[go: up one dir, main page]

WO2003036301A1 - Procede d'evaluation de cancer au moyen de marqueurs tumoraux - Google Patents

Procede d'evaluation de cancer au moyen de marqueurs tumoraux Download PDF

Info

Publication number
WO2003036301A1
WO2003036301A1 PCT/JP2001/009201 JP0109201W WO03036301A1 WO 2003036301 A1 WO2003036301 A1 WO 2003036301A1 JP 0109201 W JP0109201 W JP 0109201W WO 03036301 A1 WO03036301 A1 WO 03036301A1
Authority
WO
WIPO (PCT)
Prior art keywords
tumor
cancer
marker
stage
growth
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2001/009201
Other languages
English (en)
Japanese (ja)
Inventor
Tsuneo Kobayashi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SUDA MASAYASU
Original Assignee
SUDA MASAYASU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to JP2000102784A priority Critical patent/JP2001289861A/ja
Application filed by SUDA MASAYASU filed Critical SUDA MASAYASU
Priority to PCT/JP2001/009201 priority patent/WO2003036301A1/fr
Publication of WO2003036301A1 publication Critical patent/WO2003036301A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids

Definitions

  • the present invention relates to a method for detecting and quantifying the components of a tumor marker by examining blood or urine of a person suspected of having cancer, and detecting and evaluating the cancer at an early stage.
  • the present invention relates to a method for evaluating cancer using a tumor marker, which can accurately detect and evaluate the risk of cancer occurring in apparently healthy individuals by analyzing the combination of the two. Background art
  • histological examination is a method in which a lesion is cut out and observed under a microscope to find cancer cells. This method of detecting cancer is mainly performed before surgery for excision of the cancer. For example, during examination using an endoscope (fiber-scope) such as a gastroscope, a small piece of cancer lesion is collected and used.
  • endoscope fiber-scope
  • cytology that examine cancer cells contained in sputum and secretions.
  • Examination methods such as X-ray projection examination, CT scan examination, and magnetic resonance imaging analysis (MRI examination) in medical examinations and cancer examinations are methods to find cancer foci by morphological methods of cancer.
  • "X-ray projection examination” is to wear a contrast agent such as X-ray simple photograph or barium. This is a test method that reads the shadows of early cancers from X-ray images taken by using it and finds the lesions of the cancer. Reading the shadow of cancer from this X-ray simple photograph or X-ray using a contrast agent was a difficult task and required masterpiece art. Therefore, X-ray photography and
  • CT scan inspection “Computer evening processing X-ray tomography inspection” (CT scan inspection) has been proposed, which can analyze images in the evening and obtain sliced images.
  • This CT scan irradiates a patient's body with a small beam of X-rays, extracts the transmitted X-rays as a strong or weak electrical signal, records the projected image of the body as an electrical signal for each small pixel of 1 mm or less, Compared to conventional X-ray photography, the device is so good that the shading width and precision are incomparable.
  • a computer scans hundreds of projected images that are irradiated while rotating X-rays around the body using a computer, and draws a real image of a cross-section of the body in a cross-section to detect cancer lesions. This is an examination method that can form an image and accurately determine the size and location of the lesion.
  • the “magnetic resonance image analysis test” is a test method that accurately determines the size and location of cancer lesions by performing advanced image analysis using electromagnetic waves.
  • this magnetic resonance image analysis when the human body is placed in a strong magnetic field and irradiated with electromagnetic waves, protons (protons) of hydrogen nuclei in the body resonate and absorb the electromagnetic waves.
  • fat contains a large amount of hydrogen atoms, it is an analysis method that gives a distribution image of water and fat, and displays clear images of organs, tissues, and lesions.
  • This magnetic resonance image analysis test uses a computer to process the sharp image that is projected, and provides a very clear image of the cancer lesion inside the bone, such as a brain tumor or a cancer of the spinal cord.
  • magnetic resonance image analysis hardly captures calcium and phosphorus, which are the main components of bone, compared to CT scan examination, so that cancer inside the bone can be clearly displayed. .
