bluuebunny/crossref_metadata_2025 huggingface dataset:
A tumor‐associated antigen expressed in melanoma cells with lower malignant potential
Authors: Suter L. , Brüggen J. , Bröcker E. B. , Sorg C.
Published: February 2007

The antigen K‐1‐2, detectable by a MAb is found in nevi and melanomas. It is associated with melanoma cells of low invasive and metastatic potential as shown by immunoperoxidase studies with cell lines, biopsies and autopsies: K‐1‐2 occurs in melanoma cell line SK‐Mel 25, but not in cell line A‐375. A‐375 has a higher malignant potential than SK‐Mel 25 because, in contrast to SK‐Mel 25, it produces plasminogen activator and grows in nude mice. K‐1‐2 was frequently strongly expressed (≥ 50% cells positive) in flat (< 1.5 mm) and less frequently in medium and thick primary tumors. In thick primary melanomas K‐1‐2 positive cells were confined to the junctional zone or to marginal, flat areas of the tumor. Only rarely does K‐1‐2 occur in metastases. Strong expression of the K‐1‐2 antigen was found less often in primary melanomas, which develop early metastases, than in tumors that had not metastasized during an observation period of 18 months. In 5 patients with disseminated metastatic disease, metastases strongly expressing K‐1‐2 and those negative for this marker or containing only a minor percentage of K‐1‐2 positive cells were observed simultaneously or at different times. These findings suggest that a change from high malignancy to low malignancy—as observed in animal systems—may also occur in human melanoma.
Isolation and characterization of an activated c‐H‐ras‐1 gene from a squamous‐cell lung carcinoma cell line
Authors: Kagimoto Masaaki , Miyoshi Jun , Tashiro Kosuke , Naito Yasushi , Sakaki Yoshiyuki , Sueishi Katsuo , Tanaka Kenzo , Imamura Takashi
Published: February 2007

We determined a complete nucleotide sequence of an activated form of the c‐H‐ras‐1 proto‐oncogene cloned from the human cell line (QG56), using the DNA transfection technique and NIH3T3 cells as recipients. This cell line was established from a squamous‐cell lung carcinoma of a Japanese patient, and the activated gene had 2 nucleotide substitutions. One substitution of a thymidine for an adenosine was found at position 1069 of the 2898 nucleotide sequence in a restriction endonuclease (Sacl) fragment, which corresponds to the second base of the 61 st codon of the gene encoding P 21 protein. This nucleotide replacement was assumed to be responsible for the transforming activity. Another substitution of a guanosine for an adenosine which was detected at position 746 in the first intron was thought to be a genetic polymorphism unassociated with the transforming activity. Comparison of the various lengths of restricted fragments suggested that the activity was markedly influenced by certain sequences flanking the c‐H‐ras‐1 gene.
Characterization of murine hepatoma BW7756. III. Hematological profile of a tumor‐associated anemia
Authors: Mizejewski G. , Chao E.
Published: February 2007

A severe anemia develops in recipient C57L/J mice after syngeneic transplantation of the BW7756 murine hepatoma. The tumor undergoes an exponential growth spurt in the 14–21 days post‐implantation, accompanied by a parallel increase in serum alpha‐feto‐protein levels and a significant decrease of hemoglobin concentration and hematocrit extending to the 28th day. Concomitant with the decreased hematocrit, the blood volume displayed a 10% increase. The blood cell population was generally one of reticulocytosis and leukocytosis. Mild icteric plasma was observed and both “cold” and “warm” antibodies were detected in the sera of tumor‐bearing mice. An elevation of IgM was observed by day 7, followed by a depletion of IgG1 and IgG2 throughout the tumor growth period. When RBCs of tumor‐bearing mice were compared to those of normal mice, the same degree of osmotic fragility was found. However, the lifespan of the transfused RBC was shorter in tumor‐bearing mice than in normal mice (half‐life: 2 days vs. 4 days). The data suggest a type of auto‐immune hemolytic anemia which is analogous to various hematopoietic disturbances described for murine hosts bearing solid tumors distal to hematopoietic sites.
Effect of human serum anti‐htlv antibodies on viral antigen induction in In vitro cultured peripheral lymphocytes from adult T‐CELL leukemia patients and healthy virus carriers
Authors: Tochikura Tadafumi , Iwahashi Masato , Matsumoto Tadashi , Koyanagi Yoshio , Hinuma Yorio , Yamamoto Noaki
Published: February 2007

Leukemic cells of adult T‐cell leukemia (ATL) patients contain human T‐cell leukemia virus type I (HTLV‐I) genomes. However, viral antigens (HTLV‐A) are not usually expressed in vivo. It has been shown that HTLV‐I antigens are spontaneously induced after culture of peripheral blood lymphocytes (PBL) from patients with ATL and healthy carriers (HC), who are viral antibody‐positive. In the present communication, we show the suppressive effect of human serum antibodies against HTLV‐I on viral antigen expression in PBL derived from ATL patients and HC. Viral antigen synthesis in various PBL specimens is variable in terms of frequencies and kinetics. (I) Low concentrations (2%) of antibody‐positive but not of antibody‐negative sera efficiently suppressed HTLV antigen induction in lymphocytes from both ATL patients and HC. (2) An inhibitory effect was exerted by HTLV‐I‐specific antibodies which originated from either ATL, HC or even HTLV‐I‐positive monkeys. (3)Sera showed a fairly wide range of suppressive activity in view of their wide range of suppressive activity in view of their concentrations. (4) At the late stage of cultures even continuous presence of antibodies frequently failed to suppress antigen synthesis in lymphocytes. (5) Antibodies were less effective in suppressing the increase of antigens if they were added to cultures which had already HTLV‐A‐positive lymphocytes in antibody‐free media. (6) Pretreatment with protein A completely abolished the activities of the suppressive plasmas. (7) Antibodies did not affect the inhibition of spontaneous or chemical induction of HTLV‐A in 2 HTLV‐I‐positive cell lines. These results suggest that HTLV‐I antigen expression in leukemic cells from patients with ATL in vivo and in vitro is partly regulated by antibodies to HTLV‐I. Furthermore, at least 2 different pathways, one antibody‐sensitive and the other ‐insensitive, might exist to express HTLV‐A.
Descriptive epidemiology of colorectal cancer
Authors: Boyle P. , Zaiudze D. G. , Smans M.
Published: February 2007

