Bacteremia in neutropenic versus nonneutropenic cancer patients: etiology and outcome in 401 episodes.

Etiology, risk factors, symptomatology and outcome of 401 bacteremic episodes during the period of 6 years in a National Cancer Institute occurring among 9987 admissions were analyzed. Neutropenia as an independent risk factor was observed in 198 episodes, while 203 bacteremic episodes appeared in nonneutropenic patients. Both groups were compared in risk factors, etiology, clinical symptomatology and outcome. Proportion of particular pathogens did not show significant differences in both groups, except for E. faecalis occurring more frequently in the group of nonneutropenic patients in contrast to Enterobacteriaceae, occurring more frequently in neutropenic patients. There was significant by higher proportion of anaerobic bacteremia and fungemia in neutropenic than in nonneutropenic patients. Prior prophylaxis with quinolones with breakthrough bacteremia were also seen more frequently in the group of neutropenic patients. Septic shock and death due to bacteremia occurred more frequently in the group of neutropenic patients.

Effect of tumor cells on the activation of murine lymphocytes and macrophages by cisplatin and FK565.

Murine peritoneal macrophages on in vitro treatment with cisplatin (5 micrograms/ml) or FK565 (10 micrograms/ml) showed an enhanced production of tumor necrosis factor (TNF) and reactive nitrogen intermediates (RNI). Similarly, treatment of splenic lymphocytes with these agents also led to an enhanced production of TNF. Co-incubation of macrophages or splenic lymphocytes with P815 (a murine mastocytoma) cells in vitro in the absence of cisplatin or FK565 also resulted in an augmented TNF production, however, it had no effect on the RNI production by macrophages. TNF production of cisplatin- or FK565-treated macrophages got synergistically enhanced in the presence of P815 cells in the presence of P815 whereas the production of RNI was inhibited. Incubation of splenic lymphocytes with P815 cells in the presence of cisplatin or FK565 resulted in an inhibition of TNF production. Indomethacin-treated P815 cells were observed to be less effective in inhibiting nitrite production of macrophages compared to untreated tumor cells. Pretreatment of P815 cells with cisplatin or FK565 before co-incubation did not alter the TNF production of macrophages whereas it inhibited the same in lymphocytes. This study shows that activation of macrophages and lymphocytes is independently influenced by P815 tumor cells in combination with chemoimmunotherapeutic drugs cisplatin and FK565.

Glutathione S-transferase activity as an early marker for malignant tumors of corpus uteri.

Glutathione (GSH) concentrations and glutathione S-transferase (GST) activities were determined in 30 paired malignant human corpus uteri tumor samples and in samples of adjacent normal tissues. For GSH concentrations no difference was found between normal (126.0 +/- 52.4 nmol/mg protein) and tumor tissues (110.1 +/- 46.4 nmol/min/mg protein; p = 0.219). The GST activities were significantly higher in tumor tissues (322.4 +/- 135.54 nmol/min/mg protein) than in corresponding normal tissues (224.6 +/- 95.64 nmol/min/mg protein; p = 0.005). This activities were independent on the pathohistological and clinical factors, except for positive lymphovascular invasion and myometrial invasion (over 50%), where significantly lower GST activities were found. For normal tissues the positive correlation between GSH concentrations and GST activities was found (correlation coefficient = 0.50, p = 0.005), but not for tumor tissue (correlation coefficient = 0.20, p = 0.281). The prognosis of patients (according to the well established prognostic factors, such as tumor type, myometrial invasion and grades) who had lower GSH concentration and GST activity in normal tissue was similar to those with higher GSH concentration and GST activity. In conclusion, higher GST activities found in tumor of corpus uteri suggest, that GST activity could be used as a tumor marker for the early stages of these malignant tumors.

Inhibition of experimental murine tumors by MT81, a new mycotoxin from Penicillium nigricans.

