+

WO1997014037A1 - Determination et conrole de l'evolution du cancer de la vessie - Google Patents

Determination et conrole de l'evolution du cancer de la vessie Download PDF

Info

Publication number
WO1997014037A1
WO1997014037A1 PCT/IB1996/001083 IB9601083W WO9714037A1 WO 1997014037 A1 WO1997014037 A1 WO 1997014037A1 IB 9601083 W IB9601083 W IB 9601083W WO 9714037 A1 WO9714037 A1 WO 9714037A1
Authority
WO
WIPO (PCT)
Prior art keywords
ugp
bladder cancer
levels
cancer
individual
Prior art date
Application number
PCT/IB1996/001083
Other languages
English (en)
Inventor
Roger P. Walker
Omar El-Ahmady
Original Assignee
Chiron Diagnostics Corporation
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
Application filed by Chiron Diagnostics Corporation filed Critical Chiron Diagnostics Corporation
Priority to JP51488197A priority Critical patent/JP2002515966A/ja
Priority to EP96932751A priority patent/EP0855027A1/fr
Priority to AU71421/96A priority patent/AU7142196A/en
Publication of WO1997014037A1 publication Critical patent/WO1997014037A1/fr

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
    • G01N33/57407—Specifically defined cancers
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the present invention is directed to methods of determining the presence or absence of bladder cancer in individuals as well as methods of monitoring the effectiveness of the methodology for treating bladder cancer and for monitoring the course of bladder cancer in the body of an individual.
  • Urinary gonadotropin peptide a core fragment of the beta subunit of human chorionic gonadotropin (hCG) is used as the marker to distinguish bladder cancer as opposed to urogenital benign disease or normalcy and to allow monitoring of the course of bladder cancer before or after treatment of the cancer.
  • Bladder cancer has a high incidence throughout the world and in some countries as, for example Egypt, it is the most common type of male malignancy; and in females, ranks only after breast cancer in rate of incidence.
  • the disease as known in the art, is characterized in the Mideast and Far East by a high predominance of locally advanced lesions, and a high incidence of squamous cell carcinoma, Khaled, H.M. 1993, The Cancer J., 6,65-71 Bladder Cancer and Bilharziasis Today.
  • the predominant form of bladder cancer is transitional cell carcinoma, and 70% of these cases are superficial, noninvasive types.
  • the pathology of bladder cancer can vary as a function of the specific population, and regardless of the histologic type, the main prognostic factors are stage, grade, and spread of the tumor to tissues outside the bladder.
  • tumor markers can be used to aid in the management of disease. At least initially, for each population, the range of values of the tumor marker for normal individuals and patients with benign disease must be determined in order to allow determination of a cutoff that distinguishes patients with malignancies. Generally, a cutoff value for a tumor marker below which 95 percent of normal and benign subjects fall is chosen as the dividing point between normalcy and malignancy. This 95 percent confidence interval is useful for comparson of the sensitivity of various tumor markers in detecting malignant disease.
  • Tissue polypeptide antigen has been one of the most reliable markers and along with the use of carcinoembryonic antigen (CEA) and ferritin with TPA has increased the diagnostic value of TPA in detecting bladder cancer.
  • CAA carcinoembryonic antigen
  • ferritin with TPA has increased the diagnostic value of TPA in detecting bladder cancer.
  • urinary levels of human chorionic gonadotropin beta subunit have been evaluated in Egyptian bladder cancer patients and patients with benign urinary tract disorders. This marker was elevated in 60.3% of cancer patients, however, 29.7% of patients with benign disease were also elevated above the limits of the normal control group and thus prior studies did not determine that beta-hCG would be useful as a method of determining or monitoring of bladder cancer in individuals.
  • GYNECOLOGICAL CANCERS suggested the use of human chorionic gonadotropin beta-subunit core fragment (which is different from HCG) for detecting the progression or regression of gynecological cancers in females.
  • this marker is known as a marker for certain gynecological cancers and is known for gynecological cancer detection in women by monitoring of non-blood body fluids such as urine. It is often not used as a marker for determining cancer in some cases because the levels determined from blood body fluids are not sufficient for accurate determinations.
