Electronic Library of Scientific Literature


NEOPLASMA


Volume 50 / No. 3 / 2003


Immunohistochemical detection of dipeptidyl peptidase IV (CD 26) in thyroid neoplasia using biotinylated tyramine amplification.

Kholova I, Ludvikova M, Ryska A, Hanzelkova Z, Cap J, Pecen L, Topolcan O.

Department of Pathology, Charles University Faculty Hospital, Hradec Kralove, Czech Republic.

Differential diagnosis between malignant and benign thyroid tumors derived from follicular cells can pose certain difficulties in routine surgical pathology. The aim of the study was to evaluate dipeptidyl peptidase IV (DPP IV/CD 26) in differential diagnostics of thyroid lesions. DPP IV/CD 26 was evaluated in thyroid glands of 309 patients (261 females and 48 males, age range of patients 15-80 years). DPP IV/CD 26 was assessed in paraffin-embedded thyroid specimens immunohistochemically using commercially available antibody (Serotec) and biotinylated tyramine amplification kit (DAKO). Well-differentiated carcinoma revealed DPP IV/CD 26 positivity in 33 out of 42 cases (79%). Neither medullary nor insular carcinoma was DPPIV/CD 26 positive (only one case of each tested). DPPIV/CD 26 expression in isolated cells was seen in 18/261 (7%) benign disorders. The sensitivity of the method was 68%, the specificity was 94%, and the diagnostic accuracy was 91%, respectively, using 5% threshold of positive follicular cells. DPP IV/CD 26 can be assessed immunohistochemically using biotinylated tyramine amplification kit. DPP IV/CD 26 could be an adjunct in the thyroid gland differential diagnosis. However, DPP IV/CD 26 positivity is limited to the group of well-differentiated carcinomas, particularly papillary carcinoma. Furthermore, it is of limited value for follicular and oncocytic tumors.

Neoplasma. 2003; 50(3): 159-164.


Establishment and cidofovir sensitivity of a cell line from a heart transplant recipient with multiple cutaneous tumors.

Schacke M, Meerbach A, Thust R, Hyckel P, Wutzler P.

Institute for Antiviral Chemotherapy, Friedrich Schiller University of Jena, 07745 Jena, Germany. Michael.Schacke@med.uni-jena.de

A new cell line, designated as Tuwei00, is described. It originated from an Epstein-Barr virus-positive skin tumor biopsy of a heart transplant recipient, whose numerous cutaneous neoplasms were treated with the antiviral drug cidofovir what caused at least transient remissions. The cell line was established in vitro and maintained for more than 70 passages. Cells of early passages were characterized by a slower growth, the inability to form colonies and a higher sensitivity to cidofovir. After overcoming a crisis, the cells grew faster, to a higher density and were able to form adherent colonies from single cells as well as colonies in soft agar. Chromosome analysis showed diploidy/hyperdiploidy at the earlier and hypodiploidy at the later passages. Sensitivity to cidofovir was distinctly higher in early passages of Tuwei00 cells than in later passages and was characterized by distinct decline of cell survival after long term cidofovir exposure. Established normal human keratinocytes, HaCaT cells, which were checked for comparison, showed a low cidofovir sensitivity similar to late passage Tuwei00 cells.

Neoplasma. 2003; 50(3): 165-171.


Efficacy and toxicity of low-dose melphalan in myelodysplastic syndromes and acute myeloid leukemia with multilineage dysplasia.

Robak T, Szmigielska-Kaplon A, Urbanska-Rys H, Chojnowski K, Wrzesien-Kus A.

Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, 93-513 Lodz, Poland. robaktad@csk.am.lodz.pl

Effective therapy of myelodysplatic syndromes and acute myeloid leukemia originating from myelodysplastic syndrome has remained an unresolved problem. Advanced age of the patients and persistent pancytopenia make the treatment difficult. Despite large number of therapeutic options none of them is satisfactory. Recently palliative treatment with low-dose melphalan has been reported to have certain activity. The aim of the study was to evaluate the efficacy of low-dose melphalan in high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia with multilineage dysplasia (AML). Twenty three patients were eligible for the study: 8 with MDS and 15 with AML with multilineage dysplasia. All of them received oral melphalan in a daily dose of 2 mg. Median total dose of the drug was 120 mg (40-840 mg). Ten patients responded to the therapy. We observed complete remission (CR) in 4, partial remission (PR) in 3 and stabilization of the disease in 3 patients. Thirteen patients did not respond to the therapy. The survival time of the patients from the day of diagnosis and from the beginning of the treatment with melphalan was longer in patients responding to the therapy (median 15 and 10 months, respectively) than in non-responders (4.5 and 4 months, p=0.003 and p=0.008, respectively). Low-dose melphalan shows significant activity in high-risk MDS and AML with multilineage dysplasia with acceptable toxicity.

