bluuebunny/crossref_metadata_2025 huggingface dataset:
CA 50 Determination in body fluids: Can we screen patients at risk for gastric cancer?
Authors: Farinati F. , Holmgren J. , Di Mario F. , Cardin F. , Valiante F. , Fanton M. C. , Della Libera G. , Nitti D. , Plebani M. , Crestani B. , Naccarato R.
Published: February 2007

CA 50 (a tumor‐associated gangliosidic antigen) levels have been determined by an RIA test in serum, gastric juice and urine of patients undergoing upper gastrointestinal tract endoscopy: 22 control subjects (no macroscopic or microscopic lesions), 29 patients with chronic atrophic gastritis, 20 with epithelial dysplasia and 16 with gastric cancer entered the study. Gastric juices were also tested for pH, protein concentration and specific gravity, urines for protein concentration and osmolarity. Serum and gastric juices were also tested for CEA levels and the results obtained with the two markers compared. In patients with gastric cancer, CA 50 gastric juice levels were statistically higher than in controls; a wide overlap was however present among groups, and sensitivity and specificity were respectively 38% and 85% for serum and 69% and 82% for gastric juice. Sensitivity and specificity were respectively 23% and 89% for CA 50 determination in urines. In this case, no statistically significant difference was observed between gastric cancer and control patients. A trend toward higher median values was observed in advanced with respect to early gastric cancer. A correlation was found between gastric juice and serum CA 50 levels, as well as between serum and urine levels of the marker. A correlation was also observed between CA 50 values and protein concentration in gastric juice and with osmolarity in urines. Overall, CA 50 levels were statistically higher in patients with intestinal metaplasia than in those who did not present the lesion. Increased CA 50 gastric juice levels are also observed in patients with chronic atrophic gastritis and epithelial dysplasia. CA 50 gastric juice and urine levels appear to be dependent, at least in part, on the concentration of the fluid.
The nordic profile of skin cancer incidence. A comparative epidemiological study of the three main types of skin cancer
Authors: Magnus Knut
Published: February 2007

The data used for the inter‐Nordic comparison of the incidence of skin cancer are based on the material of the national cancer registries of the 5 Nordic countries. It is typical of these countries that the ratio between the incidence of non‐melanoma and melanoma skin cancer is much smaller than in regions near the Equator. For the detailed comparative epidemiological study of basal‐cell carcinoma (BCC), squamous‐cell carcinoma (SCC) and cutaneous malignant melanoma (CMM), the material from the Norwegian Cancer Registry 1955‐1988 is used. The etiology of CMM has frequently been debated during recent decades. There are still some obscure points, however, particularly as regards the influence of host factors and UV exposure, and their interaction. The analysis of the incidence trend of CMM on the female breast during the time interval 1970‐1988 contributes to the elucidation of these problems. Differences in the epidemiological characteristics of the 2 main types of non‐melanoma skin cancer, BCC and SCC, are described. The results indicate that the effect of UV light is not as dominating for BCC as for SCC.
Diffuse centrocytic and/or centroblastic malignant non‐hodgkin's lymphomas: Comparison of mitotic and pyknotic (apoptotic) indices
Authors: Vecchio Maria Teresa Del , Leoncini Lorenzo , Buerki Kurt , Kraft Rainer , Megha Tiziana , Barbini Paolo , Tosi Piero , Cottier Hans
Published: February 2007

Mitotic indices (Mls) and pyknotic (apoptotic) indices (Pls) were assessed in diffuse centrocytic (CC, n = 10), centroblastic/centrocytic (CB/CC, n = 18)and centroblastic(CB, n = 20) malignant non‐Hodgkin's lymphomas (NHL). Significant differences were observed. Mls were lowest in CC (median: 0.07%), intermediate in CB/CC (0.18%) and highest in CB (0.43%) NHLs. The Pls exhibited a similar pattern. The Pls of CC (0.11%) and CB/CC (0.17%) NHLs were significantly different from those of CB lymphoma (0.62%). The ratios MI/PI per case, as well as Mls and Pls per case, varied greatly and showed considerable overlapping, thus documenting a marked inter‐case and inter‐group heterogeneity. Mls tended to loosely correlate with Pls in a non‐linear fashion, which raises the question of feedback mechanisms. More information is needed on mitotic time (TM) and apoptotic time (TA), in order to estimate cell doubling time from data on Mls and Pls.
Differential sensitivity of various human tumors to inhibition of poly amine biosynthesis in vivo
Authors: Saydjari Rami , Alexander Robert W. , Upp James R. , Barranco Sam C. , Townsend Courtney M. , Thompson James C.
Published: February 2007

