A ring 12 chromosome was found in a male child with minor phenotypic alterations. No obvious loss of chromosome material was detected. Since there is no other case of a ring 12 in the literature, it was not possible to determine whether the phenotype was due to (invisible) terminal deletions or to karyotypic variation. In lymphocyte cultures 9% of the cells had either no or two rings, but the patient’s RBC had normal activities of the enzymes lactate dehydrogenase B and peptidase B, whose loci are located on the proximal portions of 12p and 12q, respectively. Dicentric rings were found in 37 cells, and all had two active centromeres, in contrast with the relatively frequent finding of latent centromeres in translocated dicentric autosomes. Two latent centromeres were found in one tricentric “rod-shaped” open ring 12, probably derived from a tetracentric ring. It is postulated that latent centromeres are rare in ring chromosomes because, if consistent suppression of centromeres in excess of one took place at each duplication, rings with four, eight, or more centromeres would be formed rather frequently, which is not the case.
Data on the long-term treatment of myeloma bone disease with bisphosphonates are scanty. In a prospective pilot trial we evaluated the effect of long-term parenteral administration of dichloromethylene bisphosphonate (Clodronate), in addition to standard chemotherapy, in 30 patients with active myeloma bone disease. Patients were treated with a mean of 4 courses (range 2-8) of Clodronate: 300 mg/day i.v. for seven days followed by 100 mg/day i.m. for 10 days, administered at a mean interval of 4 months (range 3-6). The median follow-up was 24 months (range 8-36). Clodronate reduced bone pain rapidly and significantly, and reduced the mean values of the biochemical indices of bone resorption to within normal limits; these effects were maintained throughout the follow-up. In three hypercalcemic episodes serum calcium became normal after 2-5 days of treatment with Clodronate. No toxic or side effects were noticed. The occurrence of skeletal morbidity in patients treated with Clodronate was compared with that observed in the control group of myeloma patients (p less than 0.001) in severe bone pain as well as in the incidence of new osteolytic lesions and pathological fractures (p less than 0.001). Supportive Clodronate therapy contributes significantly in controlling the progression of myeloma bone disease.
Beta-2-microglobulin ((32-MG) and CEA were measured in the sera of 186 cancer patients divided into two groups: at diagnosis (D) and at follow-up (F). Four groups of patients at diagnosis (D-I, D-II, D-III and D-IV according to TNM classification) and two at follow-up (in remission, F-RS, and in relapse, F-RP) were considered. All patients had normal serum creatinine and urea concentrations. β2-MG values in D-I were significantly (p < 0.01) lower than those for D-II and D-III, while in D-IV they overlapped those of group D-I. No significant difference was observed between F-RS and F-RP patients. Patients with serum CEA concentration > 100 ng/ml revealed pVMG values close to those of groups D-I and D-IV. In 10% of patients in stage IV or with CEA > 100 ng/ml pVMG was lower than the mean value of the healthy population. From data pVMG is probably produced by an aspecific reaction to the tumor and the decrease in advanced stages could express a decreased immunologic response. On the other hand, high serum β2-MG in the initial stages of the neoplasia may reflect an elevated cell turnover, while low β2-MG during the final stages may be due to a weak expression of the protein by highly undifferentiated cells.
CA 125 and CA 15.3 antigens were determined by enzyme immunoassay in 78 patients with ovarian cancer for a total of 540 determinations. The antigens were also investigated in sera from 100 women with other gynaecological diseases, 82 lung cancer patients and in 39 pleural fluids of varying origin. CA 15.3 reference values were evaluated in 91 healthy women (cut-off: 25 U/ml). CA 15.3 sensitivity at diagnosis (60%) and for detecting relapse (44%) was lower than that of CA 125 (90% and 64.7%, respectively). However, CA 15.3 does not increase with aspecific mesothelial cell reaction and thus it is more specific than CA 125. Combined use of the markers during follow-up improves early detection of relapse (at least one of the two was positive in 79% of cases). Therefore both CA 15.3 and CA 125 should be routinely determined for the detection and monitoring of ovarian cancer.
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