Polymorphisms of and Genes in Ovarian Cancer and Treatment Response in Poles.

Background/aim: Ovarian cancer is a lethal gynecological malignancy, with 5-year survival of only about one third of patients. The ABCB1 gene encodes the P-glycoprotein which is one of the multidrug efflux pumps. Its decreased activity may result in multidrug resistance of cancer cells.

The BCL-2 protein in precursor B acute lymphoblastic leukemia in children.

The BCL-2 protein plays an important role in controlling apoptosis. Disorders of this process can lead to the emergence and development of acute lymphoblastic leukemia (ALL) and can determine the resistance of leukemic cells to chemotherapy. The levels of BCL-2 mRNA were determined in 20 children with pre-B ALL using RT-polymerase chain reaction and the percentage of BCL-2+ cells in 51 patients using flow cytofluorometry.

p53 Tetramerization domain mutations: germline R342X and R342P, and somatic R337G identified in pediatric patients with Li-Fraumeni syndrome and a child with adrenocortical carcinoma.

Germline p53 mutations are associated with Li-Fraumeni syndrome (LFS) and other familial cancer phenotypes not fulfilling the definition for LFS. The majority of germline p53 mutations cluster in exons 5-8, corresponding to a DNA binding domain. We report the identification of two germline mutations and a somatic mutation in a tetramerization domain (TD), a rare site for mutations.

[Mean level of expression of c-myb gene in leukaemia of children].

Aim Of The Study: Measurement of c-myb expression in leukaemia cells in children and in normal cells of healthy controls.

Material And Methods: 37 patients, 23 boys and 14 girls with acute leukaemia, aged 1-17 years, were included in the study (32 with acute lymphoblastic leukaemia and 5 with acute myeloblasts leukaemia) Control group consisted of 17 healthy children, 8 boys and 9 girls, 4-18 years old. After the isolation of mononuclear cells from bone marrow I peripheral blood mRNA was isolated, then with the use of reverse transcriptase cDNA was synthesized.

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study).

Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 account for a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approach by which development of an efficient DNA-testing procedure can be implemented is to describe the nature and frequency of common mutations in particular ethnic groups. Two hundred and twenty-six patients from families matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were screened for MSH2 and MLH1 germline mutations.

Evidence for selective expression of the p53 codon 72 polymorphs: implications in cancer development.

Polymorphism at codon 72 of p53 results in either the arginine or proline form of p53, whose functional significance in carcinogenesis is controversial. We have investigated if the expression of these p53 polymorphs is selectively regulated, using mRNA from peripheral blood of healthy Asian (Chinese) and the Caucasian (Polish) arginine/proline (arg/pro) heterozygote subjects. Asians were found to preferentially express the pro allele whereas the Caucasians preferentially express the arg allele.

A high proportion of founder BRCA1 mutations in Polish breast cancer families.

Three mutations in BRCA1 (5382insC, C61G and 4153delA) are common in Poland and account for the majority of mutations identified to date in Polish breast and breast-ovarian cancer families. It is not known, however, to what extent these 3 founder mutations account for all of the BRCA mutations distributed throughout the country. This question has important implications for health policy and the design of epidemiologic studies.

Is p53 intronic variant G13964C associated with predisposition to cancer?

Germline mutations of the p53 gene confer a high risk of diverse malignancies. The highest frequency of inherited p53 defects was noted in Li-Fraumeni syndrome (LFS), but almost half of the mutations were found in families with incomplete Li-Fraumeni-like syndrome (LFL), including familial breast cancer cases. Recently, a germline intronic G13964C base change of the p53 was reported as a high-risk mutation associated with familial breast cancer (LEHMAN et al.

Family with Li-Fraumeni syndrome and no evidence of a germline mutation of the p53 gene or chromosomal aberrations.

Li-Fraumeni syndrome is a rare autosomal, dominant trait of diverse types of cancers in children and young adults, with a predominance of soft tissue sarcomas, osteosarcomas, brain tumours, adrenocortical and breast carcinomas, as well as leukaemias. We present a family with an unusual cancer history fulfilling the criteria of Li-Fraumeni syndrome. Mutational analysis of the p53 gene in constitutional DNA of several affected members of the family did not show any germline p53 defect.

Results of p53 analysis in pediatric malignancies in Poland.

Background: Mutations of the p53 gene are thought to be causally associated with the development of various neoplasms. In tumors overexpressing the wild-form of p53, its functional inactivation has been suggested, and MDM2 seems to be important in this process. We analyzed p53 in childhood solid tumors, as data on pediatric malignancies are still limited.

Screening for germline p53 mutations in pediatric and adult patients of high-risk groups in Poland.

Germline mutations of the p53 gene lead to cell transformation in various tissues. Such a complex cancer phenotype makes it difficult to recognize the carriers of the defective allele. Several studies undertaken to identify high-risk groups found germline p53 mutations in familial cancer aggregations and in patients with multiple tumors.

Local low-dose IL-2 therapy.

Interleukin-2 (IL-2) is a powerful drug for treating cancer. However, it is only powerful if it is properly applied. That is, IL-2 should be applied at the tumor site, because at the transition of normal and malignant tissue are the tumor infiltrating cells.

Effect of local interleukin-2 treatment on spontaneous tumours of different immunogenic strength.

