples .sup.63Cu .sup.65Cu Normal 65
35 Stomach Cancer Patient 72 28 Liver Cancer Patient 63 41 Lung
Cancer Patient 61 42 Breast Cancer Patient 60 35 Leukemia Patient
74 25
[0037] There were no significant differences in light isotope
levels between cancer patients and normal persons.
EXAMPLE 7
Comparison of Levels of Sulfur Isotopes in Blood
[0038] In Table 7, below, the measurements of blood sulfur isotope
content using a mass spectrometer are expressed in arbitrary
units.
TABLE-US-00007 TABLE 7 Blood Samples .sup.32S .sup.33S .sup.34S
.sup.36S Normal 55.5 20.1 2.3 1.1 Stomach Cancer Patient 62.1 25.5
9.5 0 Liver Cancer Patient 52.1 35.5 12.3 0 Lung Cancer Patient
58.9 26.5 13.2 0 Breast Cancer Patient 66.6 31.2 7.8 0 Leukemia
Patient 61.2 25.9 10.3 0
[0039] The cancer patients were found to have a higher level of the
heavy isotope than were normal persons. As for .sup.36S, however,
it was not detected in cancer patients, indicating that patients
suffering from cancer lack the isotope.
EXAMPLE 8
Comparison of Levels of Chloride Isotopes in Blood
[0040] In Table 8, below, the measurements of blood chloride
isotope content using a mass spectrometer are expressed in
arbitrary units.
TABLE-US-00008 TABLE 8 Blood Samples .sup.35Cl .sup.37Cl Normal
60.2 25.3 Stomach Cancer Patient 72.3 25.7 Liver Cancer Patient
71.5 28.8 Lung Cancer Patient 68.2 26.5 Breast Cancer Patient 77.5
21.3 Leukemia Patient 63.2 32.1
[0041] The overall levels of heavy isotopes in the blood were
observed to be higher in cancer patients compared to normal
persons.
EXAMPLE 9
Comparison of Levels of Potassium Isotopes in Blood
[0042] In Table 9, below, the measurements of blood potassium
isotope content using a mass spectrometer were expressed in
arbitrary units.
TABLE-US-00009 TABLE 9 Blood Samples .sup.39K .sup.40K .sup.41K
Normal 79.5 1.2 6.3 Stomach Cancer Patient 86.4 0 10.5 Liver Cancer
Patient 82.3 0 18.5 Lung Cancer Patient 94.3 0 6.5 Breast Cancer
Patient 77.5 0 16.2 Leukemia Patient 88.6 0 11.1
[0043] Of the potassium isotopes, .sup.40K was measured to be zero
in cancer patients, which distinguishes cancer patients from normal
persons. The heavy isotope was measured at higher levels in cancer
patients than in normal patients.
EXAMPLE 10
Comparison of Levels of Calcium Isotopes in Blood
[0044] In Table 10, below, the measurements of blood calcium
isotope content using a mass spectrometer was expressed in
arbitrary units.
TABLE-US-00010 TABLE 10 Blood Samples .sup.40Ca .sup.42Ca .sup.43Ca
.sup.44Ca .sup.46Ca .sup.48Ca Normal 57.4 1.2 2.3 1.7 0.2 0.15
Stomach Cancer Patient 66.8 3.4 9.5 6.7 5.7 1.6 Liver Cancer
Patient 31.5 6.4 25.6 27.4 15.3 1.5 Lung Cancer Patient 54.2 4.6
18.7 17.5 7.6 1.2 Breast Cancer Patient 51.2 4.3 18.6 17.9 7.8 1.8
Leukemia Patient 34.5 5.6 19.4 24.6 15.6 1.1
[0045] The heavy isotopes of element calcium were measured at
higher levels in cancer patients than in normal persons.
[0046] Taken together, the data obtained in the above examples
demonstrate that the analysis of isotope levels in blood or tissues
can be used to determine the incidence of cancer, particularly
based on an increase in isotope levels or the depletion of .sup.40K
or .sup.36S.
[0047] Although the preferred embodiment(s) of the present
invention have(has) been disclosed for illustrative purposes, those
skilled in the art will appreciate that various modifications,
additions and substitutions are possible, without departing from
the scope and spirit of the invention as disclosed in the
accompanying claims.
* * * * *