Effects of a new mycotoxin MT81 obtained from the fungal strain Penicillium nigricans on the growth of two transplantable murine tumors and the life span of the hosts were studied. Remarkable decrease in tumor volume and viable tumor cell count was found in both the tumors. Antitumor effect of the compound was more pronounced in Sarcoma 180 (S180) than in Ehrlich ascites carcinoma (EAC). The tumor-inhibitory effect was also manifested by the reduction in mitotic activity and appearance of membrane blebbing and intracytoplasmic vacuoles in the treated tumor cells. MT81 treatment prolonged the life span of the EAC tumor host by 78% and more than 100% in S180 bearing mice. Tumor inhibition by MT81 was followed by improvements in hemoglobin, RBC values and bone marrow cellularity. Thus the results suggest that MT81 has significant antitumor property against experimental murine tumors and it does not adversely affect the hematological profile of the hosts.

Differential display of RNA from tumorigenic and nontumorigenic variants of hamster cells transformed with avian sarcoma virus.

Differential display technique was applied to study expression of RNA in tumorigenic and nontumorigenic cell variants of avian sarcoma virus transformed hamster cells. Methodical conditions were worked out, which allowed identifying a cDNA fragment of an unknown gene expressed in nontumorigenic cell variant only. Its role in tumor suppression remains to be determined.

Treatment of rat gliomas with recombinant retrovirus harboring Herpes simplex virus thymidine kinase suicide gene.

The retrovirus vector containing Herpes simplex virus type 1 thymidine kinase (HSVtk) gene was constructed. The vector was transfected into the packaging cell line PG13. It was shown that individual transfected cells differ in the production of recombinant retrovirus and in their susceptibility to be killed by ganciclovir. Recombinant retrovirus with a gibbon envelope was able to transduce the HSVtk gene into rat glioma cells. In vivo studies confirmed the ability of intraperitoneal ganciclovir administration to influence subcutaneous and intracerebral tumors developed after injection of C6 rat glioma cells with subsequent injection of HSVtk retrovirus producing cells.

Quantitative immunocytofluorometry--new parameters for the definition of leukemia cells.

In our study we used for definition of leukemia/lymphoma cells a new parameter which allows the enumeration of mean fluorescence intensity expressed by the number of antigen molecules per cell. Quantitative immunofluorescence using calibration microbeads was performed in 36 patients with different acute and chronic lymphoid and myeloid leukemia and in 19 healthy volunteers. We showed that quantitative immunophenotyping allowed the definition of aberrant marker densities on neoplastic cells. We demonstrated under- and overexpression of CD8 marker in CD3/CD4/CD8 complex in T acute lymphatic leukemia and T non-Hodgkin's lymphoma and T leukemia of large granular lymphocytes as compared to normal counterparts. We pointed out that certain antigens (e. g. CD10, CD4, CD24) were expressed at different levels on different cell subsets (CD10 in early B-acute lymphatic leukemia and coexpressed in T-acute lymphatic leukemia, CD4 on T cells and monocytes, CD24 on B cells and granulocytes in chronic myeloid leukemia). We showed that quantitative immune fluorescence could provide new data contributing to a more precise definition of cell differentiation. We documented the significant difference between antigen density of early and late markers in B-cell and myeloid malignancies. Further, we demonstrated that quantitative immune phenotyping could help in determination of exact definition of pathologic clone in morphologically immature leukemia population and showed that parameters of this method are also convenient for cytoplasmic marker evaluation. In our study we were able to demonstrate that CD45 quantitative expression appeared to be a more informative parameter than its percentage of antigen-positive cells as a measure of antigen expression only and we pointed out that low and high CD45 densities enabled to differentiate between pathological clone and residual healthy population in examined sample. We showed that quantitative immune phenotyping could be another important parameter for definition of leukemia phenotype suitable for detection of minimal residual disease.

The relationship between argyrophilic proteins and some immunophenotypic markers in acute leukemia cells.

