Search

The serum level of a variety of substances shows significant changes in head and neck cancer patients. Such substances are collectively called biochemical tumor markers. To date, most markers lack a high degree of specificity and sensitivity. However, serial measurement of markers showing elevated pretreatment levels may help in monitoring response to therapy. Other potential uses of tumor markers include earlier detection of recurrence and/or metastasis, and possible prediction of prognosis. Measurement of more than one marker seems to enhance the diagnostic accuracy of the test. Some markers show significant correlations with various immune parameters in head and neck cancer patients and may have a possible role in potentiating the immunodepressed status of such patients. A review of currently reported tumor markers in head and neck cancer showing their nature, sources, uses, and limitations is presented.

In two siblings, children of non-consanguineous parents, glucosephosphate isomerase (GPI) deficiency was found to be the cause of recurrent haemolytic crises. Characterization of the variant enzyme found in both individuals revealed low specific activity in erythrocytes and leucocytes, increased electrophoretic mobility and pronounced thermolability. Evaluation of the electrophoretic data allows the conclusions that these siblings are compound heterozygous carriers of GPI deficiency. The new variant was designated GPI Calden. Further investigations revealed that isolated granulocytes of both siblings show marked reduction of bactericidal activity and decreased production of superoxide anion. With rare exceptions, deficiency of this enzyme was supposed to cause congenital nonspherocytic haemolytic anaemia only. Here we report on two siblings presenting with the characteristic haemolytic anaemia and a significant decrease in granulocyte function, both presumably as the result of GPI deficiency. Our data indicate that impairment of granulocyte function might be a more general feature of severe GPI deficiency than formerly noted.

This paper starts a series on red blood cell (RBC) metabolism in patients with chronic renal failure (CRF). The glycolytic enzyme levels and in vitro half-lives of these patients' RBCs were determined. A number of enzymes (hexokinase, glucose-6-phosphate isomerase, fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase) showed higher activities than in normal control RBCs. Other enzyme activities were normal. These results were discussed and several possible mechanisms considered. We favour the point of view of a shortened life span of the RBCs in CRF, making the most unstable enzymes of the glycolytic sequence appear increase as compared with normal controls.

In the field of oncology, the most important aim to date has been the finding of new means to improve the diagnosis and treatment of neoplastic diseases. Chronobiologically we have studied the behavior of phosphohexoseisomerase (PHI) in 11 multiple myeloma patients before treatment and in another group of 11 patients undergoing polychemotherapy treatment. From all patients, under the same standard conditions, 6 venous samples were taken at 4-hour intervals starting at 08.00 h, for a day. PHI serum levels were determined spectrophotometrically. The data obtained were analyzed by 'group mean cosinor' and from this analysis a mesor reduction of more than 50% was noted in subjects after polychemotherapy (M2) correlated with the absence of a circadian rhythm. The data suggest that PHI levels can be related to the characteristics of tumor growth and we feel they can be used as a guide in monitoring multiple myeloma patients.

A total of 3438 cord blood samples were screened for variants of erythrocyte glucose-phosphate isomerase. The five different electrophoretic, three activity/deficiency, and one thermostability variants distributed among 27 unrelated Caucasian families of that population, plus two electrophoretic variants previously described from three Amerindian tribes were subsequently examined for cryptic variation using activity and thermostability criteria. Although thermostability differences were observed between electrophoretic variants, no microheterogeneity within any one class of variant was detected.

Serum levels of phosphohexose isomerase (PHI), aldolase (ALD) and hexokinase (HK) activities have been determined in 76 patients of carcinoma cervix, in search of proper diagnostic and prognostic parameters. All the three glycolytic enzyme levels studied were found to be significantly elevated in all the groups of malignancy and showed a relation to the clinical stage and tumor. Serum PHI levels were of best diagnostic significance even at an early stage of the disease. The enzyme levels correlated well with the prognosis of the disease.