The purpose of this report is to present the descriptive epidemiology of colorectal cancer using the most recent data available to highlight two characteristics of the disease. First is the great variation which takes place in the frequency of this disease over geographic areas of all sizes. Colorectal cancer is common in most countries of North America and Europe, is rare in Asia and is particularly uncommon in Africa. Internationally, the variation in colon cancer is 60‐fold, and within Europe there is a 4‐fold difference in the incidence of colon cancer between areas with the highest and lowest rates. For cancer of the rectum, variation internationally is 18‐fold and within Europe it is 3‐fold. Within the United Kingdom, colon cancer is uniformly higher in the 5 Scottish Cancer Registry Regions than in their counterparts in England and Wales. Even within Scotland there is a 4‐fold range of colon cancer incidence rates, with the North and South clearly demarcated by a striking difference in colon cancer incidence in both sexes. Secondly, examination of international mortality rates for colorectal cancer demonstrates remarkable differences in trends over time between countries. In countries where colorectal cancer mortality rates were initially low, rates have increased substantially. In many countries where rates circa 1950 were moderately high, they have increased slightly or become stabilized. However, in countries such as Scotland, Canada, England and Wales and the United States, where rates were initially high, there have been gradual falls in mortality over time.
Seroepidemiologic Studies Of Human T‐cell leukemia/lymphoma virus type I in Jamaica
Authors: Clark Jeffrey , Ensroth Arthur , Blattner William A. , Saxinger Carl , Robert‐Guroff Marjorie , Gallo Robert C. , Gibbs W. Nigel , Lofters Wycliff , Lagranade Lois , Deceulaer Karel
Published: February 2007

The prevalence of HTLV‐I antibodies was evaluated in Jamaica among persons with various malignant, infectious, autoimmune and hematologic disorders and in clinically normal persons. Results document that: (1) the prevalence of HTLV‐I antibodies in this population increases with age; (2) overall, there is no significant difference in the antibody prevalence between males and females; (3) antibody‐positive individuals are born in all major regions of the island and geographical variance in antibody prevalence by place of birth was not prominent; (4) there is further confirmation of the high prevalence of HTLV‐I antibody‐positive lymphomas in Jamaica; and (5) the prevalence of HTLV‐I antibodies in hemophiliacs, patients with chronic lymphocytic leukemia (CLL), myelogenous leukemias, and patients with breast cancer is higher than in the age‐matched population without malignancies, although none of these differences were statistically significant. The increased prevalence in hemophiliacs is most likely related to their frequent transfusion with blood products, but it has not yet been determined whether the prevalence in patients with other diseases is related to their diseases or other as yet undefined factors in common.
Endemic african kaposi's sarcoma is not associated with immunodeficiency
Authors: Kestens Luc , Melbye Mads , Biggar Robert J. , Stevens Wim J. , Piot Peter , De Muynck Aimé , Taelman Henri , De Feyter Marc , Paluku L. , Gigase Paul L.
Published: February 2007

Twenty‐seven histologically confirmed Kaposi sarcoma (KS) patients resident in the Kivu Lake area of eastern Zaire were examined for immune competence. Only KS cases of the endemic African type have been observed in this high‐incidence area. The median duration of the symptoms was 6 years and ranged from 1 to 38 years. Forty‐one controls matched for age, sex and tribe and unrelated to the KS patients were selected from the community. Thirteen additional controls were first‐degree relatives of the KS patients. No evidence of immune suppression among KS patients was found and there were no significant differences in the immune status between KS patients and controls. Total lymphocytes, B and T cells, and OKT4 + and OKT8 + cells varied within the normal range. Grouping of the KS patients in categories according to duration and disease extent did not reveal significant differences in their immune status. The number of KS patients reacting positively in a skin test to 5 recall antigens and I mitogen was similar that of controls, except in the case of candidin, to which a higher number of KS patients were negative. The serum levels of immunoglobulins, complement factors and circulating immune complexes were comparable in KS patients and controls. Indicators of inflammatory processes [white blood cells (WBC), complement‐reactive protein (CRP)] were positive in 27% of the KS patients. The prevalence and mean titer of antibody against cytomegalovirus (CMV), Epstein‐Barr virus (EBV), hepatitis B virus (HBV) and syphilis were similar in KS patients and in controls.
Immunohistochemical localization and molecular characteristics of three monoclonal antibody‐defined epitopes detectable on carcinoembryonic antigen (CEA)
Authors: Bosslet K. , Lüben G. , Schwarz A. , Hundt E. , Harthus H. P. , Seiler F. R. , Muhrer C. , Kayser K. , Klöppel G. , Sedlacek H. H.
Published: February 2007