This study reports the immunophenotypic features of a series of 62 selected acute leukemia patients with increased incidence of argyrophilic proteins (AgNORs) at the time of initial diagnosis. Peripheral blood and bone marrow cells of patients with T-ALL, B-precursor ALL and AML were studied. The method of silver staining was used to determine the number of AgNORs per cell. Cell surface markers were detected by a standard immunofluorescence assay. To demonstrate the relationship between AgNOR quantity and cell proliferation, the expression of activation and proliferation antigens CD38 and CD71 was investigated. To characterize the immunophenotype and the discrete stages of differentiation, the wide panel of antibodies against lymphoid, myeloid and non-lineage specific antigens was used. The number of AgNORs at diagnosis ranged from 3.05 to 6.70. Immunophenotypic analysis showed a variation in CD38 and CD71 expression among different leukemia subtypes. CD71 antigen was more expressed in T-ALL than in B-precursor ALL or in AML. Notable was the relationship between increased AgNOR quantity and antigens that characterize the immaturity of leukemic cells. The association with CD7, CD2, CD5 (without CD3 membrane expression) and CD34 in T blasts was evident. High positivity of CD19, CD10, CD34 and HLA-DR in relation to the increased amount of AgNORs in B-lineage ALL was observed. The vast majority of AML patients with high numbers of AgNORs simultaneously expressed CD13, CD33, CD34 and HLA-DR. One third of AML cases coexpressed T cell marker CD7. In conclusion, the presence of increased numbers of AgNORs at diagnosis might reflect the dependence on an early stage of leukemia cell differentiation.

Inhibitory effect of radiosensitizer AK-2123 on experimental hepatic metastases and Ca2+ active transport.

A triazole group radiosensitizer AK-2123 is shown to inhibit considerably the growth of hepatic metastases induced by the intrasplenic injection of colon adenocarcinoma cells in syngenic mice. Even an extremely low dose of the drug exhibits the antimetastatic effect. It is shown that AK-2123 injected at therapeutic dose inhibits active transport of calcium ions by the (Ca2+-Mg2+)-dependent ATP-ase. The antimetastatic effect of AK-2123 is suggested to be related, at least partially, to the inhibition of the active calcium transport.

Human multidrug-resistant (MRP,p190) myeloid leukemia HL-60/ADR cells in vitro: resistance to the mevalonate pathway inhibitor lovastatin.

Mevalonate pathway inhibitor lovastatin inhibited proliferation of human multidrug-resistant promyelocytic leukemia HL-60/ADR cells in vitro, with MRP-gene coded p190 mediated drug resistance, to a markedly lesser extent than that of the parental drug sensitive HL-60 cells and also that of the other human multidrug resistant (MDR-1, P-glycoprotein) myeloid leukemia cell line HL-60/VCR. The sensitivity of the examined human leukemia cell lines to the cytostatic activity of lovastatin correlated approximately with the potential of lovastatin to induce the characteristic cell cycle alteration (i.e. the accumulation of lovastatin-treated cells in the G0/G1 phase of the cell cycle). The P-glycoprotein positive HL-60/VCR cells and the parental drug sensitive HL-60 cells were more sensitive to this cell cycle alteration than the HL-60/ADR multidrug resistant leukemia cells with MRP drug resistance. Lovastatin (72 hours, 20 micromol) induced apoptosis and cell necrosis in HL-60 cells, apoptosis but not cell necrosis in HL-60/VCR cells and neither apoptosis nor necrosis in HL-60/ADR cells.

The intermediate filaments and prognostically oriented morphological classification in ductal breast carcinoma.

The expression of cytokeratins 7, 8, 14, 18, 19 and vimentin was examined in 100 cases of ductal invasive breast carcinomas. While the predominantly diffuse immunohistological positivity of simple epithelia cytokeratins 7 (in 93), 8 (in 100), 18 (in 100) and 19 (in 97) cases represents a constant feature of these tumors, cytokeratin 14 was detected in only 36 cases which were mostly of low grade and in a focal pattern. Vimentin positivity was found in 53 intermediate and high grade tumors and, again the pattern was also rarely diffuse. The ductal carcinomas can be grouped into four classes according to vimentin and cytokeratin 14 immunoreactivity. This grouping correlates well with tumor grade and with simple histological classification of ductal breast carcinoma, consisting of the low, intermediate and high malignancy categories, as proposed here. The types ofductal carcinomas can be sorted into prognostically different subgroups, according to ICD-O morphologic terminology and commonly adopted results of morphologic and prognostic studies.