  • the marker is known to be a major component of pregnancy urine and to occur in the urine of patients with a variety of non-trophoblastic tumors including colorectal cancer, pancreatic and biliary cancer, gastric cancer and lung cancer. Studies have demonstrated it to be expressed by a wide variety of tumor tissues. The marker is expressed in a stage dependent manner in the urine of patients with cervical cancer, endometrial cancer, vulvar cancer and ovarian cancer.
  • Another object of this invention is to provide methods for monitoring the course of bladder cancer in the body and/or determining the effectiveness of a methodology for treating bladder cancer.
  • Still another object of this invention is to provide methods in accordance with the preceding objects which are non-invasive and can be carried out with the use of non-blood body fluids, including urine with minimum inconvenience and with good accuracy.
  • a test method of determining presence or absence of bladder cancer in an individual comprises obtaining a non-blood body fluid sample from an individual and then determining the urinary gonadotropin peptide (UGP) levels in the body fluid of the sample with elevated levels above normal indicating a cancer of the bladder and normal levels indicating the absence of cancer.
  • the body fluid is urine and conventional assay techniques are used to detect and quantify the amounts of urinary gonadotropin peptide (UGP).
  • an individual is monitored for the effectiveness of the methodology for treating bladder cancer in the body of the individual known to have bladder cancer.
  • the individual in a first step, is treated with any known methodology for reducing or treating bladder cancer.
  • the UGP level in a non-blood body fluid of the individual is monitored to indicate the measure of success of the treatment.
  • a non-blood body fluid sample is tested to determine the first UGP level and then testing is carried out after treatment to determine subsequent UGP levels.
  • a drop in UGP level when measured successively over a period of time after treatment indicates some degree of success for the treatment.
  • a rise in level would indicate the recurrence or growth of the cancer, while maintenance of normal values would be encouraging for success of the treatment.
  • a person known to have bladder cancer either as a result of the above tests, and/other medical procedures can be monitored for the course of the bladder cancer.
  • the recurrence of bladder cancer after successful treatment can also be determined.
  • UGP levels are determined from the urine or other non-blood body fluid over a period of time with variations noting the rise and lowering of cancer activity within the body.
  • UGP levels can be used in known methods to monitor UGP levels.
  • Another feature of this invention includes the establishment of a positive level of UGP above which one can distinguish bladder cancer from benign urological disease which level is preferably a level above 1.4 fmol/ml, but can be as low as above 0.7 fmol/ml.
  • the testing of this invention for UGP levels can be carried out non-evasively with minimum discomfort to the patient or individual being tested. A single test can indicate elevated levels of concern, whereas prolonged testing over a period of time can be used for monitoring the individual and/or monitoring the effectiveness of a standard bladder cancer treatment.
  • the urine can be tested immediately after withdrawal from the body or at substantial time periods thereafter while still maintaining good sensitivity and accuracy of the test.
  • UGP or urinary gonadotropin peptide is also known as urinary gonadotropin fragment (UGF), human chorionic gonadotropin beta-subunit core fragment and beta-core fragment.
  • UGP is a 10.5 kilodalton glycoprotein with a primary sequence identical to residues 6-40 and 52-92 of the beta-subunit of human chorionic gonadotropin (hCG) as reported by Birken, S. et. al Endocrinol. 123, 572-583 (1988), The Structure of Human Chorionic Gonadotropin Beta Core Fragment from Pregnancy Urine.
  • UGP shall mean urinary gonadotropin polypeptide as described above.
  • UGP is measured in urine and can be measured in non-blood body fluids. Urine is preferred because of its ease of collection in a non-invasive technique in the body. UGP is highly stable in urine, and studies with pregnancy urine have indicated that samples can be stored at 4° C or 25° C for 21 days, or at -20°C for six months. Preservatives are not required to maintain clinical sample stability. UGP is not readily measured in serum due to its rapid clearance rate from the circulation. It is a major component of pregnancy urine and when pregnant individuals are tested, the test may not be accurate for determination of bladder cancer unless pregnancy determinations are also carried out. If pregnancy is detected, the instant test cannot be used as an indicator of UGP.
