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Biomarker

Biomarker◎ DefinitionA biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.◎ Types of cancer biomarker1. Prognostic biomarker : 각각 cancer의 natural course에 대해 예측할 수 있게 해주고 ‘poor outcome’ tumour로부터 ‘good outcome’ tumour를 구별해주며, 어떤 사람을 치료해 줄지나 얼마나 aggressive하게 치료할 것인지를 결정하게 해준다. 예를 들어 breast-cancer gene-expression signature는 이미 수술로 제거된 breast cancer의 재발 가능성을 예측하게 해준다. 이 multigene-expression tests는 재발의 위험성을 낮추기 위해서 수술 뒤에 남아있는 tumor cell을 제거하기 위해 systemic therapy, 즉 adjuvant therapy를 누가 받아야 할지를 결정하는데 사용된다.2. Predictive (or response) biomarker : 이것은 환자가 특정 치료를 받았을 때 그것이 이익이 될 것인가를 파악하는데 사용되는 marker이다. ERBB2 (also known as HER2 or NEU) gene (+) breast cancer환자는 trastuzumab (Herceptin)이 치료에 효과적일 것이다. 반면 oestrogen receptor encoding gene이 express되고 있는 tumor는 tamoxifen이 더 효과가 좋을 것이다.Leukemia에 있어서의 biomarker는 전통적으로 cytogenetic analysis에 의해 평가되었는데 추가적인 predictive information은 genotype-based analysis에 의해 얻을 수 있다. 예를 들어 kinase domain of BCR–ABL를 encoding하는 gene에 특정 mutation이 있어 imatinib mesylate에 내성을 가지는 chronic myeloid leukaemia환자는 새로운 ABL inhibitor인 dasatinib와 nilotinib에 다른 sensitivity를 보일 것이라고 예측할 수 있다.3. Pharmacodynamic biomarker : tumor에 대한 near-term treatment effects of a drug을 측정하고 이론적으로는 새로운 anticancer drug의 clinical development의 early stage에서의 dose selection에 이용될 수 있다. 또한 Pharmacodynamic biomarker는 drug development의 clinical trial phase에도 사용될 수 있다. 최근에 target engagement assay의 결과를 토대로 약의 용량에 대한 personal selection이 타당하게 하는 것을 가능케 함으로써 magnitude of BCR–ABL kinase activity inhibition이 clinical outcome과 correlation되어 있다고 밝혀졌다.◎ cancer biomarker의 종류와 특징Tumor markerType of moleculeTumor typeType of applicationNonmalignant conditions with elevated levelsCEAglycoproteinstomach, liver,Pancreas, breastcolorectal cancerPrognosis and monitoring therapeutic responseHepatitis, cirrhosis, jaundice, inflammato -ry bowel diseaseCA 19-9Mucin-type glycoproteinPancreas cancerDiagnosis, prognosis, monitoring therapeutic responseHepatitis, cirrhosis, sclerosing cholangitisAFPOncofetal glycoproteinLiver and teaticular cancerDiagnosis, prognosis, monitoring therapeutic responseHepatitis, cirrhosis, pregnancy, inflamma -tory bowel diseasePSAOncofetal glycoproteinProstate cancerScreening, diagnosis, prognosis, monitoring therapeutic responseBPH, prostatic massage or biopsy-HCGTrophoblastic proteinCholangiocarcin-oma, H mole, invasive moleDiagnosis, prognosis, monitoring therapeutic responsePregnancyCA 125Ovarian cell surface proteinOvarian cancerprognosis, monitoring therapeutic responsePregnancy, jaundice endometriosis, menstruationCA 15-3Membranes of breast cancer cellsBreast cancerprognosisCirrhosis, hepatitis, benign breast diseaseProstatic acidphosphataseProstate cellular proteinProstate cancerprognosis, monitoring therapeutic responseBPH, dermatological disorder5-Hydroxyindoleacetic acidPeptide metab-olite of indole- acetic acidCarcinoiddiagnosis-CalcitoninHormoneMedullary thyroid cancerDiagnosis, prognosis, monitoring therapeutic response-MetanephrineCatecholamine metabolitepheochromocytomaDiagnosis, prognosis, monitoring therapeutic response-

의/약학| 2010.07.05| 2페이지| 1,000원| 조회(384)

