Bioequivalence of two oral formulations of clopidogrel tablets in healthy male volunteers.

A randomized, two-way, crossover, bioequivalence study in 32 fasting, healthy, male volunteers was conducted to compare two brands of clopidogrel 75 mg tablets, Thrombo (EIPICO, Egypt) as test and Plavix (Sanofi Pharma/Bristol-Myers Squibb, Paris, France) as reference. The study was performed in a Pharmaceutical Research Unit (PRU) using HPLC/ MS-MS. Arithmetic means for clopidogrel test versus reference formulation, respectively were for Cmax (4.39 +/- 2.58 vs. 4.30 +/- 2.65) ng/ml, AUC0-t (11.98 +/- 9.82 vs. 12.01 +/- 9.46) ng.h/ml, AUC0- yen (12.43 +/- 9.94 vs. 12.49 +/- 9.58) ng.h/ml, t1/2 (6.06 +/- 3.87 vs. 5.87 +/- 2.47) h and the medians for tmax (1 h vs. 0.75 h). Arithmetic means for clopidogrel carboxylic acid metabolite were Cmax (3.75 +/- 1.19 vs. 3.51 +/- 0.97) microg/ml AUC0-t (9.18 +/- 2.36 vs. 9.17 +/- 2.06) microg.h/ml, AUC0- yen (9.72 +/- 2.4 vs. 9.80 +/- 2.21) microg.h/ml , and t1/2 (6.43 +/- 3.52 vs. 6.33 +/- 1.71) h for test versus reference formulation respectively and there was no difference in the medians for tmax (0.75 h). The parametric 90% confidence intervals for the mean of the difference between log-transformed values were within the accepted range for bioequivalence of 80 - 125% as proposed by the US-FDA , namely for clopidogrel (90.66% - 109.66%), (90.63% - 109.73%), and (93.19% - 115.37%) for AUC0-t, AUC0- yen, and Cmax, respectively and also for clopidogrel carboxylic acid metabolite (94.90 - 104.19) , (94.04 - 103.86) and (96.47 - 114.79) for AUC0-t , AUC0- yen, and Cmax, respectively. Thus there was no significant difference between these values and therefore the two products can be considered bioequivalent.

Luminoimmunometric assay of tissue polypeptide antigen (TPA) and cancer antigen 125 (CA-125) in breast cancer patients.

Serum TPA and CA-125 were determined in 86 individuals (66 with breast cancer representing the different stages and grades of the disease and 20 normal healthy controls). TPA and CA-125 were estimated using the LIA reagents supplied by BYK Sangtec. TPA showed sensitivity rates of 31.8%, 42.4% and 51.5% while CA-125 showed sensitivities of 16.3%, 18.6% and 25.6% at specificity levels of 100%, 95% and 90% respectively. Combined determination of the two markers resulted in some improvement in sensitivity. For follow-up of breast cancer patients after surgery both markers were of value and showed near-identical patterns.

Clinical value of thymidine kinase and tissue polypeptide specific antigen in breast cancer.

Thymidine kinase (TK) and tissue polypeptide specific antigen (TPS) were determined in breast cancer (BC) patients (n = 83), normal healthy women (n = 30) and 18 women with different benign mastopathies. Mean serum levels of TK and TPS in BC patients showed significant increases from their corresponding levels in healthy women and those with benign breast diseases. Diagnostic sensitivity of TK and TPS was 47% and 58% respectively at the selected cut-off values 8 U/L for TK and 110 U/L for TPS (96% specificity). Pre-operative serum levels of TK and TPS showed significant correlation with the stage of disease and with other classical prognostic factors; clinical stage, tumour size, lymph node involvement and distant metastasis. Nineteen BC patients were followed-up by serial monthly measurements of TK and TPS (4-10 samples). Both markers seemed to be valuable in monitoring drug efficacy. TK and TPS were able to detect systemic recurrence before clinical diagnosis (average 2 months lead time). TPS was greatly affected by liver diseases.

Elevated plasma level of leukotrienes in bronchial asthma patients: a possible clinical relevance.

