An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis--this stiffening up limite, rather than accentuates, the value and reproduction potential of a stud bull past prime. But associated with these abnormalities--and not seen in age-matched cows of comparable breeds--are fascinating endocrine neoplasms that might suggest a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies, that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C-cells" of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma--in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro models with multiple drug resistance (MDR) phenotype have been frequently related to hyperproduction of the 170 kd membrane glycoprotein, the so-called 170 GP. This protein is a pump able to extrude from cytoplasm drugs with various structures and mechanisms such as doxorubicin (DXR) or vinblastin (VLB). The MDR1 gene encodes the GP 170. MDR1 gene expression is low in most of the normal tissues, but high in some tissues such as colon, kidney, or liver. In these tissues, the GP 170 would ensure a detoxifying function related to cellular toxic compounds. There is a broad range of MDR1 gene expression in human tumors as a result of several factors. Of particular importance are the tissue origin from which the cancer derives and previous chemotherapy. In some cancers which often exhibit acquired chemoresistance, such as non Hodgkin's lymphomas, leukemias, sarcomas or neuroblastomas, an increase of MDR1 gene expression following previous chemotherapy has been frequently observed. Moreover in these cancers, a relationship between MDR1 transcript levels and clinical response to chemotherapy could exist as shown in several studies including one of ours. Hematosarcoma in the adult and some pediatric cancers seem to be models in which MDR1 gene expression may have a clinical relevance. Thus, an increase of MDR1 gene expression during the course of chemotherapy would lead the clinician to choose "non MDR related" agents such as DXR, VLB; or to use agents that are able to reverse MDR phenotype.

Thyroid carcinoma and familial intestinal polyposis are not accidentally associated. A new case is described which, along with the other 32 cases already published, reveals an incidence of thyroid carcinoma 100 times higher in patients with polyposis than in the general population, and 160 times higher in female patients under 35 years of age. Several features of these thyroid carcinomas can be pointed out: greatest incidence in women, occurrence at a young age, existence of a papillary tumor appearing independently from the evolution of the polyposis, and probably familial disease. It is therefore necessary to systematically examine the thyroid body in all subjects with familial intestinal polyposis.

Genomic DNA extracted from heavily infiltrated spleens of 5 patients with hairy cell leukaemia was hybridized with genomic probes for immunoglobulin genes. The rearrangement pattern, correlating well with the immunohistochemical findings, was that of a clonal B-cell proliferation in all cases. Analysis of the lambda light chain genome with two different probes enabled more accurate localization of the clonal rearrangements within this genome. A small additional T-cell population identified in 3 cases was immunogenotypic of polyclonal (reactive) nature.

The authors describe two cases of bile duct carcinoma affecting two patients with hereditary non polyposis colorectal carcinoma (Lynch's syndrome). These two cases were observed in 14 families composed of 283 persons, 58 of whom were affected by hereditary non polyposis colorectal cancer and 15 by gynecological carcinomas. Bile duct carcinoma can therefore be associated with Lynch's syndrome but seems less frequent than observed in familial polyposis or Gardner's syndrome.

We searched for colorectal tumors in asymptomatic patients older than 40 years with family history of sporadic colorectal cancer (only first degree relatives). One hundred and four patients at risk had a left-sided (n = 60) or a total colonoscopy (n = 44) and were compared to 104 control patients, matched for age, sex and type of colonic investigation. Three cancers were detected in the group at risk, 1 in the control group (NS). One or more adenomas without carcinoma were found in 10 percent of the patients at risk and in 9 percent of the controls (NS). There was no difference between groups in the number, size, histologic type, degree of dysplasia, or location of adenoma in the colon. These results do not exclude a family predisposition to sporadic colorectal cancer or adenoma. Because of the low rate of adenoma detection, relatives of patients with sporadic colorectal carcinoma but without personal risk factors cannot be considered as a high risk group for colorectal endoscopic screening.

A 21-year old male patient with Philadelphia chromosome-positive chronic myeloid leukaemia received an autologous bone marrow transplant in consolidation of the 2nd chronic phase. The bone marrow had been treated with mafosfamide in adequate doses. The post-transplantation course of the disease was marked by an inversion: the duration of the 2nd chronic phase was more than 4 times longer than that of the first one, suggesting some degree of effectiveness of autologous bone marrow transplantation performed in the 2nd chronic phase and/for of the in vitro treatment of the bone marrow with mafosfamide. Cytogenetic monitoring was pursued throughout the course of leukaemia: regression of the Philadelphia chromosome was only partial and transient, and 3 clones appeared, each of them involving chromosome 1, for which mafosfamide was most probably responsible.