종양학, tumor marker, biomarker, 바이오마커

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Neutropenia management

혈액종양내과 ReportNeutropenia managementNeutropeniaDefinitionThe clinical consequences of prolonged phagocyte dysfunction can be life-threatening. Fortunately, acquired and inherited phagocyte dysfunction syndromes are rare. However, a reduction in the number of circulating phagocytes is more common in clinical practice, the most life-threatening instances of which result from bone marrow failure.Neutropenia is said to exist when a patient's peripheral neutrophil count is less than 2.0 × 109/L. Because the normal range in Yemenite Jews and black individuals is somewhat lower, neutropenia in these populations is defined as counts less than 1.5 × 109/L. The role of the neutrophil in phagocytic defense of the host is generally met if the neutrophil count is higher than 1.0 × 109/L.If the neutrophil count drops further, particularly below 0.5 × 109/L, the threat of recurrent, severe, life-threatening, and difficult-to-treat infections increases enormously.TreatmentImmunosuppressive therapy (e.gients.As a general rule, patients with drug-induced neutropenia (e.g., after cancer chemotherapy) recover more rapidly if they receive either GM-CSF or G-CSF. These agents are indicated in the settings of (1) bone marrow transplantation; (2) management of patients with inherited neutropenic syndromes, including cyclic neutropenia; (3) induction of stem cell mobilization from marrow to peripheral blood in preparation for transplantation; and (4) combined therapy with erythropoietin for selected patients with myelodysplastic syndromes. Large clinical studies indicate that G-CSF hastens neutrophil recovery in patients receiving cytotoxic therapy but does not reduce the rate of hospitalization for febrile episodes, prolong survival, reduce culture-positive infections, or reduce the cost of supportive care, whether given preemptively or to treat neutropenic fever.In addition, there is no evidence that these recombinant growth factors reduce mortality in non-neutropenic patients with nosocomdose intensity of the chemotherapeutic agents has a demonstrated impact on overall survival (e.g., Hodgkin's disease, germ cell neoplasms) and one of following three criteria apply: (1) serious, potentially life-threatening complications of neutropenia (e.g., documented bacterial infection) have developed in the patient in previous rounds of therapy (2) the prior probability for prolonged myelosuppression is high (e.g., patients seropositive for human immunodeficiency virus type 1) or (3) the patient's persistent neutropenia interferes with scheduled doses of chemotherapy.2. Bone Marrow TransplantationIn patients with severe aplastic anemia, the role of bone marrow transplantation is well established. Other marrow failure states (e.g., myelodysplastic syndromes and inherited neutropenia) may also respond. Before transplantation is seriously considered, the duration and severity of the neutropenia must be assessed; marrow failure must be established as the primary cause.If the patient he of communicating with the physician the moment that signs and symptoms of infection occur.In patients with neutropenia induced by cytotoxic chemotherapy for the treatment of malignant disease, prophylaxis with fluoroquinolone antibiotics decreases the incidence and severity of infections and reduces mortality. When neutropenia is caused by chemotherapy in patients with acute myelogenous leukemia or the myelodysplastic syndrome, antifungal prophylaxis with posaconazole improves survival. For all other neutropenic patients, the indications for antibiotic use are based on the individualized clinical context.If a neutropenic patient is afebrile and there is no sign of sepsis, diagnostic evaluation of the neutropenia should take place in the outpatient setting to avoid unnecessary exposure to nosocomial organisms. Patients with severe neutropenia and fever, however, should generally be hospitalized. Cultures of urine, blood, and other relevant sites should be obtained, but broad-spectrum iven. Moreover, after a full course of parenteral antibiotics, some of which may be given on an outpatient basis, another 7 to 14 days of oral antibiotics should be considered, especially in patients with invasive infections associated with necrosis, slow responses to initial antibiotic therapy, or recurrent infections in the same anatomic site.3. No organism is found, and the clinical picture has not changed for the better after 3 days of empirical treatment. This unsettling situation occurs with some regularity in practice, and the approach depends on the seriousness of the infection. For a patient who has localized disease and is not critically ill, it is sometimes helpful for empirical therapy to be discontinued and for repeat cultures to be obtained. If the patient is critically ill, however, antibiotics should be discontinued only if other antibiotics are substituted. Among the antibiotics to consider under these circumstances are antiviral and antifungal agents. Antifungal agentd.

