Hisako Ochi

Characterization of a New Primary Human Pancreatic Tumor Line

A primary human pancreatic tumor line (BxPC-3) has been established from a biopsy specimen of a histologically confirmed adenocarcinoma of the body of the pancreas. Tumorigenicity was proven by xenograft in athymic nude mice. Upon re-establishment of tumor xenografts in tissue culture, the epithelial tumor cells retained their original morphology. Histopathologically, the tumors grown in nude mice exhibited the original characteristics of the primary adenocarcinoma in the patient, producing traceable mucin and displaying moderately well to poorly differentiated adenocarcinomas with occasional lymphocytic infiltrations at the tumor peripheries. Furthermore, the tumor xenografts differentially expressed carcinoembryonic antigen, human pancreas cancer-associated antigen, and human pancreas-specific antigen. Karyotyping and glucose-6-phosphate dehydrogenase isoenzyme characterization revealed that this tumor line was of human origin and devoid of HeLa cell contamination. The BxPC-3 tumor line has been maintained for more than four years in our laboratory and represents a valuable model for primary human pancreatic cancer.

Cytogenetic studies in primary gastric cancer

We have analyzed five primary gastric cancers with a G-banding technique. All tumors had clonal chromosome abnormalities; a total of 67 numerical and 83 structural karyotypic anomalies were identified as clonal. The most prominent and recurring numerical abnormality was a missing Y chromosome (three of four tumors in the male patients). No recurrent structural abnormalities were found. However, the breakpoints at bands 1p22, 3p21, and 19p13 were frequently involved. These chromosome abnormalities and their role in oncogenesis are discussed.

Possible specific chromosome changes in large bowel cancer

Structural and numerical changes affecting chromosomes number 7 and number 12 were the most frequent karyotypic changes observed in 10 large bowel cancers. The findings are briefly discussed in relation to the development of this malignancy.

Trisomy X as a Possible Initial Chromosome Change in a Gastric Cancer

Primary and metastatic gastric tumors from a patient previously treated for five different cancers were cytogenetically examined by G-banding. Both types of tumors had cells with a 47,XX, +X karyotype; in addition, the primary tumor had a second clone with a 48,XX, +X, +12 karyotype. No other abnormality was found in either tumor. The lymphocytes of this patient revealed a normal female diploid karyotype.

Serial cytogenetic analysis of a recurrent malignant melanoma

A metastatic malignant melanoma in a 54-yr-old white female was examined cytogenetically on three different occasions. We found two different clones, one hypodiploid and another hypertriploid; however, both clones had the same markers [i.e., der(6),t(6;17), and der(17),t(1;17)]. Detailed analysis of the histopathology and clinical course suggests that these two different clones reflected different morphology and results of therapy.

Common fragile sites in chromosomes of bone marrow cells and peripheral blood lymphocytes from healthy persons and leukemia patients.

Frequency and distribution of aphidicolin-induced fragile sites (c-fra) on chromosomes of both peripheral blood lymphocytes (PBL) and bone marrow (BM) from 15 leukemia patients were studied in comparison with 22 PBL and six BM samples from healthy volunteers. In normal controls, the most frequent c-fra was 3p14 in PBL, but it was 4q21-25 in BM. The second most frequent site was 16q23 in PBL, but it was 7q11.2 in BM. These differences in fragile sites between PBL and BM may be related to distinct functions of cells in different tissues. The total number of breaks in PBL and BM showed a significant difference among individuals, but the sites were generally common. The frequency of breaks in PBL from leukemia patients was higher than in controls when the leukemic cells had any karyotypic abnormalities. In leukemia without karyotypic abnormalities and acute myeloid leukemia (AML) with (15:17), the frequency of breaks fell within normal or slightly above normal ranges. Breaks at 3p14 (22.0% of total breaks), 16q23 (7.3%), 7q32 (4.3%), Xp22 (3.7%), and 6q26 (2.9%) were frequent in PBL from seven AML patients. Breaks at 4q21-25 (2.1%), 7q22 (2.2%), 7q32, and Xp22 were more frequently induced than in controls, and 1p32 (0.1%), 3p14, 6q26, and 16q23 were less often expressed than in controls. On the other hand, PBL from acute lymphoblastic leukemia patients showed a higher frequency of breaks only at 1p22 (3.4%) and the frequency of breaks at 3p14 (30.2%) decreased (p less than 0.05). The PBL from AML patients with t(8;21) (q22;q22) showed breaks at 8q22 and 8q24, and the frequencies were significantly higher than those of other types of leukemia or in controls (p less than 0.001). The results of this study suggest that fragility of chromosomes may be related to the chromosomal rearrangement in or predisposition to leukemia.