Plasma from bronchial asthma patients and healthy controls was investigated for the content of lipoxygenase products. After lipid extraction using SEP-PAK C18 Cartridges, the lipoxygenase products were measured by Enzyme-Immunoassay. Elevated chemotactic B4 was found in plasma from asthmatic patients with mean value (483 +/- 75) pmol/L, while the mean value in normal healthy donors was (140 +/- 12.1) pmol/L (M +/- SE). The levels of spasmogenic cysteinyl containing leukotrienes were also very high in the bronchial asthma patients. Elevations of leukotriene B4 and cysteinyl containing leukotrienes were detected during attacks of bronchial asthma. These results suggest that leukotriene B4 may be important in the pathogenesis of bronchial asthma and confirmed that peptidoleukotrienes play a role as chemical mediators during the asthmatic attack.

Urinary beta-HCG in benign and malignant urinary tract diseases.

Detectable levels of HCG have been reported in conditions other than normal pregnancy, including threatened abortion, ectopic pregnancy, trophoblastic tumors, carcinomas of the stomach, liver, pancreas and breast as well as multiple myeloma and melanoma. The present study was conducted to estimate urinary beta-HCG in bladder cancer and benign urinary tract disorders. 163 individuals were included, 68 with bladder cancer (60 males and 8 females), 64 with benign urinary tract diseases (55 males and 9 females) and 31 normal healthy controls (26 males and 5 females). Urinary beta-HCG was estimated by the ELISA technique using the reagents supplied by DRG International Inc., Germany. Results of the study revealed an overexpression of beta-HCG in malignant and benign urinary tract diseases. 60.3% of the cancer patients and 29.7% of patients with benign diseases showed urinary beta-HCG values above the upper limit of the control group (2mIU/ml).

Cathepsin-D and TNF-alpha in bladder cancer.

In a study of 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 of them are operable cases and 31 are non-operable ones), serum tumor necrosis factor alpha (TNF-alpha) and cytosolic Cathepsin-D were estimated. Though both potential markers were elevated in bladder cancer patients, neither Cathepsin-D nor TNF-alpha showed associations of prognostic value since there were no positive correlations with tumor stages, grades or association of tumors with bilharzial ova or lymph node involvement.

Clinical value of squamous cell carcinoma antigen (SCC-A) in Egyptian gynecologic cancer patients.

Squamous cell carcinoma (SCC) antigen levels were measured by immunoparticle assay (IMx) in the sera of 32 patients with gynecologic malignancies, 15 with benign diseases of the genital system and 14 normal healthy controls. At a cut-off value of 4.8 ng/ml (100% specificity), the rate of SCC antigen elevation was 100% in vulvar and vaginal cancer (n = 5), 90% in ovarian cancer (n = 10), 60.0% in endometrial cancer (n = 10) and 57.2% in cervical cancer (n = 7). The benign disease's group had 80.0% false positivity at the same cut-off value. Serum SCC-A was found to correlate directly with the clinical stage of disease. A sensitivity of 73.3% was obtained at stage I which gives SCC-A a role in screening the high risk population for gynecological cancer. Concerning the histopathologic type of tumor, serum SCCA was highly sensitive in SCC tumors, in ovarian serous cystadenocarcinoma and in patients with recurrent ovarian cancer.

Epidermal growth factor receptors: status and effect on breast cancer patients.

The predictive potential of Epidermal Growth Factor Receptor (EGFR) is still a matter of debate. EGFR was quantified biochemically using an enzyme immunoassays malignant and normal tissues from the same breast (n = 94) as well as benign mastopathies (n = 40). The mean level of EGFR in malignant tissues showed a significant decrease from the control and benign ones with a weak positive correlation existing between EGFR level in malignant and control tissue of the same breast. Statistically, no cut-off line could be drawn between malignant and non malignant tumors due to the large overlap in their values. On the contrary to reports on EGFR, when the patients were classified according to the relative changes in EGFR from malignant and adjacent tissue, patients with a relative EGFR decrease (negative EGFR) in malignant tissue showed the poorer prognosis in short term follow up. Mean EGFR values in malignant or normal tissue, or the difference between them, did not show any significant correlation with the age of the patients, menstrual status, clinical stage, type and grade of the carcinoma and lymph node involvement. The present work showed also an inverse correlation between EGFR and Estrogen Receptor (ER) level in the malignant tissues.

Granulocyte-macrophage colony stimulating factor and interleukin-6 enhanced white blood cell synthesis of leukotrienes in chronic myelogenous leukemia.