  • Morphological cancer detection methods such as the X-ray projection, CT scan, and magnetic resonance imaging (MRI) examinations described above, are not cancers with a high incidence of gastric, lung, uterine, and breast cancer. However, even if cancer cells proliferated to 1 g or more, it was 'not generally detectable'. Therefore, such a method for detecting morphological cancer was not a method for detecting cancer early. For example, X-ray projection shows that 1 cm of cancer Only about 8% of them were found, and there were many cases in which reexamination six months later resulted in the progression of cancer and the terminal cancer was too late.
  • a tumor is a type of cell in the body that suddenly undergoes abnormal division and proliferates, grows and grows into a lump, and there are two types, benign and malignant. .
  • This tumor is formed in the body, a special substance that is rarely seen when healthy is produced in large quantities by the tumor and appears in the blood. This substance is called a “tumor marker”. Since this tumor marker has a feature that is strongly associated with the organ where cancer develops, when this substance comes out above the standard value in the blood, cancer You can guess that.
  • tumor tumors include “alpha. Phytoprotein” in liver cancer, “carcinoembryonic antigen” in stomach cancer and colorectal cancer, etc.
  • Tumor-specific antigens that react with 19.9 ” hormones such as“ gonadotron ”in choriocarcinoma of the uterus, and“ calcitonin ”in parathyroid carcinoma, and“ alkyra rifasphata ”in bone and liver cancer.
  • hormones such as“ gonadotron ”in choriocarcinoma of the uterus, and“ calcitonin ”in parathyroid carcinoma, and“ alkyra rifasphata ”in bone and liver cancer.
  • the above-mentioned methods for examining gastric cancer such as X-ray projection examination and gastric fluoroscopy while taking barium, indicate that cancer examinations in public and private institutions are not possible in 1'979-1980.
  • cancer cells are a group of abnormal cells that continue to proliferate and are wrapped in placenta-like tissues called “interstitium” like a fetus dwelling in the mother, and extend special blood vessels called “tumor blood vessels”. Get nutrients and drain waste from normal blood vessels.
  • This cancer 'cells are excreted
  • An object (tumor marker 1) is a trace substance in blood that serves as a marker for cancer.
  • this tumor marker was difficult to detect unless the cancer grew to a certain size. Therefore, in the conventional methods for detecting and evaluating cancer using tumor markers, the sensitivity and the specificity without disease (specificity) were low.
  • the true diagnosis rate refers to the percentage of patients who correctly evaluated cancer patients as having cancer
  • the non-diagnosis rate refers to the percentage of persons who correctly evaluated healthy persons as having no cancer. Therefore, conventional methods for detecting cancer using tumor markers are mainly performed as a kind of auxiliary test for diagnosing cancer, or as follow-up test for treating cancer. Met.
  • the inventor of the present invention proposes that a growing neoplasm is composed of a mass of cancer cells, a stroma supporting the cancer, and a tumor blood vessel, and produces carcinoembryonic antigen, carcinogenic placental antigen, and tumor blood vessel-related substance, respectively. They noted that these three substances are important in early detection of cancer. Furthermore, these carcinoembryonic antigens, carcinostatic antigens and tumor vascular related substances can be regarded as the same as their respective tumor-specific markers, tumor-related markers and cancer growth markers. We thought that it would play an important role in the evaluation method of the present invention, and invented a new method of evaluating early cancer by analyzing a combination of tumor markers, that is, a combination of several types of tumor markers.
  • an object of the present invention is to determine the risk level, classify the tumor stage based on the cut-off value of the tumor marker response, and classify the tumor occurrence, so that the time of cancer occurrence Continuous follow-up not only to detect early cancer in specific organs, but also to detect early cancer in any area, identify high-risk groups, and prevent tumors and tumors that can prevent cancer
  • An object of the present invention is to provide a method for evaluating cancer by one car. Disclosure of the invention
  • the method for evaluating cancer using a tumor marker is a method for evaluating cancer using a tumor marker, which comprises the steps of collecting blood or urine, and firstly in the occurrence of cancer from the collected blood or urine.
