bluuebunny/crossref_metadata_2025 huggingface dataset:
Separation of high mammary tumor incidence from high hepatoma incidence in backcross mice during segregation of the viable yellow gene
Authors: Smith Gilbert H. , Vlahakis George
Published: February 2007

Mammary tumorigenesis in strain C3H‐vyfB female mice (approximately 90% incidence) is not due to exogenous mouse mammary tumor virus (MMTV) but to genetic factors transmitted by either parent. Prominent among these genetic factors is the viable yellow (Avy) gene which may increase either the virulence of the endogenous MMTV provirus (Mtv‐l) by promoting expression or the susceptibility of the mammary tissue to tumorigenesis by endogenous MMTV. Crosses were made between the viable yellow strain, C3H‐AvyfB/He(AvyAay) and C3H/Sm (AA) to give heterozygous (AvyA) F1 yellow hybrids from which yellow (Avy) and agouti (AA) back‐cross progeny were produced by mating with C3H/Sm males. AvyA backcross females were expected to have at least twice as many mammary tumors as the AA back‐cross females if the Avy gene were solely responsible for the high incidence of mammary tumors in C3H‐AvyfB since mammary tumor incidence is 90% in AvyfB and 40% in (AA)C3HfB. Alternatively, if the high tumor incidence in C3H‐AvyB were due to a more active endogenous MMTV (Mtv‐l), then a much smaller difference in the mammary tumor incidence of AvyA versus AA backcross females would be expected. The more reactive endogenous MMTV would occur equally between yellow and agouti females, since the C3H Mtv‐l gene is present on a separate chromosome from the Avygene. Unexpectedly, the F1 hybrid females (AvyA) developed mammary tumors at a relatively low rate (28.9%) although hepatoma incidence remained high (89.5%). Both yellow (AvyA) and agouti (AA) backcross females showed an even greater reduction in mammary tumor incidence, 7.9% and 3.8% respectively. In contrast, the high rate of spontaneous hepatoma development segregated with the Avy gene since 86‐5% of the yellow (AvyA) backcross females development hepatomas by 19 months of age, while only 25% of the agouti (AA) backcross females had liver tumors at 24.4 months. The reduction of mammary tumor incidence in (C3H‐AvyfB × C3H/Sm)F1 hybrids was unexpected since earlier studies had shown that reciprocal F1, hybrids between strains BALB/c and C3H‐AvyfB continued to show a 90% mammary tumor incidence. The present result is consistent with the possibility that strain C3H/Sm possesses a heritable factor(s) which attenuates the ability of endogenous MMTV to malignantly transform mammary epithelium.
Geographic pathology of latent prostatic carcinoma
Authors: Yatani Ryuichi , Chigusa Ichiro , Akazaki Kaneyoshi , Stemmermann Grant N. , Welsh Ronald A. , Correa Pelayo
Published: February 2007

Prostates obtained at autopsy from black and white males in the United States of America, from Colombians, from Japanese migrants in Hawaii, and from Japanese in Japan (all over 50 years old) were serially step‐sectioned and examined microscopically using identical techniques and diagnostic criteria. The age‐adjusted overall prevalence of latent carcinoma was significantly higher in US blacks (36.9%), in US whites (34.6%) and in Colombians (31.5%) than in Japanese in Japan (20.5%). There was no significant difference in prevalence between Japanese migrants in Hawaii (25.6%) and Japanese in Japan. When the carcinomas were subdivided into latent infiltrative type (LIT) and latent non‐infiltrative type (LNT), the LIT component reflected upon the overall prevalence of latent carcinoma. There was an increase in the overall prevalence of latent carcinoma and in the prevalence of LIT tumors with age in Japanese migrants to Hawaii and in Japanese of Japan but only a suggestive increase in blacks and whites in the United States. There was no significant relation between age and prevalence in Colombia. In LNT tumors, there was no consistent trend related to race or age. The size of LIT tumors was significantly greater than that of LNT tumors in all races or in each decade of total material. There were many large LIT tumors in blacks and whites in the United States. These results suggest that the prevalence of LIT tumors shows a race variation similar to the incidence of clinical carcinoma of the prostate, and that LNT tumors probably remain latent during the individual's life span.
A monoclonal antibody with anti‐burkitt lymphoma specificity. I. Analysis of human haematopoietic and lymphoid cell lines
Authors: Wiels J. , Lenoir G. M. , Fellous M. , Lipinski M. , Salomon J. C. , Tetaud C. , Tursz T.
Published: February 2007

38‐13 is a hybridoma‐produced monoclonal rat IgM which appears to define a Burkitt's lymphoma‐associated antigen (BLA). In this paper, we describe the reactivity of 38‐13 with a panel of human haematopoietic and lymphoid cell lines. In indirect immunofluorescence (IF) assays, 15 of 26 Burkitt's lymphoma (BL) lines studied were clearly stained with 38‐13 (from 13 to 100% positive cells) by microscope, with varying numbers of heavily labelled cells. In these positive cell lines, fluorescence‐activated cell‐sorter (FACS) analysis demonstrated that BLA was actually present on all the cells. Positive BL included Epstein‐Barr virus (EBV) genome‐carrying lines and EBV‐negative ones; thus, BLA is not related to the presence of EBV. Most of the 15 BL cells that reacted with 38‐13 contained a typical t(8;14) translocation, but had variant translocations such as t(2;8) and t(8;22). The cells were derived from BL patients of different geographical origins and clinical features. Four BL lines were poorly stained and seven were negative with 38‐13 in IF assays. The 32 EBV‐positive lymphoblastoid cell‐lines (LCL) studied were negative. In three line pairs, consisting of a tumor line and an LCL from the same patient, only the BL line was demonstrated to react with 38‐13. A series of non‐BL cells, including haematopoietic, lymphoid and solid tumor lines, all failed to react with 38‐13. Various attempts to modulate the expression of BLA on BL cells were unsuccessful. However, it cannot be ruled out that BLA is actually a transient B‐cell differentiation marker.
SOMATOSTATIN‐REDUCED PROLIFERATION OF MURINE APLASTIC CARCINOMA CONDITIONED TO DIABETES
Authors: Vuk‐Pavlović S. , Božikov V. , Pavelić K.
Published: February 2007

