Antibodies to Epstein-Barr virus in nasopharyngeal carcinoma and other neoplastic conditions.

Sera from patients with nasopharyngeal carcinoma (NPC) or other malignant diseases and from apparently healthy controls were examined for Epstein-Barr virus (EBV) antibodies. A difference existed in the percentage of positive sera among the groups studied. High-titer antibody levels were observed in the NPC group, but no statistical difference was found among other groups of patients and controls. The data reaffirmed the association of EBV with NPC but did not support its etiologic role in the development of other human neoplasms.

P53 gene mutations in women with breast cancer and a previous history of benign breast disease.

Mutations of the p53 tumour suppressor gene are the most common genetic lesions in human cancers and have been reported in breast cancer as part of the Li-Fraumeni syndrome. In the present study, we determined frequencies and types of the p53 mutations in breast cancer tissues in women with a history of benign breast disease (BBD) identified in Florence, Italy, with (n = 6) or without (n = 10) a family history of breast cancer. Among the cases with a family history of breast cancer and BBD, 2 out of 6 had p53 gene mutations in cancer samples. 1 patient had a mutation at codon 248 and the other had double mutations at codons 243 and 241. In these cases, the p53 gene was also analysed in the tissue samples from previous BBD lesions; however, no mutations were observed (0 out of 6). These results suggest that the p53 mutations occur during advanced stages of tumour progression. In sporadic breast cancer cases with a history of BBD, p53 point mutations were observed of tumour progression. In sporadic breast cancer cases with a history of BBD, p53 point mutations were observed in four samples (4 out of 10). Two of these mutations turned out to be silent changes and one of the samples showed triple mutations at amino acid positions 267, 277 and 296. No p53 gene mutations were found in the breast tumour tissues of 10 additional women from the same area with a family history of breast cancer, but no previous BBD (0 out of 10). Family history of breast cancer does not appear to affect the frequency of p53 mutations in women with a previous history of BBD.

Establishment and characterization of a B-cell line from a patient with acute lymphoblastic leukemia.

A permanent lymphoblastoid cell line was established from the peripheral blood of a child with acute lymphoblastic leukemia. The cell line, designated SDK, grows in a stationary suspension culture, forming aggregates, in RPMI medium supplemented with 10% FCS, with a doubling time of 50-60 h. Immunologic markers and cytological features suggested that the SDK cells should be identified as being of B-cell origin. The cells failed to form rosettes with sheep erythrocytes, did not express T-cell antigens as defined by monoclonal antibodies, and exhibited surface and cytoplasmic immunoglobulin determinants. Chromosome analysis revealed the presence of three cell populations with (a) 46XY; (b) t(8q-; 14q+) or 2p-; 14q+) and (c) cells with unidentifiable markers. SDK demonstrated susceptibility to TPA-induced differentiation toward plasma cells.

Expression of ets family of genes in systemic lupus erythematosus and Sjogren's syndrome.

We have examined the expression of three members of the ets family of genes, ETS1, ETS2 and ERGB/Fli-1, in lymphocytes from patients with systemic lupus erythematosus and in two murine autoimmune model systems. The ERGB/Fli-1 gene is expressed at a higher level in lymphocytes from autoimmune disease patients than healthy individuals. In addition, we found that the ERGB/Fli-1 gene expression is higher in splenic T-cells from lupus prone mice and in infiltrating lymphocytes in the salivary glands of HTLV-I tax transgenic mice. Taken together, these results suggest that the elevated expression of the ERGB/Fli-1 gene in lymphocytes may be a prelude to the development of autoimmune diseases.

Relative paucity of p53 gene-mutations in male breast carcinomas.

Mutations of the p53 suppressor -ene are the most common genetic lesion noted in human cancers and appear to be relatively common (30%) as somatic cell mutations in female breast cancer. p53 mutations have also been frequently reported in familial breast cancers as in Li-Fraumeni syndrome (LFS). Males with breast cancer are far rarer than females. We investigated the mutational spectra of the p53 gene in male breast cancers. Of 10 samples analyzed for p53 mutations in exons 5, 6. 7 and 8, only two showed point mutations corresponding to amino acid residues 248 and 290. One of the point mutations turned out to be a silent change, thus representing only DNA polymorphism. Although the number of male breast cancer samples thus far examined is small, the p53 mutations in male breast cancer (10%), unlike females (30%), does not appear to be as frequent.

Establishment and characterization of a hepatoblastoma cell-line from a patient with secondary acute myeloid-leukemia.

A girl who had been treated, apparently successfully, with surgery and chemotherapy for a hepatoblastoma, fell ill two years later with what was diagnosed as an AMF M(4). A cell line was established from her peripheral blood. This cell line had epithelial morphology and grew both in suspension culture and as a monolayer. The cells were positive for epithelial surface markers, including the liver-specific alpha-fetoprotein, but not for leukocyte markers. The cell-line's karyotype was markedly abnormal. It did not have any specific aneuploidies or any other aberrations characteristic of leukemias; instead it had gains of 2q and chromosome 20, the most common cytogenetic changes in hepatoblastoma. It is most likely that the patient had a relapse of hepatoblastoma with massive seeding of the blood leading to a leukemia-like picture without, of course, excluding other possibilities.

Regional intraarterial infusion of methotrexate with leucovorin rescue in a rat tumor model.