Three murine monoclonal antibodies (MAbs) reactive to different epitopes on CEA were selected according to their ability to bind to various human tissue sections. The most selective MAb, BW 431/31, bound to the majority of colon carcinomas but only faintly to normal colon mucosa. In addition to the tissues stained by MAb BW 431/31, MAb BW 250/183 reacted with granulocytes, colon mucosa and faintly with pancreatic ducts. The third MAb, BW 374/14, reacted with granulocytes, colon mucosa, strongly with pancreatic ducts and with alveolar and bronchial epithelium. The antigenic determinants recognized by the 3 MAbs in human tissue sections were resistant to formaldehyde fixation and paraffin embedding as well as to periodic acid oxidation and neuraminidase treatment. The last two treatments suggest that the epitopes are protein in nature. Using MAb affinity chromatography, 3 antigen preparations were isolated from a human colon carcinoma xenograft with an approximate molecular weight of 180 kd. These preparations were shown to bear the epitopes from each of the MAbs and from a polyclonal antiserum specific for purified CEA. Furthermore, the ability of MAb BW 431/31 to localize its antigenic determinant in vivo on a human colon carcinoma xenograft is evaluated and its possible application in the patient is suggested.
Tumor‐derived chemotactic factor(S) from human ovarian carcinoma: Evidence for a role in the regulation of macrophage content of neoplastic tissues
Authors: Bottazzi B. , Ghezzi P. , Taraboletti G. , Salmona M. , Colombo N. , Bonazzi C. , Mangloni C. , Mantovani A.
Published: February 2007

Supernatants from freshly disaggregated human ovarian carcinomas maintained in vitro for 24 hr, from primary ovarian carcinoma cultures (4–6 days in culture) and from established ovarian cancer cell lines were examined for chemotactic activity on blood monocytes in blind‐well chemotaxis chambers. Tumor‐cell culture supernatants induced migration of peripheral blood monocytes across polycarbonate filters with considerable heterogeneity among different tumors. Induction of migration occurred only in the presence of a gradient between the lower and upper compartments of the chamber. Chemotactic activity was characterized by means of supernatants from primary ovarian carcinoma cultures. Chemotactic factor(s) was (were) produced in serum‐free conditions and the production was inhibited by emetine but not by mitomycin C. The activity was destroyed by exposure to proteolytic enzymes and by heating at 100°C but was unaffected by RNase, DNase, lipase and exposure to extreme pH values or heating at 56°C. Upon fractionation on Sephadex G 75, the activity eluted as a single peak in the cytochrome C region, corresponding to an apparent molecular weight of about 12 kd. The percentage of macrophages was assessed in 25 freshly disaggregated tumor specimens. Ovarian carcinomas were heterogeneous in their macrophage content with values ranging from 4 to 36%. A significant (r = 0.62; p = 0.00097), though far from absolute, correlation was found between chemotactic activity of culture supernatants and percentage of tumor‐associated macrophages. Tumor‐derived chemotactic factor(s) could be one of the mechanisms involved in the regulation of the macrophage content of human ovarian carcinomas.
Migration and death from malignant melanoma
Authors: Cooke K. R. , Fraser J.
Published: February 2007

The age‐standardized mortality rates for malignant melanoma of the skin in immigrants to New Zealand were compared with those of New Zealand‐born non‐Maoris. Immigrants from European countries had mortality rates that were generally similar to those prevailing in their countries of origin, although, among immigrants from the British Isles, early age at migration was associated with a mortality rate similar to that of New Zealand‐born non‐Maoris. In a community survey, British immigrants were not less likely to have had severe sunburn, but had fewer moles, than New Zealand‐born non‐Maoris. The lower melanoma mortality, and the effect of age at migration, could be mediated by differences in mole frequency.
Prevalence of polyps in an autopsy series from areas with varying incidence of large‐bowel cancer
Authors: Clark John C. , Collan Yrjö , Eide Tor J. , Estève Jacques , Ewen Stanley , Gibbs Norman M. , Jensen Ole M. , Koskela Erkki , MacLennan Robert , Simpson John G. , Stalsberg Helge , Zaridze David G.
Published: February 2007

The results of this multicentre autopsy study emphasize the relationship between the prevalence of adenomas and the incidence of large‐bowel cancer. The highest proportion of autopsies with adenomas was observed in the area with the highest incidence of large‐bowel cancer. The segmental distribution of adenomas within the colon was found to be similar to the site distribution of cancer. However, the lowest proportion of adenomas was found in the rectum, the segment in which cancer is most frequent. The latter finding suggests that either the adenoma‐carcinoma sequence is a less important pathway in the pathogenesis of rectal cancer, or that more rectal than colonic adenomas become malignant. The high proportion of hyperplastic polyps in the rectum, and statistically significant regional differences following the same patterns as the incidence of rectal cancer suggest that there could be at least an indirect relationship between hyperplastic polyps and cancer of the rectum. Adenomas of both colon and rectum were more frequent in men than in women, contrary to findings with colon cancer. However, as for colon cancer, the sex ratio of adenomas changed with age, from slightly below unity in persons under 65, to above unity for those aged 65 and over. A major difficulty that emerged was the histological identification of ‘polyps’ because of the degree of autolysis of epithelial cells in the mucous membrane, and this difficulty largely contributed to the poor consistency of histological reporting. Regular consistency surveys of histological preparations should be recommended in any type of multicentre study in which histological examination is included.
Detection of sialylated lewisX antigen in cancer sera using a sandwich radioimmunoassay
Authors: Kawahara Masaaki , Chia David , Terasaki Paul I. , Roumanas Athan , Sugich Lee , Hermes Mark , Iguro Takashi
Published: February 2007