Murine mammary aplastic carcinoma, when it is passed from one alloxan‐diabetic animal to another, after several passages becomes conditioned to hypoinsulinemia by secreting its own substances(s) immunologically cross‐reactive with insulin (SICRI). Although not cytotoxic, the total daily dose of 2.5 mg of synthetic linear somatostatin per one kg body mass, administered in three or more portions, retards tumor growth in normoinsulinemic mice and the proliferation of tumors preconditioned by three serial passages in diabetics. After the first passage, somatostatin treatment has no effect on the already slow growth of the unconditioned tumor. Somatostatin‐reduced tumor proliferation is accompanied by the strong suppression of insulin and SICRI levels, respectively; this effect is completely abolished by the administration of modest doses of crystalline insulin. It is concluded that somatostatin retards tumor growth by diminution of plasma levels of insulin and SICRI, respectively.
Possible role of a retrovirus in the expression of tumor‐specific antigens of the meth a sarcoma.
Authors: Deleo Albert B. , Chang Kenneth S. S. , Wivel Nelson A. , Appella Ettore , Old Lloyd J. , Law Lloyd W.
Published: February 2007

The serologically defined tumor‐specific surface antigen (TSSA) of the chemically‐induced BALB/c Meth A sarcoma, highly restricted to one of 20 sarcomas of BALB/c origin, has been detected on a Moloney murine sarcoma virus (Mo‐MuSV)‐transformed BALB/c 3T3 cell line, designated IIA(v). The immunogenicity of the IIA(v) cell in tumor‐rejection assays was specific for the Meth A sarcoma, supporting the evidence for a close relationship between the TSSA and the tumor‐associated transplantation antigen (TATA) of this tumor. Infection of SC‐I cells with retroviruses present in cultured filtrates of IIA(v) cells resulted in Meth A antigen expression. The retroviruses associated with Meth A antigen expression have been tentatively identified as replication and/or transformation‐defective XC‐ MuLV. The possible roles of Mo‐MuSV and cellular genes of the BALB/c strain of mice in the expression of the Meth A antigen are discussed.
Antigens of the basement membrane and the peritumoral stroma in human colonic adenocarcinomas: An immunofluorescence study
Authors: Burtin P. , Chavanel G. , Foidart J. M. , Martin E.
Published: February 2007

Twenty colonic adenocarcinomas were studied by immunofluorescence with antisera against components of the basement membrane: type IV collagen, laminin and heparan sulfate‐rich proteoglycan, as well as antisera against antigens of the connective tissue: type‐III collagen, fibronectin and hyaluronectin. Marked alterations of the basement membranes were consistently observed on staining with each one of the first three antisera. In contrast, staining of the normal components of connective tissue was in most cases as intense as in normal colonic mucosa. Hyaluronectin, a marker of peritumoral stroma, was found to be present in 12 out 15 tumors studied.
Histopathological features of rapidly progressing breast carcinoma in Tunisia: A study of 94 cases
Authors: Costa J. , Webber B. L. , Levine P. H. , Muenz L. , O'Conor G. T. , Tabbane F. , Belhassen S. , Kamaraju L. S. , Mourali N.
Published: February 2007

The histological features of 94 cases of carcinoma of the breast seen in Tunisia were recorded and subsequently correlated with the clinical classification of the patients in terms of poussée évolutive (PEV) categories. Histological features analyzed in the breast tissues and skin included tumor type, nuclear grade, number of mitoses, involvement of the dermis, cutaneous inflammatory infiltrate and edema. Twenty‐eight percent of the cases in which the skin was examined showed tumor emboli in the lymphatics of the dermis. The frequency of cutaneous permeation correlated with the PEV categories. The percentage of cases with nuclear grade 3 was higher for the group with rapid progression of the disease (PEV 1,2,3) than for the cases belonging to the PEV‐0 category (90% versus 64.2%). The present study demonstrates that a large proportion of breast carcinoma patients in Tunisia suffer from “inflammatory carcinoma of the breast”.
Hepatitis B virus and primary hepatocellular carcinoma: Family studies in Korea
Authors: Hann Hie‐Won L. , Kim Chung Yong , London W. Thomas , Whitford Pamela , Blumberg Baruch S.
Published: February 2007