The diagnostic significance of three polyamines (putrescine, spermidine and spermine), of carcinoembryonic antigen and of phosphoglucose isomerase have been compared in sera of patients with breast cancer or benign breast disease and normal age matched controls. The results of the study indicate that the performance of spermine was more striking than that of any of the other markers. The estimation of spermine may prove to be a valuable parameter not only in detection but also in prediction of recurrence of the disease.

Transplacental passage of cells from mother to fetus during murine pregnancy was examined by using glucose phosphate isomerase (GPI) or fluorescein tagging as markers. Female mice of strains (BALB/cCr X C3H/HeJ)/F1 or (A/J X C57BL/6J)F1 (both Gpi-1a/b) were mated to the corresponding Gpi-la males (BALB/cCr or A/J, respectively). Cells of the liver, blood, and/or spleen in the offspring were typed at days 15, 16, 17, or 18 of gestation, the day of delivery, or 1 day postpartum. Only two of 172 Gpi-1a/a mice obtained from these matings showed evidence of maternal cell trafficking. Sensitivity of the assay was 1% Gpi-1a/a population. Fluorescein-labeled BALB/cCr peripheral red blood cells (RBC) or white blood cells (WBC) were injected i.v. into syngeneically mated BALB/cCr mothers on day 18. After 24 hr, the blood or liver of the neonates was formalin-fixed and examined in the fluorescence-activated cell sorter (FACS). Some RBC crossed the placenta, but WBC were usually not detected in fetal liver in significant numbers. This technique was very sensitive, and we estimated that no more than 225 WBC could enter the fetus via this route. Thus, we conclude that passage of significant numbers of maternal WBC into the fetus is rare, and perhaps this passage is related to a placental abnormality.

In a comparative study of A/J (Gpi-1a) and C57BL/6J (Gpi-1b) mice, we observed that erythrocytes of A/J mice exhibited significantly higher glucose phosphate isomerase (GPI) activity compared to erythrocytes of C57BL/6J mice on a per cell, per gram of protein, or per gram of hemoglobin basis. Higher GPI activity per cell was detected for peripheral blood lymphocytes of A/J compared to C57BL/6J mice. (A/J X C57BL/6J)F1 mice expressed erythrocyte and peripheral blood lymphocyte GPI activities intermediate to those of the parental mouse strains. The GPI activities of spleen lymphocytes from A/J, C57BL/6J, or (A/J X C57BL/6J)F1 mice were not significantly different from each other. The higher activity in the A/J mice could be due to GPI of a higher catalytic rate or to the presence of more GPI molecules. In order to distinguish these two possibilities, GPI was purified to homogeneity from both strains of mice. The specific activities (activity per milligram of protein) of the purified enzymes from the two strains were found to be similar, indicating that GPI from the A/J strain was not a more active enzyme. Antibody to the purified enzymes was prepared and used in an enzyme-linked immunosorbent assay (ELISA) to compare the relative amounts of enzyme molecules in cells of A/J and C57BL/6J mice. Results of the ELISA tests on peripheral blood lymphocytes indicated that A/J mice contain more molecules of GPI per cell and, therefore, have a higher GPI activity than C57BL/6J mice.

A total of nearly 1,000 persons belonging to a number of caste, religious and tribal groupings in Kerala and the Nilgiri Hills of South India have been tested for genetic variation in 4 blood group, 5 serum protein and 17 enzyme systems as well as haemoglobin. The distribution of blood groups, serum protein and enzyme groups is similar to that reported for other South Indian populations. Abnormal haemoglobins were detected in several populations. Abnormal haemoglobins were detected in several populations, HbS being present in more than 20% of the Irula and Kurumba in the Nilgiri Hills. In the Kerala populations there were 4 examples of Hb AD and 1 of Hb AE. Genetic distance estimates using the gene frequency data indicate that the closest groups are the Nayar and Izhava and the Brahmin and Nayar. The tribal populations are approximately twice as far from the Nayar as they are from the Izhava. The Todas of the Nilgiri Hills are somewhat closer to the Brahmin of Kerala than they are to the other tribal populations.