Searching for a functional analogy between yeast Pso4 and bacterial RecA proteins in induced mitotic recombination.

The pso4-1 mutant of S. cerevisiae is phenotypically similar to the recA mutant of E. coli; it is sensitive to DNA cross-linking agents and defective in both recombination and mutagenesis. In this paper we have measured the effect of the recA gene expression on the frequency of mitotic crossing-over and mitotic gene conversion in response to DNA damage induced by photoactivated 8-methoxypsoralen (8-MOP + UVA), ultraviolet radiation (UV) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The diploid pso4-1 mutant and the repair wild type strain were transformed with the multicopy plasmid carrying the recA gene placed under the control of the ADH1 promoter. The results showed that RecA is not able to restore block in induced mitotic recombination in pso4-1 cells after DNA damaging agents used. Thus RecA protein is not able to substitute Pso4 protein in homologous mitotic recombination indicating that they have probably different functions in this process.

Measurement of DNA strand breakage and DNA repair induced with hydrogen peroxide using single cell gel electrophoresis, alkaline DNA unwinding and alkaline elution of DNA.

Three techniques: single cell gel electrophoresis (SCGE), alkaline elution of DNA (AE), and alkaline DNA unwinding (ADU) were chosen to compare the sensitivity among these methods in detection of DNA damage and repair in human diploid VH10 cell line after short-term exposure to hydrogen peroxide. Using SCGE technique a dose-dependent increase in DNA migration was found in cells exposed to hydrogen peroxide in concentration range from 10 micromol/l to 100 micromol/l. Alkaline DNA unwinding method detected increased level of single strand breaks (ssb) in concentration range from 25 micromol/l to 100 micromol/l of H2O2, and alkaline elution of DNA estimated increased DNA elution rate from concentration 50 micromol/l of H2O2. In a time course study to evaluate the kinetics of DNA repair, both SCGE and ADU techniques showed that the repair of DNA strand breaks is very rapid; the level of ssb in treated cells has returned to near the background level within two hours. After this time damage remaining in the DNA was in the form of oxidised bases as revealed the incubation of treated cells with specific DNA repair endonuclease, formamidopyrimidine-DNA glycosylase.

Polarographic testing of carcinogenicity of some chemotherapeutics.

This work is devoted to the study of polarographic reduction of three antibiotic compounds including adriamycin, chloramphenicol and erythromycin and of a synthetic antibacterial chemotherapeutic compound--5-nitrofurantoin. The polarographic reduction was performed in the strictly anhydrous N,N-dimethylformamide with or without alpha-lipoic acid (LA) by the means of DC polarography. The values of half-wave potentials E1/2 and parameter of potential carcinogenicity were determined for the all compounds. Adriamycin was reduced during the five-step process, other compounds were reduced in two steps. The presence of LA in a polarographic solution resulted in a new polarographic one-electron wave in the range of -1.120 V to -1.790 V vs. SCE possessing a diffuse and reversible character. Its height is linearly dependent on the LA concentration in solution. The highest parameter of potential carcinogenicity tg alpha was determined for adriamycin (0.575) which belongs among compounds classified by WHO as "probably carcinogenic to humans". The lowest determined value of parameter tg alpha belonged to 5-nitrofurantoin (0.290) which has not yet been included into the IARC classification.

Plasma selenium concentration in patients with stomach and colon cancer in the Upper Silesia.

Plasma selenium concentration was assessed in 44 patients with cancer of the gastrointestinal tract (19 subjects with stomach cancer and 25 with colon cancer) and 25 age-matched healthy control subjects. Selenium concentration was determined by the fluorometric method. The observed plasma selenium concentrations in gastrointestinal cancer patients (37.0 +/- 11.05 ng Se/ml or 38.4 +/- 12.6 ng Se/ml in stomach or colon cancer patients, respectively) were significantly lower as compared to the healthy age-matched control group (51.4 +/- 14.4 ng Se/ml). The diagnosed low selenium status may be considered as a high risk for cancer development.

Helper T lymphocyte precursor frequency analysis in alloreactivity detection.