  • the tests of this invention are sufficient to evaluate the expression of UGP in preoperative and postoperative patients with invasive bladder cancer and/or benign urogenital disease and in normal individuals in order to determine levels of UGP for use in the management of malignancy if present.
  • the testing to determine the UGP levels can be by conventional assay techniques.
  • one assay can involve the determination of levels of UGP by determining the levels of hCG beta fragment and beta subunit and then testing for the C-terminal peptide (which is not present on the fragment).
  • a preferred assay involves the use of a monoclonal or polyclonal antibody that recognizes any of hCG beta-fragment or beta-subunit.
  • Known assays useful in this invention include Triton® UGP EIA kits available from CIBA Corning Diagnostic Corp. of Alameda, California for the testing and quantitative measurement of UGP in urine.
  • the Triton® UGP EIA kit is a two-site enzyme immunoassay utilizing a specific monoclonal capture antibody and an enzyme-label polyclonal antibody directed towards different antigenic sites on the molecule.
  • Polystyrene tubes coated with mouse anti-UGP are incubated with urine specimens or the appropriate Calibrator or Control. During this incubation, the UGP molecules present in the specimen, calibrator and control are bound by the antibody onto the solid phase. Unbound materials present in the specimen are removed by washing of the tubes.
  • polyclonal anti-UGP Conjugated with horseradish peroxidase is added to the tube. If UGP molecules are present in the specimen, the Anti-UGP Conjugate is bound to the UGP on the tubes. Unbound conjugate is removed by tube washing.
  • the tubes are next incubated with a TMB Substrate Solution (hydrogen peroxide and 3,3',5,5'-tetramethylbenzidine) to develop a color which is a measure of the amount of bound Anti-UGP Conjugate.
  • the intensity of the color developed is read with a spectrophotometer set at 450 nm. Color intensity is proportional to the concentration of UGP in the specimen, within the working range of the assay.
  • a Calibration Curve is obtained by plotting the UGP concentration of the Calibrators versus the absorbance. The UGP concentration ofthe specimen and Control, run concurrently with the Calibrators, can be determined from the Calibration Curve.
  • creatinine levels in the urine can be used to compensate for this variation.
  • the UGP values are divided by their respective creatinine values to give normalized values (fmol UGP/mg or mmol creatinine).
  • 24 hour urine samples can be used or urines can be normalized by other factors, such as specific gravity.
  • 450 individuals were classified into three groups and testing was carried out to determine presence or absence of bladder cancer.
  • the present study included 450 individuals classified into three groups.
  • the first group included 237 patients with urinary bladder cancer that were admitted to the Egyptian National Cancer Institute. This group consisted of 171 males and 66 females ranging in age from 24 to 70 years. Lymph node involvement was present in 32 patients, and absent in 205 patients. Histopathological examination of the tumor tissues indicated 134 squamous cell carcinomas, 83 transitional cell carcinomas, 10 adenocarcinomas, 2 verrucous carcinomas, 2 leiomyosarcomas, and 6 undifferentiated carcinomas. As a function of stage 14 patients were stage T I and T II, 179 patients were stage T III, and 44 patients were stage T IV. When stratified by grade , 41 patients were grade 1, 118 patients were grade 2, and 78 patients were grade 3.
  • Bilharzial ova were identified in 143 tumors, and absent in 94 tumors. Staging and grading were conducted according to the established TNM and WHO systems, respectively.
  • the second group consisted of 97 patients with benign urinary tract disease recruited from the urology outpatient clinic, Kasr El-Aini Hospital, Egypt, and included 90 males and 7 females ranging in age from 20 to 63 years.
  • the benign disease categories includes 83 patients with urinary tract bilharziasis, and 14 with other benign disorders including benign prostatic hyperplasia, renal stones, varicocele, and bladder ulcers.
  • the third group included 1 16 normal healthy controls who were free of disease as evidenced by clinical and laboratory investigations. This group consisted of 107 males and 9 females ranging in age from 20 to 52 years that were recruited from students and workers at Al-Azhar University, Cairo, Egypt.
  • Urinary gonadotropin peptide (UGP) was determined in freshly-thawed urine samples. UGP was measured using an enzyme-linked immunoassay (Triton UGP EIA, Ciba Corning Diagnostics, Alameda, California).