The assumption that human granulocyte-macrophage colonies have a unicellular origin and thus are true clones has been directly tested. Cells from seven females heterozygous for the common glucose-6-phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA were cultured in semisolid medium for granulocyte-macrophage colony growth and the enzyme type of individual colonies was determined. When the colony density was less than 20/dish, more than 95% of colonies had either type A or type B G-6-PD, but not both. At colony densities greater than 30/dish, between 15% and 75% of colonies had both enzyme types and therefore arose from more than one cell. These results are consistent with a unicellular origin for the colonies only when they are cultured at low densities. With increasing colony density, there was a greater frequency of colonies with both type A and type B activity, suggesting that accurate enumeration of committed stem cells can only be performed at low colony concentrations.

Studies of a Mexican kindred present evidence for a unique phenotype of erythrocyte glucosephosphate isomerase, GPI Valle Hermoso. The proband was apparently the homozygous recipient of a mutant autosomal allele governing production of an isozyme characterized by decreased activity, marked thermal instability, normal kinetics and pH optimum, and normal starch gel electrophoretic patterns. Unlike previously known cases, leukocyte and plasma GPI activities were unimpaired. This suggested that the structural alteration primarily induced enzyme instability without drastically curtailing catalytic effectiveness, thereby allowing compensation by cells capable of continued protein synthesis. Age-related losses of GPI, however, were not evident by density-gradient fractionation of affected erythrocytes.

A method is described in which the extent of myocardial infarction in man is assessed by mathematical analysis of the rise in plasma enzyme levels after infarction. Five enzymes are used in this study: lactate dehydrogenase (LDH); alpha-hydroxybutyrate dehydrogenase (alpha-HBDH); aspartate aminotransferase (GOT); creatine phosphokinase (CPK); and phosphohexoseisomerase (PHI). It is shown that a reasonable assessment of the total enzyme release, reflecting the extent of the infarcted area, can be made when a sufficient number of blood samples are taken after infarction. This could provide a method by which to judge therapeutic effects of intervention in the course of a myocardial infarction, as demonstrated in this study by the assessment of the effect of urokinase on the enzyme release after an infarct.

--The authors study in psoriasis an enzyme of the glucolytic way, the Phospho-hexose-isomerase. --They find significant high levels in blood and damaged skin, while these were "normal" in healthy skin. --Phospho-hexose-isomerase acts as a biological marker in psoriasis, and acquires the significance of an active cellular proliferation. --The highest values are those of the erythrodermaes which become normal with clinical involution. --The authors suggest that psoriasis, by an exaggerated cellular division inhibition mechanism, metabolism is deviated in order to bring the energetic elements and substrate to form the new cell. --Phospho-hexose-isomerase is not specific of the malignant process.

Blood samples wer collected from three populations of full-blood Aborigines, and twelve different enzymes were assayed in red blood cells. These results were compared with those of Caucasian controls. In the majority of enzymes studied significant differences were observed between the Aboriginal populations and also between individual Aboriginal populations and the Caucasian controls.

Of five glycolytic enzymes tested, only the serum activity of phosphohexose isomerase (PHI) was elevated in the vast majority of 140 patients with gastrointestinal, kidney or mammary carcinomas. However, in the tumor tissues all enzymes were increased to about the same extent. Thus, the measured increase in the serum activity of PHI is not due to a specific overproduction in the malignant cells. A general rise in the glycolytic enzyme activities in the malignant tissue could be detected already in early stages without metastases and in well-differentiated tumors.

The levels of serum acute phase reactant proteins (APRPs) have been examined in untreated kidney carcinoma and during the evolution of metastases. These proteins can provide a warning of the likelihood of extensive local or metastatic spread at first presentation. The levels of APRPs rise with increasing tumour burden but the system is insensitive to small tumour burdens. beta 2-Microglobulin levels do not contribute additional information. Serum phosphohexose isomerase tends to be elevated when there is a large tumour burden but its change does not accurately mirror the rate of expansion of the tumour. The APRPs and phosphohexose isomerase are useful in alerting the clinician to the probability of metastases or large local masses in kidney cancer, but have a limited use in monitoring.