Transplantable tumour lines established from spontaneous tumours of BALB/c, CBA, and DBA/2 mice displayed different immunogenic strength. This report describes tumour susceptibility to interleukin-2 (IL-2) therapy in relation to tumour immunogenicity. The following tumour lines were used: X5, X6, and X9 mammary tumours of DBA/2, BALB/c, and CBA origin respectively, X7 carcinoma of BALB/c and X18 papilloma of CBA mice.

Therapeutic potential of biological response modifiers against transplantable mouse tumors of spontaneous origin. II. Local interleukin 2 treatment of tumors of different immunogenic strength.

This report describes tumor susceptibility to interleukin 2 (IL-2) therapy in relation to tumor immunogenicity. The following lines recently established from spontaneous tumors were used: X5, X6, and X9 mammary tumors of DBA/2, BALB/c and CBA origin, respectively, X7 carcinoma of BALB/c and X18 papilloma of CBA mice. Two spontaneous tumors of long transplantation history, SL2 lymphoma (SL2) of DBA/2 and M109 Madison lung carcinoma (M109) of BALB/c origin, were used as control systems.

Therapeutic potential of biological response modifiers against transplantable mouse tumors of spontaneous origin. I. Characterization of biological properties of tumor lines and preliminary data on response to cytostatic drugs and biomodulators.

Several transplantable lines were derived from spontaneous tumors of mouse strains of low and high cancer incidence (CBA, BALB/c and DBA/2), and eight of them were used for an evaluation of the therapeutic potential of BRM. The lowest number of cells inducing tumors was in most cases around 10(4) cells. In transplantation tests, tumors of CBA and DBA/2 mice were non-immunogenic, while tumors of BALB/c mice showed different level of immunogenicity.

Introduction of the activated N-ras oncogene into human fibroblasts by retroviral vector induces morphological transformation and tumorigenicity.

The introduction of activated N-ras cDNA into normal diploid human skin fibroblast cell cultures using the retroviral vector pZIPneo results in a spectrum of morphologies ranging from near normal to, in rare instances, dense piled-up colonies of morphologically transformed cells. However, none of the clones isolated were transformed as assessed by growth on agar or tumorigenicity in nude mice. Introduction of both c-myc and N-ras oncogene cDNAs into normal skin fibroblasts failed to produce transformation as assessed by growth on agar and tumorigenicity in nude mice, although c-myc infection alone conferred immortality and the resultant doubly infected cell line was immortal.

Antineoplastic activity of new linear hydrazine derivatives.

A series of hydrazine derivatives was tested for antineoplastic activity. Cyanoacetic acid hydrazide (I), cyanoacetic acid methylhydrazide (II) and N-thioamido-N'-cyano-acethylhydrazine (VI) appeared to be the most active agents against sarcoma 180, Ehrlich carcinoma and Nemeth Kellner lymphoma. The maximum tumor weight inhibition ranged from 70 to 90%.

Antineoplastic activity of azacarbazoles. II. Effect of alpha-carboline and its derivatives on transplantable animal neoplasms.

The antineoplastic properties of alpha-carboline, alpha-carboline hydrochloride, alpha-carboline N-1 methyl iodide and c-6 substituted fluoro-, chloro, nitro- and phenyl-alpha-carboline were studied. None of the compounds proved to be active when tested against i.p.

Enzyme activity in mice with transplantable leukemia.

Activity of cobalt activated acylase, gamma-glutamyltransferase, leucylaminopeptidase and alanylaminopeptidase in serum and liver of mice with transplantable leukemias (L1210, L1210/ara-C, L1210/CH3-G, AKSL-4, plasmacytoma ADJ-PC-5) were determined. Adenosinotriphosphatase, 5'-nucleotidase and alkaline phosphatase were histochemically localized in lymphatic nodes and spleen. Among the investigated enzymes the rise in serum activity of cobalt activated acylase and gamma-glutamyltransferase was demonstrated.

Biological activity of 1,4-dihydropyridine derivatives.

Six new 1,4-dihydropyridine derivatives were evaluated in vitro for antimicrobial and cytotoxic effects and in vivo for antineoplastic activity. These compounds inhibited the growth of most of Gram-positive and Gram-negative bacteria at concentrations of 50 and 100 micrograms/ml. Concentrations effective against fungi were somewhat lower (25-50 micrograms/ml).

Chemical, pharmacological and oncostatic properties of 5-(4'-hydroxybenzylidenoimino)-4, 6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole (compound IP-10).

Advanced preclinical studies on IP-10 preparation (4,6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole) were carried out. The drug was shown to be devoid of the irritating local effect, mildly toxic and hardly absorbing when administered per os. The toxic effect showed tendency toward cumulation.

Morphological changes in organs of mice induced by the combination of adriamycin and pustulan.

In CDF1 mice treated with the combination of pustulan (50 mg/kg) and a low dose of adriamycin (10 mg/kg), the profound changes were noted in the liver. They included both destructive lesions in hepatocytes and the proliferation of the RES. Similar morphological changes, though generally less pronounced, were observed in mice treated with a high dose of adriamycin (20 mg/kg).

Effects of combined treatment of L1210 leukemia with adriamycin and pustulan.

The development of L1210 leukemia transplanted i.v. into CDF1 or BDF1 mice was not affected by pustulan.