The effect of Granulocyte-Macrophage, Colony Stimulating Factor (GM-CSF) and Interleukin-6 (IL-6) on leukotriene production by CML white blood cells induced by calcium ionophore (A23187) was investigated and the leukotrienes formed were identified and quantified using high performance liquid chromatography (HPLC). The in vivo levels of IL-6 and LTB4 were determined by enzyme immunoassay reagents, while GM-CSF was measured by enzyme amplified sensitivity immunoassay. Although GM-CSF or IL-6 alone did not stimulate the synthesis of 5-lipoxygenase product, preincubation of the white blood cells of CML with GM-CSF or IL-6 for 30 minutes at 37 degrees C enhanced the ionophore A23187 induced leukotrienes synthesis, thus the CML white blood cell suspension primed with GM-CSF or IL-6 produced 26.6 +/- 2.8 and 18.9 +/- 1.3 pmol LTC4/10(6) cells respectively, and 30.2 +/- 3.6 and 25.5 +/- 2.5 Pmol LTB4/10(6) cells. In contrast minute amount of leukotrienes were produced by the control cells. In vivo levels of GM-CSF, IL-6 and LTB4 were investigated in CML and normal healthy donors, elevated chemotactic B4 was found in plasma from CML (267 +/- 70.4) while the mean value in normal healthy donors was (127 +/- 13.6) pg/ml. The plasma level of GM-CSF was 32.4 +/- 15.7 pg/ml and 10.5 +/- 3.1 pg/ml respectively in CML and normal healthy donors, while the mean value of GM-CSF and IL-6 in normal healthy donors were 6.7 +/- 2.2 and 4.9 +/- 2.4 pg/ml respectively. No significant correlation was observed between the level of LTB4 and the level of GM-CSF or IL-6 in CML.

The clinical value of CYFRA21-1 in bladder cancer patients: Egyptian experience.

There are a wide variety of tumor markers now available that proved to be of value in the management of cancer patients. Of these markers, tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS) are well known in the field of bladder cancer. TPA was found to be a mixture of cytokeratins 8, 18 and 19 and recent investigations proved that TPS is keratin 18. The aim of the present study was to assess the clinical value of urinary cytokeratin 19 (CYFRA21-1) in the differential diagnosis between bladder cancer and benign urinary tract diseases represented by bilharziasis. Two hundreds and seventy individuals were included in the present study: 186 with bladder cancer representing the different stages and grades, 44 with urinary tract bilharziasis and 40 normal healthy controls. CYFRA21-1 was evaluated in 24-hour urine samples by ELISA using the automatic set supplied by Boehringer Manheim, Manheim, Germany (ES 300). Results of this study revealed significant elevation of CYFRA21-1 in bladder cancer followed by bilharziasis. 82.3% (153/186) of bladder cancer patients and 11.4% (5/44) of bilharzial patients exhibited CYFRA21-1 levels above the upper limit of the control group (3 micrograms/24-hr). CYFRA21-1 was more sensitive in advanced than early stages of bladder cancer and in patients with positive than those with negative lymph nodes, but association of tumor with bilharziasis did not markedly affect its level.

UGP in urogenital disorders: Egyptian experience.

UGP (Urinary gonadotropin peptide) also know as urinary gonadotropin fragment (UGF) or the beta-core of hCG (c beta hCG), was identified as a peptide with a molecular weight of 10.5 kD, having the same amino acid sequence as the core section of the beta-subunit of human chorionic gonadotropin. UGP has been found in normal pregnancy urine as well as in the urine of patients with gestational trophoblastic and non-trophoblastic malignancies. The aim of the present work was to investigate the clinical value of UGP in Egyptian patients with urogenital disorders. The study included 793 cases (462 males and 331 females) classified into 5 groups: 277 with bladder cancer, 121 with benign urinary tract disorders, 27 with different gynecological malignancies, 53 with benign gynecological disease and 315 apparently healthy individuals as a control group. The normal females included 88 premenopausal and 71 postmenopausal women. UGP was determined in 24- hour urine samples from all cases, and in morning urine samples from 151 subjects by ELISA technique using the reagents supplied by Ciba Corning Diagnostics, CA, USA (Triton UGP - EIA). The results of this study revealed significant elevation of UGP in cancer patients when compared to either normal controls or patients with benign diseases. Females in the control and benign diseases groups expressed higher UGP values than males and UGP in postmenopausal women was significantly elevated when compared to premenopausal control females. A a tumor marker, UGP was more sensitive and more specific in bladder than in gynecological cancer. A significant correlation (r = 0.934) was obtained between UGP levels in 24-hr and morning urine samples.

