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PubMed1994

Effects of exercise training on coronary circulation: introduction.

The purpose of this symposium was to evaluate the hypothesis that the beneficial effects of training are the result of training-induced adaptations in the coronary circulation. The approach is to review, summarize, and evaluate data concerning the effects of exercise training on the coronary circulation. Results indicate that aerobic exercise training induces an increase in both blood flow capacity and capillary exchange capacity. These functional changes are the result of two major types of adaptive responses: structural vascular adaptation and altered control of vascular resistance. Structural vascular adaptation occurs in response to exercise training in at least two forms: increases in the cross-sectional area of the proximal coronary arteries, and angiogenesis. Training-induced changes in coronary vascular control have been shown to include altered responses of the coronary circulation and isolated coronary arteries to vasoactive substances, changes in endothelium-mediated vasoregulation, and alterations in the cellular-molecular control of intracellular free Ca2+ in both endothelial and vascular smooth muscle cells isolated from coronary arteries of exercise trained animals. The potential impact of these training-induced adaptations on the coronary collateral circulation and atherosclerotic coronary disease are discussed.

Adaptation, Physiological↗
PubMed1984

Circulation control of experimental and clinical profound left ventricular failures by automatic left ventricular assist system.

It is desirable that circulation control of the patient using a left ventricular assist device (LVAD) should be achieved appropriately and safely. We have developed an automatic LVAD system, which can maintain the normal circulation irrespective of the severity of heart failure and can restore the failing heart by decreasing the bypass flow (BF) through the LVAD as the heart recovers. The main part of the control-drive unit is an automatic level control (ALC) system for left atrial pressure (LAP) and total flow (TF). Profound left ventricular failure (LVF) was made by complete interception of blood supply to the extent of 50% (5 goats) and 70% (5 goats) of the LV free wall. The air-driven diaphragm-type LVAD was implanted between LA and aorta. At the beginning of LVAD pumping, BF tended to be very high to keep LAP at the preset level (0-5 mmHg) and to maintain TF at somewhat higher level (120-140 ml/kg/min). The recovering heart was able to decrease LAP gradually. Since the LAP was set at a certain level, the ALC of LAP decreased BF to maintain LAP at the preset level. During the recovering stage from LVF, preset level of LAP was gradually raised while checking the pulmonary function. When natural heart output exceeded 100 ml/kg/min, LVAD was removed. The 50% LVF group recovered between 17 hours and 3 days, and 70% LVF group between 6th and 16th postoperative day. This LVAD system was then applied to the postoperative profound LVF in a MVR patient whose entire circulation was maintained normal during 14 day pumping. The failed heart gradually recovered and the pump was successfully removed. We consider that the decompression of LV will prevent overextension of impaired myocardium and simultaneously accelerate the solid scar formation. And gradual increase of LV work will promote the compensation ability of the residual myocardium. Continuous LVAD assistance can therefore earn time for the impaired myocardium to recover while maintaining normal circulation.

Adult↗
PubMed2000

Influence of age (body size) on the Fontan circulation--analysis by a theoretical model.

Among the original selection criteria for the Fontan operation, the recommended age at the time of surgery has been 4 years or older, but recent clinical data have indicated the feasibility of this procedure in younger patients. Because age may influence the properties of the systemic vascular bed, changes in systemic vascular resistance (Rs) and systemic vascular compliance (Cs) associated with physical development were quantified in 86 pediatric patients without known abnormalities of the systemic circulation, and the effects of age (body size) on Fontan circulation were then analyzed using an analytical model of the cardiovascular system. As the body surface area (BSA) of the patient decreased, Cs also decreased significantly (r=0.81, p<0.001). Based upon this relationship between BSA and Cs, the analytical model showed that the impedance (ventricular afterload) of the Fontan circulation significantly increased as Cs decreased with the decrease in BSA. Moreover, the increase in impedance in response to changes in heart rate or Rs was inversely proportional to the BSA. However, these findings were significant only when the BSA was below 0.3 m2. Small BSA, or a lower age, has minimal effects on the Fontan circulation until it comes close to the infant value, and thus the Fontan procedure may be feasible much earlier than formerly recommended when the hemodynamics are otherwise acceptable.

Age Factors↗
PubMed2004

Bovine Doppel (Dpl) and prion protein (PrP) expression on lymphoid tissue and circulating leukocytes.