A monoclonal antibody directed against sialylated Lewisx (SLEX) was tested with the serum of 615 cancer patients, 166 patients with non‐malignant diseases, and 136 normal persons. The SLEX antibody reacted with the sera of the cancer patients in the following percentages: 29% lung, 19% breast, 12% ovary, 25% colorectal, 13% head and neck, and 13% miscellaneous. SLEX was positive for 22% of stages III and IV (latestage) cancers as compared with 5% early‐stage tumors. Among 80 patients with adenocarcinoma of the lung in the late stages, 45% were positive for SLEX. However, among 54 patients having squamous‐cell lung cancer in the late stages, 15% were positive. In 25 cases of small‐cell lung cancer, 24% were positive. Among patients who had measurable lung cancer, 4/7 with adenocarcinoma over 3 cm in diameter were positive whereas 0/16 patients with tumors under 3 cm were positive. Four patients who had tumor regression showed a more than 50% decrease in SLEX values whereas in 7 patients with progressive tumors, a more than 50% increase in SLEX levels was found. When tested simultaneously with CEA, SLEX produced positive reactions with the sera of some patients who were negative for CEA. The reaction pattern was distinct, indicating that another antigen was being detected. When used in combination, the percentage of sera that were positive increased. We conclude that the use of SLEX is useful for monitoring of cancer patients.
Hereditary malignant melanoma is not linked to the hla complex on chromosome 6
Authors: Bale Sherri J. , Greene Mark H. , Murray Christine , Goldin Lynn R. , Johnson Armead H. , Mann Dean
Published: February 2007

Detailed HLA typing was performed in 11 families with hereditary cutaneous malignant melanoma (CMM) and dysplastic nevi to determine if the melanoma susceptibility locus was genetically linked to the major histocompatibility complex. Previously published data from 19 other families were re‐analyzed in the same manner. When data from all 30 families were pooled and CMM was defined as the disease trait, the hypothesis of linkage was rejected for all values of recombination (θ) less than 40%. Data on family members′ status regarding dysplastic nevi (DN), a well‐characterized precursor of hereditary CMM, were available for our 11 families and 7 previously‐reported families. Linkage analysis between the combined CMM/DN trait and HLA provided strong evidence against this hypothesis. Significant heterogeneity was observed when various sub‐groups of families were compared; these data suggested that preferential reporting of positive linkage findings and misclassification of study subjects′ CMM susceptibility status may have contributed to previous beliefs that the hereditary melanoma gene was linked to HLA. When our data are combined with previously‐published information, we conclude that there is strong evidence against linkage of a CMM/DN gene with the major histocompatibility complex.
Selective cytotoxicity of aids virus infection towards HTLV‐I‐transformed cell lines
Authors: Koyanagi Yoshio , Harada Shinji , Yamamoto Naoki , Takahashi Mutsuo , Uchino Fumiya
Published: February 2007

Previously, we reported that cells of the human T‐cell lymphotropic virus type 1 (HTLV‐I)‐transformed lines MT‐2 and MT‐4 were extensively killed by infection with AIDS retrovirus HTLY‐III. We have investigated this phenomenon more systematically using light and electron microscopy as well as immunofluorescence. The cell lines used in the present studies included 14 of those carrying not only human HTLY‐1 but also related simian agents and 6 HTLY‐I‐negative T‐ and B‐cell lines. The results showed that the cytocidal effects occurred in the HTLY‐I‐transformed cell lines exclusively and were not present in further subcultures. In these cell lines the cytotoxic response was closely correlated with the induction of HTLV‐III antigens after virus infection. However, cells of 6 HTLV‐I‐free lines were not killed to a marked extent by HTLV‐III and were passaged as continuous producers of AIDS virus. Only 2 cell lines were resistant to the cytocidal effect of HTLV‐III among 14 HTLV‐I carrying cell lines. They were also resistant to the replication of infected HTLV‐III. This AIDS virus‐specific cytotoxic effect observed in HTLV‐I‐transformed cell lines did not appear to be associated with gene expression of the gag and pXs region of HTLV‐I genomes. This result may indicate that HTLV‐III specifically interferes with some steps of HTLV‐I transformation.
Expression of cell surface glycoproteins in human melanoma cell lines with different tumorigenic properties
Authors: Berthier‐Vergnes Odile , Portoukalian Jacques , Doré Jean‐François
Published: February 2007

Human malignant melanoma cell lines characterized by either a high or a low ability to grow subcutaneously in athymic nude mice have been examined for their cell‐surface glycoproteins. Striking differences were demonstrated between these 2 groups. Cells from lines of low tumorigenicity (LT group) displayed twice as much Vibrio cholerae neuraminidase and galactose oxidase accessible glycoproteins as cells from lines of high tumorigenicity (HT group) and each group of cell lines could be characterized by specific glycoprotein profiles. LT and HT group cells displayed similar amounts of periodate accessible glycoproteins, but sialoglycoprotein profiles were characteristic for each group of cell lines. Furthermore, whereas 87% of the sialic acid released by V. cholerae neuraminidase came from cell surface glycoproteins in HT group cells, only 53–55% of the released sialic acid came from surface glycoproteins in LT group cells. These results suggest that human melanoma cell lines exhibiting different tumorigenicity in nude mice can also be characterized by differences in composition and organization within the plasma membranes of their cell‐surface sialoglycoproteins.
Stimulation of human monocyte oxidative burst and related cytotoxicity by tumor‐promoting and non‐tumorpromoting diterpene esters, indole alkaloids and polyacetate‐type agents
Authors: Keisari Yona , Geva Ita , Flescher Eliezer , Goldin Hedva , Lavie Gad
Published: February 2007