Tissue and serum c-erbB-2 and tissue EGFR in breast carcinoma: three years follow-up.

Amplification of erbB-1 and c-erbB-2 genes has been shown in human breast cancer. Expression of these protooncogenes results in production of epidermal growth factor receptor (EGFR) and c-erbB-2. Both are transmembrane receptors with tyrosine kinase activity. Recent data have indicated that the external domain of c-erbB-2 is shed into the culture supernatant of certain breast cancer cell lines and sera of breast cancer patients. A body of literature has shown that the overexpression of these receptors in malignant tissue and c-erbB-2 when shed into serum is associated with bad prognosis. In the present work, tissue EGFR and c-erbB-2 were determined in the membrane fractions of histopathologically verified malignant and normal tissues from the same breast of 94 patients. These values were also determined in 48 tissue specimens of benign mastopathies. Serum c-erbB-2 was quantified in breast cancer patients (n = 105), patients with benign breast disease (n = 48) and 30 apparently healthy women as controls. Patients were followed up by determination of serum c-erbB-2 for one year and clinically for three years to detect any distant metastasis or recurrence. The levels of tissue and serum c-erbB-2 and Estrogen receptors were significantly higher in the carcinomas and sera of breast cancer patients than benign breast diseases or normal controls. Follow-up, although short, of pre-operative serum c-erbB-2 showed a prognostic value (P = 0.007) better than that of tumor size (P = 0.04), EGFR (P = 0.18), nodal involvement (P = 0.25) and tissue c-erbB-2 (P = 0.85). The shedding of soluble fragments of c-erbB-2 into the serum seems to be a characteristic of the potentially malignant cell. The EGFR mean level, however, was significantly lower in malignant tissues than benign and normal ones. A new definition of EGFR status was developed. Accordingly, the recurrence of the disease was more frequent among patients with negative EGFR. The present work did not reveal any correlation between tissue, serum c-erbB-2 or EGFR on one hand and age, menopausal status, stage, histological type and grade of carcinomas and nodal involvement on the other hand. The present work showed an inverse correlation between estrogen receptor level and level of EGFR in malignant tissues.

The clinical value of cathepsin-D and TNF-alpha in bladder cancer patients.

This study included 34 normal healthy controls, 35 patients with urinary tract bilharziasis and 93 bladder cancer patients (62 were operable cases and 31 non-operable). Serum tumor necrosis factor alpha (TNF-alpha) was determined using the enzyme immunoassay reagents supplied by Medgenix Diagnostics, Belgium. Cytosol Cathepsin-D was estimated using the immunoradiometric assay supplied by CIS BIO International, France. The results revealed that at 100% and 90% specificities, cytosol Cathepsin-D had 35.7% and 59.5% sensitivity in bladder cancer patients. Serum TNF-alpha showed sensitivity of 17.0% and 55.0% at 100% and 90% specificities in operable bladder cancer patients and 48.0% and 77.0% in non-operable cases respectively. Cytosol cathepsin D and TNF-alpha did not show prognostic values like positive correlation with tumor stages, grades or association of tumors with bilharzial ova or lymph node involvement.

Multivariate analysis of bcl-2, apoptosis, P53 and HER-2/neu in breast cancer: a short-term follow-up.