  • a cancer growth marker that appears in the blood a tumor-related marker that appears next, The presence of the substance of the tumor-specific marker that appears last, the step of screening each order of appearance, and the step of classifying the tumor growth level into several stages of tumor growth by screening each of the tumor markers;
  • This is a method of estimating the cancer that occurs in apparently healthy people and analyzing the risk of the cancer by analyzing the combination of markers. '
  • the classification of the tumor growth degree stage is performed based on a power-off value set according to the growth degree of a cancer growth marker, a tumor-related marker, and a tumor-specific marker determined for each stage. This cut-off value was set according to the normal value of the individual over time. In addition, this tumor growth stage is classified into a stage containing an abnormal level of 2 or more.
  • the growth level of the tumor by the screening of the tumor marker is as follows: an ideal state without microcancer is stage I, a precancerous state is stage II, a precancerous state is stage III, and a clinical cancer state is stage IV. It is desirable to classify the state in which the presence of 1 g or more of cancer is presumed into stage V and five tumor growth stages.
  • the growth level of the tumor by the screening of the tumor marker is defined as a stage I in an ideal state with no small cancer, the presence of a small cancer in a narrow sense is estimated, and no abnormality is recognized even in the cancer growth marker.
  • a state in which the cancer growth marker 1 and the tumor-related marker are slightly abnormal is referred to as a tumor stage III, a preclinical cancer state, and the cancer growth marker and the tumor
  • a state in which the value of the relevant marker is considerably abnormal is defined as tumor stage IV.
  • the presence of 1 g or more of cancer is estimated, and not only the above-mentioned tumor growth marker but also the above-mentioned tumor-related marker is remarkable.
  • a state in which an abnormality is observed and an abnormality is also observed in the tumor-specific marker can be classified into a tumor stage V and five tumor growth stages.
  • the method for evaluating cancer using a tumor marker it is possible to detect early cancer and identify a high-risk group by continuously tracking the time course of cancer occurrence.
  • a carcinoembryonic antigen tumor-specific marker 1
  • a cancer placental antigen tumor-related marker
  • a substance related to a tumor blood vessel cancer growth marker
  • tumor-specific marker 1 tumor-specific marker 1
  • tumor-specific marker 1 tumor-specific marker 1
  • tumor-related marker and a cancer growth marker are detected and quantified. Therefore, regarding the order of appearance of tumor markers, cancer growth markers and tumor-associated markers appear early in the growth of microcarcinoma (tumor stage III), followed by tumor-specific markers. (Tumor stage 1 ⁇ .
  • the cancer growth factors are alkaline phosphatase isozyme (ALP) and ribonuclease (RNase).
  • the tumor-related markers are ferritin (FT), immunosuppressive acidic protein ( ⁇ ), and sialic acid.
  • the tumor-specific markers are carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA 19.9), thermostable alkaline phosphatase (HSAP), and tissue polypeptide antigen (TPA). From the standpoint of simply screening for cancer, it was not always necessary to identify the organ where the cancer resided. However, in the present invention, tumor markers that are not organ-specific are also considered to be important in determining the presence or absence of cancer, and three different types of tumor markers, namely, tumor-specific markers In addition, three types were used: tumor-related markers and cancer growth.
  • the correct diagnosis rate is as high as 80% to 90%.
  • the correct diagnosis rate was 84% to 85%, and the correct diagnosis rate was 83% to 88%.
  • the stage of development corresponding to the actual tumor was classified based on the cut-off value of the marker reaction and used for risk assessment. Therefore, this evaluation method can evaluate cancer in the same way from small cancer to clinical cancer by introducing a stage classification model based on the natural history of preclinical cancer and clinical cancer. -Brief description of drawings
  • Fig. 1 is a graph showing the distribution of examinees classified by tumor stage.
  • Figure 2 is a graph showing the tumor stage distribution of 2 126 individuals divided into 4 age groups
  • FIG. 3 is a graph showing the correlation between each tumor marker and each tumor stage.