Neoplasma. 2003; 50(3): 172-175.


Administration of liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) and diclofenac in the combination attenuates their anti-tumor activities.

Fedorocko P, Hoferova Z, Hofer M, Brezani P.

Institute of Biology and Ecology, Department of Cell Biology, Faculty of Science, P. J. Safarik University Kosice, Slovak Republic. fedvox@kosice.upjs.sk

The anti-tumor effects of i.p. administered cyclooxygenase inhibitor - diclofenac and i.v. administered liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were investigated using a s.c. growing murine fibrosarcoma tumor. Tumor growth was assessed by measuring tumor volumes and survival of the mice. Both of the drugs were administered either alone or in combination. Repeated application of diclofenac in two schedules (150 microg/mouse/day for 14 consecutive days or 2 x 150 microg/mouse/week for 4 weeks) or application of liposomal MTP-PE (2 x 20 microg/mouse/week for 4 weeks) starting on day 5 after tumor cell transplantation significantly suppressed the tumor growth and increased the percentage of surviving mice. However, the volume of tumors and the survival time in tumor bearing mice treated with the two agents were similar to untreated counterparts. Thus, these data suggest the anti-tumor activity of either of the two drugs is lost when they are used in combination. Hematological examinations confirmed previously observed hematopoiesis-stimulating activities of the drugs when given alone. However, mutually potentiating effects after combined administration of liposomal MTP-PE and diclofenac were observed only exceptionally. Our findings corroborate the recommendation that the interactions of drugs used for the treatment of tumors must be carefully checked, if the drugs are applied in combination.

Neoplasma. 2003; 50(3): 176-184.


Serum Helicobacter pylori IgG and IgA levels in patients with gastric cancer.

Atalay C, Atalay G, Altinok M.

Department of General Surgery; Ankara Oncology Hospital, 06510 Ankara, Turkey. atalay_can@hotmail.com

The association between Helicobacter pylori and gastric cancer has been debated in the last decade and evidence for such a causal relationship has been claimed. This study aimed to detect the seroprevalence of Helicobacter pylori in patients with gastric cancer and compare it to the other cancer patients. In addition, the value of IgG and IgA in Helicobacter pylori detection was compared in patients with gastric cancer. Consecutive gastric and other cancer patients treated between 1999-2001 were prospectively studied. Serum Helicobacter pylori IgG and IgA levels were determined. Serological tests revealed IgA and IgG positivity as 53.9% and 50.9%, respectively, while 74.5% had positive results for either IgA or IgG. Serum IgA positivity was significantly higher in gastric cancer group compared to control group (p=0.02). In contrast, serum IgG positivity did not show a significant difference in both groups and either IgG or IgA seropositivity was significantly higher in patients with gastric cancer compared to control patients (p=0.04). This study revealed a higher seroprevalence of Helicobacter pylori in gastric cancer patients and IgA was a better predictor of Helicobacter pylori seropositivity in gastric cancer patients.

Neoplasma. 2003; 50(3): 185-190.


The evaluation of left ventricular function in childhood cancer survivors by pharmacological stress echocardiography.

Elbl L, Hrstkova H, Chaloupka V, Novotny J, Michalek J.

Department of Cardiopulmonary Testing, Faculty Hospital Brno, 639 00 Brno, Czech Republic. lelbl@fnbrno.cz

