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.

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.

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.

Interactions between human fibroblasts and HeLa cells in vitro.

Affinity toward each other was demonstrated in co-cultures between HeLa cells and fibroblasts originating from human tumor stromal or normal tissues. Both cell types in the mixed cultures (ratio 1:1, 1:2, 2:1) proliferated normally as shown by 3H-thymidine labeling index estimation for up to 48 hr of co-culture. At ratios of fibroblasts: HeLa lower than 1:10, fibroblasts were eventually eliminated after serial passaging. It was shown that 3H-nucleotides could be transferred between heterologous cells in either direction. Contact of cells was essential for this phenomenon. Transfer of the label from HeLa to fibroblasts required a longer interaction time and was evidently lower than the transfer from fibroblasts to HeLa. 3H-thymidine incorporated into the DNA of either cell type could not be transferred from one cell to another. The model provides a means for studying neoplastic X normal (or tumour stromal) cell interactions in vitro.

Interactions between human lymphoblastoid cells and human fibroblast feeder layers in vitro.

Lymphoblastoid (LB) cells interact in vitro with human fibroblasts. Cell complexes can be dissociated by trypsin treatment. Binding on fibroblasts is higher for Epstein-Barr virus-producer LB cells than for nonproducers, and depends on the origin of the fibroblastic cells. Stromal fibroblasts isolated from a metastatic lymph node tumor exhibited a highly increased potency of binding LB cells in comparison with fibroblasts isolated from normal breast epidermis or the primary breast tumor from the same patient. After a 10-hour interaction period, LB cells undergo abnormal divisions giving rise to the formation of 'mini cells'.

Uncontrolled growth of tumour stromal fibroblasts in vitro.

The disturbance of the growth control mechanisms in tumour cells in vivo may be manifested as uncontrolled growth of the tumour stroma in vitro. Stromal fibroblast-like finite cell lines produced from benign or malignant human breast tissue specimens exhibited cell overlapping which ranged from multilayers to dense piling up colonies, while cells derived from normal tissues exhibited intense contact inhibition of growth and locomotion, under the same culture conditions. 6 out of 13 lines derived from malignant tissues and 2 out of 5 lines derived from benign lesions exhibited the phenomenon of 'periodic appearance of piling up colonies'.