  • Triton UGP EIA is a double-determinant enzyme immunoassay, which utilizes a monoclonal capture antibody immobilized on a coated tube, and an affinity-purified polyclonal antibody conjugated with horseradish peroxidase as the detection antibody.
  • the assay has a minimum detectable concentration of 0.1 fmol/ml.
  • Recovery of known quantities of UGP spiked into urine samples ranges from 86 to 109%, with a mean of 96%.
  • the intra- and interassay reproducibility range from 4.12% to 4.95%, and 6.07 to 7.85%, respectively, over the range of the assay.
  • Pathological urine samples exhibited linear dilution response, with a mean correlation coefficient of 0.999.
  • the assay is highly specific for UGP, exhibiting the following molar cross-reactivities: human chorionic gonadotropin (hCG, 0.11%), hCG beta subunit
  • hCG alpha subunit 0.009%, human luteinizing hormone (hLH. 0.001%), hLH beta subunit (0.005%), human thyroid stimulating hormone and beta subunit (hTSH and hFSH-beta subunit, ⁇ 0.001%), and human follicle stimulating hormone and beta subunit (hFSH and hFSH-beta subunit, ⁇ 0.001%).
  • the assay has been optimized to eliminate cross-reactivity with fragments derived from luteinizing hormone that are present in urine. The following urinary analytes do not interfere with the assay at levels up to the following concentrations: urea (5 g/dL), uric acid
  • the acceptable pH range of urine samples is from about 5.5 to about 8.5.
  • UGP levels were determined in 450 timed 24-hour urine samples from normal individuals, subjects with benign urological disease, and subjects with invasive bladder cancer.
  • the normal, benign disease control, and cancer patient cohorts were predominantly male, consisting of 107 (92%), 90 (93%), and 171 (72%) male subjects, respectively.
  • the distribution of UGP values in these subject categories is shown in the Figure.
  • UGP values are reported in units of fmol/ml in the 24-hour urine samples.
  • Statistical analyses were performed using JMP software (SAS Institute). Population means were compared using the Tukey-Kramer HSD method.
  • the mean UGP level in the bladder cancer patients was 4.86 fmol/ml, compared with 0.06 fmol/ml in the normal subjects, and 0.11 fmol/ml in the benign urological disease patients.
  • the mean UGP levels in these populations were significantly different (p ⁇ 0.01 ).
  • the first cutoff was 0.7 fmol/ml, which was the calculated 95% specificity level based on two standard deviations above the mean UGP level of the benign disease population.
  • the second cutoff was 1.4 fmol/ml, which was the 100% specificity level based on the distribution of UGP values in the same population. Using these cutoffs, the epidemiological sensitivity of UGP for detecting bladder cancer was evaluated according to various clinical parameters.
  • Table I shows the expression of UGP in 1 16 normal subjects, and 97 patients with benign urological disease.
  • the majority of disease control patients (N 83,86%) had benign urinary bilharziasis.
  • the benign bilharziasis group showed the greatest number of patients exceeding the 0.7 fmol/ml cutoff, at 7.2%. None of the patients exceeded the 1.4 fmol/ml cutoff.
  • Table II shows the expression of UGP in bladder cancer patients as a function of histologic type of disease. The mean UGP value for all patients was 4.86 fmol/ml.
  • SCC squamous cell carcinoma
  • TCC transitional cell carcinoma
  • stage T I and T II patients the percent of patients exceeding the cutoff levels increased as a function of stage.
  • stage T III disease the percent of patients exceeding the cutoff levels.
  • stage T IV patients the percent of patients exceeding the cutoff levels.
  • the number of patients exceeding the 1.4 fmol/ml cutoff followed the same trend, but was correspondingly lower, ranging from 57% of stage T I and T II patients, to 73% of stage T IV patients.
  • UGP was demonstrated to be a sensitive and specific marker for malignancy.
  • UGP was only marginally elevated in samples from normal individuals, and in patients with benign urogenital disease.
  • Mean UGP levels in patients with bladder cancer were 81 and 44-fold higher than those in normal individuals, and patients with benign disease, respectively.
  • 95% and 100% specificity levels an overall sensitivity of 73 and 60%, respectively, was observed.
  • No statistically significant correlation of UGP levels with histologic type, stage, grade, nodal involvement, or bilharzial association was demonstrable, although a trend of increasing mean UGP levels with stage of disease was observed.