BACKGROUND: Several molecular genetic alterations in breast cancer, including aneuploidy, altered apoptosis, aberrant expression of p53, HER-2/neu and Bcl-2, have been associated with poor prognosis in breast cancer patients. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathological prognostic factors, multivariate analysis was performed. PATIENTS AND METHODS: Ninety-four fresh tissue samples of primary breast carcinoma were studied with flow cytometry for DNA ploidy. On the same specimens, steroid hormone receptors (ER and PR) were measured in the cytosol fraction using Abbott ELISA assays. HER-2/neu was determined in the membrane fraction and mutant p53 protein in the nuclear fraction, both, by Oncogene Science ELIZA procedures. Bcl-2 and apoptosis (cell death) were measured in cell lysates by Oncogene Science & Boehringer Mannheim ELISA assays. In addition, information regarding surgical-pathological features of the tumor was obtained. Multivariate analysis using an unconditional logistic regression model was done to identify variables predictive of poor prognosis. RESULTS: Using univariate analysis, histological grade, tumor stage, lymph node status, HER-2/neu and mutant p53 were predictive of poor short-term prognosis. By multivariate analysis, tumor stage, lymph node status and HER-2/neu were independent factors. Grade subgroup analysis versus time of relapse, illustrated a predictive value of Bcl-2 in only low-grade tumors while apoptosis was significant in high-grade type. CONCLUSION: Among a panel of molecular-genetic factors investigated, HER-2/neu was the most strongly predictive of poor short-term prognosis in breast cancer. Patients with HER-2/neu-positive tumors can benefit from Herceptin therapy.

Comparative study between sonography, pathology and UGP in women with perimenopausal bleeding.

Adenocarcinoma is the commonest primary malignancy encountered in the endometrium. Adenomatous hyperplasia represents an important precancerous endometrial lesion. In this study, different techniques have been applied in a trial to early detect endometrial carcinoma and to distinguish between hyperplasia with minimal and high risk of progression to endometrial adenocarcinoma. Eighty women were included in this study and classified into 4 groups: 10 with adenocarcinoma, 28 with simple hyperplasia, 12 with hyperplasia with atypia and 30 normal healthy women. All individuals were subjected to Doppler endovaginal ultrasonography (EVS) for endometrial thickness and uterine artery resistance index (RI). Endometrial biopsy was taken for histopathological examination and DNA analysis. 24-hr urine was collected for the estimation of UGP by ELISA using reagents supplied by Ciba Corning Diagnostica, Alameda, CA, USA (Triton UGP-EIA). On referring to histopathological findings, no single parameter was seen to be specific and sensitive enough to differentiate between benign and malignant endometrial lesions. Doppler endovaginal ultrasonography could detect 76% of endometrial abnormalities. DNA ploidy and UGP showed equal sensitivity rate (60%) in endometrial carcinoma but DNA ploidy was more specific than UGP (0% and 10% false positivity in benign endometrial diseases respectively.

Diagnostic value of urinary molecular markers in bladder cancer.

OBJECTIVES: In an attempt to find a more sensitive and specific non-invasive diagnostic assay for the detection of bladder cancer cells, the authors assayed the exfoliated cells from patient's voided urine and bladder washing fluids for the presence of telomerase, an enzyme that maintains a cell's chromosomal length, metalloproteinase-9 (MMP-9), which has been associated with tumor cell invasion and metastasis. Their results were compared with both voided urine cytology (VUC) and bladder wash cytology (BWC) for the detection of bladder cancer cells. MATERIALS AND METHODS: The authors used preoperative voided morning urine samples from 110 subjects for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash samples were obtained for telomerase and cytology. Of 110 cases 73 were histologically diagnosed as bladder cancer, whereas the remaining 16 had benign urological disorders. A group of 21 healthy volunteers were also enrolled in this study. Cystoscopy was done for all patients as the reference standard for the identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. RESULTS: Receiver-operator characteristics (ROC) curves were used to determine the optimal threshold values for telomerase activity in urine, bladder wash and MMP-9 [0.05, 0.088 and 0.51 (ng/ml), respectively]. The levels and the positivity rates of telomerase activity and MMP-9 were significantly higher in the malignant group compared to either the benign group or normal controls. Bladder cancer patients with positive cytology revealed positive telomerase activity in urine, bladder wash, and MMP-9 in 92%, 87% and 61%, respectively. Also, these positive rates were significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%, respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase activity in urine, and in bladder wash, respectively. 66.6% and 80% for MMP-9, 58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher than either combined sensitivity of VUC with one of the biomarkers or than that of the biomarker alone. CONCLUSION: Urinary telomerase and MMP-9 had superior sensitivities over VUC; moreover, combined use of these markers increased the sensitivity of cytology from 58.46% to 95%. The higher sensitivities of markers in bilharzial bladder cancer than non-bilharzial type highlight their clinical utility in screening patients with urinary bilharziasis.

The clinical value of serum TPS in gynecological malignancies.