The utility of IL-2 secreting helper T lymphocyte precursors (HTLp) frequency testing has been evaluated for detecting alloreactivity. The frequency of HTLp was approached by limiting dilution assay. High HTLp frequency was detected in 20 out of 30 HLA matched unrelated pairs (67%). The comparison of HTLp and CTLp (cytotoxic T lymphocyte precursors) frequencies in HLA matched unrelated pairs showed that the two examinations are not fully alternative in detecting alloreactivity. This could suggest the utility of combined testing of both HTLp and CTLp frequencies for alloreactivity assessment. In contrast, five positive HTLp values were only found among 28 HLA genotypic identical siblings (18%). Previous CTLp limiting dilution studies showed very low or undetectable CTLp frequency results in that group. For that, HTLp assay remains to be the only cellular in vitro technique detecting alloreactivity in these combinations.

The effect of protein kinase C inhibitors on invasion of human ovary cancer cells.

In the present work we tested whether invasiveness of ovarian carcinoma cells could be considered as protein kinase C (PKC) dependent process. The migration and invasion studies were performed in Transwell chambers. Staurosporine, sphingosine and tamoxifen were used as PKC inhibitors. Also the effect of prolonged treatment with TPA was the subject of observation. The obtained results indicated that invasion understood as three step process (attachment, migration and matrix degradation) was affected by PKC inhibitors. The detailed studies, however, showed that attachment and matrix degradation ability of ovarian cancer cells was not changed by PKC inhibitors as opposed to migration which was, at least partly, regulated by protein kinase C.

The significance of anti-sialyl-Tn antibodies in patients with colorectal and breast cancer.

The sera of 54 individuals with colorectal or breast cancer, and 50 healthy volunteers were assayed for the presence of anti-bovine submaxillary mucin antibodies using an enzyme linked immunoassay. The serum levels of these antibodies were found to be significantly lower in people with breast (p < 0.001) or colorectal cancer (p < 0.001) with respect to healthy individuals. Within the colorectal cancer group the presence of antibodies was significantly lower in those individuals with poorly differentiated tumors compared to other histological grades (p < 0.05), but did not correlate with the presence of local or distant metastases or anatomical location of the tumor (p > 0.05). No correlation was found with respect to the age of the patient and the level of anti-sialyl-Tn antibodies (p > 0.05). Competition analysis with the anti-sialyl-Tn monoclonal antibody 3C2 indicated that the activity against bovine submaxillary mucin was primarily due to specificity for the sialyl-Tn epitope of the glycoprotein. In contrast to findings with other tumor associated antigens, we could find no evidence of an increase in the level of antibodies against this epitope.

Soluble TNF receptors release by polymorphonuclear cells and the serum levels in breast cancer patients before and after treatment.

Soluble cytokine receptors by binding to circulating cytokines play an important role in the regulation of immune response of the host. Measurement of their release may be helpful in the evaluation of cytokine-mediated reactions in patients with cancer disease. Soluble tumor necrosis factor receptors (sTNF-Rs) in the culture supernatants of PMNs and in the sera obtained from patients with breast cancer were determined. The examinations were carried out before and after treatment involving surgery and chemotherapy. The highest concentrations of sTNFRp55 and sTNFRp75 were observed in the culture supernatants of PMNs from patients before any treatment, the lower concentrations of them were found in the supernatants of PMNs after treatment. Sera from breast cancer patients presented increased levels of sTNFRp55 and sTNFRp75. Surgery treatment resulted in higher concentrations of sTNFRp55 and sTNFRp75. Decreased sTNF-Rs serum levels were obtained in patients after adjuvant chemotherapy. Different ability of PMNs to the release of TNF-regulatory proteins-sTNFRs appears to confirm PMNs participation in TNF-mediated reactions of the host during malignant process via sTNF-Rs release.

The value of CYFRA 21-1, a new tumor marker, in nasopharyngeal carcinoma.