Polyamines are essential for normal and neoplastic growth. Ornithine decarboxylase (ODC) is the first and rate‐limiting enzyme in the polyamine biosynthetic pathway. α‐Difluoro‐methylornithine (DFMO) is an enzyme‐activated irreversible inhibitor of ODC, and a known anti‐neoplastic agent. The purpose of this study was to examine the susceptibility of various human cancers to inhibition by DFMO in vivo. We have studied three human pancreatic adenocarcinomas, designated CAV, SKI, and PGER, two human colon adenocarcinomas (LS‐180 and WIDR), and three metastatic cell lines of a human gastric adenocarcinoma (BHM, BMM, BLM) that were growing in congenitally athymic (nude) Balb/c mice. Mice bearing each tumor were divided into two groups; one group served as controls and the other group received DFMO 3% in drinking water. Tumor growth and weight, and content of DNA, RNA, protein and polyamines were determined and correlated. DFMO significantly inhibited the growth of three of the three gastric tumors, two of the three pancreatic tumors and neither of the two colon tumors. The tumor content of DNA, RNA and protein exhibited a pattern that was parallel to tumor growth. The tumor polyamine concentration did not correlate with sensitivity to DFMO. These findings provide clear evidence for important differences in the sensitivity of various human cancers to growth inhibition by DFMO and indicate that endogenous polyamine levels alone do not predict the sensitivity of the tumors to DFMO.
Antigen shedding vs. development of natural suppressor cells as mechanism of tumor escape in mice bearing ehrlich tumor
Authors: Viñuela Juan E. , Rodriguez Rosa , Gil Juana , Coll Javier , De Concha Emilio G. La , Subiza Jose L.
Published: February 2007

C57BL/6J mice immunized with devitalized Ehrlich tumor (ET) ceils produce high serum levels of IgM antibodies to ET cell‐surface carbohydrates that are critical in the observed resistance against this tumor. However, this response is not found in ET‐bearing mice at any stage of tumor development. Since previous studies had shown splenic natural suppressor (NS) cells in ET‐bearers, their role in such IgM impairment was assessed. Here we show that tumor‐bearers' spleen cells (TBSC) are unable to produce IgM in vitro in response to LPS, due to the presence of NS cells. Nevertheless, TBSC do produce IgM antibodies to ET cell‐surface carbohydrates in increasing amounts as the tumor progresses. Yet these antibodies are not detected in sera of ET‐bearers and are greatly decreased in immunized mice with a growing tumor. Moreover, increasing amounts of circulating carbohydrates, able to absorb most specific IgM, are found in ET‐bearing sera associated with a large molecular size structure(s). These carbohydrates are also found in ET cell‐culture supernatants and cell‐free ascites fluid derived from this tumor, indicating their tumor origin. Taken together, our results indicate that lack of specific IgM antibodies in ET‐bearing mice is not due to faulty production, but to in vivo absorption by carbohydrates shed from ET cells in increasing amounts as the tumor progresses. Thus, NS cells are unable to suppress this IgM production in vivo, despite the strong suppressor activity they show for many responses in vitro.
Production of heparanase by normal and neoplastic murine B‐lymphocytes
Authors: Laskov Reuven , Michaeli Rivka‐Ishai , Sharir Hava , Yefenof Eitan , Vlodavsky Israel
Published: February 2007

The production of heparanase, an endoglycosidase capable of degrading heparan sulfate from the subendothelial extracellular matrix (ECM), was investigated in various murine B‐lymphoid tumors representing distinct maturation stages of the B‐cell lineage. We found that heparanase is produced and released by 3 out of 4 pre‐B lymphomas and by 4 B lymphomas examined. In contrast, 5 plasmacytomas and resting normal B lymphocytes, expressed little, if any, heparanase activity. Treatment with LPS resulted in high expression of the enzyme by normal B‐lymphocytes, but there was no effect on the constitutive production of heparanase by myeloma or B‐lymphoma cells. Our results indicate that heparanase is produced by B cells during discrete stages of their maturation. We suggest that heparanase may play a role in B‐cell migration by enabling pre‐B and B lymphocytes to leave the bone‐marrow compartment and recirculate among peripheral lymphoid organs.
Meta‐Iodobenzylguanidine (mIBG) uptake and storage in the human neuroblastoma cell line SK‐N‐BE(2C)
Authors: Lashford L. S. , Hancock J. P. , Kemshead J. T.
Published: February 2007