Multiple cancers in a Turner's syndrome with 45,X/46,XXp - /46,XX/47,XXX karyotype

A female patient with a clinical picture of Turners syndrome had five separate malignant tumors (three squamous cell carcinomas of the tongue, a colon cancer, and a glioblastoma multiforme). Her peripheral blood cells showed a 45,X/46,XXp-/46,XX/47,XXX mosaicism. The findings are discussed in relation to other extragonadal tumors in Turners syndrome reported to-date.

Changes of common fragile sites on chromosomes according to the menstrual cycle

SummaryThe frequencies of chromosomal breaks and sister chromatid exchanges (SCE) are influenced by pregnancy, oral hormonal contraceptives and the menstrual cycle. The changes in the number and sites of spontaneous and aphidicolin-induced breaks on chromosomes from peripheral blood lymphocytes during the menstrual cycle were examined in 8 healthy women. Menstrual cycle was determined by menstruation and the quantity of serum estrogen, progesterone and luteinizing hormone. The number of spontaneous breaks at the follicular phase, the interval phase (which includes ovulation) and the luteal phase were 3.1 ± 1.1, 2.7 ± 2.3 and 3.9 ± 2.6 per 100 mitoses, respectively. The frequencies of aphidicolin-induced breaks in the same phases were 95.8 ± 23.3, 90.6 ± 14.3 and 122.7 ± 20.1 per 100 mitoses, respectively. The higher frequency at the luteal phase was statistically significant compared with the other phases. In the luteal phase, bands 2q32, 3q27, 6q26 and 16q23 had higher frequencies of breaks (P < 0.05); however, breaks at band 9q32 decreased significantly. SCE showed considerable variation, but with no statistical significance.

Characterization of a renal cell carcinoma cell line suitable as a target for immunological studies in vitro and in the nu/nu mouse.

A continuous human renal carcinoma cell line designated RPMI-SE was established from a patient with a poorly to moderately differentiated renal cell carcinoma. The cells are anchorage dependent, have a well defined globular shape with pseudopod-like structures, a doubling time in vitro of 24 hr. and are able to grow subcutaneously in female ICR Swiss nu/nu mice. RPMI-SE cells obtained from tissue culture and the nude mouse had the chromosome number of near-tetraploidy. Common morphologic rearrangements were present in both the cell line and nu/nu mouse tumor. RPMI-SE was evaluated as a target cell line in an in vitro Indium-111 release assay. Three patterns of cytotoxicity were observed at an effector to target cell ratio of 100:1. The highest degree of cytotoxicity (75 per cent) was obtained with autologous lymphocytes. An intermediate level of cytotoxicity (50 per cent) was obtained with allogeneic lymphocytes. The lowest level of cytotoxicity (27 per cent) was obtained with normal lymphocytes and was comparable to the level of cytotoxicity observed with the NK sensitive K562 target cell line. Morphologic data and chromosomal analysis indicate that the RPMI-SE cell line has maintained characteristics of the original tumor. This cell line will be useful for immunological studies as a target cell line in vitro as well as in vivo in the nude mouse.

Cytogenetic studies of a diffuse mixed cell lymphoma of T cell origin.

The chromosome finding obtained from a lymph node of a patient with T cell lymphoma is described. Two different abnormal clones were found; one of them had a t(14;18)(q32;q21), along with other structural and numerical abnormalities, including 1p+q-,1p-,2p+q+, der(11),t(11;?)(q13;?),+20,+21,22p+. The other clone contained der(13),t(13;?)(q22;?).