Late cardiotoxicity after anthracycline chemotherapy for childhood cancer is well recognized sequelae. Many long-term survivors may have subclinical cardiac dysfunction undetectable at a baseline evaluation. Various tests have been utilized for the diagnosis of left ventricular impairment. Recently, low-dose dobutamine stress echocardiography has been proposed as a more sensitive screening test. We have applied low-dose dobutamine stress echocardiography (5-10 microg/kg/min) in 36 asymptomatic survivors (20 male/16 female aged 14.6+/-4.7 years) treated with a cumulative dose of 226+/-106 mg/m2 of doxorubicin. The median follow-up was 5 years. Control group consisted of 20 sex and age matched volunteers (12 male/8 female aged 12.6+/-4.9 years). We found significant differences in mean velocity of circumferential fibre shortening, myocardial performance index (Tei index), left ventricular posterior wall thickening and endsystolic wall stress at a baseline. The stress response was significantly blunted only in a patient group in the following parameters: endsystolic wall stress, isovolumic relaxation time and myocardial performance index. The threshold response was abnormal (0-5% improvement of a variable only) in 45% of subjects from a control group in one or two parameters. On the contrary, 63% of subjects from a patient group responded pathologically (the worsening of a variable) in one or more parameters. We have not found a good correlation between risk factors of late cardiotoxicity and stress changes of left ventricular function parameters. Low-dose dobutamine stress echocardiography is safe and feasible diagnostic tool in children and adolescents. Dobutamine significantly increases the differences in cardiac variables between healthy population and asymptomatic survivors for childhood cancer. In comparison to the controls, most asymptomatic patients revealed subclinical myocardial damage at test. The predictive value for the development of clinical symptoms and cardiac complications need to be assessed in a large prospective study.

Neoplasma. 2003; 50(3): 191-197.


Immunohistochemical evaluation of P21ras and P53 proteins expression in human non-small-cell lung cancers.

Przybojewska B, Rydzynski K, Stepnik M, Jakubiak M, Kozak J, Szymczak W.

Department of Toxicology and Carcinogenesis, The Nofer Institute of Occupational Medicine, 90-950 Lodz, Poland. mstep@imp.lodz.pl

Human non-small-cell lung cancers (NSCLCs) of 48 patients were analyzed immunohistochemically to detect P21 ras and P53 proteins expression. The relationship between P21 ras and P53 proteins expression and clinicopathologic findings was also assessed. DAKO EnVision TM detection system was employed in the study. The P21 ras and P53 proteins expression was shown in 75% (36/48) and 33.3% (16/48) studied NSCLCs, respectively. In both cases the difference was significant when compared with adequate negative control. Simultaneous expression of both studied proteins was observed in all cases in which P53 expression was noticed. No significant association of P21 ras and P53 expression was found with age, histologic type, histologic grade, tumor size or lymph node metastasis of the studied NSCLCs. Therefore, our study suggests that P21 ras and P53 protein play a role in the pathogenesis of NSCLCs but they have no value as a prognostic markers in the case of lung cancers.

Neoplasma. 2003; 50(3): 198-203.


Weekly paclitaxel for advanced non-small cell lung cancer patients not suitable for platinum-based therapy.

Juan O, Albert A, Villarroya T, Sanchez R, Casan R, Caranana V, Campos JM, Alberola V.

Department of Medical Oncology, Hospital Arnau de Vilanova, 46015 Valencia, Spain. juan_osc@gva.es

Platinum-based combinations are efficacious in the treatment of advanced non-small cell lung cancer (NSCLC) but their toxicity makes them unsuitable for elderly and for patients with co-morbidities. We assessed the efficacy and toxicity of low-dose of paclitaxel in patients who were elderly or who had contraindications against cisplatin therapy. Seventy-one patients (median age 68; range 42-82 years) with unresectable NSCLC were treated with weekly paclitaxel (80 mg/m2) infusion (1 h) for several cycles without intervening rest periods. Thirty-seven patients had PS 1 and 34 had PS 2 status. A total of 614 courses were administered (median 9, range 2-20). There were no episodes of grade 4 toxicities and only 1 patient had grade 3 thrombopenia. Grade 3 anemia or neutropenia were not observed and severe non-hematological toxicity was uncommon: grade 1-2 fatigue in 52%; grade 1-2 motor neuropathy in 42% and grade 3 in 5.5%; grade 1-2 sensory neuropathy in 46.3% of patients. Twenty-seven of the 67 evaluable patients (40.3%) had an objective response, whereas 26 patients (38.8%) had stable disease. The median overall survival for the entire group was 8.4 months (95% CI = 5.6 to 11.2) and the 1-year and 2-year survival was 37.4% and 12.1%, respectively. The median time-to-progression was 5.4 months (95% CI = 3.3 to 7.4). Our data show that low-dose weekly paclitaxel is active and well tolerated in this group of patients with NSCLC and poor prognosis and, as such, is useful for patients in whom platinum-based combinations are not suitable.

Neoplasma. 2003; 50(3): 204-209.