Chronic infection with hepatitis B virus (HBV) is closely associated with the etio‐pathogenesis of primary hepatocellular carcinoma (PHC). It has been proposed that infection with HBV early in life, frequently transmited by an HBV‐carrier mother, leads to persistent infection with HBV, which in turn is associated with the development of chronic active hepatitis (CAH), post‐necrotic cirrhosis and PHC. If this view is correct, then there should be clustering of chronic carriers of HBV in families of patients with chronic liver disease. We tested this hypothesis in Korea by collecting serum from 132 patients with these chronic liver diseases admitted to the Seoul National University Hospital and 664 of their first‐degree relatives. Controls (636) were members of two churches in Seoul and a rural village population; 261 of the controls were between the ages of 30 and 59, the age range that included 95% of the cases of chronic liver disease. Sera were assayed for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti‐HBs) and antibody to hepatitis B core antigen (anti‐HBc). Almost all cases showed evidence of present or past infection with HBV; 80% were HBsAg(+) and 14% were anti‐HBs(+); 100% of 47 cases of PHC, 100% of 35 cases of cirrhosis, and 94% of 50 cases of CAH were anti‐HBc(+); 6% of males and 4% of females in the control population (30–59 years of age) were HBsAg(+), 71% were anti‐HBc(+), and 51% were anti‐HBs(+), HBsAg(+) patients with chronic liver disease tended to be younger than HBsAg(−) patients with anti‐HBs or anti‐HBc antibodies. Mothers of patients were more frequently HBsAg(+) (9 of 33) than agematched women in the control population (0 of 34) or wives of patients (5 of 68). Five of 23 fathers were also HBsAg(+) compared with 1 of 25 age‐matched controls. As first observed in Africa, there was a deficit of anti‐HBs in the fathers of cases compared with the controls. Siblings of patients were frequently HBsAg(+) (45% of 154), with the highest prevalence in brothers (53%). Family history shows that five fathers, two mothers and five brothers of cases have died of PHC. These data are compatible with the hypothesis tested and lend further support to the view that prevention of infection with HBV will lead to a marked decrease in the incidence of CAH, cirrhosis and PHC in areas where these diseases are endemic. Members of the families of patients with these diseases are at high risk of developing persistent infection with HBV and chronic liver disease. It would be appropriate to focus preventive strategies on infants and children in such families.
Growth responses of rat stomach cancer cells to gastro‐entero‐pancreatic hormones
Authors: Kobori Oichiro , Vuillot Marie‐ThérèSe , Martin François
Published: February 2007

Various hormones and peptides were added to rat stomach cancer cells growing in vitro in a serum‐free medium and the cell number was determined by a spectro‐photometric method. Five gastro‐entero‐pancreatic hormones or related peptides (tetragastrin, glucagon, secretin, cholecystokinin‐pancreozymin and cerulein) significantly increased the number of stomach cancer cells from 150% to 310% of the number of control cells cultivated in a serum‐free, hormone‐free medium. On the other hand, insulin and vasoactive intestinal peptide, and other hormones (thyroxin, epinephrine, hydrocortisone, β‐estradiol, progesterone, testosterone), peptone broth and bovine serum albumin had no significant growth effect. All the active substances belong to the two major families of gastro‐entero‐pancreatic polypeptide hormones, suggesting the existence of hormone receptors at the surface of stomach cancer cells.
In vivo localization of anti‐osteogenic sarcoma 791T monoclonal antibody in osteogenic sarcoma xenografts
Authors: Pimm M. V. , Embleton M. J. , Perkins A. C. , Price M. R. , Robins R. A. , Robinson G. R. , Baldwin R. W.
Published: February 2007

Monoclonal antibody 791T/36, (mouse IgG2b) to the human osteogenic sarcoma 791T was isolated from hybridoma supernatants or ascites fluid and labelled with radioiodine. Following injection into immuno‐deprived CBA mice with subcutaneous xenografts of human osteogenic sarcomas 791T, 788T and 20s, reactive antibody was detectable in the circulation and there was a preferential uptake into tumour tissue compared with muscle, bone or visceral organs. The tumour uptake of radioactivity correlated with the size of the xenograft, up to 20% of the total body counts being within the tumour. Autoradiography of tissue sections showed activity mainly within the subcapsular regions of the xenografts. There was no tumour localization of radio‐labelled normal IgG. Furthermore, with a colon carcinoma and a bladder carcinoma, both unreactive with the 791T/36 antibody, there was no localization of radiolabelled antibody in xenograft growths. With 791T/36 monoclonal antibody labelled with 131I localization into 791T xenografts could be visualized by whole‐body gamma scintigraphy with computerized 99mTc‐pertechnetate or 113mIn‐indium chloride‐labelled blood pool subtraction. These studies demonstrate the potential of monoclonal antibody to a human tumour for in vivo localization both for diagnostic purposes and as a carrier for therapeutic agents.
The characterization of non‐histone proteins whose amounts increase in chromatin from mouse hepatocarcinomas
Authors: Medvedev Zh. A. , Buchanan J. H. , Medvedeva M. N. , Crowne H. M.
Published: February 2007

A fraction containing liver‐ and hepatoma‐specific nonhistone proteins has been isolated from the chromatin of mice. Amino acid analysis of this fraction shows that it contains 16 mol of glutamic acid, 10 mol aspartic acid, 7 mol of both arginine and lysine per 100 mol and contains no cysteine or tyrosine. The proteins in this fraction are strongly associated with DNA and are co‐extracted with histones from chromatin with 0.25 M HCI. In chromatin from age‐related hepatomas, the amount of this fraction increased six‐fold. This increase in concentration of these chromatin proteins may be associated with changes of chromatin structure necessary to initiate malignant growth in liver cells.
The role of differentiation in the suppression of tumorigenicity in human cell hybrids
Authors: Peehl Donna M. , Stanbridge Eric J.
Published: February 2007