  • UGP Due to the extreme difference in UGP levels between patients with benign disease, and bladder cancer patients, UGP is useful for the differential diagnosis of these patients.
  • UGP is a highly stable marker that is measurable in urine, which is a readily obtained and non-invasive sample.
  • the above example established a level for differentiating bladder cancer in the humans tested for benign urological disease, that is malignant (or bladder cancer) from benign disease.
  • the levels indicate that levels above 0.07 fmol/mL are significant as a distinguishing point with a level above 1.4 fmol/mL defining a clear-cut distinguishing point of malignant cancer herein bladder cancer, over benign disease.
  • urine may indicate the presence of cancer other than bladder cancer.
  • women who, when tested, test positive have to be further tested or pretested to rule out other forms of cancer or pregnancy.
  • Biopsy can be used, as can and other known methods for confirming the absence of other cancers or the presence of bladder cancer. Similarly, in pregnancy, in some cases, higher levels of UGP may require further testing to be certain of an indication of bladder cancer.
  • the level for differentiating bladder cancer from benign disease may vary between populations, however, the above example indicates the method for applying the use of UGP to different populations, or additionally with other methods of urine collection such as spot urines that require creatinine or other types of normalization.
  • the UGP determination can be used as a screening test for bladder cancer .
  • bladder cancer i.e., malignancy
  • benign disease i.e., benign disease
  • UGP expression is independent of the histologic type of bladder cancer, therefore, it can be used for the detection, monitoring, or screening of any histotype of disease, especially transitional cell and squamous carcinomas.
  • the determination of UGP in the urine of males and females can be used to monitor the progression of bladder cancer in an individual known to have bladder cancer. Higher levels of UGP are observed in advanced stages and grades, and stage 1 and 2 disease can be statistically
  • UGP levels can be determined in an individual otherwise known to have bladder cancer.
  • the determination of bladder cancer can be made by the test of this invention with or without the use of biopsy.
  • a first level of UGP at an elevated level is established in a bladder cancer patient, that level can be monitored at 24 hour, 4 day, one week, monthly or other periods to determine the progression or regression of the disease, with higher levels indicating increased cancer and lower levels indicating reduced cancer, and normal levels indicating absence of disease.
  • Normal levels would be considered any level below 0.7 fmol/mL or at least below 1.4 fmol/mL in the urine, when measured in 24 hour urine samples. However, the optimum cutoff for distinguishing normal individuals and individuals with benign disease from individuals with malignancy may need to be determined for each population that is being studied. Other non-blood body fluids such as interstitial fluids and the like, lymph fluids or other fluids found in the urinary tracts of individuals can also be used for determining UGP level.
  • UGP levels are determined using the Triton® Ciba-Corning kit, as known in the art during preselected time periods, as discussed above.
  • Other assay techniques utilizing monoclonal and/or polyclonal antibodies in sandwich or competitive assay formats can similarly be used to measure UGP levels.
  • the patient can be treated with a methodology for reducing bladder cancer. Any known methodology can be used as, for example, X-ray treatment, chemical treatments, intravesical
  • the monitoring of the patient after treatment with a cancer therapy can be accomplished by carrying out quantitative determination of UGP levels at any selected period desired.
  • a patient having bladder cancer at stage T3 is treated by surgery.
  • the UGP quantitative level in the urine of the patient is determined prior to the treatment at a level of 4.8 fmol/mL. After treatment, the patient is monitored at monthly intervals and found to have levels of 0.3 fmol/mL at 1 month, 2 months, and 3 months post surgery, indicating that the patient was free of residual disease.
  • the patient has declining UGP values to normal, indicating success of the treatment and return of the patient to normal, at least for that period of time. Rising or original values would be an indicator of lack of success of the treatment.
  • the invention comprises the determination of UGP levels, to indicate presence or absence of bladder cancer and distinguish it from benign urinary disease and/or to monitor treatment of patients having bladder cancer.