Effect of different neoadjuvant chemotherapy regimens on locally advanced breast cancer.

Coskun U, Gunel N, Onuk E, Yilmaz E, Bayram O, Yamac D, Cihan A, Ucan B, Yildirim Y, Celenkoglu G, Ozkan S.

Department of Medical Oncology, Gazi University Medical School, 06560 Ankara, Turkey. ugurcos@hotmail.com

In this retrospective study, we evaluated the results of 91 locally advanced breast cancer (LABC) patients (30 patients in stage IIIA - 33.0%, 61 patients in stage IIIB - 67.0%) who had been treated with different neoadjuvant chemotherapy regimens. Forty-three (47.3%) patients treated with FAC (5-Fluorouracil, doxorubicin, cyclophosphamide) or CA (cyclophosphamide, doxorubicin), 33 (36.3%) with FEC (5-Fluorouracil, epirubicin, cyclophosphamide) or CE (cyclophosphamide, epirubicin) and 15 (16.5%) with CMF (cyclophosphamide, methotrexate, 5-Fluorouracil) combination as neoadjuvant setting. Median follow-up duration was 33 (6-116) months in 91 patients. There was no significant difference in the pretreatment characteristics of patients receiving FAC/CA, FEC/CE and CMF including age, disease stage, menopausal and estrogen/progesteron receptor (ER/PR) status (p>0.05). In CMF group, no patient was treated with taxan as adjuvant setting. However, ten patients (30.3%) in FEC/CE group and 21 patients (48.8%) in FAC/CA group were treated with taxans. Overall response rate was lower in CMF group (60.0%), when compared to FEC/CE (81.9%) and FAC/CA (91.0%) groups (p<0.05). Median overall survival (OS) and diseases free survival (DFS) were similar in three groups; 28.0 months (range: 14.8-41.1) and 12.0 months (range: 5.3-18.6) in CMF, 45.0 months (range: 16.8-73.1) and 23.0 months (range: 0.0-48.6) in FEC/CE, 46.0 months (range: 41.1-50.8) and 22.0 months (range: 11.1-32.8) months in FAC/CA groups, respectively (p>0.05). In conclusion, overall response rates were found to be higher in anthracycline-based combinations than CMF, but these regimens had no additional survival advantage over CMF regimen. Long-term effects of these regimens should be investigated in further randomized trials.

Neoplasma. 2003; 50(3): 210-216.


The value of 18F-fluorodeoxyglucose positron emission tomography with the additional help of tumor markers in cancer screening.

Shen YY, Su CT, Chen GJ, Chen YK, Liao AC, Tsai FS.

Department of Nuclear Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. m001022@ms.skh.org.tw

Cancer screening is a major healthcare issue. Screening modalities are constantly changing due to improvements in technology. Whole body positron emission tomography (PET) with 18F-fluoro-2 deoxy-D-glucose (FDG) and the additional help of the serum levels of tumor markers have been considered as non-invasive methods for cancer screening in asymptomatic subjects. A total of 1283 subjects underwent whole-body FDG PET studies with the additional help of the serum levels of tumor markers in our center for cancer screening. The final diagnoses were confirmed by other imaging modalities or pathological findings in subjects with positive FDG-PET findings, and follow-up for at least 6 months were held in subjects with negative FDG-PET findings. Among a total of 18 (1.4%) subjects with cancers, FDG-PET detected cancers in 15 (1.2%) subjects but with false negative studies in 3 subjects with hepatoma (AFP = 129.6 ng/ml), prostate cancer (PSA = 25.1 ng/ml), and breast cancer (CEA and CA-153 were normal). False-positive FDG-PET studies were found in 24 (1.9%) subjects. However, none had abnormal serum levels of tumor markers. Whole body FDG-PET with the additional help of tumor markers could reduce the false negative and false positive results of FDG-PET only.

Neoplasma. 2003; 50(3): 217-221.

Comparing thallium-201 spect mammoscintigraphy and ultrasonography to detect breast cancer in mammographical dense breasts.

Chen DR, Jeng LB, Kao A, Lin CC, Lee CC.