Doppel (Dpl) protein shares some structural features with prion protein (PrP), whose pathologic isoform (PrPsc) is considered to be the causative agent of transmissible spongiform encephalopathies. Dpl is mainly expressed in testes but, when ectopically expressed in the central nervous system, is neurotoxic. We have examined the expression pattern of Dpl and PrP on bovine lymphoid tissues and circulating leukocytes. A polyclonal anti-Dpl antibody along with a panel of monoclonal antibodies specific for leukocyte membrane antigens or PrP were used to examine frozen sections from spleen, lymph nodes, and bone marrow by immunohistochemistry. Blood was analyzed by flow cytometry. Double staining was used to study the possible coexpression of the two proteins and to characterize cells expressing Dpl and/or PrP. Dpl was expressed in B-cells, in dendritic cells within lymphoid follicles, bone marrow, circulating myeloid cells, and circulating B-cells. The distribution of Dpl was quite similar to that of PrP. The only differences in expression observed concerned the low number of Dpl+ cells in lymph nodes and the strong Dpl positivity of circulating granulocytes. The two proteins were rarely co-expressed, suggesting an independent expression mechanism in resting cells. The role of Dpl+ leukocytes in the pathogenesis of Dpl- or PrP-induced diseases merits further investigation.

Animals↗
PubMed1997

Coronary circulation in the failing heart.

In congestive heart failure, vascular resistance increases because of vasoconstriction caused by activation of the neurohumoral system. On the other hand, vasodilatory responses can partially compensate for vasoconstriction by increasing vasodilatory substances. Although vasoconstrictive forces predominate as a whole, there is heterogeneity in the responses of different vascular beds to vasoactive agents. Especially, as for coronary circulation in the setting of heart failure, many factors may cause disturbances in coronary circulation. Thus, in this review, we discuss from the point of view of neurohumoral modification of coronary flow, coronary flow reserve, endothelial dependent and independent control of vasomotor tone, vascular responses in relation to vessel size or the severity of heart disease, and mechanical factors that determine coronary circulation. Throughout these discussions, the mechanism responsible for the reduction in coronary dilatory capacity is also described. Depressed myocardial blood flow and a blunted flow response to cardiovascular stimulation together may be one important mechanism responsible for the progression of disease in patients with cardiac dysfunction. Accordingly, even though it is not known whether abnormal coronary circulation is a cause or effect of heart failure, the treatment of impaired coronary flow reserve seems to be essential in the care of patients with cardiac dysfunction.

Cardiac Volume↗
PubMed2006

[Effects of metformin on endothelial dysfunction of the renal circulation resulting from acute hyperglycemia in non-diabetic rabbits].

OBJECTIVE: To assess the effects of metformin (Met) on the endothelial dysfunction of the renal circulation of non-diabetic rabbits acutely induced by levels of glucose usually observed in diabetic patients in daily clinical practice. METHODS: Isolated perfused kidneys from non-diabetic rabbits were exposed for 3 h to normal (100 mg/dl--control group) or high (270 mg/dl) D-glucose with or without Met (100 microM). The glucose levels used correspond to 2 h post-breakfast median values (272 mg/dl) obtained from a cohort of 780 type 2 diabetic (DM2) outpatients seen in our service. Vascular reactivity was evaluated with endothelium-dependent (ED) [acetylcholine-ACh] and independent (EI) [sodium nitroprusside-SNP] vasodilating agents. RESULTS: Kidneys perfused with high glucose had ED maximal vasodilation blunted in comparison to controls (respectively 25 +/- 3 and 41 +/- 3%; p < 0.01). A 3 h Met infusion restored the vasodilating effect of ACh in the renal circulation in the presence of high glucose, no different from controls (respectively 43 +/- 1.5 vs. 41 +/- 3% p > 0.05). Met did not affect maximum vasodilation induced by ACh in the presence of normal glucose levels. Finally, renal vasodilation induced by SNP was not modified by simultaneous infusion of glucose and Met. CONCLUSIONS: Acute hyperglycemia corresponding to the range observed in patients with DM2 induces endothelial dysfunction in the renal circulation of normal rabbits. Acute treatment with Met was able to protect the renal circulation against the effects of high glucose. The mechanisms involved in this protector effect deserve further investigation.

Animals↗
PubMed2004

Reactive oxygen species in the cerebral circulation: physiological roles and therapeutic implications for hypertension and stroke.