HeLax human keratinocyte hybrid cell populations behave like transformed cells in culture but do not form progressive tumors when inoculated into athymic nude mice. In this respect they behave like HeLa/fibroblast hybrids (Stanbridge et al., 1982). However, the small nodules that do form occasionally have the appearance of moderate to highly differentiated squamous‐cell carcinomas. These observations suggest that differentiation might be the signal suppressing growth of human hybrid cells in vivo. Differentiation occurs rapidly and is not sitespecific. Reconstitution of HeLa/keratinocyte hybrid cells in culture from differentiated nodules gave rise to a line of stem cells, capable of renewed proliferation and differentiation, and a line which lost the ability to differentiate and formed large, progressive tumors when reinjected. These tumors are anaplastic carcinomas that resemble tumors formed both by HeLa and tumorigenic segregant HeLa/fibroblast hybrid cells. Morphological evidence indicates that non‐tumorigenic HeLa/fibroblast hybrid cells also respond to differentiation signals, whereas the tumorigenic segregants do not. Furthermore, the non‐tumorigenic hybrid cells in the nude mouse take on the “phenotypic signature” of the normal parental cell irrespective of the tumorigenic parental cell. Efforts to identify factors in vitro mimicking these differentiation signals have so far failed, but such factors may be important elements in the regulation of proliferation in vivo.
Inhibitory action of BHA on carcinogenesis in F1 and F2 descendants of mice exposed to DMBA during pregnancy
Authors: Rao A. Ramesha
Published: February 2007

Administration of 500 μg of DMBA to female mice during late pregnancy results in the occurrence of tumors in F1 and F2 generation individuals. F1 progeny had a higher percentage of tumor‐bearing individuals than the F2 progeny. All the five litters of F1 females displayed tumor risk but the risk declined progressively in successive litters. Perinatal administration of BHA to the pregnant mice (P generation) receiving 500 μg of DMBA would result in significant reduction in tumor risk among the individuals of F1 generation (p < 0.01) and F2 generation (p < 0.05).
The comparative epidemiology of benign breast lumps and breast cancer in Western Australia
Authors: Fleming N. T. , Armstrong B. K. , Sheiner H. J.
Published: February 2007

Totals of 313 patients with breast cancer and 1,283 patients biopsied for benign breast lumps were found in Western Australia in 1978 through review of all histopathological, hospital and cancer registry records. The incidence of breast cancer rose to 146.9 per 100,000 at age 45–54 years and thereafter increased little. The biopsy rate for benign breast lumps rose more sharply to 420.2 per 100,000 at age 45–54 years and then fell. This pattern was mainly due to benign mammary dysplasia (BMD); fibroadenoma showed an earlier peak biopsy rate (30–34 years) and other (mainly non‐neoplastic) benign lumps were biopsied at a relatively constant rate throughout adult life. Rates of breast cancer, BMD and fibroadenoma showed similar relationships to the other descriptive variables studied. The rates of each were higher in single than married women, in residents of the Perth area than residents of other parts of the State and in women employed in professional and related occupations than other employed women. They were lower in migrants from Europe (excluding Great Britain) than native‐born Australians and in women of low socio‐economic status than women of high status. Not all these differences were statistically significant. Rates of other breast lumps did not generally vary in these ways and were conversely related to country of birth, area of residence and socioeconomic status. The parallels in descriptive epidemiology between breast cancer, BMD and fibroadenoma suggest that they may share aetiological factors.
Effects of human γ interferon on cell growth, replication of virus and induction of 2′‐5′oligoadenylate synthetase in three human lymphoblastoid cell lines and K562 cells
Authors: Tomita Yoshimi , Cantell Kari , Kuwata Tsuguo
Published: February 2007

Human α interferon (IFN‐α) and β interferon (IFN‐β) showed antiviral and anticellular effects on human lymphoblastoid Daudi and P3HR‐1 cells, but up to 1,000 units/ ml of γ interferon (IFN‐γ) showed no such effect. Though a fairly high level of dsRNA‐dependent 2′‐5′‐oligoadenylate synthetase (2–5A synthetase) was found in Daudi cells, treatment of these cells with IFN‐α and β enhanced the enzyme level in cells at least four‐fold, but IFN‐γ did not show any such effect. Lymphoblastoid Raji cells were insensitive to the antiviral and anticellular activities of IFN‐α, β and γ, but 2‐5A synthetase was induced in cells by the treatment with IFN‐α and β, though the enzyme level was lower than that found in interferon‐treated Daudi cells. Human leukemic K562 cells were completely insensitive to IFN‐α, β and at the same time to IFN‐γ with regard to the antiviral, anticellular activities and to the induction of 2‐5A synthetase.
Mechanisms of cellular cytotoxicity mediated by effector cells from rats with spontaneous tumors
Authors: Zöller M. , Matzku S.
Published: February 2007

We have previously shown that effector cells from BD X rats bearing spontaneous tumors display increased cytotoxicity towards syngeneic tumor cells compared to effector cells from untreated rats (Zöller and Matzku, 1980a). The increased in vitro cytotoxicity of lymphoid cells from tumor‐bearing (TB) animals was not T‐cell mediated and the question was raised, whether it was due solely to increased natural killer (NK) cell activity, or whether humoral factors could also be involved. We now prove that in a long‐term assay, the presence of B cells is indeed mainly responsible for increased TB cytotoxicity, since: (1) After depletion of surface immunoglobulin positive cells (s‐Ig+), TB cytotoxicity no longer exceeds cytotoxicity of effector cells from untreated rats; (2) Mixtures of s‐Ig+ cells from TB animals with Fc‐receptor positive (Fc‐R+) cells from untreated rats restore the increased TB cytotoxicity; (3) Addition of rabbit Fab' anti rat F(ab')2 reduces TB‐effector cell cytotoxicity. A minor contribution of the increased TB cytotoxicity by activation/numerical increase of NK cells will be discussed.
Demonstration of the tumorigenicity of transformed rat kidney cell‐lines by intravenous allotransplantation in the neonate
Authors: Hard Gordon C.
Published: February 2007