CYFRA 21-1 (CYFRA) is a newly-developed tumor marker which is useful in evaluating non-small cell lung carcinoma, especially the squamous cell type. The purpose of this study was to assess the clinical value of CYFRA in patients with nasopharyngeal carcinoma (NPC). Serum levels of CYFRA (CIS bio-International, France) were measured in 80 patients with untreated NPC. The histologic diagnosis of all patients was confirmed by biopsy. Twenty two (27.5%) of the tumors were classified as undifferentiated carcinoma, and 58 (72.5%) as squamous cell carcinoma. All patients with malignancy were classified according to the International Union Against Cancer (UICC) TNM classification system. In addition, 77 patients without evidence of neoplasm were included as controls. The cut-off value of CYFRA, determined at the 95th percentile of the standard Gaussian variate of controls, was 2.48 ng/ml. The results show that (1) the mean values of serum CYFRA in patients with NPC were significantly higher than those in the control subjects, (2) the overall diagnostic sensitivity of CYFRA in patients with NPC is 58.75%, (3) there was no significant difference between the CYFRA concentrations in patients with squamous cell carcinoma and those in patients with undifferentiated carcinoma, and that (4) there was good correlation between CYFRA values and the tumor stage. There is a statistical difference between T1-T2 patients and T3-T4 patients, and between N0 to N1 patients and N2 to N3 patients. Our results suggest that the CYFRA test may have a potential clinical role as a valuable test in patients with NPC.

Characterization of two new permanent glioma cell lines 8-MG-BA and 42-MG-BA.

The establishment and characterization of two permanent glioma cell lines (8-MG-BA and 42-MG-BA) are described. Both cell lines were derived from the human glioblastoma multiforme. Analyzed cells were within the passage 200 to 220. The cells in both cultures showed similar morphology. In majority they consisted from flat polygonal cells. Growth kinetic studies demonstrated a population doubling time of 20 to 24 h in cell line 8-MG-BA and 48 to 54 h in cell line 42-MG-BA. The cell lines showed different hyperdiploid karyotypes. The immunofluorescence staining was performed for glial fibrillary acidic protein (GFAP) and vimentin. In the culture 8-MG-BA only a small amount of cells showed the GFAP-positive staining. At confluent 42-MG-BA culture the GFAP-positive cells reached 50 to 70% of all cells. Vimentin was found in all glioma cells in both cultures.

Antitumor action of bovine seminal ribonuclease. Cytostatic effect on human melanoma and mouse seminoma.

This paper reports on the antitumor activity of BS RNase on human melanoma and mouse seminoma. Human melanoma cells established in culture were extremely susceptible to BS RNase, administered in concentrations ranging from 1-100 microg/ml. Concentrations of BS RNase over 10 microg/ml caused complete inhibition of cell growth. Bovine pancreatic ribonuclease (RNase A), a prototype of the ribonuclease superfamily, did not exert any effect under these conditions. Based on our previous results, athymic mice bearing human melanoma or mouse seminoma were treated with intratumoral administration of BS RNase (12.5 mg/kg b.w.). This dose was injected for five consecutive days excluding weekends. The intratumoral administration of BS RNase to nude mice bearing human melanoma showed a significant antitumor effect. There were no tumors seen in eighty percent of mice treated for three weeks, and tumors in the other mice diminished significantly. After some delay the tumors started to regrow. Prolonging of the treatment to five weeks had a similar effect. The effect of BS RNase on mouse seminoma was well pronounced. Five to seven doses of BS RNase were sufficient to eliminate tumors in all treated mice. However, as in the previous experiment, the growth of tumor tissue later reappeared.

Granulocyte colony-stimulating factor demonstrates antitumor activity in melanoma model in mice.

Granulocyte colony-stimulating factor (G-CSF) was found to exert antitumor activity against murine MmB16 melanoma when administered intratumorally. However, subcutaneous administration of this cytokine at a site distant from the growing tumor did not show any antitumor effects. G-CSF did not influence the proliferative activity of MmB16 in vitro. Intraperitoneal administration of G-CSF resulted in decreased secretion of nitric oxide (NO) by peritoneal macrophages and their decreased tumoricidal activity against MmB16.

Signal-averaged ECG in patients after anthracycline therapy for childhood cancer.