It is now clear that reactive oxygen species (ROS) can act as signalling molecules in the cerebral circulation under both physiological and pathological conditions. Some major products of superoxide (O(2)(.)(-)) metabolism, such as hydrogen peroxide (H(2)O(2)) and hydroxyl radical (OH(.)), appear to be particularly good cerebral vasodilators and may, surprisingly, represent important molecules for increasing local cerebral blood flow. A major determinant of overall ROS levels in the cerebral circulation is the rate of generation of the parent molecule, O(2)(.)(-). Although the major enzymatic source of O(2)(.)(-) in cerebral arteries is yet to be conclusively established, the two most likely candidates are cyclo-oxygenase and nicotinamide adenine dinucleotide phosphate (reduced form) [NADPH] oxidase. The activity of endogenous superoxide dismutases (SODs) play a vital role in determining levels and effects of all individual ROS derived from metabolism of O(2)(.)(-). The term 'oxidative stress' may be an over-simplification that hides the complexity and diversity of the ROS family in cerebrovascular health and disease. Although a generalised increase in ROS levels seems to occur during several vascular disease states, the consequences of this for cerebrovascular function are still unclear. Because enhanced breakdown of O(2)(.)(-) by SOD will increase the generation of the powerful cerebral vasodilator H(2)O(2), this latter molecule could conceivably act as a compensatory vasodilator mechanism in the cerebral circulation under conditions of elevated O(2)(.)(-) production. Some recent clinical data support the concept of a protective role for cerebrovascular NADPH oxidase activity. Although it is quite speculative at present, if NADPH oxidase were to emerge as a major source of beneficial vasodilator ROS in the cerebral circulation, this may represent a significant dilemma for treatment of ischaemic cerebrovascular conditions, as excessive NADPH oxidase activity is associated with the progression of several systemic vascular disease states, including hypertension and atherosclerosis. Despite data suggesting that antioxidant vitamins can have beneficial effects on vascular function and that their plasma levels are inversely correlated with risk of cardiovascular disease and stroke, the results of several recent large-scale clinical trials of antioxidant supplementation have been disappointing. Future work must establish whether or not increased ROS generation is necessarily detrimental to cerebral vascular function, as has been generally assumed, or whether localised increases in ROS in the vicinity of the arterial wall could be beneficial in disease states for the maintenance of cerebral blood flow.

Animals↗
PubMed1996

Effects of L-arginine on utero-placental circulation in growth-retarded fetuses.

BACKGROUND: To evaluate the effects of L-arginine (ARG) infusion, the nitric oxide as substrate, on the utero-placental circulation at third trimester. METHODS: Three groups of nine pregnant women each were infused i.v. with 30 g ARG, for 30 minutes. One group served as control, and the two remnants were composed by patients with intrauterine growth retardation with (IUGR-B) or without (IUGR-A) increased resistances in the utero-placental circulation. Changes of blood flow velocity waveforms of both uterine arteries and umbilical artery were recorded for 60 minutes. Blood pressure, serum nitrites/nitrates and growth hormone levels were also measured. RESULTS: No hemodynamic changes in utero-umbilical circulation were observed during infusion in any of the three groups. Considering the uterine arteries separately as placental and non-placental sided we found a significant decrease of non-placental side resistances in IUGR-B women. Indeed, the pulsatility index was lowered by 14%, in respect of baseline value. Serum nitrites/nitrates as well as serum growth hormone levels were significantly increased by ARG, in every woman, irrespective of the presence of fetal growth retardation. Blood pressure remained unaffected during infusion in every woman. CONCLUSIONS: These findings suggest that L-arginine infusion affects utero-placental circulation in patients with IUGR associated with increased uterine resistances. Such an action is specific and appears possibly to be mediated by a release of nitric oxide.

Adult↗
PubMed1986

Effects on blood pressure of cross circulation between spontaneously hypertensive and normotensive rats.

In order to examine the role of humoral factors for the development of hypertension in the spontaneously hypertensive rat of the Münster strain (SHR) cross circulation experiments with normotensive Wistar Kyoto rats were performed. Cross circulation between SHR and normotensive rats for 30 min increased mean arterial pressure in the latter by 29.1 +/- 7.6 mm Hg (p less than 0.01). Transmission of hypertension by cross circulation was abolished by nephrectomy, adrenalectomy, volume depletion or chronic salt restriction in the SHR. It is concluded that hypertension in SHR is caused by a circulating hypertensive agent produced in kidneys and adrenals, the secretion of which can be suppressed by volume or salt depletion.

Adrenalectomy↗
PubMed1975

Plasma potassium and insulin during extracorporeal circulation using a glucose-containing pump prime.