Whilst many human neuroblastoma cell lines have been studied to see if they are capable of taking up mIBG, few appear to have this ability. This contrasts markedly to the situation in vivo, where uptake has been demonstrated in the majority of tumours investigated. Here we report on the human neuroblastoma cell line SK‐N‐BE(2C) and demonstrate that mIBG uptake can occur in this cell line through 2 mechanisms. At low concentrations of mIBG (approximately 10−8 m) an active transport process predominates, whereas at non‐physiological levels (10−4 m) uptake occurs through passive diffusion. The active transport process is ATP‐, Na+_‐ and temperature‐dependent. Uptake is blocked by 10−6 m desipramine, an inhibitor of the uptake‐1 mechanism involved in amine transport. In contrast, desipramine has no effect on the passive diffusion of mIBG into cells. The active transport mechanism for mIBG uptake appears rather promiscuous for biogenic amines, as dopamine, tyramine and nor‐adrenaline were highly efficient at blocking mIBG entry to the cell. Serotonin and histamine were capable of interfering with mIBG uptake only at much higher concentrations. Electron microscopy of SK‐N‐BE(2C) cells revealed a paucity of neurosecretory granules. Biochemical investigations demonstrated the majority of mIBG to be present in the cytoplasm of cells. The availability of a human neuroblastoma cell line that grows well, both as xenograft and in culture, should further our understanding of the cytotoxic effects of mIBG and thus enhance its clinical usefulness.
Comparative biochemical, cytotoxic and pharmacokinetic properties of immunotoxins made with native ricin a chain, ricin A1 chain and recombinant ricin a chain
Authors: Wawrzynczak Edward J. , Cumber Alan J. , Henry Raymond V. , Parnell Geoffrey D.
Published: February 2007

Immunotoxins were constructed by attaching native ricin A chain, ricin A1 chain and recombinant ricin A chain to the mouse monoclonal IgG2a antibody Fib75 by means of a disulphide linkage using the hetero‐bifunctional cross‐linker SPDP. The Fib75 immunotoxins were of similar composition and exerted identical cytotoxic effects against the EJ human bladder carcinoma cell line in tissue culture. All 3 immunotoxins broke down to the same extent upon incubation with glutathione in vitro. The clearance of the immunotoxins from the circulation of normal Wistar rats was determined following i.v. administration. The concentration of intact immunotoxin in serum samples taken at various intervals up to 48hr after injection was measured by a ricin A chain‐specific ELISA. The Fib75 immunotoxin made with native ricin A chain was removed from the circulation most rapidly. Fib75‐recombinant ricin A chain persisted in the circulation at a higher level than Fib75‐ricin A, chain. A higher proportion of the ricin A, chain immunotoxin was lost from the bloodstream during the α‐phase. The β‐phase half‐lives of Fib75‐recombinant ricin A chain and Fib75‐ricin A, chain were similar, consistent with the identical susceptibility of the immunotoxins to cleavage by glutathione. The presence of the complex‐type oligosaccharide side‐chain on the A1 chain may have accelerated the clearance of the A1 chain immunotoxin in relation to that of the immunotoxin made with the aglycosyl recombinant A chain.
Suppression of established pulmonary metastases by murine melanoma‐specific monoclonal antibodies
Authors: Hearing Vincent J. , Leong Stanley P. L. , Vieira Wilfred D. , Law Lloyd W.
Published: February 2007

The intravenous administration of melanoma‐specific monoclonal antibodies (MAbs) 9B6 and T97, both of the IgG2b isotype, consistently suppressed the growth of established JB/MS murine melanoma lung metastases. This activity was not dose‐dependent, lower doses of MAbs often being more suppressive than higher doses. Intravenous administration of antibodies at days 5 and 8 following challenge appeared to be optimal for suppression whereas no inhibition was seen with intravenous treatment at days 0 and 3 or at days 10 and 13. Consistent and significant inhibition was also observed using established B16F10 lung metastases but only at lower doses, whereas both MAbs were ineffective against the T92497 sarcoma in syngeneic mice. These MAbs appear to act not as direct anti‐tumor agents but as host immune response regulators, since specific anti‐tumor effects were abrogated in tumor‐bearing hosts following pre‐treatment with antibodies directed against asialo‐GM1 and NK‐1.1, surface markers of natural killer cells.
Loss of Y chromosome with retention of Y heterochromatin in a marker chromosome from a human melanoma
Authors: Doneda Luisa , Larizza Lidia
Published: February 2007