  • FIG. 4 is an explanatory diagram showing a cancer growth process and a five-step evaluation method using a tumor marker.
  • FIG. 5 is an explanatory diagram showing a cancer growth process and a coping method in a five-step evaluation method using a tumor marker. Best mode for carrying out the invention.
  • the cancer evaluation method using the tumor marker of the present invention is a cancer evaluation method including the steps of: ⁇ collecting blood, and detecting and defining each tumor marker from the collected blood. . It is also possible to collect urine instead of collecting this blood, detect and quantify each tumor from the collected urine.
  • the classification of the growth level of this tumor includes two or more abnormal levels of stages, and there is no ideal stage of microcancer, stage I, pre-cancerous stages of stage II, III, and The clinical cancer state was set as stage IV, and the state in which 1 g or more of cancer was estimated to be present was set as stage V.
  • cancer growth marker that first appears in the blood
  • the presence of tumor-related markers, the last occurrence of a tumor-specific marker substance, and the order of appearance are screened. Therefore, we consider that the carcinoembryonic antigen in cancer growth is the same as a tumor-specific marker, the carcino-placental antigen is the same as a tumor-associated marker, and the tumor vascular-related substance is the same as a cancer growth marker. Analyze by combining one.
  • cancer growth markers and tumor-associated markers appear early in the growth of microcarcinomas (tumor stage III), followed by tumor-specific markers. Appears (tumor stage V). By analyzing these tumor markers in combination, the risk of the cancer can be accurately evaluated.
  • the cancer evaluation method of the present invention is an evaluation method based on a model of the natural history of cancer.
  • microcancer was present in theory.
  • microscopic cancers may be pathologically present from sections of the stomach and other organs of patients with 'malignant or benign disease. Therefore, according to the present invention, micro-cancer and neoplazia (preclinical cancer) are specifically classified into the following four tumor stages (stages I to IV), and it is estimated that clinical cancer of 1 g or more exists. Stage ⁇ Classified.
  • Tumor stage I has no abnormality in any of the tumor markers.
  • ALP issozyme ⁇ R Nase without abnormalities, meaning that there is no cancer and ideal normal condition.
  • Tumor stage III is presumed to exist at a stage before transition to preclinical cancer (million to several hundred milligrams [M2]). This is a state where abnormalities are seen.
  • Tumor stage IV is a conventional stage 0 (G 0), preclinical cancer state, in which there are considerable abnormalities in the values of cancer growth markers and tumor-related markers, and occasionally tumor specific A slight abnormality in the value of the car.
  • Tumor stage V is a state in which the presence of 1 g or more of cancer is estimated.T1 to T4 of clinical cancer stages (clinical cancer is classified into four stages according to the ⁇ ⁇ ⁇ classification, and (Corresponding to G1 to G4 in the model of the invention). Not only tumor growth markers but also tumor-related markers showed remarkable abnormalities, and occasionally tumor-specific markers. This is a state where abnormalities are seen.
  • the manner in which subjects are sampled in cancer screening is very important to avoid biased research results.
  • Table 2 the age distribution of the examinees in the present invention was performed in a manner similar to the distribution in the conventional examination. Also, the proportion of examinees in each tumor stage, by venue, was similar to their proportion in the total number of examinees, and the sampling in this example was relatively unbiased. The cancers found for each tumor stage are diverse. 30 The incidence of cancer in various organs is similar to that from epidemiological data throughout Japan.
  • the method of evaluating cancer of the present invention' was as follows. Using these serum samples, comprehensive evaluation of tumor markers was performed. The following tumor markers were analyzed simultaneously:
  • C EA Carcinoembryonic antigen
  • Carcinoembryonic antigen is a tumor-specific marker and is a type of protein found only in fetal digestive tissue. This carcinoembryonic antigen (C EA) was measured by an enzyme immunoassay using a C EA.EIA kit.