In order to investigate the possible relationship between a glucose-containing pump prime and changes in plasma potassium during extracorporeal circulation, determinations were made of blood glucose and plasma insulin, potassium, and magnesium in 18 subjects undergoing open-heart surgery. In 6 of the patients, the same parameters had been measured during a pre-operative glucose tolerance test. It was found that the elimination of glucose was considerably impaired during extracorporeal circulation, in spite of high insulin levels. During the first minutes of extracorporeal circulation, plasma potassium fell more than during the glucose tolerance test, in spite of comparable insulin levels. It is concluded that changes in plasma potassium during extracorporeal circulation do not reflect insulin activity to any noticeable extent.

Adolescent↗
PubMed1990

Surgical treatment of unruptured aneurysms of the posterior circulation.

With the ever-increasing number of intact aneurysms revealed by modern imaging, the options for their management are assuming great importance. While some knowledge has emerged as to their natural history and the results of surgical treatment of those in the anterior circulation, little information has been published concerning unruptured aneurysms arising from the posterior circulation. The authors report their experience since 1971 with 167 patients operated on for 179 unruptured vertebrobasilar aneurysms up to 25 mm in diameter. Overall, 160 aneurysms were treated by direct clip obliteration, while 19 were managed by alternative methods. Fifty-three patients (32%) had solitary aneurysms and the other 114 patients (68%) had multiple aneurysms or an associated arteriovenous malformation, which were commonly treated concurrently. Many of these coexisting vascular anomalies had ruptured in the recent or remote past, adding to the complexity of management and interpretation of specific surgical results related to the intact posterior circulation aneurysm. There were 78 documented postoperative complications including 23 systemic complications, seven postoperative hematomas, six brain injuries from retraction, five cases of aseptic meningitis, three instances of seizures, three wound infections, and three patients with hydrocephalus. Multiple complications occurred in 23 patients. Seventy-one of the patients with these untoward events recovered, without disability, with time or treatment. There were only six poor results and one death in the series, resulting in a 4.2% combined morbidity/mortality rate. However, since two of these poor outcomes and the single death were attributable to a coexisting aneurysm, the actual surgical morbidity related specifically to the posterior circulation aneurysm was only 2.4%. This experience suggests that non-giant, intact vertebrobasilar aneurysms can be obliterated surgically at a very low risk, and this treatment should eliminate the greater lifetime risk related to an unsecured aneurysm.

Adolescent↗
PubMed1986

Actions of opiate agonists, naloxone, and paraben preservatives in the rat lung circulation.

Previous studies have documented direct vascular effects of opiate substances in the systemic circulation. Because opiate receptors have been identified in the lung, we wondered whether opiate substances might affect vasoreactivity in the lung circulation. We studied the pulmonary vascular effects of three opiate agonists: morphine, leucine-enkephalin, and dynorphin, as well as the opiate receptor antagonist naloxone, in isolated rat lungs perfused with a cell- and plasma-free salt solution. Because of previous reports of the smooth muscle effects of the methyl- and propylparaben preservatives in the naloxone preparation, we also studied the pulmonary vascular effects of these preservatives in the rat lung circulation. We found that morphine, a mu-receptor agonist, leucine-enkephalin, a delta-receptor agonist, and dynorphin, a kappa-receptor agonist, caused no immediate vascular effect when injected into the pulmonary artery. In addition, morphine did not affect the pulmonary vasoconstrictions induced by hypoxia, angiotensin II, or potassium chloride. The commercial preparation of naloxone, Narcan, caused a marked vasodilation during hypoxic pulmonary vasoconstriction. However, this effect was entirely attributable to the preservatives methyl- and propylparaben, as pure naloxone had no effect on either the baseline pulmonary vascular tone or the vasoconstrictive response to hypoxia. We conclude that opiate receptor agonists and antagonists do not affect vasoreactivity in the rat lung circulation and that the methyl- and propylparaben preservatives in Narcan are pulmonary vasodilators.

Angiotensin II↗
PubMed2000

The detection of circulating breast cancer cells in peripheral blood by reverse transcriptase-polymerase chain reaction.