의/약학| 2010.07.05| 4페이지| 1,000원| 조회(170)

HEMATOLOGY, 혈액종양내과, 혈액학, neutropenia, 백혈구감소증, Neutropenia manage

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Lung abscess

Definition Pulmonary parenchymal necrosis and cavitation resulting from infection (Harrison 17th) Cause Aspiration(m/c) - esophageal dysmotility, seizure disorders, other neurologic disorder Periodontal disease AlcoholismMicrobiologyAnaerobic bacteria m/c Aerobic of facultative bacteria - S.aureus , Klebsiella pneumoniae, Nocardia sp. Gram negative organism. Fungi, Parasite Immunocompromised host - aerobic bacteria, opportunistic pathogen

의/약학| 2010.07.05| 8페이지| 1,500원| 조회(119)

감염, 폐농양, 농양, Lung abscess

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Atypical Pneumonia

..PAGE:1DISEASE REVIEWAtypical Pneumonia..PAGE:21. EtiologyTypical pneumoniaS. pneumoniae, Haemophilus influenzae, S. aureus,gram-negative bacteria (K. pneumoniae, P. aeruginosa)Atypical pneumoniaMycoplasma peumoniae, Chlamydophila pneumoniae,Legionella spp., respiratory viruses (influenza viruses,Adenoviruses, RSVs)..PAGE:32. 특징Cannot be cultured on standard media, nor can they be seen on Gram’s stainIntrinsically resistant to all β-lactam agentsmust be treated with a macrolide, fluoroquinolone, or a tetracyclineslow onset, dry cough, dyspneaExtra-pulmonary Sxheadahe, myalgia, fatigue, sore throat, N/V, diarrheaM. pnemoniae : m/c cause..PAGE:43. Clinical manifestation1. Mycoplasma pnuemoniaBullous myringitis(수포성 고막염), hemolytic anemia, erythema multiforum, encephalitis 등 합병증 가능사춘기의 m/c community acquired pneumonia군대, 학교, 기숙사 등에서 호발잠복기 길고(2~3주) 전염력 약해서 전파는 느림Tx. : macrolide antibiotics..PAGE:52. Legionella pneumonia (전염력 약함)고열(>40℃), CNS Sx.(의식장애 등), GI Sx., 간, 신기능 이상, hyponatrema 등 합병증 가능오염된 냉각타워, 냉방기 등에서 호발위험인자 : 남성, 흡연, DM, cancer, hematologic malignancy, ESRD, HiV infection 등3. Primary viral pneumoniaInfluenza, RSV, CMV, measles, varicella, Hantan virus 등4. Chlamydia pneumoniae : hoarseness, wheezing, 인후통 등이 흔함3. Clinical manifestation..PAGE:64. Typical vs AtypicalTypical pneumoniaAtypical pneumoniaAgeAnyyoungCoughProductiveNon-productiveOnsetAcutesubacutePleurisyPresentabsentExtra-pulmonaryAbsentPresentWBC countIncreased, shift to Lt.Normal or increasedChest X-rayLocalized infiltrateDiffuse infiltrateRadiographic onsetPeripheralcentralConsolidation의 signPresentabsent방사선 소견과 진찰 소견samedifferent객담 Gram stainNeutrophils & bacteriaNeutrophils with scanty organismAbscess formationoftenrare..PAGE:75. Diagnostic approach*..PAGE:8ReferenceHarrison 17thHandbook of internal medicine 3rd

의/약학| 2010.07.05| 8페이지| 1,500원| 조회(205)

폐렴, Atypical Pneumonia, 호흡기계질환, 비전형적 폐렴, 이형폐..

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Hypertrophic Cardiomyopathy(확장성심근증)