Landscapes

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

Abstract

Méthode de test destinée à déterminer la présence d'un cancer de la vessie par détermination des niveaux de peptide gonadotrophine urinaire (UGP) dans des liquides biologiques autres que le sang. Le procédé peut également être utilisé pour suivre l'évolution d'un cancer de la vessie et son traitement ainsi que la récidive de la maladie.
PCT/IB1996/001083 1995-10-12 1996-10-11 Determination et conrole de l'evolution du cancer de la vessie WO1997014037A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP51488197A JP2002515966A (ja) 1995-10-12 1996-10-11 膀胱癌の決定およびモニタリング
EP96932751A EP0855027A1 (fr) 1995-10-12 1996-10-11 Determination et conrole de l'evolution du cancer de la vessie
AU71421/96A AU7142196A (en) 1995-10-12 1996-10-11 Determination and monitoring of bladder cancer

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US558595P 1995-10-12 1995-10-12
US60/005,585 1995-10-12

Publications (1)

Publication Number Publication Date
WO1997014037A1 true WO1997014037A1 (fr) 1997-04-17

Family

ID=21716619

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB1996/001083 WO1997014037A1 (fr) 1995-10-12 1996-10-11 Determination et conrole de l'evolution du cancer de la vessie

Country Status (4)

Country Link
EP (1) EP0855027A1 (fr)
JP (1) JP2002515966A (fr)
AU (1) AU7142196A (fr)
WO (1) WO1997014037A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998051824A1 (fr) * 1997-05-15 1998-11-19 Abbott Laboratories Reactifs et procedes utiles au depistage de maladies du tractus urinaire
WO1998055656A1 (fr) * 1997-06-05 1998-12-10 Abbott Laboratories Reactifs et procedes utiles en vue de la detection de maladies des voies urinaires
WO1999002734A1 (fr) * 1997-07-08 1999-01-21 Abbott Laboratories Reactifs et procedes utilises pour deceler des maladies des voies urinaires

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008103815A2 (fr) * 2007-02-23 2008-08-28 Predictive Biosciences Corporation Procédé diagnostique destiné à une intervention clinique

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5356817A (en) * 1988-06-09 1994-10-18 Yale University Methods for detecting the onset, progression and regression of gynecologic cancers

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5356817A (en) * 1988-06-09 1994-10-18 Yale University Methods for detecting the onset, progression and regression of gynecologic cancers