A single copy of a der 15 chromosome (m3) characterized by a C‐ and distamycin A‐Dapi‐positive region was observed in the ‐Y hyperploid karyotype of a primary human melanoma (Me 1402). The heterochromatic region was located pericentromerically, adjacent at one end to the NOR region of chromosome 15, and at the other to an unclassifiable chromosomal piece. We established that the C‐positive block in the marker chromosome originated from Y heterochromatin by high‐stringency in situ hybridization with a DNA probe for the 2.1 Hae III Y‐specific repeat. Loss of the Y chromosome in tumors has been considered to be a secondary event associated with malignant evolution. It is significant that Me 1402 cells, which are highly malignant, lack the Y chromosome, but retain its heterochromatic portion in the rearranged m3 chromosome.
Carcinoma‐associated mucin serum markers CA M26 and CA M29: Efficacy in detecting and monitoring patients with cancer of the breast, colon, ovary, endometrium and cervix
Authors: Yedema Kees A. , Kenemans Peter , Wobbes Theo , Van Kamp Gerard J. , De Bruijn Henk W. , Thomas Chris M. , Massuger Leon F. , Schuf Charles P. , Bon Gijsbert G. , Vermorken Jan B. , Voorhorst Feja , Hilgers Jo
Published: February 2007

Two recently developed monoclonal antibody (MAb)‐based anti‐mucin assays, CA M26 and CA M29, were studied in 250 cancer patients and compared to 3 well‐established marker tests, viz., CA 125, CA 15.3 and SCC, in order to assess their clinical usefulness as serum tumor markers. Pre‐treatment sera were obtained from patients with predominantly low‐stage epithelial malignancies comprising 200 adenocarcinomas (of the ovary, endometrium, breast and large intestine) and 50 squamous‐cell carcinomas (of the uterine cervix). Pre‐treatment sera of 50 patients with benign ovarian tumors were included to evaluate levels in benign disease. CA M26 and CA M29 cut‐off levels were established in 89 healthy controls. In patients with adenocarcinomas, overall positivity for CA M29 was 24%, ranging from 10% in breast cancer to 60% in ovarian cancer. Overall positivity was highest for CA 125 (30%) and lowest for CA M26 (18%) with CA M29 (24%) being similar to CA 15.3 (25%). In adenocarcinomas the combined CA M26‐CA M29 assays equalled results obtained with the CA 125‐CA 15.3 combination (33% vs. 36%). Elevation of 2 or more markers was highly indicative of advanced disease (p < 0.025). A majority of positive patients showed either CA M26 or CA M29 elevations, indicating that both antibodies detect distinct epitopes. After adjustment for tumor site and stage, the profile of CA M26 as a single marker differed significantly from the profiles of CA 125 and of CA M29. CA M26 was frequently (32%) elevated in patients with squamous‐cell carcinoma of the cervix and CA M26 levels were often independently elevated. CA M26 seems to be valuable as an additional marker in breast cancer and perhaps as a new marker in cervical cancer. CA M29 may be useful in ovarian cancer in addition to CA 125.
Monoclonal antibodies to glutathione S‐Transferase π–immunohistochemical analysis of human tissues and cancers
Authors: Kantor Raphe R. S. , Giardina Steven L. , Bartolazzi Armando , Townsend Allen J. , Myers Charles E. , Cowan Kenneth H. , Longo Dan L. , Natali Pier G.
Published: February 2007

Mouse monoclonal antibodies (MAb) have been generated against the anionic isozyme of human glutathione S‐transferase (GST π). MAb AGST I can inhibit 50‐70% of GST π enzymatic activity and reacts with a 3‐dimensional epitope which includes a putative glutathione binding site on GST π. A sandwich enzyme‐immunoassay established using MAb AGST I and a polyclonal antibody displayed a sensitivity of 0.5 ng/ml. Immunohistochemical analysis of human tissues demonstrated marked increases in GST π levels in cancers of the brain, cervix, endometrium, colon, rectum and testis and in fibro‐and chondrosarcomas.
Coffee consumption and bladder cancer risk
Authors: Clavel J. , Cordier S.
Published: February 2007