Some circulating cancer cells in the blood play a central role in the metastatic process and may have a major influence on patient progress. Their numbers can be very small and techniques for their detection need to be both sensitive and specific. Polymerase chain reaction (PCR) has been successfully used to detect small numbers of tumor cells in cancer. We used a reverse transcriptase-polymerase chain reaction (RT-PCR) to detect circulating breast cancer cells in venous blood samples before operations and assessed cytokeratin-19 (CK-19) and cytokeratin-20 (CK-20) as target mRNA markers in the blood of healthy donors (n=6) and breast cancer patients (n=30) with American Joint Committee on Cancer stages 0 to IIIa. CK-19 mRNA was expressed in all blood samples of healthy donors and patients. But CK-20 was the only mRNA marker not detected in the blood from healthy donors. Seven of 30 (23%) venous blood isolates of breast cancer patients yielded a CK-20 mRNA with positive results. There was no correlating CK-20 mRNA expression with stage and axillary lymph node status. In conclusion, CK-19 showed no diagnostic value as a mRNA marker in the detection of circulating cancer cells by RT-PCR assay because this was expressed in the blood of healthy donors. CK-20 mRNA was an useful marker to detect circulating cancer cells in breast cancers.

Breast Neoplasms↗
PubMed2004

Detection of micrometastasis of gastric carcinoma in peripheral blood circulation.

AIM: To detect the micrometastasis of gastric carcinoma in peripheral blood circulation using immunomagnetic beads sorting technique and RT-PCR technique, and to discuss its significance and the difference between the two methods. METHODS: Density gradient centrifugation was used to isolate mononuclear cells from peripheral blood, immunomagnetic beads sorting technique and RT-PCR technique were used to detect the disseminated carcinoma cells. HE, immunocytochemical and immunofluorescence staining were also used to identify the characteristics of the cells separated with immunomagnetic beads sorting technique. RESULTS: Cells expressing cytokeratin were separated and enriched from the peripheral blood specimens of patients suffering from gastric carcinoma or chronic gastritis. After HE staining, two kinds of cells with little cytoplasm were found. Majority of these cells had small and round nuclei, even chromatins and the thickness of nuclear membrane was normal. Immunohistochemical staining indicated that there were CD34 and CD45 expression on the cell membrane of this kind of cells and these cells also showed expressed human telomerase reverse transcriptase by immunofluorescence staining, but the expression of carcinoembryonic antigen was absent. So, these cells might hematopoiesis precursors. Another kind of cells had larger and abnormal nuclei with thicker nuclear membranes. Massed chromatins and poly-nucleoli were found in the nuclei. These cells expressed human telomerase reverse transcriptase and carcinoembryonic antigen, but CD34 and CD45 were not found on the cell membrane. So, these cells were considered as gastric carcinoma cells escaping from the original focuses and existing in the peripheral blood circulation. Carcinoma cells were found in 25 of 60(41.7%) specimens of peripheral blood from patients with gastric carcinoma, while there were no such cells separated from the blood specimens of chronic gastritis patients. The difference of positive rates of disseminated carcinoma cells between two groups was markedly significant (P<0.005). The expressions of CK20 mRNA in peripheral blood specimens were examinated with RT-PCR. CK20 mRNA was detected from 32 of 60(53.3%) peripheral blood specimens in the group of gastric carcinoma patients, while none of the specimens from patients suffering from chronic gastritis had CK20 mRNA. Significant difference was also found between two groups (P<0.005). Statistic analyses also showed that there was a significant difference between the positive rates of two methods in detecting the disseminated carcinoma cells from the peripheral blood circulation of gastric carcinoma patients (P<0.05). CONCLUSION: The results demonstrated that there were disseminated carcinoma cells in the peripheral blood circulation of some patients with gastric carcinoma. Disseminated carcinoma cells can be detected from the peripheral blood samples with immunomagnetic beads sorting technique and RT-PCR technique. The positive rate of RT-PCR technique is higher than that of immunomagnetic beads sorting technique in detecting micrometastasis.

Carcinoma↗
PubMed2006

Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer.