Human peripheral blood monocytes were cultured and exposed to plant diterpens, indole alkaloids and polyacetates with various degrees of tumor‐promoting activity. The effect of the above‐mentioned encounter on monocyte function was examined, as expressed by H2O2 production and lysis of dog erythrocytes by the cells, and the inhibition of 3H‐PDBu binding to the monocytes by the various test agents. The most effective reagents in both activation of monocyte function and inhibition of 3H‐PDBu binding were 12‐0‐tetradecanoyl‐phorbol 13‐acetate (TPA), phorbol 12, 13 dibutyrate, teleocidin, and aplysiatoxin which are known to be strong tumor promoters. Strong stimulation of monocyte function was also exerted by the weak tumor promoters, phorbol 12‐retinoate 13‐acetate, mezerein and debromoaplysiatoxin. Non‐tumor‐promoting phorbol diterpens such as phorbol 12, 13‐diacetate, phorbol 12‐myristate, phorbol 13‐acetate and 4‐alpha TPA were 1,000 times less effective than TPA in monocyte stimulation and inhibition of 3H‐PDBu binding. These results indicate that stimulation of human monocyte H2O2 production and related cytotoxicity might discriminate effectively between tumor‐promoting and non‐tumor‐promoting reagents.
Cholera‐toxin‐enhanced growth of human breast cancer cell lines in vitro and in vivo: Interaction with estrogen
Authors: Sheffield L. G. , Welsch C. W.
Published: February 2007

Cholera toxin (which increases intracellular cAMP levels) significantly (p < 0.05) increased the growth of MCF‐7, T47‐D and Hs578T human breast carcinoma cells in vitro. The effect of cholera toxin on growth of MCF‐7 and T47‐D cells was more pronounced in the presence of 17β‐estradiol (p<0.05), indicating a synergism between cAMP and estradiol in growth control of estrogen‐receptor‐positive breast carcinoma cells. This interaction was not observed in the estrogenreceptor‐negative cell line Hs578T. Daily injections of cholera toxin into female athymic nude mice bearing MCF‐7 or Hs578T tumors resulted in significantly (p < 0.05) increased growth of the tumors. Cholera toxin treatments, in addition, significantly (p < 0.05) increased cAMP levels in tumor cells and tumor tissue, in vitro and in vivo, respectively. The results of this study clearly demonstrated that an increase in cAMP levels via cholera toxin treatment causes enhanced growth (in vitro and in vivo) of estrogen‐receptorpositive and ‐negative human breast carcinoma cells and, although estrogen alone was not mitogenic to the estrogen‐receptor‐positive breast carcinoma cells in vitro, the steroid was mitogenic to these cells in the presence of elevated cellular cAMP levels.
The effects of single versus triple intravenous injections of B16 melanoma cells on the development of pulmonary tumors in mice
Authors: Ward P. M. , Weiss L.
Published: February 2007

During natural metastasis, cancer cells are released continuously into the bloodstream and arrested in target organs; the process is repetitive rather than a single event. In this communication, the effect of preceding on successive „pulses”︁ of cancer cells is discussed in relation to the arrest, retention and tumor formation of B16 melanoma cells in the lungs of mice receiving 3 separate tail‐vein injections at 2‐hr intervals. When animals received the same total number of cells in either 1 or 3 injections, no significant differences were detected in the initial arrest and subsequent retention in the lungs. However, 15 days after injection, mice which had received 3 pulses of cancer cells were found to have fewer pulmonary tumors than those which had received a single pulse of cells. The results show that interactions between 2 successive waves of B16 melanoma cells and their host did not affect the initial arrest and „short‐term”︁ retention of a third wave of radiolabelled cells. However, the „longer‐term”︁ experiments on tumor formation show that preceding pulses of cancer cells resulted in the lungs becoming more hostile to a succeeding pulse than was the case in appropriate controls. The results indicate that the relative metastatic capacities of cancer cells arrested in microvascular beds during hematogenous metastasis could well be diminished by antecedent interactions of this type.
Parity and cancer risk in slovakia
Authors: Plesko I. , Dimitrova E. , Somogyi J. , Preston‐Martin S. , Day N. E. , Tzonou A.
Published: February 2007

Mortality data from women aged 45‐74 who died between 1968 and 1977 in Slovakia, Czechoslovakia, were used to examine the effect of parity (number of live‐born children) on risk of dying from each of 20 common cancers. After controlling for the effects of age and year of death, the effect of parity on risk was statistically significant at the p < 0.001 level, for cancers of the stomach, liver, gall‐bladder, breast, cervix, and ovary; and at the p < 0.01 level for uterine corpus and brain. No effect of parity was seen for cancer of the colon or rectum. Among parous women the trend relating risk to level of parity was significant at the p < 0.001 level for cancers of the breast, uterine corpus, ovary and brain; and at the p < 0.01 level for stomach cancer. The findings relating parity to cancers of the breast and reproductive organs are consistent with previous reports. The associations of parity with cancers of the digestive tract deserve further study.
Prognostic value of concentration of pregnancy‐specific β1‐glycoprotein (SP1) in serum of patients with breast cancer
Authors: Fagnart O. C. , Cambiaso C. L. , Lejeune M. D. , Noel G. , Maisin H. , Masson P. L.
Published: February 2007

Pregnancy‐specific β1‐glycoprotein (SP1) was assayed by particle counting immunoassay in serum from 46 healthy female blood donors, 33 patients with benign mastopathy and 84 patients with breast cancer before operation and during follow‐up. Values > I μg/I were found more frequently with benign mastopathies (11/33) and in patients with breast cancer at stage 2 (20/48), 3 (4/9), and 4 (7/10) than in healthy female blood donors (3/46). The survival rate after 4 years was significantly lower in patients with SP1 level > 1 μg/1 before tumor resection (52% vs. 87%). The difference remained significant when only patients in stage 2 were taken into account (57% vs. 85%). A highly significant (r = 0.64; N = 46) negative correlation was observed between the concentration of SP1 in serum and the concentration of estrogen receptor in the tumor. The longitudinal study of patients in stage 2 indicated that, of the 15 whose SP1 concentration fell below 1 μg/1 after operation, 14 survived over 4 years whereas during the same period, 9 of the 10 patients whose SP1 value remained higher than I μg/1 died.
A glycoprotein antigen detected with new monoclonal antibodies on the surface of human lymphocytes infected with human T‐cell leukemia virus type‐I (HTLV‐I)
Authors: Tanaka Yuetsu , Inoi Takeshi , Tozawa Hideki , Yamamoto Naoki , Hinuma Yorio
Published: February 2007