The relationship between coffee drinking and the risk of bladder cancer was analyzed within the framework of a French hospital‐based case‐control study conducted between 1984 and 1987, which included 690 cases of histologically confirmed bladder cancer (599 males and 91 females), and 690 age‐, sex‐ and hospital‐matched controls. To dissociate the effects of smoking and coffee drinking among males, the analysis of the male group was restricted to 2 contrasted subgroups: non‐smokers on the one hand, and current smokers and inhalers of black tobacco cigarettes on the other. Coffee drinking was found to be significantly associated with the risk of bladder cancer among men in both groups and the increase in the risk was dose‐dependent (OR = 1, 2.9, 5.1 respectively, for drinking 1, 2, × 3 cups of coffee per day among non‐smokers, and 1, 2.5 and 3.0 respectively, for drinking 1‐4, 5‐7, >7 cups among smokers). This result was not observed for women.
Histological and urinary reactivity of monoclonal antibody 1be12 in bladder carcinoma. Purification of the antigen from urine
Authors: Pancino Gianfranco , Toubert Marie‐Elisabeth , Osinaga Eduardo , Chatelet François , Leroy Martine , Schlageter Marie‐HéLèNe , Du Roure François Desroys , Calvo Fabien , Teillac Pierre , Najean Yves , Roseto Alberto
Published: February 2007

We have previously reported the production of monoclonal antibody (MAb) IBE 12, which recognizes a glycoprotein in breast‐cancer cells. In the present work, IBE 12 reactivity was tested by immunohistochemistry in bladder carcinoma (92 cases) and in non‐tumoral bladder samples (15 cases). In 71% of bladder tumors, more than 30% of cells were intensely stained by I BE 12. The percentage of reactive cells was higher in cancers invading the muscle than in more superficial tumors (p = 0.039). In non‐tumoral bladder, immuno‐staining, when present, was usually confined to the superficial layers with a low number of cells stained (<30%) in 13/15 cases. Slot blots, performed on urine samples from 43 bladder‐cancer patients and 21 healthy controls, were quantified by densitometry scanning. We found higher optical density (OD) values in urine from muscle‐invasive‐cancer patients than in urine from more superficial tumors and healthy controls, with a significantly different distribution (p = 0.005). The urinary antigen was detected by immunoblotting with IBE 12 as high‐molecular‐weight species (> 150 kDa). The reactive glycoprotein could thus be purified by immunoaffinity and FPLC filtration from the perchloric‐acid‐soluble fraction of urine from patients with invasive bladder carcinoma. The availability of purified antigen will allow us to quantitate our assay, in order to evaluate its potential use as a prognostic indicator in bladder‐cancer patients.
Characterization of a highly invasive and spontaneously metastatic human malignant melanoma cell line
Authors: Welch Danny R. , Bisi J. E. , Miller B. E. , Conaway D. , Seftor E. A. , Yohem K. H. , Gilmore L. B. , Seftor R. E. B. , Nakajima M. , Hendrix Mary J. C.
Published: February 2007

Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, especially its metastatic properties. Here we describe C8161, a highly invasive and spontaneously metastatic human melanoma cell line, which grows progressively in the subcutis of athymic nude mice with an average doubling time of approximately 6 days. By the time the tumor reaches a diameter of I cm, amelanotic metastases in lymph nodes, skin, peritoneal wall, spleen and lungs have formed. By comparing C8161 to variants from other well‐characterized human malignant melanomas (A375 and MeWo) with differing metastatic traits, properties presumed to be involved in metastatic propensity were examined. C8161 showed a 2‐ to 14‐fold higher ability to invade reconstituted basement membrane barriers in the MICS and correspondingly high type‐IV collagenase mRNA levels and collagenolytic activity, as compared with other melanoma cell lines. Likewise, differential adhesion to immobilized RBM or HUVEC monolayers was observed, but did not correlate to rank orders of malignant properties. Recently, a correlation between surface expression of ICAM‐I and secondary tumor formation by human melanomas has been described in several laboratories. Basal levels of ICAM‐1 on C8161, A375 and MeWo human melanomas were compared, but no correlation with metastatic potential was noted. Proto‐oncogene expression in C8161 cells was compared with A375P and A375M variants using Northern blot analysis, c‐mycexpression was 6‐fold greater than both A375 variants; c‐fosexpression was 3.4‐fold less than A375P and 1.7‐fold less than A375M; c‐junin C8161 cells was 2.5‐fold and 2.1‐fold greater than expression in A375P and A375M, respectively. Because C8161 is so highly malignant, amenable to experimental manipulation, and its behavior in nude mice mimics the clinical course of malignant melanoma, this cell line will prove valuable for studying properties associated with human melanoma tumor progression.
Skin fibroblast cell lines derived from non‐hodgkin's‐lymphoma (NHL) patients show increased sensitivity to chronic gamma irradiation
Authors: Hannan Mohammed A. , Greer William , Smith Blake P. , Sigut David , Ali Mohammed A. , Amer Mageed H.
Published: February 2007