Late cardiac complications after anthracycline therapy is an increasingly common problem among survivors of childhood cancer. Routine clinical examination may be normal, but subclinical cardiac abnormalities, which may progress with time, are documented in high percentage of these patients. Microstructural myocardial alterations may result in production of micropotential level signals (late potentials, LP) and altered frequency components of signal-averaged ECGs (SAECG). SAECG abnormalities are valuable in risk stratification of patients with various heart diseases culminating in fatal arrhythmias or heart failure. Forty-five pediatric oncologic patients (mean age 14.4 +/- 4.1 years) were included in the study. SAECG was performed 3 months-12 years (median 5.5 years) following completion of anthracycline therapy. The total cumulative doses of anthracyclines were 90-555 (median 230) mg/m2. The control group consisted of 30 healthy age-matched volunteers. LP were present in six (13.3%) patients after anthracycline therapy at 40 Hz high-pass filter setting. Using frequency-domain analysis within the QRS complex, area ratio 1 (area of 20 to 50 Hz/area of 0 to 20 Hz) and area ratio 2 (area of 40 to 100 Hz/area of 0 to 40 Hz) were calculated. Twenty (44.4%) and fourteen (31.1%) had abnormal values in area ratios 1 and 2, respectively, within the QRS complex. Area ratios 1 and 2 of patients after anthracycline therapy were significantly higher than those in control group (p = 0.0187 and p = 0.0043). Our preliminary results suggest that chemotherapy with anthracyclines, even in low dosage, is associated with increased incidence of SAECG abnormalities. The potential of this simple, noninvasive method to detect subclinical anthracycline-induced myocardial alterations and facilitate prognostic stratification of cancer survivors is promising, however, the clinical value of SAECG remains to be established in a larger and a longer study.

Granisetron in repeated cycles of chemotherapy with platinum.

The aim of the present study was to assess the antiemetic efficacy of granisetron in repeated cycles of chemotherapy with platinum derivatives. The study included 50 patients (28 females, 22 males; aged 17-72, mean age 51 years). From 2 to 5 cycles of chemotherapy with cisplatin or carboplatin were performed. Granisetron was administered intravenously at a dose of 3 mg, 5 minutes before commencement of cytostatic chemotherapy. In case of 2 episodes of vomiting and severe nausea 2 additional doses of granisetron were given. Total control of emesis was achieved in 60% of patients after the first cycle of chemotherapy, and this percentage did not change significantly over the 5 cycles of chemotherapy. There were no differences in the antiemetic efficacy of granisetron in relation to patient sex up to cycle III, while in cycles IV and V a tendency towards less efficacy in females was observed. The adverse effects (headache, dizziness) were observed with the same frequency in the first 3 cycles of chemotherapy, while these were absent in cycles IV and V. Severe side effects were recorded only in cycle I, after that they were less expressed. In conclusion, granisetron is highly effective in prevention of emesis, induced by platinum derivatives and its efficacy is maintained over repeated cycles of chemotherapy. The toxicity of granisetron is mostly expressed in the first cycle, while after that it decreases significantly.

The impact of diagnosis and treatment on the quality of life in breast cancer patients.

Over the past years, quality of life (QOL) in patients with breast cancer has continued to be a noteworthy area of research. The diagnosis and management of cancer can have a major impact on every aspect of a patient's QOL. Sixteen women with breast cancer (during chemotherapy and 4 months after adjuvant chemotherapy) and 15 healthy women controls underwent 42-item QOL questionnaire in eight dimensions which assessed general well-being, physical symptoms and activity, sleep disturbance, appetite, sexual dysfunction, cognitive functions, medical interaction, social participation, and work performance. The subjects were asked to choose only one of five predefined constant options, which were scored from one to five in a Likert scale with multiple options, and total QOL scores were obtained. Although the total QOL score was not statistically different between the groups (p > 0.05), general well-being, physical symptoms and activity, and sleep disturbance showed significant regression in breast cancer patients compared to the controls (p < 0.05). Appetite (p < 0.02) and physical symptoms and activity (p < 0.05) significantly improved in the group after chemotherapy compared to the group during chemotherapy.

The multidrug resistance in human leukemias. Minireview.