Department of Surgery, Medical College Hospital, Taichung 404, Taiwan. albertkaotw@yahoo.com.tw

The aim of our study was to compare the usefulness of thallium-201 (Tl-201) single photon emission computed tomography (SPECT) mammoscintigraphy and ultrasonography to detect breast cancer in mammographical dense breasts. This study included 32 Taiwanese female patients with indeterminate mammographic probability of malignancy due to mammographical dense breasts. Both Tl-201 SPECT mammoscintigraphy and ultrasonography were performed for each patient. Then, all of the 32 breast masses undervent biopsies or operations to obtain finally pathological diagnoses. Based on the finally pathological diagnoses, 24 masses were breast cancer and 8 masses were benign breast tumors among the 32 patients. Twenty-two cancers and one benign tumor had positive Tl-201 SPECT mammoscintigraphic findings. The sensitivity, specificity, and accuracy were 92%, 88%, and 91%. Twenty-two cancers and 5 benign tumors had positive ultrasonographic findings. The sensitivity, specificity, and accuracy were 92%, 38%, and 78%, respectively. To detect breast cancer in patients with non-diagnostic mammogram because of mammographically dense breasts, Tl-201 SPECT mammoscintigraphy and ultrasonography have the same sensitivity to screen breast masses. However, due to its higher specificity, Tl-201 SPECT mammoscintigraphy should be useful to confirm the ultrasonographic findings.

Neoplasma. 2003; 50(3): 222-226.

Palliative treatment of cancer anorexia with oral suspension of megestrol acetate.

Tomiska M, Tomiskova M, Salajka F, Adam Z, Vorlicek J.

Department of Internal Medicine-Hematooncology, Masaryk University Hospital, 62500 Brno, Czech Republic. mtomiska@fnbrno.cz

Megestrol acetate (MA) is a progestational agent, currently known as one of the most effective appetite stimulants in patients suffering from cancer anorexia/cachexia syndrome. Oral suspension of this drug may be particularly useful in patients with far advanced disease, where taking larger amount of pills may lead to the decrease of patient compliance. The influence of oral MA suspension on quality of life and nutritional status was evaluated in 22 patients with far advanced cancer suffering from anorexia and more than 5 per cent weight loss, all beyond the scope of anticancer treatment. Most patients had lung or gastrointestinal cancer. QLQ-C30 questionnaire, visual analogue scale (VAS) for appetite, anthropometry, maximal handgrip strength and laboratory data were obtained before treatment and then after 2, 4, and 8 weeks of therapy. Despite of a known high mortality in this prognostically unfavorable group of patients (36% within two months in this study), overall quality of life after the daily dose of 480-840 mg of MA was improved in 63, 56, and 55% of patients remaining on therapy after 2, 4, and 8 weeks, respectively. Appetite was the most successfully influenced parameter with an improvement in VAS in 95% of cases after 2 weeks of therapy (p=0.0001). The drug was well tolerated by the great majority of patients. Oral suspension of megestrol acetate maybean effective palliative treatment for many patients with far advanced cancer suffering from anorexia/cachexia syndrome.

Neoplasma. 2003; 50(3): 227-233.

Fluid intake and bladder cancer. A case control study.

Radosavljevic V, Jankovic S, Marinkovic J, Djokic M.

Institute of Preventive Medicine, 11080 Zemun-Belgrade, Serbia. rvladan@eunet.yu

To examine the relation of the total intake of fluids and the types of beverages to the risk of bladder cancer, we conducted a hospital based case-control study with 130 newly diagnosed bladder cancer patients and the same number of matched controls. Information of total fluid intake was derived from the reported frequency of consumption of the different types of beverages on the food frequency questionnaire. Univariate and multivariate logistic regression analyses were performed in statistical analysis. There was no statistically significant difference between the cases and the controls in total daily fluid intake. Multivariate logistic regression model showed consumption of: soda (OR=8.32; 95%CI=3.18-21.76), coffee (OR=1.46; 95%CI=1.05-2.01) and spirits (OR=1.15; 95%CI=1.04-1.28) as statistically significant risk factors, while mineral water (OR=0.52; 95%CI=0.34-0.79), skim milk (OR=0.38; 95%CI=0.16-0.91), yogurt (OR=0.34; 95%CI=0.12-0.97) and frequency of daily urination (OR=0.27; 95%CI=0.18-0.41) were statistically significant protective variables. In our study no statistically significant association was observed for total fluid intake. The findings suggest consumption of soda, coffee and spirits were indicated as a risk factors for bladder cancer, while mineral water, skim milk, yogurt and frequency of urination as protective factors for bladder cancer.

Neoplasma. 2003; 50(3): 234-238.

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