The tumorigenic potential of allogeneic rat kidney cell‐lines transformed in vivo by a carcinogenic dose of dimethylnitrosamine (DMN) was investigated by intravenous injection of single cell suspensions into neonatal outbred rats within 24 h of birth. The cell‐lines tested included mesenchymal populations obtained from DMN‐induced renal mesenchymal tumors (RRMT‐2,‐8,‐9) and transformed mesenchymal (TRKM‐5,‐7,‐8) and epithelial (TRKE‐1) cell‐lines derived from the kidneys of rats treated only hours previously with the carcinogen. Additionally, spontaneous nephroblastoma‐derived embryonal cell‐lines (REN‐1,‐2) were included in the study to extend the potential of the neonatal rat system over a range of differentiation lineages. The transplantation system proved to be a rapid and efficacious assay for demonstrating the malignancy of the mesenchymal and embryonal cell‐lines. The major sites for tumor growth were the lungs, heart and eye, but differences in organ predilection were observed for individual cell‐lines. The transformed epithelial cell‐line (TRKE‐1) proved refractory to the single intravenous inoculation but was transplantation‐positive when a follow‐up subcutaneous dose was administered several days later. The resultant growths produced by the diverse differentiation lineages were histologically characteristic for the tumor tissue affiliate of each cell‐line. The results demonstrate the utility of this transplantation system for testing the malignant potential of morphologically transformed cells across the allogeneic barrier as well as proving that DMN is capable of inducing malignant transformation in both mesenchymal and epithelial cell types of the rat kidney after a very short period of exposure in vivo.
Regulator‐induced suppression of myelomonocytic leukemic cells: Clonal analysis of early cellular events
Authors: Metcalf Donald
Published: February 2007

Mouse WEHI‐3B myelomonocytic leukemic cells were cloned in semi‐solid agar in the presence of post‐endotoxin serum (ES) or semi‐purified differentiation factor (DF). At the 2‐cell, 4‐cell and 8–32‐cell stage, individual cells were washed and recloned in control cultures to test for clonogenicity and the ability to form differentiating progeny. With increasing clone size, an increasing proportion of treated cells either failed to proliferate or generated differentiating colonies of reduced size. The observed suppression indicated that both ES and DF exert irreversible effects on leukemic stem cell self‐replication within one or two cell cycles. The stem cell suppression observed was markedly asymmetric and most often involved premature differentiation and death of progeny of the affected cells rather than immediate death of the cell. The results are consistent with the possibility that the regulator DF irreversibly modifies one or more of the newly synthesised daughter chromatids of myeloid leukemic cells during the induction of stem cell suppression and differentiation.
Monitoring the effect of anti‐cancer drugs on L1210 cells by a mitochondrial probe, rhodamine‐123
Authors: Bernal Samuel D. , Shapiro Howard M. , Chen Lan Bo
Published: February 2007

The cancer chemotherapeutic agents 1‐β‐D‐arabinofuranosylcytosine (Ara‐C), methotrexate, and 5‐fluorouracil cause a rapid loss of mitochondrial Rh‐123 uptake in L1210 cells, which correlates with the loss of clonogenic ability. The loss of Rh‐123 uptake is irreversible and occurs prior to Trypan Blue staining. Thus, the antimetabolites, unlike freeze‐thawing and detergent treatments, generally cause mitochondrial damage prior to changes in plasma membrane permeability. Since the effect of antimetabolites on Rh‐123 uptake is maximal at 24 h, the Rh‐123 assay may provide a rapid alternative to the clonogenic assay for monitoring the cytotoxic effects of these drugs. Our results also suggest that the inhibition or impairment of mitochondrial function may be an important step in the cytocidal and/or cytostatic action of anti‐cancer drugs.
NK‐patterned binding expressed by non‐NK mouse leukocytes
Authors: Piontek Gerald E. , Grönberg Alvar , Ährlund‐Richter Lars , Kiessling Rolf , Hengartner Hans
Published: February 2007

Previous studies demonstrated that NK‐cell‐enriched spleen cells bind to sensitive but not to resistant mouse lymphoma targets, measured by a single‐cell target binding assay. In the present report we further analyzed this “NK‐patterned” binding using effector cells with high, low or no NK activity. In agreement with previous results, nylon‐wool‐passed spleen cells as well as a cloned cytotoxic cell line with NK activity bound tumor targets largely according to their NK sensitivity; NK‐sensitive tumors had a higher frequency of binders than the more resistant ones. The correlation coefficient relating the percentage target binding cells (TBC) for each tumor with the ability of the same tumor to inhibit lysis in cold target competition assays was consistently higher than that relating percentage TBC with direct NK lysis. A non‐lytic variant of the cloned cytotoxic cell line had a binding pattern identical to that of the lytic line, demonstrating that “NK‐patterned” binding occurred in the absence of lysis. Thymocytes, which are totally devoid of NK activity, also bound preferentially NK‐sensitive targets, and their binding was decreased after trypsin treatment or in the presence of EDTA. Peritoneal macrophages also showed “NK‐patterned” binding, thus demonstrating that this was not restricted to cells in the T‐cell lineage. Variants from a mouse lymphoma selected for decreased NK sensitivity bound a lower frequency of NK‐active (nylon‐wool‐passed spleen cells) and inactive cells (thymocytes, peritoneal macrophages). This study therefore showed that the membrane property conferring NK‐binding selectivity exists on several types of non‐NK leukocytes.
Human interferon inhibits the growth of established human breast tumours in the nude mouse
Authors: Balkwill F. R. , Moodie E. M. , Freedman V. , Fantes K. H.
Published: February 2007