PURPOSE: Development of targeted therapeutic agents in colorectal cancer (CRC) is impeded by the lack of a noninvasive surrogate of drug effect. This pilot study evaluated the ability of immunomagnetic separation to isolate circulating tumor cells (CTCs) and of the fluorescent microscope system and flow cytometry to enumerate and characterize CTCs from patients with metastatic CRC. PATIENTS AND METHODS: Fifty patients with metastatic CRC contributed 50 mL of blood at treatment initiation and disease evaluation timepoints. Fresh tumor specimens were obtained from 17 patients for comparison of circulating and in situ tumor cell characteristics. Epithelial cells were magnetically isolated from whole blood targeting the antiepithelial cell adhesion molecule (EpCAM). Circulating tumor cells were defined as EpCAM isolated, cytokeratin positive, nuclear stain positive, and CD45 negative. Total RNA was isolated from EpCAM-enriched CTCs and multigene reverse-transcriptase polymerase chain reaction analyses were performed. RESULTS: The median number of CTCs detected by flow cytometry was 2/7.5 mL blood. Mean change in cell count was significantly different for patients with tumor progression versus nonprogression (+6.7 vs. +0.2/7.5 mL; P = 0.001). A correlation was noted between mean fluorescence intensity (flow cytometry) of cytokeratin in CTC and matched tumor specimens (r = 0.79, P = 0.06). Nearly 80% (15 of 19) of samples with >or= 2 CTCs expressed >or= 1 epithelial marker gene (CK19, CK20, carcinoembryonic antigen, or epidermal growth factor receptor). CONCLUSION: Isolating and characterizing CTCs from patients with metastatic CRC is feasible. Change in the CTC number might reflect clinical status, and flow cytometric and gene expression data suggest similarity of circulating and in situ tumor cells. Further evaluation of CTCs for pharmacodynamic and clinical monitoring in patients with CRC is warranted.

Adult↗
PubMedDate not supplied

Detection of tumor-associated circulating mRNA in serum, plasma and blood cells from patients with disseminated malignant melanoma.

Reverse transcription polymerase chain reaction (RT-PCR)-based detection of tyrosinase mRNA is a frequently used method for the identification of circulating tumor cells in melanoma patients. The significance and practical value of this procedure for the diagnosis of tumor dissemination in melanoma patients are unclear. The conflicting results may at least partially be related to very low amounts of circulating tumor cells and to our observation that melanoma cells only transiently persist in the peripheral blood. The purpose of the present study was to evaluate the relevance of detection of extracellular melanoma-specific mRNA in serum and plasma samples in comparison to blood cell samples from patients with disseminated disease (stage IV). We therefore compared the presence of specific mRNA for tyrosinase, gp100, and MART-1 by RT-PCR amplification of specific cDNA from serum, plasma, and whole blood samples of 10 melanoma patients. Melanoma-specific mRNA was detectable in whole blood samples of all ten patients tested indicating the presence of circulating melanoma cells. In addition, tyrosinase mRNA could be detected in the serum and/or plasma of 6 of 10 melanoma patients whereas gp100 and MART-1 specific transcripts were not detectable in any of the samples tested. The presence and integrity of amplifiable RNA was shown in all serum and plasma samples of patients and controls by RT-PCR-specific amplification of porphobilinogen deaminase (PBDG) mRNA. We conclude that tyrosinase mRNA but not gp100 and MART-1 mRNA can be amplified from serum and/or plasma in a subset of melanoma patients showing circulating melanoma cells. Therefore, extracellular-directed assays appear to be less sensitive and efficacious in detecting melanoma-specific transcripts compared to cellular-based assays.

Adult↗
PubMed1991

Cerebral circulation demystified.

Basic anatomic and physiologic concepts related to cerebral circulation are summarized. The arterial blood supply is traced from its origins to the major divisions of anterior and posterior circulation. The circle of Willis, the major arterial vessels and territories, and the peculiarities of the cerebral venous circulation are discussed. Finally, concepts of cerebral circulations are applied to clinical practice to assist the nurse in accurately assessing, monitoring, and predicting human responses to alterations in cerebral blood supply.

Brain↗
PubMed2003

Detection of circulating melanoma cells by a two-marker polymerase chain reaction assay in relation to therapy.

Malignant melanoma is one of the most rapidly increasing cancer types, and patients with metastatic disease have a very poor prognosis. Detection of metastatic melanoma cells in circulation may aid the clinician in assessing tumor progression, metastatic potential, and response to therapy. Tyrosinase is a key enzyme in melanin biosynthesis. The gene is actively expressed in melanocytes and melanoma cells. Melan A is a differentiation antigen that is expressed in melanocytes. The presence of these molecules in blood is considered a marker for circulating melanoma cells. In this study, we analyzed the usefulness of this marker combination in evaluating the response to therapy in the blood of 30 patients with malignant melanoma. Circulating cells were detected by a reverse-transcriptase-polymerase-chain reaction. The tyrosinase expression was observed in 9 (30%) patients and Melan A in 19 (63.3%) patients before therapy. Following treatment, the tyrosinase mRNA was detected in only one patient, while Melan A transcripts were still present in 14 patients. We suggest that this molecular assay can identify circulating melanoma cells that express melanoma-associated antigens and may provide an early indication of therapy effectiveness.

Antigens, Neoplasm↗