  • this carcinoembryonic antigen mean that the progress of various cancers has become worse. Conversely, if the value is kept low after treatment such as surgery, there is no recurrence, which is an indicator that treatment is going well. Therefore, this carcinoembryonic antigen (CEA) is indispensable for monitoring the progress of cancer, judging the therapeutic effect, and detecting recurrence and metastasis.
  • HSA Heat-resistant Alkaline Phosphatase
  • Thermostable alkaline phosphatase is a tumor-specific marker that has been found in the sera of cancerous tissues and various cancer patients. For example, after measuring the serum of 50 ju1 at 56 ° C for 7 minutes, the fluorescent substrate '(naphth 0 1 .A S. MX phosphate ), Deproteinize it with acetone, and measure the fluorescence intensity in the supernatant with a fluorometer.
  • Ferritin (FT) is one of the tumor-related markers. This ferritin (FT) was measured by radioimmunoassay (radioactive, substance-based immunoassay). In the present invention, the ratio of ferritin (FT) to serum iron (FT / Fe) was used as another tumor marker.
  • IAP Immunosuppressive acidic protein
  • Immunosuppressive acidic protein has been positioned as a tumor-associated marker, and it has been shown that phytohemagglutinin-induced lymphoblast formation and lymphocyte mixing test in vitro Can be characterized by inhibiting both.
  • the immunosuppressive acidic protein (AP) was measured by a single-radiation immunodiffusion method. That is, 51 samples were placed in each well of an agar gel plate containing anti-IAP serum, incubated at 37 ° C for 48 hours, and the diameter of the sedimentation ring was measured.
  • Serum ribonuclease is positioned as one of the most important factors in cancer growth. This abnormal elevation of ribonuclease (RNase) is found in various cancer patients. This increase can be seen with severe renal impairment, but testing for creatinine has ruled out this risk.
  • the activity of this ribonuclease (RNase) was measured using polycytidylic acid as a substrate.
  • Sialic acid is one of the tumor-related markers. This high level of sialic acid is found in the sera of various cancer patients. Sialic acid was measured by an automatic analyzer using a sialic acid reagent kit based on the enzyme measurement method. "Alkaline phosphatase (ALP) isozyme"''
  • Alkaline phosphatase (ALP) isozyme is one of the markers of cancer growth.
  • the alkaline phosphatase (ALP) isozyme was separated and measured by cellulose acetate membrane electrophoresis. Within the normal range of ALP activity, serum ALP isozymes in cancer patients show significant fluctuations with disease status.
  • the three parameters (ALP l, ALP 2/3, APT) were calculated by comparing the densitometry of the AL force phosphatase (ALP) isozyme at 56 ° C and 37 ° C. .
  • the carbohydrate antigen (CA 19.9) is positioned as a tumor-specific marker. This sugar chain antigen (CA 19.9) was measured by immunoradiometric assay or time-resolved fluorescent immunoassay. This carbohydrate antigen (CA19.9) 'is used for screening of gastrointestinal cancers, since it is remarkably increased in serum such as carcinoma of the kidney, gallbladder and bile duct. .
  • the carbohydrate antigen (CA 19.9) is used to monitor the progress of cancer and to check for recurrence after surgery.
  • TPA tissue polypeptide antigen
  • Tissue polypeptide antigen is one of the tumor-specific markers. This tissue polypeptide antigen (TPA) is a commonly used tumor marker with high levels in gastrointestinal, lung, lung, mammary and prostate cancers. This tissue polypeptide antigen (TPA) was measured by immunoradiometric assay.
  • TPA tissue polypeptide antigen
  • Ratio of iron, albumin and globulin (AZG ratio), glutamine 'transoxaminase (GOT;), glutamine' pyruvate transaminase (GPT), torpedomid resistance test (TTT), ALP total activity and creatinine were measured by an automatic analyzer. These tests were used to rule out false positive results due to liver and renal dysfunction. ' In the cancer evaluation method of the present invention, each of the above-mentioned tumor markers was classified into three groups.
  • alkaline phosphatase (ALP) isozymes [ALP2, ALP2 / 3 APT] and ribonuclease '(R_Nase), which first appear in the blood, are expressed in "cancer growth”. Marker ".
  • furitin FT
  • immunosuppressive acidic protein IAP
  • sialic acid sialic acid
  • CEA carcinoembryonic antigen
  • CA 19.9 chain antigen
  • HSAP thermostable alkaline phosphatase
  • TPA tissue polypeptide antigen
  • the tumor stage is determined according to the cut-off value of each of the tumor markers shown in Table 3 in accordance with the above-mentioned 12 items of the tumor markers (CEA, HSAP, FT, FT). / F e, IAP, RNa.se, sialic acid, three ALP isozyme parameters overnight, CA19.9, TPA).