We have prepared two new mouse monoclonal antibodies (MAbs) named TARM‐34 (IgM) and TAG‐34 (IgG I), that react with surface antigens of lines of human lymphocytes bearing a human T‐cell leukemia virus type‐I (HTLV‐I.) The characters of these antibodies are compared with those of anti‐HTLV‐I gp21 MAb (TA‐21, IgGI), anti‐HTLV‐I p19 MAb (GIN‐14, IgGI) and human antibodies from patients with adult T‐cell leukemia (ATL). An indirect membrane immunofluorescence assay showed that TARM‐34, TAG‐34 and TA‐21 all reacted specifically with cell‐surface antigens of HTLV‐I‐positive T‐ and B‐cell lines and cultured peripheral blood lymphocytes from HTLV‐I‐infected adults, Radioimmunoassay showed that serum antibodies from the ATL patients interfered with the binding of TA‐21 antibody to cells of the HTLV‐I‐positive T‐cell line MT‐2, but not with the bindings of TARM‐34 and TAG‐34 antibodies. TARM‐34 and TAG34 both precipitated a 34‐kd glycoprotein (gP34), while TA‐21 precipitated gp21 from a lysate of 3Hmine‐labelled MT‐2 cells. TARM.34 and TAG‐34 also precipitated the 34‐kd protein from Iysates of MT‐2 and HUT 102 cells labelled with 125l‐ or 35S‐cysteine. Interestingly, TARM‐34 and TAG‐34 also precipitated 35‐kd protein from a lysate of other HTLV‐I‐positive cells (F‐Taj cell line) derived from an ATL patient. TA21 precipitated the 21‐kd protein from the Iysates of 35S‐cysteine‐labelled HTLV‐IMT‐2 virions, but TARM‐34 and TAG‐34 did not precipitate any protein from this lysate. TARM‐34 lysed HTLV‐I‐bearing cells in the presence of rabbit complement. These results indicate that TARM‐34 and TAG‐34 both recognize a glycoprotein antigen that is expressed on the surface of HTLVI‐infected cells.
Ag‐Nor staining in human chromosomes: Differential staining in normal and leukemic bone‐marrow samples
Authors: Arden K. C. , Pathak S. , Frankel L. S. , Zander A.
Published: February 2007

A silver staining technique developed by Goodpasture and Bloom (1975) stains a specific protein associated with the activity of ribosomal cistrons during the preceding interphase. By counting the number of chromosomes with darkly stained nucleolus organizer regions (NORs), the number of active NORs per metaphase can be determined. A comparison of NOR activity in bone‐marrow cells from leukemic patients in different stages of disease with that of bone marrow from normal, healthy individuals was conducted and differential NOR activity was detected. The control group showed significantly lower NOR activity when compared with a group of patients with acute lymphocytic leukemia (ALL). These preliminary data indicate that this simple cytochemical technique can be effectively used to differentiate between normal and ALL bone‐marrow samples.
Recognition by a natural cytotoxic antibody of lactoneotetraglycosyl ceramide as an antigenic molecule in a syngeneic rat fibrosarcoma
Authors: Takimoto Masato , Suzuki Eiji , Naiki Masaharu , Itaya Toshiyuki , Takeichi Noritoshi , Hosokawa Masuo , Kobayashi Hiroshi
Published: February 2007

Conventionally bred rats possess in their sera an NA4 which hasαcytotoxic effect onαtumor cell line (KMT‐17) derived fromαfibrosarcoma induced by 3‐methylcholanthrene and which can be absorbed by normal rat tissues. We have succeeded in purifyingαglycosphingolipid as an antigen reactive to NA. GSLs isolated from the tumor cells were separated into neutral and acidic fractions. The former fraction was judged to be antigenic as detected by its capacity to absorb NA. The antigenic fraction was further separated into 7 fractions (Frs. A to G) by silicic acid chromatography. The antigenic activity was detected in only Frs.D and E, although Fr.D wasαmore potent antigen than Fr.E. Chemical and immunochemical analyses showed that both fractions are composed of lactoneotetraglycosyl ceramide (paragloboside), Gal(β 1‐4)GlcNAc(β 1‐3)Gal(β 1‐4)GIc(β 1‐1 )ceramide, and that the more active GSL, Fr.D, contains larger amounts of long fatty‐acid chains. Inhibition studies using disaccharides and monosaccharides indicated thatαN‐acetyllactosamine moiety, Gal(β 1‐4)GlcNAc, of the GSL isαspecific site of NA. These results suggest that paragloboside is an NA antigen and thatαsugar chain portion of this GSL is required for defining specificity while the ceramide portion playsαrole in potentiating the antigenicity of this GSL antigen for NA.
No loss of estrogenic or anti‐estrogenic activity after demethylation of droloxifene (3‐OH‐Tamoxifen)
Authors: Löser R. , Seibel K. , Eppenberger U.
Published: February 2007

The binding affinity of 3‐OH‐Tamoxifen (Droloxifene or DROL) and N‐demethyl‐droloxifene (NDDROl) to the cystosolic estrogen receptor of rabbit uteri was 10 times higher than that of Tamoxifen. Both compounds exhibited similar stimulation (estrogenic effect) and inhibition (anti‐estrogenic effect) of uterine growth of immature female rats. 3H‐Uridine incorporation into the RNA of MCF‐7 and ZR‐75 cells as a measure of anti‐estrogenic activity was equally inhibited by concentrations of 0.05 ‐ 1.0 μ mol/l of both compounds. Thus, the pharmacological properties of DROl were not changed by N‐demethylation.
Induction of cytotoxicity by interleukin‐2 in tγ‐lymphoproliferative disorders
Authors: Allavena P. , Introna M. , Rambaldi A. , Zanaboni F. , Rossini S. , Villa A. , Bassan R. , Barbui T. , Mantovani A.
Published: February 2007