It was the aim of this study to evaluate the clinical significance of the monoclonal test system CA 125 in comparison to 7 conventional laboratory procedures (TPA, PHI, CEA, LDH, GGT, AP, ESR) as tumour marker in ovarian cancer. Serum samples from 327 patients with histologically proven cancer of the ovary were analysed. Marker results were correlated to tumour activity as defined by the criteria of the UICC. Furthermore, in 175/327 patients who were clinically symptom-free after primary therapy, marker courses were analysed with regard to the development of recurrence. Positive rates and median values of CA 125, TPA, PHI and ESR showed significant increases with progression of the disease, whereas correlation was less clear-cut with CEA, LDH, GGT and AP. In clinically tumour-free patients without evidence of recurrence during the further course, intermittent increases of PHI, ESR and especially TPA were found in 19-47%. However, such "false positive" marker courses were not seen with CA 125. Those patients who developed recurrent disease exhibited increasing CA 125 titres in 68%. The incidence of such "true positive" markers courses was less frequent with PHI, ESR and TPA. Our results indicate that CA 125 and--with limitations--TPA, PHI and ESR may be used in ovarian cancer control. When monitoring tumour-free patients, CA 125 exhibited the highest specificity and sensitivity. Using 65 U/ml as cut-off, a positive CA 125 titre indicates recurrent disease with great certainty. When employing PHI, ESR and especially TPA, however, the possibility of "false positive" increases has to be taken into account.(ABSTRACT TRUNCATED AT 250 WORDS)

Significant differences in the thermostability of both glucosephosphate and triosephosphate isomerase were noted among a series of six primate and five nonprimate species. The enzyme structural differences among species, as assessed by thermostability profiling, was greater than expected from electrophoretic mobility patterns. Microheterogeneity of GPI, i.e. differences in thermostability within a species that are not detectable by electrophoresis, was detected in two primate species. Major differences in the levels of erythrocyte enzyme activity were observed with human and cow differing by 18-fold for TPI and baboon and cow differing by seven-fold in GPI activity.

Blood from 10 normal healthy adults and cord blood from 8 healthy full term infants were infiltrated through a mixture sulfoethylethycellulose-Sephadex G 25 in order to eliminate the platelets and the leukocytes. Then the erythrocytes were fractionated into young and old cells by centrifugation in microhematocrit tubes. The enzyme activity and the immunologic reactivity of glucose phosphate isomerase (EC.5.3.1.9), phosphoglycerate kinase (EC.2.7.2.3), pyruvate kinase (ec.2.7.1.40), glucose 6-phosphate dehydrogenase (EC. 1.1.1.49), and 6-phosphogluconate dehydrogenase (EC.1.1.1.44) were measured in every fraction. As previously reported, the enzyme activities were far higher in cord blood than in adult blood red cells; nevertheless, the age-related loss of enzyme activity was similar in both cord and adult blood. The decrease of the enzyme activity of glucose phosphate isomerase and phosphoglycerate kinase in old cells was singly associated with a lowered concentration of the enzyme-related antigen; by contrast, the age-related decrease of the enzyme activity of pyruvate kinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase was associated with both a lowered concentration of the enzyme-related antigen and a lowered "molecular specific activity" (i.e., a lowered ratio of enzyme activity to enzyme-related antigen concentration). This phenomenon was especially marked for pyruvate kinase, which had a molecular specific activity in old cells that was 68% of that in young cells. Phosphofructokinase had a lower enzyme activity in cord blood erythrocytes than in adult blood erythrocytes; the difference was especially important in old cells from infants in which phosphofructokinase activity was 53% of that in old cells from adults. Phosphofructokinase from old cells of full term infants and from unfractionated cells from two premature infants (21 and 32 weeks of gestation) was less neutralized by anti-muscle phosphofructokinase serum and more inhibited by ATP than the enzyme from adult blood erythrocytes.