  • the power-off value to determine the tumor stage of preclinical cancer is the result of a correlation between tumor markers and tumor size for clinical cancer patients consulted based on the examples from 1980 to 198'5 Was determined.
  • CEA (ng / mi) 2.9 3.0-3.5 3.5-3.9 4, 0-4.3, 4
  • each tumor stage has two or more abnormal levels based on the power-off value of each tumor marker determined for each stage. Including the stage.
  • Figure 1 is a graph showing the distribution of patients classified by tumor stage. '' The number of patients for each tumor stage was 2 for stage I (0.1%), 250 for stage II (11.8%), 125 for stage III (58.8%), Stage IV was 528 (24.8%) and stage V was 95 (4.5%).
  • FIG. 2 is a graph showing the tumor stage distribution of 2126 patients divided into four age groups.
  • the tumor stage distribution was shown by dividing the patient into 4 age groups of 2126 patients. As shown in Table 2 above, this distribution chart is almost the same as the distribution in the conventional cancer population in Japan. The proportion of stage III patients was highest in all age groups and gradually decreased with age. The proportion of tumor stage II decreased with age, whereas tumor stages IV and V increased. '
  • stage V 29.5% of patients who were finally diagnosed as having cancer were stage V (28 out of 95), stage IV 2.7% (14 out of 528), Stage III is 0.7% (125/9 people), Stage II is 0.4% '(1/250 people), Stage. I is 0.0% (2 people) 0 people).
  • Cancer sites were 10 in lung, 10 in breast, 7 in stomach, 6 in large intestine, 2 in uterus, 1 in bladder, 2 in oral cavity, 1 in esophagus, 1 in spleen , 1 bone, 1 tongue, 1 prostate gland, 1 gallbladder, 1 pharynx, 1 ovary, 1 brain, 1 posterior neck, 1 thyroid There were a total of 52 cases, including 3 cases.
  • the tumor detection rate from tumor stage V during the observation period of 5 to 7 years was more than 10 times higher than that of tumor stage IV.
  • the cancer detection rate from the high-risk group (tumor stages IV, V) was 6.7% (42 out of 623), and the cancer detection rate from the low-risk group (tumor stages I, .11, III).
  • FIG. 3 is a graph showing the correlation between each tumor marker and each tumor stage. The illustrated example shows, for each stage, the proportion of persons who showed a high value of each tumor marker among the examinees in each group.
  • [Tumor stage classification and risk assessment]-Table 4 shows the cancer incidence for each stage during the 0.5 to 2.0 years after the cancer was evaluated according to the present invention.
  • the incidence of cancer from stage V was 23.2% (22/95).
  • Three of the 528 stage IV patients (0.57%) were diagnosed with cancer, with zero cancer from other stages. 5 to 7 years from stage I, II, III, W ⁇ V Discovery rate ⁇ ; 0%, 0.4%, 0.7%, respectively
  • the detection rate from this normal group is lower than 0.67% (10 out of 1503) of the method for evaluating cancer of the present invention.
  • the detection rate of 1.4% (27 out of 2000) in the population of these tests is the result of continuous investigation for 1 to 6 years.
  • the method is not only for detecting early cancer in a specific organ, but also for detecting early cancer at any site and identifying high-risk groups.
  • stage III five out of six people move to low risk, while in stage IV one out of two people and in stage V one out of ten.
  • stage III may explain why the proportion of this stage is high in all age groups.
  • a study of pathological reports of latent cancer at necropsy showed that approximately 30% of cancers were present at the time of necropsy in people in their 50s, and that of those in their 70s had a 5.0% potential cancer. The presence of cancer has been confirmed. Assuming that stage IV matches the underlying cancer and that stage V matches the clinical and preclinical cancers, the combination of stage IV and stage V is 36% in the 50s and 70% in the present invention. Account for 43% of all teens. These proportions correspond to the proportions of latent and preclinical cancers identified at necropsy, respectively.
  • the growth model of the natural history of cancer of the present invention is schematic and needs to be modified based on the results obtained in this study, for example, that each stage includes a long stationary phase. However, the method for evaluating cancer using the tumor marker of the present invention used as described above is very effective in screening for cancer and evaluating risk.
  • Fig. 4 is an explanatory diagram showing the cancer growth process and a 5-step evaluation method using a tumor marker.
  • C Fig. 5 is an explanatory diagram showing a cancer growth process and a coping method in a 5-step evaluation method using a tumor marker. . '