We have studied 7 patients with Tγ‐lymphoproliferative disorders, in whom 78‐88% of circulating nonadherent lymphocytes had the morphology of large granular lymphocytes (LGL) as assessed by light and transmission electron microscopy. The main common features of the membrane phenotype of these LGL expansions included expression of T3, HNK‐I and AB8,28. Other monoclonal antibody‐defined surface markers of LGL (OKMI, B73.I, N90I) were variably expressed or absent in these patients. Patients' LGL had little or no natural killer (NK) activity but mediated antibody‐dependent cellular cytotoxicity (ADCC). Exposure to interferons (type B or γ) for 20‐72 hr resulted in no appreciable induction of cytolytic activity. In contrast, culture in the presence of interleukin‐2 (IL‐2) for 3 days resulted in the expression of strong cytolytic activity in all the patients tested against an NK‐susceptible (K562) and an NK‐resistant (Daudi) target. The expression of T3 antigen, the low levels or lack of native NK activity and the induction of consistent cytotoxicity by prolonged exposure to IL‐2 led us to suggest that the cells expanding in these subjects are related to the effectors involved in lymphokine‐activated killer (LAK) activity.
The association of replacement estrogens with breast cancer
Authors: Nomura Abraham M. Y. , Kolonel Laurence N. , Hirohata Tomio , Lee James
Published: February 2007

This epidemiologic case‐control study examined the relationship between replacement estrogen use and breast cancer risk in 2 population groups in Hawaii. No significant associations were observed when 161 Caucasian cases were compared with either their neighborhood controls (RR = 0.9; 95% CI = 0.5‐1.3)5 or their hospital controls (RR = 0.7; 95% CI = 0.4 to 1.1) and when 183 Japanese cases were compared with either their neighborhood controls (RR= 1.1; 95% CI = 0.7‐1.6) or their hospital controls (RR= 1.0; 95% CI = 0.6‐1.4). The results indicate that the use of replacement estrogens cannot account for the large difference in breast cancer incidence between the 2 Hawaiian ethnic groups. However, further data analysis involving neighborhood controls was suggestive of a possible increase in breast cancer risk with estrogen use for certain sub‐groups of women who are at high risk for the disease. These included estrogen users with a family history of breast cancer or a history of benign breast disease. These findings are in agreement with other studies which have used non‐hospitalized controls. Because the numbers of cases in this study are not substantial, it is recommended that a large population‐based case‐control study be undertaken to clarify the relationship between breast cancer risk and replacement estrogen use, especially in sub‐groups of women at high risk for the disease.
Human papillomavirus types 16 and 18 in carcinomas of the penis from brazil
Authors: McCance D. J. , Kalache A. , Ashdown K. , Andrade L. , Menezes F. , Smith P. , Doll R.
Published: February 2007

Human papillomavirus (HPV) type‐16 DNA sequences were found in 26/53 (49%) and HPV type‐18 in 5/53 (9%) of penile cancers. In only one specimen was HPV 18 found on its own. HPV 16 sequences were integrated into the host cell chromosomes although some monomeric and oligomeric free forms of DNA were detected in a few tissues. HPV 18 was, as far as detectable, free and unintegrated in all tissues tested. HPV 16 DNA was also detected in 40% of cases of carcinoma of the cervix in 19 women from the same social groups as the males. The viral DNA in the female cases was a mixture of integrated and free forms. The DNA binding protein (ICSP 11/12) of herpes simplex type 2 (HSV‐2) was not detected in 10 penile cancers tested with a monoclonal antibody.
Molecular cloning and characterization of the dna of a new human papillomavirus (hpv 30) from a laryngeal carcinoma
Authors: Kahn Tomas , Schwarz Elisabeth , Hausen Harald Zur
Published: February 2007

DNA from a human laryngeal carcinoma was molecularly cloned in Lambda L47. The gene library was screened for human papillomavirus (HPV)‐related sequences by hybridization analysis with 32P‐labelled HPV 16 DNA at conditions of low stringency (Tm −40°C). One of the clones (4‐5) with an insert of 7.8 kb showed cross‐hybridization with most of the known HPV types (Tm −40°C), and with several of them even under more stringent conditions (Tm ‐30°C). No signal was detected under high‐stringency conditions (Tm −20°C). The co‐linear alignment of clone 4‐5 with HPV 16 DNA could be demonstrated by hybridization experiments and also by partial DNA sequence analysis. We conclude that clone 4‐5 represents a new HPV type tentatively designated HPV 30. HPV 30 DNA was also detected in 2 genital lesions but not in 41 laryngeal carcinomas analyzed so far. Its presence in other tumor DNA is now under investigation.
Hydrocortisone and some other hormones enhance the expression of HTLV‐III
Authors: Markham Phillip D. , Salahuddin S. Zaki , Veren Keith , Orndorff Sharon , Gallo Robert C.
Published: February 2007