..PAGE:1Hypertrophic CardiomyopathyDISEASE REVIEW..PAGE:2CardiomyopathyA group of disease that primarily affected the heart muscleNot the result of congenital / acquired valvular, hypertensive, coronary arterial, or pericardial abnormalitiesClinical classification of cardiomyopathyDiated: Left and/or right ventricular enlargement, impaired systolic function, congestive heart failure, arrhythmias, emboliRestrictive: Endomyocardial scarring or myocardial infiltration resulting in restriction to left and/or right ventricular fillingHypertrophic: Disproportionate left ventricular hypertrophy (typically involving septum)usually of a nondilated left ventricular cavity..PAGE:3Hypertrophic CardiomyopathyHypertension이나 aortic stenosis 등의 뚜렷한 원인을 발견할 수 없고, chamber dilatation이 없는 LV hypertrophyTwo features of HCMasymmetric LV hypertrophy(often hypertrophy of the interventricular septum : ASH)a dynamic LV outflow tract pressure gradient,related to narrowing of the subaortic area( systolic anterior motion of MV : SAM )..PAGE:4Basic mechanism of dynamic pressure gradientincreased LV contractility: ejection velocity ↑ → SAM of MVdecreased ventricular volume (preload): outflow tract 크기를 더욱 감소시킴decreased aortic impedance and pressure (afterload): ejection velocity ↑ → SAM of MVHemodynamics..PAGE:5Genetic Consideration약 50%에서 family history를 가짐 : Autosomal dominantMutationcardiac β-myosin heavy chain gene on chromosome 14 : most commoncardiac α- myosin heavy chainscardiac troponins C, I, and Tcardiac myosin-binding protein C→ Screening: by echocardiography of first-degree relatives between the ages of 12 and 20 should be carried out every 1224 months(unless the diagnosis is established or excluded by genetic testing)..PAGE:6clinical course of HCM : highly variable- asymptomatic or mildly symptomatic ~ sudden cardiac deathmost common cause of SCD : in young competitive athletesSymptomDyspnea : most common complaint, diastolic ventricular dysfunction에 의함syncope, angina pectoris, and fatigue→ 증상들은 outflow pressure gradient의 존재여부 및 severity와 밀접한 관련 없음Systolic murmurharsh, diamond-shapedlower left sternal border 에서 가장 잘 들리며 S1뒤에 시작됨apex에서는 MR에 의해 holosystolic murmurClinical Feature..PAGE:7EKGLV hypertrophyWidespread deep, broad Q wave : severe septal hypertrophy 반영Arrhythmia : ambulatory (Holter) monitoring에서 AF, VT 등 보임Chest X-ray대부분 normalLaboratory Evaluation..PAGE:8Echocardiography : mainstay of the diagnosis of HCMLaboratory Evaluation..PAGE:9Echocardiography : mainstay of the diagnosis of HCMLaboratory EvaluationM modeechocardiography..PAGE:10Cardiac CatheterizationHCM with an outflow tract gradient- a pressure gradient (difference) between the left ventricle and the aortaLaboratory Evaluation..PAGE:11Principle of Treatment심근 수축력 억제Preload Afterload 증가strenuous activities, dehydration 금기 (SCD위험 증가시킴)Medical treatmentAmiodarone : reduce the risk of SCD, arrhythmiaverapamil and diltiazem : reduce the stiffness of the left ventricle, elevated diastolic pressures, the severity of outflow tract pressure gradientsDisopyramide : reduce LV contractility, the outflow pressure gradient, symptomsβ- blocker : ameliorate angina pectoris and syncope (SCD줄여주는 효과는 없음)금기Digitalis, diuretics, nitrates, nifedipine, vasodilators, and β -adrenergic agonists, alcoholTreatment..PAGE:12Surgical treatmentTreatmentSurgical myectomy..PAGE:13Surgical treatmentTreatmentAlcohol septal ablation..PAGE:14Atrial fibrillation : common late in the course of the diseaseInfective endocarditis : occurs in 30 mmA family history of SCDGenetic mutationsPrognosis..PAGE:15Harrison’s Principlr of Internal Medicine 17th editionReferenceDiastole 때 ant. MV leaflet이 hypertrophied septum쪽으로 가까워짐에 따라 subaortic area가 좁아짐- SAM3often with the septum 1.3 times the thickness of the posterior LV free wall"ground-glass" appearanceLV cavity typically is small in HCM89HCM with an outflow tract gradient, there will be a pressure gradient (difference) between the left ventricle and the aorta,with the left ventricular pressure higher than the aortic pressure.10Alcohol ingestion may produce sufficient vasodilatation to exacerbate an outflow pressure gradient.11Myomectomy is the resection of excess muscle tissue.Myomectomy can relieve the obstruction of the left ventricular outflow tract by cutting out the muscle tissue just below the aortic valve.Severe환자들 중 ¾에서 증상개선 효과보임Image: Copyright 2004 Massachusetts Medical Society. All rights reserved. N Engl J Med 2004;350:1320-27.12The procedure involves the injection of absolute alcohol into a carefully selected blood vessel of the heart. The alcohol kills a segment of muscle tissue that is interfering with the flow of blood out the heart.Obstruction과 증상 개선Image: Copyright 2002 Massachusetts Medical Society. All rights reserved. N Engl J Med 2002;347:1306-7.13

의/약학| 2010.07.05| 15페이지| 2,000원| 조회(255)

순환기내과, 확장성심근증, Hypertrophic cardio, H-CMP

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