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
MARCILLAC I ET AL: "FREE HUMAN CHORIONIC GONADOTROPIN BETA SUBUNIT IN GONADAL NONGONADAL NEOPLASMS", CANCER RESEARCH, vol. 52, no. 14, 15 July 1992 (1992-07-15), pages 3901 - 3907, XP000608910 *
NISHIMURA, RYUICHIRO ET AL: "Expression and secretion of the.beta. subunit of human chorionic gonadotropin by bladder carcinoma in vivo and in vitro", CANCER RES. (1995), 55(7), 1479-84 CODEN: CNREA8;ISSN: 0008-5472, 1995, XP002022535 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998051824A1 (fr) * 1997-05-15 1998-11-19 Abbott Laboratories Reactifs et procedes utiles au depistage de maladies du tractus urinaire
WO1998055656A1 (fr) * 1997-06-05 1998-12-10 Abbott Laboratories Reactifs et procedes utiles en vue de la detection de maladies des voies urinaires
US6949357B2 (en) 1997-06-05 2005-09-27 Abbott Laboratories Reagents and methods useful for detecting diseases of the urinary tract
WO1999002734A1 (fr) * 1997-07-08 1999-01-21 Abbott Laboratories Reactifs et procedes utilises pour deceler des maladies des voies urinaires

Also Published As

Publication number Publication date
JP2002515966A (ja) 2002-05-28
EP0855027A1 (fr) 1998-07-29
AU7142196A (en) 1997-04-30

Similar Documents

Publication Publication Date Title
EP2982761B1 (fr) Utilisation de he4 et d'autres marqueurs biochimiques dans l'évaluation de cancers de l'endomètre et de l'utérus
US20190072556A1 (en) Detection of Cancer by Elevated Levels of Bcl-2
US6972180B1 (en) Method of diagnosing and monitoring malignant breast carcinomas
Blackman et al. Human placental and pituitary glycoprotein hormones and their subunits as tumor markers: a quantitative assessment
US20140271621A1 (en) Methods of prognosis and diagnosis of pancreatic cancer
CA2682132C (fr) Utilisation de he4 pour l'evaluation du cancer du sein
WO1997014037A1 (fr) Determination et conrole de l'evolution du cancer de la vessie
EP4533094A1 (fr) Méthodes et systèmes de stratification du risque et de la gestion du cancer de la vessie
Wu et al. Development of a microplate assay for serum chromogranin A (CgA): establishment of normal reference values and detection of elevated CgA in malignant diseases
EP3698138B1 (fr) Essai et kit pour le diagnostic du cancer de l'ovaire
CA2234253A1 (fr) Determination et controle de l'evolution du cancer de la vessie
El-Ahmady et al. Urinary gonadotropin peptide (UGP) in Egyptian patients with benign and advanced malignant urological disease
CN116298319B (zh) 一种用于联合检测人Tg和Cyfra21-1的试纸条
Børmer et al. Tumour markers as seen from the clinical laboratory: physiological, biochemical, and analytical aspects
Krishnamoorthy Karuvaje Thriveni, Vijayalaxmi Deshmane, Girija Ramaswamy &
Rowe et al. The utility of the free/total PSA ratio in prostate cancer detection in younger men aged 50–65 years with a ‘normal’total PSA
Azzouzi et al. Relevance of PSA-nanotest on capillary blood in organised mass screening of prostate cancer
Miano et al. Evaluation of a new qualitative, one-step PSA rapid-screen test for screening program on prostate cancer
Väisänen et al. Sensitive two-site immunoassays for measurement of the free and total forms of human glandular kallikrein 2 (hK2)
Nyström et al. Hypercalcemia in a patient with mammary carcinoma; metastases or primary hyperparathyroidism?
Schmitt et al. BTA TRAK™-A USEFUL DIAGNOSTIC TOOL IN URINARY BLADDER CANCER?

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IL IS JP KE KG KP KR KZ LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG US UZ VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2234253

Country of ref document: CA

Ref country code: CA

Ref document number: 2234253

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1996932751

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1996932751

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 1996932751

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载