In this paper we describe a model system for looking at the effects of human interferon, IFN, on an established human tumour. Highly purified human IFN derived from lymphoblastoid cells (HuIFNα‐Namalwa) strongly inhibited the growth of a human breast cancer growing as a xenograft in nude mice. The effect was dose‐dependent, required daily treatment for an optimal effect and was time‐dependent, little inhibition being seen before 2 weeks of therapy. With the doses used, however, neither tumour regression nor disappearance were seen and on morphological examination, treated tumours appeared as miniatures of control tumours. The inhibition of the tumour by HuIFNα‐Namalwa appeared to be due to a direct effect on the human cells as this IFN had little effect on the mouse immune system in vitro as measured by NK cells activity. Also HuIFN therapy had no effect on levels of an interferon induced enzyme, 2–5A synthetase, in the mouse spleen cells but stimulated this enzyme in the human tumour.
Role of 3′‐end of viral genome in tumor heteroinduction by the avian sarcoma virus
Authors: Altaner C. , Reinerová M.
Published: February 2007

Transformation defective virus was derived by restriction endonuclease cleavage from a clone of the avian sarcoma virus Schmidt‐Ruppin strain, strongly oncogenic for rats. The transfection experiments of chicken cells by digested proviral DNA gave rise to transformation defective virus. The td virus was possible to recover in vivo in chickens. The tumors obtained after a long latent period contained the sarcoma virus which was able to transform chicken cells in vitro and to induce tumors in chickens. All viruses, parental, td‐ and recovered were of D subgroup specificity. The tumor induction experiments in rats have shown that the recovery of viral genome deletion in td mutant by cellular sequences was not enough to regain the oncogenicity for rats. The results stressed the importance of 3‐end sequences of the virus genome, probably the sequences in C region for heteroinduction ability of the avian sarcoma virus.
The human type‐C retrovirus, HTLV, in blacks from the Caribbean region, and relationship to adult T‐cell leukemia/lymphoma
Authors: Blattner William A. , Kalyanaraman V. S. , Robert‐Guroff Marjorie , Lister T. Andrew , Galton David A. G. , Sarin Prem S. , Crawford Michael H. , Catovsky Daniel , Greaves Melvin , Gallo Robert C.
Published: February 2007

Type‐C RNA tumor viruses have been implicated in the etiology of naturally occurring leukemias and lymphomas of animals. Human T‐cell leukemia/lymphoma virus (HTLV) is the first human virus of this class consistently identified in association with a specific type of human leukemia/lymphoma. The isolation of HTLV was made possible by the ability to grow mature T‐cells in tissue culture usually with T‐cell growth factor (TCGF). We now report a cluster of adult T‐cell leukemia/lymphoma among Blacks from the Caribbean in which all eight cases are positive for HTLV virus and/or antibody. These patients have disease that appears indistinguishable from Japanese adult T‐cell leukemia/lymphoma which, as we have also reported, is associated with HTLV in over 90% of cases. The finding of HTLV antibodies in some of the normal population in the Caribbean and Japan, and the clustering of a specific form of T‐cell leukemia/lymphoma in these virus‐endemic areas, suggest that HTLV infection may be associated with the occurrence of a distinctive clinico‐pathologic entity.
Antigens in an adult T‐cell leukemia virus‐producer cell line: Reactivity with human serum antibodies
Authors: Yamamoto Naoki , Hinuma Yorio
Published: February 2007

Sera from patients with adult T‐cell leukemia (ATL) or other diseases and from healthy adults, whose titers of antibodies against ATL‐associated antigens (ATLA) had been determined by indirect immunofluorescence, were analysed by a procedure of immunoprecipitation followed by SDS‐polyacrylamide gel electrophoresis. For this an ATL virus (ATLV)‐producer cell line, MT‐2, was labelled with [35S]‐methionine. All 12 anti‐ATLA‐positive sera but none of the eight anti‐ATLA‐negative sera tested reacted specifically with four polypeptides with molecular weights of 70,000, 53,000, 36,000 and 24,000 daltons. Furthermore, enrichment of three polypeptides with molecular weights of 76,000, 43,000 and 28,000 daltons was observed on reaction with anti‐ATLA‐positive sera. In control experiments using ATLA‐negative T‐cell lines, Molt‐4 and HPB‐ALL, none of these seven polypeptides were precipitated by reaction with anti‐ATLA‐positive sera. All six anti‐ATLA‐positive sera tested were shown to react with a polypeptide with a molecular weight of 24,000 of purified ATLV.
Detection of S‐100 protein as an aid to the identification of melanocytic tumors
Authors: Cochran Alistair J. , Wen Duan‐Ren , Herschman Harvey R. , Gaynor Richard B.
Published: February 2007

We sought S‐100 protein in sections prepared from formalin‐fixed paraffin‐embedded tumor and normal tissues by an immunoperoxidase technique with a rabbit antibovine S‐100 protein antiserum as first antibody and aminoethyl carbazole as developer. S‐100 protein was demonstrated in 56 of 56 cutaneous melanomas, regardless or their primary of metastatic status, and in 35 of 35 nevocytic nevi. The amount of S‐100 protein was independent of the degree of melanization of the tumors. Only 1 of 51 non‐neural non‐melanocytic tumors tested contained S‐100 protein. The technique is valuable in confirming the melanocytic nature of primary or metastatic tumors and in detecting small foci of metastatic melanoma in lymph nodes and other tissues. It also seems applicable to research on melanocytic anomalies.
Glutaminase‐free asparaginase from vibrio succinogenes: An antilymphoma enzyme lacking hepatotoxicity
Authors: Distasio John A. , Salazar Ana M. , Nadji Mehrdad , Durden Donald L.
Published: February 2007