The effects of experimental anaemia on the levels of reduced glutathione (GSH) and the activity of glycolytic enzymes in the erythrocytes of normal and GSH-deficient Merino sheep were investigated. There was a rise in red cell GSH levels in both groups of sheep; the magnitude of this response was, however, quite different. When expressed as a percentage of the initial value, the rise in GSH level was 18% in normal and 263% in GSH-deficient animals. There was also an increase in the activities of various enzymes following phlebotomy but this increase was similar in the two groups of sheep.

Serum levels of fucosyltransferase (FT), phosphohexoseisomerase (PHI), tissue polypeptide antigen (TPA), Tennessee antigen (TAG), carcinoembryonic antigen (CEA) and prostatic acid phosphate (PAP) were determined in 75 healthy individuals and in 86 patients with prostatic carcinoma and 38 patients with bladder tumors. The discrimination capacities of the different markers were compared by using inverse distribution plots. At a rate of 5% false positive values the sensitivities for bladder tumors were: FT 30%, TPA 24%, CEA 16%, TAG 15%. The sensitivities for prostatic carcinoma were: PAP 63%, PHI 36%, TPA 18%, CEA 14%, TAG 14%.

The purpose of this study was to reevaluate the significance of serum PHI in gastrointestinal cancer at histopathologically defined stages prior to primary treatment. A total of 248 patients with malignant tumors of the gastrointestinal tract and a collective of 42 patients with noncancerous diseases were studied. The results are compared with those obtained with the established markers tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA). Phosphohexose isomerase (PHI) revealed an overall diagnostic sensitivity of 69%, combined with a specificity of 74%. The corresponding data for TPA were found to be 73 and 47% while for CEA 26 and 95% respectively were determined. Even in the early stages of colorectal and esophageal carcinoma, PHI showed a sensitivity of about 60%. A continuous rise of PHI serum levels, correlating well with the extent of the tumor disease, could be detected. In contrast to TPA and CEA, PHI assay can be carried out with a minimum of laboratory efforts, in a short time and at low costs. These findings suggest that serum PHI assay is a useful aid for screening of gastrointestinal cancer, especially esophageal and gastric carcinoma, and a reliable marker for treatment control and follow-up.

The present study was designed to test if both the intensity and duration of the 45-min Square-Wave Endurance Exercise Test (SWEET) would produce changes in serum enzyme activities. Nine men, four sedentary (S) and five athletes (A), performed VO2 max and SWEET, at their Maximal Intensity of Endurance (MIE45) as defined by maximal heart rate and the impossibility of maintaining MIE 45 + 5% for 45 min. Arterial blood was sampled at rest (R), exercise (Ex) (45th min) and during recovery (15th min) for measurements of levels of Haemoglobin (Hb), Haematocrit (Hct), pH and seven serum enzymes: Creatine kinase (CPK), Hexose-phosphate isomerase (PHI), Aldolase (ALD), Lactate dehydrogenase (LDH), Malate dehydrogenase (MDH), Aspartate amino-transferase (ASAT or GOT), and Alanine aminotransferase (ALAT or GPT). Five enzymes increased significantly during exercise (MIE45), the delta % (Ex - R/R) increases were as follows: PHI (72%), MDH (28%), LDH (21%), CPK (17%), and GOT (13.5%), whilst only a 10% increase was observed for Hct and Hb and there was no significant change in the arterial pH. There was no correlation between the delta % of Hb, Hct, pH, and the results for the enzymes. Thus, it does not seem that haemoconcentration and arterial blood acidosis which occur during exercise are only at the origin of the observed increases in enzymes. A difference between "sedentary" and "athletes" subjects was found at rest and exercise (delta % = A - S/S) for CPK (R = 222%; Ex = 235%), GOT (R = 90%; Ex = 75%) and ALD (R = 99%; Ex = 54%). These results suggest that the MIE45, by measured increases in enzymatic activity, seems to require great muscular effort.