The ability to productively infect fresh normal human peripheral blood mononuclear leukocytes with HTLV‐III was improved by supplementing cell culture medium with either the gonadal steroid, chorionic gonadotropin, or insulin, and more substantially with the adrenocortical steroid, hydrocortisone. Several other sex hormones and another corticosteroid, dexamethasone, had no significant effect. In addition, the isolation of HTLV‐III from lymphocytes established in culture from patients with the acquired immunodeficiency syndrome (AIDS), AIDS‐related complex (ARC), and healthy, at‐risk donors was greatly facilitated by the inclusion of hydrocortisone in cell culture media. In 13/20 primary cell cultures tested from AIDS and ARC patients from whom virus was isolated, the amount of virus produced was elevated from low to easily detectable levels in those containing hydrocortisone. In 3/20 specimens tested, virus was detected and isolated from cell cultures supplemented with hydrocortisone but was undetectable in those lacking the hormone. These experiments demonstrate that hydrocortisone, a readily available, inexpensive supplement to cell culture media, can facilitate the detection and isolation of HTLV‐III. These studies, furthermore, suggest a role for corticosteroids and possibly gonadal steroids in the modulation of virus expression and/or release and suggest that the viral inductive capacity of these and other compounds should be considered as they are evaluated for clinical use.
Firm persistent binding between activated macrophages and tumor cells is not a prerequisite for the mediation of cytolysis
Authors: Keller R. , Keist R. , Groscurth P.
Published: February 2007

The present study seeks to reassess the roles of macrophage activation and persistent firm binding to tumor cells as a prerequisite for tumoricidal activity. To this end, macrophage effector populations from various tissues, expressing diverse functional activities, were made to interact in vitro with different suspension tumor cell lines. The resultant binding and cytolytic effector cell capacities were determined. Macrophage activation appears to be an absolute prerequisite for binding and for killing of tumor cells. Activated macrophages firmly bind and form clusters with D‐12 rat fibrosarcoma cells, which are relatively resistant to macrophage‐mediated tumoricidal action. In contrast, P‐815 murine mastocytoma cells, highly susceptible to the lytic activity of macrophages, bind rather poorly with activated macrophages and do not form clusters. Since susceptible target cells are readily killed by activated rat macrophages in the absence of persistent firm contact, it appears that firm binding and killing are not causally related events.
Peroxisome proliferators show tumor‐promoting but no direct transforming activity in vitro
Authors: Lillehaug Johan R. , Aarsaether Niels , Berge Rolf K. , Male Rune
Published: February 2007

The chemically unrelated hypolipidemic drugs, tiadenol, niadenate, and clofibrate4 have been tested for carcinogenic and tumor‐promoting potential in the C3H/10T1/2 C18 cell test system. None of these chemicals were carcinogenic, while both niadenate and clofibrate were active tumor promoters at micromolar concentrations. All 3 drugs induced the differentiation of C3H/10T1/2 C18 cells to adipocytes. This latter finding confirms previously observed effects of the tumor promoter TPA.
Xenografts in pharmacologically immunosuppressed mice as a model to test the chemotherapeutic sensitivity of human tumors
Authors: Floersheim G. L. , Bieri A. , Chiodetti Nicole
Published: February 2007

A human tumor xenograft model using pharmacologically immunosuppressed mice was assessed for its suitability to test preclinically the sensitivity of colorectal carcinomas, bone sarcomas and melanomas against anticancer agents. Besides ionizing radiation, 14 cytotoxic drugs including 5‐fluorouracil (5‐FU), dimethylmyleran (DMM), cytosine arabinoside, cyclophosphamide, melphalan, BCNU, mitomycin C, adriamycin, bleomycin, etoposide, vinblastine, cisplatin, procarbazine and DTIC were assayed. Ionizing radiation, 5‐FU and DMM were also applied at lethal doses followed by bone‐marrow rescue heavy therapy. Four colon carcinomas responded poorly to most of the agents but one tumor displayed marked sensitivity to BCNU. Lethal doses of radiation, 5‐FU and DMM could also show considerable activity. High sensitivity was shown by a Ewing sarcoma to DMM and cyclophosphamide and by an osteosarcoma to the latter drug. No strong effects were seen against melanomas. Lethal doses of DMM induced the best regression of one colon carcinoma. In general, the superiority of heavy therapy for solid human tumors compared to maximally tolerated doses was demonstrated. Individual carcinomas of the same type displayed different drug sensitivity.
Acquired resistance towards immune defense during metastatic progression represents a secondary phenomenon
Authors: Zöller M.
Published: February 2007

The role of natural immune defense in the control of metastatic spread of tumor cells was evaluated by adapting an s.c.‐grown, antigenic, but non‐immunogenic rat fibrosarcoma (Bsp6S) to ascitic growth (BSp6A) in the strain of origin (BDX), where peritoneal cells display a high level of NK and macrophage activity. Parallel tests were performed to determine whether tumor cells can selectively adapt to non‐specific immune defense, i.e. whether antigenicity of the non‐immunogenic tumor remains unaltered, and whether this is accompanied by metastatic progression. During adaptation to ascitic growth the tumor line gradually lost susceptibility to NK cells and macrophages. This was due to the appearance of an increasing number of resistant clones (BSp6S, none; BSp6A, 50% of clones), which had lost binding structures for NK cells and macrophages. No alteration could be observed in antigenicity of the BSp6A variant as revealed by clonal analysis using LD of CTL. Neither BSp6S nor BSp6A cells metastasized. When the ascitic variant was retransplanted s.c. (BSp6AS), susceptibility to NK cells and macrophages was further decreased, in the sense that all clones of the BSp6AS variant became resistant. Furthermore, the BSp6AS variant had lost some of the tumor‐associated antigens (TAAs) found on BSp6S and A variants. More important, upon s.c. transplantation BSp6AS regularly metastasized to the draining LN, contrary to BSp6S and BSp6A. When locally growing tumors were excised, rats implanted with BSp6AS frequently died with metastatic tumor burdens in LNs and lung, while other animals survived after excision of BSp6S or BSp6A. The data indicate a correlation between resistance to lysis, morphology and metastatic capacity. But the initial loss of susceptibility to NK cells and macrophages during adaptation to ascitic growth, which can be considered as an escape mechanism, was not accompanied by increased metastatic capacity. Hence, we suppose that with respect to metastatic progression of the BSp6AS variant, resistance to lysis by loss of binding structures represents only a secondary, but not a causative, element.