  • the growth level of the tumor is from stage I in an ideal state without micro-cancer.
  • stage II in a state where small cancer is presumed, that is, cancer cells In the state of several hundred to 100,000, it is time to take preventive measures by removing carcinogenic and promoting factors.
  • stage IV is a preclinical cancer state, that is, from 100 million cancer cells to 0.1 billion cancer cells.
  • the growth of cancer progresses when carcinogens, promoters and stress are added, but it is the time when preventive treatment is possible if it fully exerts its natural healing ability (immunity and biological defense ability).
  • the stage of progression of clinical cancer is the stage of early cancer G1, advanced cancer G2, G3, and terminal cancer G4.
  • the cancer evaluation method of the present invention can treat cancer in the same way from small cancer to clinical cancer by introducing a stage classification model based on the natural history of preclinical cancer and clinical cancer. It became so.
  • This cancer evaluation method has a system to study cancer while closely linking basic research with clinical research. 0
  • the method for assessing cancer by tumor markers detects and quantifies not only tumor-specific markers but also tumor-associated markers and cancer growth markers, and the tumor marker Regarding the order of appearance, tumor growth markers and tumor-associated markers appear early in the growth of small 5 small tumors, then tumor-specific markers appear, combining these tumor markers. By analyzing the results, it is possible to find cancer that appears in apparently healthy people and to evaluate the risk of the cancer.
  • the risk is determined, the tumor stage is classified, and the stage of tumor occurrence is divided into stages, so that the time course of cancer occurrence can be continuously monitored.
  • high-risk groups can be identified by detecting early cancers in any position.
  • gastric cancer screening and uterine cancer screening which account for about half of cancers in Japan, were performed using PAP tests (cytology), including morphological conventional projection tests such as X-ray projection and CT scan.
  • PAP tests cytology
  • morphological conventional projection tests such as X-ray projection and CT scan.
  • the cancer detection rate was extremely low5.
  • the detection rate of clinical cancer was increased as described above, and the sensitivity was at least several hundred times higher than conventional morphological examination.
  • the cancer evaluation method according to the present invention has excellent effects such as significantly improving the efficiency of cancer screening and being applicable to most cancers.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Chemical & Material Sciences (AREA)
  • Cell Biology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Hospice & Palliative Care (AREA)
  • Oncology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un procédé permettant l'évaluation de cancers par utilisation de marqueurs tumoraux grâce auxquels le processus cancérigène est classifié par étapes de sorte qu'il permet la détection non seulement d'un cancer précoce touchant un organe spécifique, par surveillance de l'oncogenèse au cours du temps, mais aussi d'un cancer précoce affectant un emplacement quelconque, ainsi que l'identification d'un groupe à haut risque. Le procédé comprend les étapes suivantes: prise de sang; criblage, à partir du sang prélevé, pour déterminer l'existence et l'ordre d'apparition d'un marqueur de prolifération cancéreuse apparaissant en premier dans le sang au cours de l'oncogenèse, puis un marqueur associé à la tumeur, puis un marqueur spécifique de la tumeur; et classification du processus de développement tumoral en différentes étapes dépendant des niveaux de développement tumoral par criblage de ces marqueurs. Selon ce procédé, un antigène carcino-embryonnaire du développement cancéreux est référé comme identique au marqueur associé à la tumeur, et une substance associée à l'angiogenèse tumorale est référée comme identique au marqueur de prolifération tumorale. L'analyse combinée de ces marqueurs permet la détection d'un cancer apparaissant chez un sujet apparemment sain et, dans le même temps, l'évaluation du niveau de risque du cancer.
PCT/JP2001/009201 2000-04-04 2001-10-19 Procede d'evaluation de cancer au moyen de marqueurs tumoraux Ceased WO2003036301A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2000102784A JP2001289861A (ja) 2000-04-04 2000-04-04 腫瘍マーカーによる癌の評価方法
PCT/JP2001/009201 WO2003036301A1 (fr) 2000-04-04 2001-10-19 Procede d'evaluation de cancer au moyen de marqueurs tumoraux