Successful treatment of neoplastic disease has been impeded by the lack of therapeutic agents which specifically destroy tumor cells. Enzymes which selectively deplete substrates required by tumor cells, but not by normal tissue, could improve therapeutic indices dramatically. Presently, microbial asparaginases are used clinically for treating acute lymphocytic leukemia. While these enzymes should destroy neoplastic cells and spare normal tissues, their use is accompanied by many toxic effects and immunosuppression. The administration of Escherichia coli or Erwinia carotovora asparaginase depletes circulating glutamine as well as asparagine. It has been suggested that this glutaminase activity may be responsible for the observed toxicities. We have isolated a glutaminase‐free asparaginase from Vibrio succinogenes with potent antilymphoma activity. Previously, we demonstrated that administration of Vibrio asparaginase does not cause the immunosuppression of humoral or cell‐mediated responses associated with treatment by other microbial enzymes. In the present communication we have evaluated the hepatotoxic effects of different asparaginases since liver damage is the major toxicity associated with treatment by these microbial enzymes. BALB/c mice treated with 50 IU of E. coli asparaginase daily for 4 days exhibited diffuse microfatty infiltration within hepatocytes throughout the liver. Cross‐sections of liver from V. succinogenes asparaginase‐treated mice appeared normal as compared to specimens from control animals. Quantitation of the total amount of extractable lipid from the livers of E. coli asparaginase‐treated animals indicated a 45% and 127% increase in lipid concentration as compared to controls after 4 and 5 days of treatment, respectively. The Vibrio enzyme did not cause a change in extractable lipid concentration as compared to control animals. Plasma antithrombin III activity and albumin, triglyceride and cholesterol concentrations all decreased in E. coli asparaginase‐treated mice, confirming hepatotoxicity. No modifications in plasma proteins were observed in mice treated with asparaginase from V. succinogenes. The plasma lipids did decrease minimally but only the levels of cholesterol were shown to be statistically significant from those of controls. The data strongly support the concept that specific asparagine depletion is not significantly hepatotoxic. More importantly, the asparaginase from V. succinogenes may serve as a potent antileukemic agent without causing damage to normal tissues.
The interaction of non‐transforming Epstein‐Barr virus (EBV) with cell‐associated EBV DNA in superinfected lymphoblastoid cell lines
Authors: Stoerker Jay , Yajima Yoshihiro , Glaser Ronald
Published: February 2007

Two human lymphoblastoid cell lines were established by the transformation of human cord‐blood lymphocytes with transforming Epstein‐Barr virus (EBV). One cell line (HLB‐R1) was established with EBV obtained after the superinfection of Raji cells with HR‐1 EBV and the other (HLB‐B1) was established from B95‐8 EBV‐infected human cord‐blood lymphocytes. Both the HLB‐R1 and HLB‐B1 lines were susceptible to superinfection with HR‐1 EBV. We found that EBV DNA was replicated in the superinfected cell lines and that transforming EBV was produced in both the HLB‐B1 and HLB‐R1 cells. The average titer of transforming EBV obtained in the HR‐1 EBV superinfected HLB‐B1 and HLB‐R1 cell lines was 104 transforming units (TU)/ml, whereas the average titers of transforming EBV obtained by the superinfection of Raji cells was 10 TU/ml. Epstein‐Barr virus capable of inducing early antigen (EA) in superinfected Raji cells (lytic virus) was not detected in any transforming virus preparation. Restriction enzyme digestion patterns of virus DNA isolated from HR‐1 and B95‐8 cells, as well as from superinfected cells, were compared. The EBV DNA that was replicated in the superinfected HLB‐R1 and HLB‐B1 cell lines showed a more complex pattern. Our data suggest that recombination between input HR‐1 EBV DNA and latent cell‐associated EBV DNA occurs. Presumably this recombination results in a change in the biological properties of the newly synthesized virus.
Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer
Authors: Crawford L. V. , Pim D. C. , Bulbrook R. D.
Published: February 2007

Antibodies reacting with the host protein p53 were found in the sera of patients with primary or secondary carcinoma of the breast. Fourteen out of the 155 sera from breast cancer patients tested were positive for anti‐p53 antibodies (9%) and no positives were detected among 164 control sera from normal women tested. The locations of the first metastasis in patients with positive sera were unusual, with more lung metastases and fewer bone metastases than expected. The detection of anti‐p53 antibodies indicates that p53 is altered in amount, type or presentation in breast tumors so that it becomes immunogenic.
Serological response of melanoma patients receiving melanoma cell vaccines. I. Autologous cultured melanoma cells
Authors: Livingston Philip O. , Watanabe Tadashi , Shiku Hiroshi , Houghton Alan N. , Albino Anthony , Takahashi Toshitada , Resnick Lois A. , Michitsch Richard , Pinsky Carl M. , Oettgen Herbert F. , Old Lloyd J.
Published: February 2007

Our past studies have defined Class 1 (unique), Class 2 (shared) and Class 3 (widely distributed) melanoma cell surface antigens by serological typing with autologous antibody. These definitions provide the basis for determining the immunogenicity of a series of melanoma vaccines in patients with malignant melanoma. The first vaccine we tested in this way was prepared from autologous melanoma cell lines, and the results of our trial are the basis of this report. Thirteen patients with metastatic malignant melanoma were vaccinated with irradiated, cultured autologous melanoma cells mixed with BCG in an attempt to induce a serological response to Class 1 or 2 melanoma antigens. Antibodies were measured by protein A (PA), mixed hemadsorption (MHA), immune adherence (IA), C3‐mixed hemadsorption (C3‐MHA) and antibody‐dependent cell‐mediated cytotoxicity (ADCC) assays. The specificity of observed reactions was defined by absorption analysis. Eight patients showed an increase in the titer of antibodies to autologous melanoma cell surface antigens after vaccination. In two of these patients, the antibodies had specificity for shared melanoma antigens. In six patients, the antibodies were directed solely against antigens related to the fetal calf serum (FCS) used in growing cells for serological testing and vaccine preparation. We conclude that unmodified autologous cultured melanoma cells, administered as they were in this trial, induce a serological response to melanoma cell surface antigens only in exceptional cases.
Glucocorticoid receptors in hairy‐cell leukemia
Authors: Kontula K. , Paavonen T. , Vuopio P. , Andersson L. C.
Published: February 2007