Nucleoside phosphorylase activity was assayed in two previously reported patients with trisomy for the proximal portion of 14q. A sesquialter dosage effect was demonstrated in erythrocytes as well as in leucocytes. These results are in favor of an ubiquitous expression of the gene and confirm its assignment to 14q13.

Glucose phosphate isomerase reaction was shown to be important in turnover of fructose-6-phosphate in extracts of human thrombocytes as a result of deterioration of glycolytic process. Effect of fructose-6-phosphate concentration on its consumption and on formation of glucose-6-phosphate was studied. Alterations in content of fructose-6-phosphate and glucose-6-phosphate in presence of various NADP concentrations were estimated.

Effect of therapeutic doses of alpha-tocopherol (50 mg) exceeding 10-12-fold the daily consumption of the vitamin, on glycolysis was studied in erythrocytes of rats maintained on a usual diet. After loading of the animals with tocopherol utilization of glucose was increased 2.4-fold, with simultaneous activation of aldolase and phosphohexoisomerase by 34% and 48%, respectively; content of lactate was increased by 40%.

The enzyme activities of Lactate dehydrogenase (LDH). prostate fluid LDH isoenzymes phosphohexose isomerase (PHI), Aldolase (ALD) and Hexokinase (HK) were determined in the sera of 77 samples of males. There were 12 cases of carcinoma prostate with metastases, 15 without metastases, 25 with benign prostatic hypertrophy and 25 nontumor. The enzyme activities of nontumor and benign group were statistically similar. The prostatic fluid LDH5/LDH1 ratio and PHI has been found to be the most sensitive parameter for detecting carcinoma prostate. Serial determinations of LDH, PHI, ALD and HK were found valuable for following the course of the disease during therapy.

A 58-year-old white male with a history of bronchogenic carcinoma presented with a total retinal detachment overlying a choroidal metastasis. His main tumor burden had been extirpated by pneumonectomy followed by radiation therapy four months prior to admission. With the development of a painful, glaucomatous eye, unresponsive to conventional therapy, enucleation was performed. Histologic examination of the enucleated globe revealed a metastatic tumor to the choroid, consistent with primary bronchogenic carcinoma. Aqueous humor and plasma examination revealed elevated ratios (Aqueous humor:Plasma) of lactate dehydrogenase (LDH) and phosphoglucose isomerase (PGI). Furthermore, subretinal fluid examination demonstrated concentrations of LDH and PGI higher than aqueous humor. While the level of carcinoembryonic antigen (CEA) in the plasma was normal (less than 2.5 ng/ml) following pneumonectomy, it was 121 ng/ml in the subretinal fluid. This would suggest that a choroidal lesion alone, in the absence of a clinically detectable primary tumor, is insufficient to elevate the plasma CEA.

Resorption of petrotic bone in osteopetrotic (mi/mi) mice was brought about by transplantation of bone marrow to X-irradiated recipients. In an attempt to learn more about the donor cell line involved in this process, both normal and defective marrow were used. The consequent repopulation of the lympho-myeloid complex was monitored by isoenzymes of glucose phosphate isomerase. The progress of normal marrow grafts was contrasted with that of a defective marrow (We/Wv). Despite the observation with We/Wv marrow showed reduced ability to form colonies in the spleen of an irradiated recipient, this marrow was as effective as normal marrow in inducing resorption of petrotic bone. The primordial stem cell for the osteoclast (haematopoietic stem cell?) is thus not a CFUS. Chimaeras with resolution of osteopetrosis by We/Wv bone marrow may exhibit erythropoiesis from residual stem cells of the host but leucocytes and platelets from the donor.