Experimental and epidemiological studies concur to show that carcinogenesis is a multistep process. Over fifty years ago, two steps were identified which were termed initiation and promotion. Initiation is caused by a defect in the cellular genome which is generally provoked by a genotoxic agent. Promotion generally involves epigenetic mechanisms. In those human cancers in which detailed studies have been carried out, the number of steps appears to be generally greater than 2, from 3 to 6. Epidemiologic studies have underlined the long duration and the complexity of human carcinogenesis and show that non gene-toxic agents may play an important role in progression from a premalignant to a fully malignant cell. A large proportion of human cancers have a multifactorial origin. Important advances have been made recently. They have emphasized the usefulness of close cooperation between basic research and epidemiologic studies for the elucidation of the mechanisms involved in the origin of human cancer.

To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans and which types of short-term tests are more relevant for predicting human hazards, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in human and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxicity among four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 66) was determined. Each of the groups 1, 2A and 2B contained a high proportion (80-90%) of genotoxic carcinogens, which were also multiple-species or multi-tissue carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and many group 3. Although limited by the data-base available through the Monographs Series, this analysis implies that genotoxic carcinogens add more to the human cancer burden than non-genotoxic carcinogens. Thus, the continued use of in vitro/in vivo short-term tests, involving as endpoints DNA chromosomal damage, to identify genotoxic carcinogens or the isolation of carcinogenic components in complex mixtures is fully justified. It is concluded that a) an agent or complex mixture with unknown carcinogenic potential showing sufficient evidence of activity in genotoxicity assays in vitro or in vivo is likely to represent a hazard to humans and b) an agent or complex mixture showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity for rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall one can deduce that identification and subsequent lowering of exposure to genotoxic agents/mixtures will remain one of the main goals for primary cancer prevention in man.

The authors report their observations on acute myeloid leukemias associated with the 8;21 translocation. Two cases have less than the required percentage of blasts for the cytological diagnosis of acute myeloid leukemia. In one case, the 8;21 translocation is superimposed on a constitutional trisomy 21. Conclusions from the 4th International Workshop on chromosomes in leukemia are highlighted, as well as certain new data relative to the biology of acute myeloid leukemias.

Experimental studies of cell malignant transformation have shown that such transformation requires the alteration of genes that can control the expression of the transformed phenotype. In human oncology, the role of genes that suppress malignant transformation is suggested by the fact that specific genic deletions have been detected by polymorphism-detecting probes in many malignant tumours. The only oncosuppressor gene that is characterized at the moment is the inactivated RB gene in retinoblastoma. Molecular biology studies have shown that in retinoblastoma and other malignant tumours this gene is altered in its structure or expression. In addition to retinoblastoma, nephroblastoma in children and colonic carcinoma constitute models for the study of oncosuppressor genes in human oncology.

Immunologic typing has demonstrated considerable heterogeneity among the acute leukemias. The most significant recent advance has been development of monoclonal antibody techniques. Some markers identified using these techniques seem to be specific for a given stage of maturation of one lymphoid or myeloid cell line. Most acute lymphoblastic leukemias (ALLs) are malignant proliferations whose differentiation appears to have become 'stuck' at one stage of maturation. Results of immunologic typing correlate well with the other clinical and biological data. For prognostic purposes, several patterns can be identified. Among B line ALLs, four varieties have been differentiated, i.e., CD10 negative ALLs, common ALLs, pre-B ALLs, and B ALLs. T ALLs include a broad spectrum of heterogeneous proliferations whose immunologic classification is made difficult by the large number of phenotypes encountered. Among acute myeloblastic leukemias (AMLs), some highly undifferentiated forms have been recognized, by means of immunologic typing, as originating in one of the myeloid cell lines. However, the nosologic and prognostic significance of these studies is less obvious than in ALLs.

The familial observations of multiple endocrine neoplasia are rare such that there are only four known cases in France. In our family, two children and their mother are affected. Their mother, at the age of 16, was operated on a medullary thyroid cancer (MTC) and now presents with a phaeochromocytoma. Vanessa also presents with a MTC but without either phaeochromocytoma nor hyperparathyroidism. Her sister was then systematically screened and the only positive test was Pentagastrin. This allowed us to practice a thyroidectomy which will confirm the presence of a medullary thyroid cancer. In all three cases, the Marfan-like features, the abnormal facies and lingual neuromas are all features of the disease. These observations are of interest for the systemic familial screening of MTC by tumour markers (calcitonin, ACE) and by the Pentagastrin test, while awaiting for the use of specific probes on chromosome 10.