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000102784A JP2001289861A (ja) 2000-04-04 2000-04-04 腫瘍マーカーによる癌の評価方法
PCT/JP2001/009201 WO2003036301A1 (fr) 2000-04-04 2001-10-19 Procede d'evaluation de cancer au moyen de marqueurs tumoraux

Publications (1)

Publication Number Publication Date
WO2003036301A1 true WO2003036301A1 (fr) 2003-05-01

Family

ID=27614945

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2001/009201 Ceased WO2003036301A1 (fr) 2000-04-04 2001-10-19 Procede d'evaluation de cancer au moyen de marqueurs tumoraux

Country Status (2)

Country Link
JP (1) JP2001289861A (fr)
WO (1) WO2003036301A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3425404A4 (fr) * 2016-02-29 2020-07-29 KOBAYASHI, Tsuneo Procédé de collecte de données à utiliser lors de la classifications de la vie du cancer

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007029300A1 (fr) * 2005-09-05 2007-03-15 Tsuneo Kobayashi Methode d'evaluation du cancer par un examen complet faisant intervenir des marqueurs tumoraux
WO2011157446A1 (fr) * 2010-06-18 2011-12-22 B.R.A.H.M.S Gmbh Biomarqueurs permettant de prédire un cas de cancer incident
US20160245815A1 (en) 2013-10-01 2016-08-25 Toray Industries, Inc. Method for detecting pancreatic tumor, antibodies, and kit for the detection of pancreatic tumor
DK3252474T3 (da) 2015-01-26 2020-11-09 Toray Industries Fremgangsmåde og kit til detektering af galdevejskræft

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KAWANISHI: "Shuyou maker wo mochiita suigan shindan no houhou ni kansuru kenkyuu", HIROSHIMA DAIGAKU IGAKU ZASSHI, vol. 34, no. 2, 1986, pages 289 - 306, XP001055050 *
KOBAYASHI T., KAWAKUBO T.: "Prospective investigation of tumor markers and risk assessment in early cancer screening", CANCER, vol. 73, no. 7, 1 April 1994 (1994-04-01), pages 1946 - 1953, XP001055049 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3425404A4 (fr) * 2016-02-29 2020-07-29 KOBAYASHI, Tsuneo Procédé de collecte de données à utiliser lors de la classifications de la vie du cancer

Also Published As

Publication number Publication date
JP2001289861A (ja) 2001-10-19

Similar Documents

Publication Publication Date Title
Morikawa et al. A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population
Meng et al. Performance value of high risk factors in colorectal cancer screening in China
JP7619934B2 (ja) 尿中バイオマーカーにより前立腺癌をｉｎ ｖｉｔｒｏで診断する方法
KR100976218B1 (ko) 비행시간이차이온질량분광법을 이용한 질병의 진단 방법,질병 지표의 스크린 방법, 및 질병 지표
EP2558865A1 (fr) Procédé et trousse pour le diagnostic du cancer
EP2661628B1 (fr) Procédé diagnostique
Chen et al. Accuracy of immunochemical fecal occult blood test for detecting colorectal neoplasms in individuals undergoing health check-ups
WO2003036301A1 (fr) Procede d'evaluation de cancer au moyen de marqueurs tumoraux
Arhan et al. DR-70 as a novel diagnostic biomarker for gastric cancer
Muretto et al. An endogastric capsule for measuring tumor markers ingastric juice: An evaluation of the safety and efficacy of a new diagnostic tool
Tsui et al. Comparisons of voided urine cytology, nuclear matrix protein‐22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China
JP6834747B2 (ja) 肺癌を検出する方法及び検出用キット
US20190056401A1 (en) Diagnostic Method
Seicean et al. Performance of the standard 22G needle for endoscopic ultrasound-guided tissue core biopsy in pancreatic cancer
CN113917148A (zh) 胃癌诊断的蛋白标志物组合及其应用
CN108318688B (zh) 外周血外泌体中Smad3蛋白作为分子标记的应用、肝癌检测试剂盒
Stejskal et al. Evaluation of urine N1, N12-Diacetylspermine as potential tumor marker for urinary bladder cancer
US20230417752A1 (en) Immunohistochemistry (ihc) protocols and methods for diagnosing and treating cancer
Levin Colorectal cancer screening: new opportunities
Sahyouni et al. Diagnostic values of duodenal endoscopic markers in paediatric coeliac patients
Rabea et al. Assessment of Annexin A2 as A Marker for Diagnosis of Hepatocellular Carcinoma in Compensated and Decompensated Hepatitis C Virus Treated Patients
KR100999199B1 (ko) 비행시간이차이온질량분광법을 이용한 질병의 진단 방법, 질병 지표의 스크린 방법, 및 질병 지표
Xie et al. Comparison of Three Prediction Rules for Assessing the Risk of Gastric Cancer in Chinese Health Examination Populations
Steele Colorectal cancer screening
Khadka et al. Histopathological Evaluation of Gastric Biopsies and its Association with Endoscopic Findings

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA KR NZ US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase