A case report of testicular tumors in non-twin siblings is presented. A 42-year-old male was admitted to Kansai Electric Power Hospital with the complaint of swelling of the left scrotal contents. Left radical orchiectomy was performed with the diagnosis of a left testicular tumor. Histological examination revealed a seminoma of the left testis. Fifteen years later, his 43-year-old younger brother was admitted to Osaka University Hospital with the complaint of painless swelling of the left scrotal contents. Left radical orchiectomy was carried out with the diagnosis of a left testicular tumor. Histological examination showed a seminoma of the left testis. The former patient had a history of a scrotal trauma, but there was no history of orchitis or cryptorchism in these two siblings. To our knowledge, there have been reported 44 sets of testicular tumors in siblings. Eleven of these sets appeared in twins, while the other 33 sets were described in non-twin siblings. We discussed the 45 cases including our case of testicular tumors in siblings.

Complete mole is a form of natural allograft since it carries paternal genetic traits alone which differ antigenetically from those of the mother. Successful growth of mole is likely to be immunologically protected. Because the immune system is genetically controlled, the effect of HLA system on the development of androgenetic ova into moles is a subject of interest. In this study, HLA-A and -B specificities in the mole and its parent were compared with the ones of general population in Japan. Fifty-six molar tissues were used for absorption of HLA specificities determined by HLA typing of each patient and her husband. Results obtained were as follows. 1) HLA antigens were expressed on all molar tissues examined, and those antigen were derived selectively from paternal specificities, but not maternal one. 2) Fifty molar tissues had received the paternal haplotype and remaining six molar tissues had showed heterozygosity which were consistent with the paternal diplotype. Those suggested the fertilization of an empty egg by two spermatozoa. 3) A significant association was found with decreased frequency of HLA-Aw19 and HLA-Bw22 in the molar tissues (3.6% and 2.7%) compared with general population (16.4% and 11.5%). 4) The compatibility of HLA-A and -B types among moles with sequelae and the parents was higher(81%) than the estimated value(68%) in the control families. As a result, HLA analysis was useful for distinction of zygosity of molar tissues. Decreased frequencies of HLA-Aw19 and -Bw22 in the mole were assumed to be resulted from the wastage of androgenetic ova.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study was undertaken to disclose the mechanism which concerned to the propensity to malignancy of complete moles. For this purpose, the incidence of chromosomal aberrations and sister chromatid exchanges(SCE) after the administration of 0-30 ng/ml mitomycin C(MMC) were compared among cells cultured from molar and normal villi, and peripheral blood. Abnormally high induction of chromosomal aberrations and SCE was observed in molar cells without MMC treatment when compared with those of the remaining two cells. Then, higher susceptible responses to the low concentration of MMC were also noticeable in molar cells rather than two kinds of cells. As a result, it was assumed that chromosome instability possibly played an important role for choriocarcinogenesis of molar cells. Homozygosity of paternally derived genes may be responsible for this chromosome fragility. Six chromosomal bands (1q 21, 2p 24, 2p 13, 7q 31, 8q 22, 13q 33) were preferentially involved in the formation of chromosomal aberrations occurred spontaneously in molar cells. Four of these six bands were identical with the break points necessary for the production of the marker chromosomes in various tumors described previously, though one band was consistent with the N-myc oncogene locus. Thus, the possible association between chromosome rearrangements occurred in those six bands and the choriocarcinogenesis was assumed, though further accumulation of cytogenetic and molecular data was absolutely necessary.

The nineteenth kindred of familial pheochromocytoma in Japan is reported. A 13-year-old girl had an extra-adrenal pheochromocytoma and her 40-year-old mother had a right adrenal pheochromocytoma. This is the first case of an extra-adrenal pheochromocytoma in familial pheochromocytoma. A statistical analysis was performed on the 46 cases in 19 kindreds reported so far in Japan.

Complete hydatidiform moles may originate from either the fertilization of an empty egg by a haploid sperm followed by duplication (producing a monospermic, homozygous mole) or the fertilization of such an egg by 2 haploid sperm (producing a dispermic, heterozygous mole). This difference in the mechanism leading to the formation of complete moles raises the question of whether the risk of subsequent malignancy is influenced by the zygosity of the mole. In the research reported here, we compared the incidence of postmolar sequelae between patients with homozygous and heterozygous moles. Using chromosomal heteromorphism, HLA and PGM1 polymorphisms, we established the androgenetic origin of complete mole in 82 of 91 cases. Homozygosity was confirmed in 51 moles, and we found 10 heterozygous moles. Five of 10 patients with heterozygous moles developed postmolar trophoblastic disease, whereas only 2 of the 51 patients with homozygous moles had postmolar trophoblastic disease (an additional 5 patients showed signs of degenerating residual trophoblasts). A high incidence of sequelae after the expulsion of heterozygous moles suggests that the heterozygous constitution of allelic genes plays an important role in the process of malignant transformation of trophoblasts.

The presence of a transforming gene in the DNA of bone marrow cells from patients with myelodysplastic syndrome (MDS) was studied using an in vivo selection assay in which NIH 3T3 cells transfected with human DNA were injected into nude mice in order to observe the growth of the tumor. The transforming gene was present in 12 out of 18 cases. The Alu sequence was demonstrated in the tumor grown after injection of transfected NIH 3T3 cells from 10 patients. Among these 10 Alu sequences, the human N-ras oncogene was present in 3 cases. Analysis of nucleotide sequences of the exons of human N-ras oncogenes cloned from the tumors revealed a single point mutation of the codon encoding the 13th amino acid of exon 1 from guanine to cytosine in all 3 cases of MDS. A one-year follow-up study of these MDS cases showed that in the patients positive for the transforming gene, the disease state progressed from PARA, PASA to RAEB or from RAEB to acute leukemia in 6 out of 7 cases, while in the 6 negative patients, no change was observed in their disease states. It was considered that the mutation of the N-ras gene at the 13th amino acid codon of exon 1 was fairly specific to MDS and that presence of the transforming gene may be used for predicting the progress of the disease.

We have identified a novel transforming gene, hst, from a human stomach cancer, and the results of our studies on hst are reviewed. From a total of 26 patients with stomach cancer, DNAs from 21 of their stomach cancers, 16 metastatic lymph node tumors from stomach cancers and 21 non-cancerous stomach mucosae, were assayed for their transforming activity to NIH3T3 cells. Three samples of DNA were positive; one was from a primary stomach cancer, the second from a non-cancerous portion of the same patient's stomach mucosa, and the third from a lymph node metastasis stomach cancer from a different patient. A portion of the transforming gene and near full-length cDNA for this gene was cloned. From the results of cDNA sequence and Southern blot analyses, this transforming gene was shown to have no homology with the oncogene reported previously. We applied the term, hst (human stomach cancer), to this novel transforming gene. The hst gene was found to be responsible for acquisition of transforming activity of all the three different samples of DNAs.

Oncogene studies have become an area of general interest in the field of cancer research following the identification of the cellular counterparts of viral oncogenes. It may be possible to attribute some steps in the initiation or progression of cancer to point-mutations or altered expression of proto-oncogenes. Elucidation of the normal functions of proto-oncogene products as growth factors, growth factor receptors or other growth regulatory elements will facilitate biochemical analysis of the mechanisms of normal and malignant cell growth.

During the period from 1950 to 1983, 1633 patients with cervical carcinoma in situ (CIS) were treated at the Cancer Institute Hospital, Tokyo. These cases were retrospectively investigated to determine the relation between the epidemiologic features and social phenomena. The number of patients with CIS tends to increase year by year. The incidence of CIS tends to be larger in the younger age group. Delay in the age of primiparity, a lower incidence of multiparas and a higher incidence of artificial abortion were seen in the CIS patients. Recurrence was seen in 0.4% of the CIS patients, and the recurrence site was most frequently the vaginal stump.

The c-erbB-2 gene was first identified by virtue of its cross-hybridization with v-erbB. Nucleotide sequence analysis of complementary DNA clones suggested that the c-erbB-2 gene encodes a growth factor receptor similar to that for EGF. Antibodies against the carboxyl terminal sequence of the c-erbB-2 protein immunoprecipitated a 185-kDa glycoprotein which showed protein-tyrosine kinase activity in vitro. Despite the extensive similarity between the c-erbB-2 protein and EGF receptor, neither EGF nor TGF-alpha bound to the c-erbB-2 protein. Phosphorylation of the c-erbB-2 protein was stimulated by TPA via protein kinase C in vivo. EGF also induced phosphorylation of the c-erbB-2 protein. This phosphorylation occurred not only on serine and threonine residues but also on tyrosine residues. Preliminary data suggested that the latter was mediated by the kinase activity of the EGF receptor. Southern blot analysis of DNAs from primary tumors revealed that the c-erbB-2 gene tends to be amplified in adenocarcinomas, mostly of the stomach and the breast. By screening both human genomic and cDNA libraries using v-yes DNA as a probe, we obtained DNA clones of the c-yes gene, the pseudogene of c-yes, c-fgr gene and c-src gene and two novel yes-related genes, fyn and lyn. Complete nucleotide sequence analysis of the cDNA clones of c-yes, fyn and lyn revealed that these genes encode proteins similar to p60src both in size and sequence.

Cultured murine erythroleukemia (MEL) cells can be induced to differentiate into erythrocytes. During this induced differentiation, a certain type of sequentially programmed gene expression and repression appears to occur in addition to the induction of globin mRNA. This system provides a commitment model for erythrodifferentiation and decancerization. By transfection of a beta-globin/TK chimeric gene into a B8/3 cell line, we examined the regulatory factors controlling beta-globin gene expression. Our results suggested that the timing of the appearance of inducible, positive trans-acting factor (s) and activation of chromatin conformation occur during induction. We demonstrated that a novel MEL cell line, TSA 8, could be induced to be committed to CFU-E, an erythropoietin-mediated progenitor cell, with the addition of DMSO. In the commitment process, we observed an asymmetric cell division, which could explain the self-renewal and the commitment of multipotential hemopoietic stem cells. For this commitment, the receptor for erythropoietin is required, but is insufficient and the other factor (s) are induced in the earlier phase of induction. Finally, we found that erythropoietin induced two signals for proliferation and differentiation of the progenitor cells and that these two signals are not coupled.