Mouse blastocysts were microsurgically injected with embryonal carcinoma cells from in vitro teratocarcinoma cell lines C17, C86, SIKR-OSB, and PCC3/A/I. The embryos were allowed to develop to term and the resulting offspring were analysed for chimaerism using coat colour markers and isozyme differences of the enzyme glucose phosphate isomerase. When injected into blastocysts, cell line C86 produced tumours in six of 74 animals born. The tumours were detected at birth and were poorly differentiated neuroectodermal teratocarcinomas. Cell line C17 gave 13 chimaeras in 77 mice born, five of which showed chimaerism only in normal tissues, mainly melanocytes of the coat and eye. The other eight chimaeras developed tumours. Seven of these developed in adult animals and were mainly fibrosarcomas. Cell line SIKR-OSB resulted in one normal chimaera in 44 mice born. Of 86 animals born following injection of cell line PCC3/A/1, there was one chimaera with a small tumour and three normal chimaeras. The levels of chimaerism were generally very low. The mice were test bred but with no evidence of germ line chimaerism. The karyotypes of all the cell lines were abnormal. How this and other factors such as cell cycle times might affect the incorporation of embryonal cells into the developing embryo is discussed.

Intracellular activities of total lactic dehydrogenase (LDH) and phosphohexose isomerase (PHI) were investigated in the leukaemic cells of 14 patients with acute myeloid leukaemia (AML), five with chronic myeloid leukaemia (CML), seven with acute lymphoblastic leukaemia (ALL), 19 with chronic lymphocytic leukaemia (CLL), 16 with leukaemic non-Hodgkin's lymphoma (NHL) and in the lymphocytes of 14 normal persons. Intracellular total LDH-activity of the blasts of AML and ALL was in the same range as the normal lymphocytes. Patients with CLL and NHL had significantly lower levels (P less than 0.01) of total intracellular LDH than the controls. Intracellular PHI activity was consistently lower in the lymphoid malignancies (ALL, CLL, NHL) than in normal lymphocytes (P less than 0.05), or in leukaemic myeloblasts (P less than 0.01). The intracellular LDH/PHI index of the leukaemic lymphoblasts was significantly elevated as compared to lymphocytes from normal subjects (P less than 0.0001) or to leukaemic cells from patients with AML (P less than 0.001), with CLL (P less than 0.0001) or with NHL (P less than 0.001). The patients with CLL and NHL, on the other hand, had significantly lower levels of LDH/PHI ratio than the normal subjects (P less than 0.0001 and P less than 0.025 respectively).

Many biological substances are commonly used as markers for malignant neoplasms, but no single marker with high specificity and sensitivity has been found for cancer to date. In this study we evaluated simultaneously the serum levels of five biomarkers of malignancy: phosphohexose-isomerase (PHI), creatine kinase isoenzyme BB (CK-BB), alpha 1-acid glycoprotein (AAG), beta 2-microglobulin (BMG), and ferritin. In 89 female patients with breast lesions, we identified 30 benign lesions, 32 primary breast cancers, and 27 metastatic breast cancers (pulmonary and/or bone metastases). Each marker was assayed individually and in a combination and was compared with other markers. The results revealed that in benign lesions only 7% had PHI values higher than our cut-off limit value, while 3% had elevated values of AAG, BMG, and ferritin. In primary breast cancer we discovered pathological values of CK-BB and AAG in 71%, of PHI in 69%, of BMG in 50%, and of ferritin in 47%. Metastatic disease was associated with elevated values in 88% of CK-BB, in 70% of PHI and AAG, and in only 55% of BMG and ferritin. Combined pathological values for primary and metastatic breast cancer were 79% for CK-BB, 71% for AAG, 70% for PHI, and only 55% for BMG and ferritin. These data were assessed by the Student t test, which revealed for each marker a significant capacity (P less than 0.01) to discriminate between benign lesions and neoplastic diseases. The same capacity to distinguish between primary and metastatic cancer was obtained by the simultaneous use of three markers (CK-BB, PHI, and AAG).(ABSTRACT TRUNCATED AT 250 WORDS)