Walker 2S6 carcinosarcoma was transplanted in the paw of 52 male Wistar rats. A week later, the animals were divided into 6 separate groups and treated in different ways, as follows. Group I (control): no treatment. Group II: femoral artery ligation (FAL). Group III: ligation-intraarterial chemotherapy (LIC) with methotrexate (MTX). Group IV: the same treatment followed by leucovorin rescue (LIC+RES). Group V: tourniquet intraarterial chemotherapy and rescue (TIC+RES). Group VI: the same treatment applied via the iliac artery (iliac TIC+RES). The best results (primary tumor eradication: 8/10 cases, propagation of the tumor to the inguinal region: 4/10 cases, necroses of the distal part of the paw: 0/10 cases, p > 0.05) were observed in group VI, where iliac LIC+RES was performed. Analysis of the treatment's mechanism of action revealed that there is an area of optimal treatment in the middle of the limb, and two peripheral zones of under-treatment. At the proximal zone (inguinal region) propagation of the tumor can occur, whereas at the distal zone necrosis of the paw can be manifested.

Heat turn-over during hyperthermic peritoneal perfusion. An experimental study.

In order to study heat turnover, 3 experimental models of chemotherapeutic hyperthermic intraperitoneal perfusion (CHIP) were tested, using 15 rabbits divided into 3 separate groups of 5 animals each. A normal saline perfusate, containing a standard concentration of 10 mg of methotrexate per liter, was recycled through the peritoneal cavity, transmitting, in every group, 6,000 calories of heat. In model I, heat transmission was achieved by a high temperature gradient, in model II by the increased thermocapacity of a great priming volume of perfusate, using a peritoneal expander, and in model III by a high flow rate. The rectal and oesophageal temperatures were recorded and the indications converted to calories. The bowel showed a statistically higher heat uptake in model III, whereas thermodilution was more important in model I and especially in model II. The results indicated that the ideal model of CHIP must combine efficiency and safety. The temperature gradient must be ample, but within safe limits, only for cost-efficiency reasons. The priming volume ought to be abundant enough to achieve homogeneity and constancy of heating, but not excessive, in order to avoid abdominal distension and bodily thermo-dilution. Under these conditions, the target level of heating, always calculated in calories, must be administered by appropriate adjustment of the perfusion flow rate.

Human papillomaviruses in cervical cancer I. HPV-16 and 18 predominate in the Greek population.

Human papillomaviruses (HPV) and their role in carcinogenesis have been the subject of extensive investigation Specific types of HPV have been associated with cervical carcinoma HPV 16 and 18 are mainly associated with malignant progression and considered "high risk" viruses Using Southern blot analysis and in situ hybridization we investigated the presence of papilloma viruses in cervical carcinoma patients as well as appropriate controls. The results presented here support the aetiological role of HPV 16 and 18 in cervical carcinoma and demonstrate the prevalence of these viruses in Greek women. The role of viruses in carcinogenesis in well established in almost all species from fishes, to birds, to mammals. Although not well circumstantiated, viruses probably play as-great a role in human cancer as in other species. The role of human papillomaviruses (HPV) not only in benign proliferations, but also in a number of malignancies has long been postulated (1,2). Presently over 20 HPV types have been identified and there is evidence now associating specific types with certain human anogenital cancers, notably cervical cancer (3,4). Advance neoplasias such as squamous cell carcinomas are associated with types, 16,18 and 31, with type 16 prevailing in these lesions (5,6). In this paper we shall present evidence which extends and confirms that previously reported on the prevalence of HPV 16 and 18 in Greek women.

Human papillomaviruses in cervical cancer: II. Application of PCR and in situ hybridization and HPV significance.

Human papillomaviruses especially type 16 and 18 are associated with cervical cancer. These viruses encode transforming proteins which are capable of binding and form complexes with p53 protein. Tumour-tissue samples from women with cervical cancer as well as normal controls were analysed for the presence of HPV and the expression of p53 by in situ hybridization and PCR analysis. The results showed that HPV 16 and 18 predominated in all pathological conditions and that p53 expression was related to the presence of certain types of HPV. The significance of HPV in cervical carcinoma is well demonstrated.

Nasopharyngeal carcinoma: Epstein-Barr Virus significance.

Thirty-one cases of NPC were investigated by in situ hybridization, PCR analysis and serology to assess the presence of EBV and to interrelate these findings. Statistical analysis showed a significant correlation between the probability of detecting EBV and NPC. There was no significant association between in situ hybridization, PCR and serology. Tumor size correlated with EBNA, but no correlation between smoking and NPC was found.

Histological types of nasopharyngeal carcinoma as compared to EBV serology.

One hundred and thirteen cases of nasopharyngeal carcinoma (NPC) were classified histologically according to the WHO-, French and Cologne systems. The various histological tumor types were then correlated with data on Epstein-Barr virus (EBV) serology (EA, VCA, EBNA, CF, IgA-VCA). The results showed non-keratinizing carcinomas with lymphoid infiltration, and undifferentiated carcinomas to be associated with significantly elevated anti-EBV titers. These two tumor types can be easily grouped together according to the French classification scheme as "undifferentiated carcinoma of the nasopharyngeal type (UCNT)". Such a procedure, which may have therapeutic implication, simplifies the rapid diagnostic screening of NPC patients and also may enhance the reproducibility of histological tumor typing.