This study included 75 cases; 39 with gynecological cancer of different types, stages, and grades (14 ovarian, 11 endometrial, 9 cervical, and 5 vulvovaginal); 23 patients with benign gynecological diseases and 13 normal healthy controls. Serum TPS was estimated using the ELISA kit supplied by Beki Diagnostic AB, Bromma, Sweden. The results of the present study revealed that serum TPS was significantly elevated in cancer patients followed by those with benign diseases. When the cutoff values were adjusted to 137 and 101 U/L, we obtained sensitivities of 56.4% and 82.1% at specifities of 100% and 85%, respectively. The benign diseases group had false positive rates of 13% and 34.8%, respectively. When considering tumor site, vulvo vaginal cancer showed the highest sensitivity (80%) followed by cervical (66.7%), ovarian (50%), and lastly endometrial cancer (45.5%). Serial measurement of TPS was shown to be of important value in the post-surgical follow-up of cancer patients.

Simultaneous determination of urinary CEA, ferritin and TPA in Egyptian bladder cancer patients.

Urinary carcinoembryonic antigen (CEA), ferritin (Fer) and tissue polypeptide antigen (TPA) were determined in 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract disease and 70 healthy controls). CEA was determined by the kit supplied by Roche Diagnostica (CEA EIA Doumab 60), ferritin by the Tandem-E Fer kit supplied by Hybritech and TPA by the Prolifigen TPA-IRMA kit supplied by Sangtec Medical. The results of this work revealed that combined determination of urine CEA and Fer, CEA and TPA or Fer and TPA showed higher sensitivity than determination of the individual markers. There was no significant difference between combined and individual marker determination with respect to false positivity in non-malignant urinary tract diseases. At 97% specificity, the sensitivities of urine CEA, Fer and TPA were 82.1%, 71.7% and 90.6%, respectively, while combined urine CEA & Fer, CEA & TPA and Fer & TPA showed sensitivities of 92.5%, 99.1% and 98.1%, respectively. When the specificity was related to the entire non-cancer group (patients with benign urinary tract diseases and normal controls), some reduction in the sensitivities of the combined markers was noted compared to the normal group only. In conclusion, combined determination of urine markers is superior to determination of individual markers in the diagnosis of bladder cancer.

Serum TPS versus TPA in Egyptian bladder cancer patients.

This study included 328 cases (106 with bladder cancer, 152 with non-malignant urinary tract diseases and 70 healthy controls). Serum TPA was determined using the Prolifigen TPA IRMA kit supplied by AB Sangtec Medical, Bromma, Sweden and serum TPS was determined using the TPS IRMA kit supplied by Beki Diagnostics AB, Bromma, Sweden. The results of this study revealed that serum TPA had better sensitivity than serum TPS while no marked difference was found in the false-positivity rates in the non-malignant urinary tract diseases. A correlation coefficient of 0.83 was found between serum TPA and TPS. No relation was found between either TPA or TPS and histopathological stage, grade or association of the tumor with bilharziasis. As regards the histopathological type of the tumor, serum TPS was slightly higher in squamous cell than transitional cell carcinoma but TPA showed no difference. In the follow-up of bladder cancer patients after surgery both TPA and TPS showed an excellent concordance with the clinical state of the patients. In conclusion, TPS does not seem to be an optimal test in Egyptian patients with bladder cancer but serial determinations of one of the two markers can be used in the follow-up of these patients after surgery.

Serum copper, zinc, and iron in patients with malignant and benign pulmonary diseases.

Some environmental factors and diseases have been demonstrated to affect trace-element homeostasis. Ninety individuals were included in the present study (30 with bronchogenic carcinoma, 30 with some nonmalignant lung diseases, and 30 normal healthy controls). Serum copper, zinc, and iron levels were determined by the atomic absorption spectrophotometry. Results of this study revealed that serum copper was markedly elevated in benign lung diseases followed by bronchial carcinoma. Serum zinc was significantly reduced, whereas serum iron was not significantly decreased in both benign and malignant lung diseases compared to normal healthy controls. As to the sensitivity of the studied elements in lung disorders, neither serum copper nor serum iron can be used to detect benign or malignant diseases. Serum zinc and copper/zinc ratios showed reasonable values for prediction of pulmonary diseases but cannot be recommended as tumor markers in lung cancer.