In order to clarify the role of spontaneous apoptosis of non-Hodgkin's lymphomas in the growth regulation system, apoptotic indices (AI) assessed by DNA nick end-labeling and proliferative activity, estimated in terms of KI-67 labeling indices (KI) and mitotic indices (MI), were compared. In addition, expression of bcl-2, p53 and c-myc was also examined in relation to these indicators. For this study, 103 lymphoma cases were used, comprising 72 of B cell and 31 of T cell origin (42 nodal and 62 extranodal). AI, KI and MI were significantly increased in line with bcl-2 negativity and p53 positivity, and there was no relation to the T, B cell classification or expression of c-myc. These indicators positively correlated overall. Positive correlation was stricter in groups believed to represent a good prognostic predictive factor, such as B cell origin, bcl-2(+), p53(-) and c-myc(-). Significant cross-correlation was noted only between bcl-2 versus T, B cell classification. However, no inverse correlation between bcl-2 and p53 was evident. These results suggest, in non-Hodgkin's lymphomas, that apoptosis plays an important role together with proliferative activity in counter-balancing tumor volume, and is strictly linked to bcl-2 expression, less so to p53 expression, but independent of T, B cell classification and c-myc expression. Apoptotic indices may be a predictive indicator for prognosis similar to proliferative activity.

Apoptosis↗

PubMedDate not supplied

Hyperthermic treatment of canine tibia through RF inductive heating of an intramedullary nail: a new experimental approach to hyperthermia for metastatic bone tumours.

Although the incidence of metastatic bone tumours is recently increasing, the local control rate of conventional treatment modalities is not satisfactory. If an intramedullary nail for the fixation of a weakened bone with metastatic lesions can be used as a heat-generating material for hyperthermia, the treatment result is expected to improve. This new approach to hyperthermic treatment of bone tumours has been investigated in a canine tibia. An intramedullary nail made of stainless steel was put into a medullary canal of a canine tibia. The leg was exposed to an alternating magnetic field of 100 kHz in the frequency and 100 Oe in the maximum intensity. The nail was inductively heated for 60 min. The temperature of the nail > 50 degrees C and the cancellous bone 5 mm from the nail was heated to a therapeutic temperature, 42.5 degrees C. After a bone labelling with tetracycline and calcein, the dogs were killed 2, 4 and 12 weeks after the heating. The area of osteonecrosis was evaluated by fluorescence microscopy analysis. The heated cancellous bone around the nail showed osteonecrosis in 2 weeks after the treatment, but it recovered completely in 12 weeks. This experiment has demonstrated the heating capability of the new hyperthermic technique and minimal toxicity to the bone, and suggests the clinical application to metastatic bone tumours.

Animals↗

PubMedDate not supplied

Anti-tumour effects of localized hyperthermia on an experimental bone tumour using an intramedullary nail.

A new localized hyperthermia system for an experimental bone tumour in the rabbit tibia was developed. This system was composed of an induction coil, generator and a Kirschner wire, which was inserted into the medullary canal of the tibia as a heat-generating ferromagnetic implant. The metastatic bone tumour model was created by implantation of VX2 carcinoma in the medullary canal of the tibia diaphysis. The days after VX2 implantation, hyperthermia was induced for 50 min. Three weeks after the treatment, rabbits were sacrificed for histological and radiological evaluation. According to the semi-quantitative scoring system, anti-tumour effects of the single dose of hyperthermia was noted radiologically (p < 0.01) and histologically (p < 0.05) where the temperature was at a sufficient level to cause hyperthermia (> 42.5 degrees C). This new heating method, which is relatively simple and clinically applicable, appears to be promising for the treatment of metastatic tumours of the long bone.

Animals↗

PubMedDate not supplied

Modulation of O6-methylguanine-DNA methyltransferase-mediated 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea resistance by O6-benzylguanine in vitro and in vivo.

Our previous studies have indicated that O6-methyl-guanine-DNA methyltransferase (MGMT) is a key factor determining tumor cellular resistance to 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). This study describes the modulation of MGMT-mediated ACNU resistance by O6-benzylguanine pretreatment. The ACNU sensitivity of MGMT proficient human tumor HeLa S3, SMMC-7721, and Cc801 cells in tissue culture was markly enhanced by 10 mm O6-benzylguanine, and a correlation between the extent of enhancement and the level of MGMT activities was observed. A single i.p. injection of 100 mg/kg of O6-benzylguanine caused a complete inhibition of MGMT activities in HeLa S3 tumor xenografts and combination of O6-benzylguanine with ACNU (7.5 mg/kg) significantly inhibited HeLa S3 tumor growth. The results demonstrated that O6-benzylguanine could be used as a potential adjuvant in combination chemotherapy with ACNU to treat MGMT proficient tumors.

Animals↗

PubMedDate not supplied

Loss of heterozygosity and tumor suppressor gene mutations in chondrosarcomas.

Loss of heterozygosity (LOH) of chromosomes 13q and 17p and mutations of the retinoblastoma (Rb) and p53 gene were studied in 28 tumors from 22 patients with chondrosarcomas. Allele loss at polymorphic loci on 13q was found in 36% of tumors and the frequency was much higher in grade II (56%) or high grade (40%) tumors than in grade I tumors (18%). LOH of 17p, which was detected in 25% of all tumors, was of low frequency in low grade tumors (8% in grade I and 20% in grade II), whereas 80% of tumors with high grade tumors were positive for LOH. These observations may imply that LOH on 13q and 17p contributes to the tumor development at different stages. In low grade cases (grade I and II), tumor recurrence was observed more frequently in primary tumors with LOH on 13q (86%) than those without (8%), suggesting the significance of LOH analysis in the assessment of biological behavior of tumors. Structural alteration of the Rb gene was found in one dedifferentiated tumor, and point mutations of the p53 gene were found in all of five high grade tumors, indicating that high grade chondrosarcomas were genetically equivalent to other high grade sarcomas such as osteosarcomas.

Adolescent↗