Glucocorticoid receptors were measured from leukemic cells of five patients with hairy‐cell leukemia as well as a cell line (JOK‐1) derived from one of the patients studied and grown in continuous culture in vitro. Receptor analyses were accomplished using a whole‐cell binding assay with [3H]dexamethasone as the ligand. Glucocorticoid receptor sites in the leukemic hairy cells ranged from 5,710 to 11,400 sites/cell, and the mean dissociation constant (KD) between the receptor sites and [3H]dexamethasone was 0.67±0.03 × 10−8 M. The glucocorticoid receptor nature of the binding activity was verified by demonstration of an appropriate order of competing ability for a selected group of ligands. The cell line JOK‐1 contained 9830 receptor sites/cell with a KD of 0.78 × 10−8 M. The in vitro growth pattern of this cell line was characterized by an almost complete insensitivity to glucocorticoids. We conclude that the postulated general presence of glucocorticoid receptors in various types of normal and malignant leukocytes extends to hairy‐cell leukemia, a disease often characterized by resistance to antileukemic drugs, including corticosteroids. The sole presence of the glucocorticoid receptor thus does not seem to signify steroid responsiveness.
Age at menarche, urine estrogens and breast cancer risk
Authors: Macmahon Brian , Trichopoulos Dimitrios , Brown James , Andersen A. P. , Cole Philip , Dewaard Fritz , Kauraniemi Tapani , Polychronopoulou Antonia , Ravnihar Božena , Stormby Nils , Westlund Knut
Published: February 2007

In 511 nulliparous women aged 15–19 years and 347 aged 30–39, an analysis has been undertaken of the relationship of urine concentrations of the three principal estrogens to age, age at menarche and Quetelet's index of adiposity. The analysis was undertaken by means of multiple regression, controlling for each of the 12 centers from which the data originated, as well as for the other study variables. In the younger women, age was strongly and positively related to concentrations of El and E2 and less so to E3. In the age group 30–39, folluiar phase specimens showed positive relationships with age for all three fractions but luteal specimens did not. Age at menarche showed inverse relationships to levels of El and E2 which were significant in the younger but not in the older age group. The associations of estrogens with Quetelet's index were weak and not statistically significant. The data suggest that women whose menarche occurs early not only have a longer duration of exposure to estrogens during years which are probably important in the initiation of breast cancer but, in addition, their exposures are at a higher level during those years and probably at later ages also. These observations support the hypothesis that the mechanism of the association of early menarche with breast cancer risk is via the association of both with estrogen stimulus.
Identification of Hodgkin and sternberg‐reed cells as a unique cell type derived from a newly‐detected small‐cell population
Authors: Stein Harald , Gerdes Johannes , Schwab Ulrich , Lemke Hilmar , Mason David Y. , Ziegler Andreas , Schienle Wolfgang , Diehl Volker
Published: February 2007

In this study the antigenic profile of Hodgkin (H) and Sternberg‐Reed (SR) cells from cases of Hodgkin's disease was analysed using a large panel of monoclonal and polyclonal antibodies reactive with cells of lymphoid and haemotopoietic origin. The aim of this investigation was, firstly, to throw light on the origin of H and SR cells and, secondly, to determine whether there is any evidence to support recent suggestions that H and SR cells differ antigenically between different histological categories of Hodgkin's disease. Frozen sections (from 24 cases) and paraffin sections (83 cases) were stained by immunoenzymatic methods and the results compared with those obtained from staining a wide variety of reactive and neoplastic tissue samples (including examples of tuberculosis, sarcoidosis, malignant histiocytosis, histiocytosis X, osteomyelosclerosis and non‐Hodgkin's lymphoma). The results revealed that H and SR cells of all types of Hodgkin's disease consistently lack markers found on null cells, B cells, T cells, cells of monocyte/macrophage series, interdigitating reticulum cells, dendritic reticulum cells and erythropoietic and thrombopoietic cells. However, H and SR cells constantly expressed an antigen detectable with the recently produced monoclonal antibody Ki‐1. The vast majority of typical and lacunar type H and SR cells contained the granulocyte‐related antigens detected by monoclonal antibodies TÜ5, TÜ6, TÜ9 and 3C4, whereas other more or less specific granulopoietic cell markers (such as peroxidase, chloroacetate esterade, lysozyme, cationic leukocyte antigen and OKMI) were consistently absent. H and SR cells in cases of nodular paragranuloma (nodular type of Hodgkin's disease with lymphocyte predominance) were not monotypic in light chain type (as has been previously reported), but rather contained x and λ chains within the same cells, as do typical and lacunar type H and SR cells. Immunostaining of normal and hyperplastic lymphoid tissue with the Ki‐I antibody led to the detection of a new, as yet unidentified, small‐cell population of unknown origin and function, which is present between, around, and within cortical follicles. It is concluded from these findings that H and SR cells constitute a unique cell type that differs in many properties from all other known cell types. Furthermore, H and SR cells of the various histological types of Hodgkin's disease are more closely related than previously believed. It is suggested that the hitherto unknown cell population detected with the monoclonal antibody Ki‐I in normal lymphoid tissue is the normal equivalent of H and SR cells.