Leukemia/lymphoma cells, clinically refractory to therapy are often associated with expression of P-glycoprotein (P-gp), which is encoded by the multidrug resistance (MDR) gene, mdr1. Cell lines expressing mdr1 exhibit resistance to several structurally unrelated lipophilic drugs, such as anthracyclines, vinca alkaloids, and epopodophyllotoxins. This MDR can be conferred to drug-sensitive cells mdr1 cDNA transfer. In resistant cells, MDR is characterized by overexpression of P-gp and by the enhanced efflux, and P-gp fluorescence probe, rhodamine 123 (Rh 123). This can be circumvented by addition of certain non-cytotoxic drugs, such as verapamil and cyclosporin A.

Prediction of lung cancer mortality in four Central European countries, 1990-2009.

During the post-war decades the cancer mortality in Europe has undergone deep changes. In the 1980s, remarkable increases in lung cancer mortality in the Central and Eastern European area resulted in rates equaling or exceeding those in most Western countries. In the present work, the future development of the lung cancer epidemic has been assessed in four Central European countries (Austria, Czech Republic, Hungary, and Slovakia) for the period 1900-2009, taking into consideration previously observed lung cancer mortality trends (1960-1989), in the same countries. The estimation of the predicted mortality trends was based on log-linear Poisson regression age/period/cohort model, using GLIM for calculation. In the twenty-year period from 1985-1989 to 2005-2009, the age-adjusted (world standard) lung cancer mortality rates for men are predicted to increase in Hungary and Slovakia, and show little change in Austria and the Czech Republic. For women, approximately exponential increases in lung cancer mortality rates (both adjusted all-age, and age-specific at young adult ages up to 44 years) can be expected, with highest rates in Hungary, intermediate in the Czech Republic and Austria, and lowest in Slovakia. Lung cancer mortality in women is still much smaller than in men, however, rapidly increasing, with less variation in trends between countries than in men. The current and predicted high and/or increasing lung cancer mortality rates in the countries under study, presumed to be associated with elevated exposure to respiratory carcinogens, mainly cigarette smoke, in previous decades, underlines that the control of smoking continues to be a priority among approaches to cancer prevention.

Antitumor properties of boron complexes with hydroxy biguanide and salicyl hydroxamic acid against Ehrlich ascites carcinoma.

A new derivative of hydroxamic acid, hydroxy biguanido hydrochloride monohydrate and its boron derivative, dihydroxy-oxybiguanido boron (III) hydrochloride monohydrate were synthesized. Another boron compound, hydroxo-salicyl-hydroxamato boron (III) was synthesized from known salicyl hydroxamic acid. Antitumor properties of all the compounds evaluated against Ehrlich ascites carcinoma in mice show enhanced survival time when boron is incorporated in the compounds. Hematological parameters, alkaline phosphatase in serum of the treated animals show minimum toxic effects after boron is coupled with their respective hydroxamic acids.

Effect of hyperthermia on transmembrane potential of HeLa cells--a flow cytometric analysis.

The effect of hyperthermia on transmembrane potential was studied in HeLa cells in vitro using a 3',3'-dipentyl oxacarbocyanine [Di-0-C5(3)], a lipophilic cation probe that equilibrates across the plasma membrane according to the transmembrane potential. Uptake of the fluorescent probe was measured by flow cytometry. The flourescent intensity (FI) increased with increase in temperature, and the increase was statistically significant when the duration of heat treatment was 30 minutes or more. At each temperature studied the depolarization was higher after longer duration of heat treatment (p value: 41 degrees C < 0.05; 42 degrees C < 0.005; 43 degrees C < 0.001 and 44 degrees C < 0.001, respectively). The lack of significant depolarization after shorter duration of heating, particularly at lower temperatures could be due to the repair of membrane damage that could have occurred in the holding interval between heating and measurement. The results suggest that depolarization of membrane potential, i.e. increase in the intracellular cation concentration, can be considered as an indicator of cell injury by hyperthermia and may be mechanistically related to cell death by heat treatment. The technique may be suitable for studying repair of damage after hyperthermia.