Cultured fibroblast cells from 19 patients with non‐Hodgkin's lymphoma (NHL), 3 patients with ataxia telangiectasia (AT), 3 AT heterozygotes and 11 (presumed) normal subjects were studied for impaired colony‐forming ability after chronic gamma irradiation. Five cell lines from the NHL patients were also examined for the sensitivity to acute gamma irradiation, as compared with those of normal subjects. To ascertain the degree of radiosensitivity of different cell lines, a comparison was made of the Dl0 values (radiation dose resulting in 10% survival) for each cell line, estimated “by eye” from the actual survival curves, and also from the calculated curves fitted to a log‐linear model. It was observed that the acute gamma irradiation failed to show any appreciable difference in the radiation response of the cell lines from NHL patients as compared with those of normal subjects. However, chronic irradiation demonstrated significantly increased radiosensitivity in at least 10‐12 NHL patients with a p value of < 0.05, when the D,10 values of each patient's cell line were compared with the calculated composite values for the normals. When the Dl0 values of the NHL patients and the normal subjects were compared as 2 groups, the former appeared to be significantly more sensitive to chronic gamma irradiation (p < 0.0001). The same level of significant difference in radiosensitivity was found between the 2 groups when their D37 values (radiation dose resulting in 37% survival) were compared. In general, the radiation response of the NHL patients was similar to that of the AT homozygotes and heterozygotes used as a positive control group. Our data thus show that increased radiosensitivity is associated with the NHL patients studied, indicating an underlying abnormality of their DNA repair.
Preparation and characterization of monoclonal antibodies specific to synthetic peptide of carcinoembryonic antigen
Authors: Tsujisaki Masayuki , Imai Kohzoh , Hishikawa Noriyuki , Tokuchi Shigeru , Hinoda Yuji , Matsukawa Hirokazu , Oikawa Shinzo , Nakazato Hiroshi , Yachi Akira
Published: February 2007

Monoclonal antibodies (MAbs) were prepared to a synthetic peptide (PI: 119‐140 amino acids) in domain I of the carcino‐embryonic antigen (CEA) molecule. The majority of the amino acids in peptide PI show a hydrophilic character, and similar sequences are repeated in domains I, II and III of this molecule. These MAbs appear to recognize new epitopes of CEA, since representative conventional MAbs to CEA do not show reactivity to synthetic peptide PI. The resulting MAbs were divided into 2 groups; group 1 (MAb PI‐706) reacted with peptide PI, but not with purified CEA preparation, while group 2 (MAb PI‐234 and PI‐255) reacted with either type of antigen, in the immunoblotting assay using purified CEA and in immunostaining of colonic carcinoma tissues. Furthermore, group‐1 MAb PI‐706 was reactive to purified CEA after treatment with periodate.
Detergent extraction and characterization of tumor hemolytic factor from plasma membranes of oncogene transformed fibroblasts
Authors: Zuucker Stanley , Dimassimo Betty I. , Lysik Rita M. , Vuaridel‐Bonanomi Evelyne
Published: February 2007

Cancer cells have the capacity to lyse erythrocytes by a cell‐contact‐requiring phenomenon. Subcellular fractionation procedures have revealed that the hemolytic principle resides in the cancer cell plasma membrane. In this study we report the detergent extraction of a potent hemolytic factor from the plasma membranes of ras‐oncogene‐transformed fibroblasts. Ammonium‐sulfate partitioning (60‐100%) of detergent‐extracted proteins was used to enrich hemolytic activity. Tumor membrane Hemolytic Factor (mTHF) was inactivated by treatment with papain, suggesting that it is a protein. mTHF was inhibited by serum, but was unaffected by extremes of temperature and pH, also by metal chelation with EDTA. Surface radio‐iodination of tumor cells and isolation of cell organelles was used to characterize the outer plasma membrane localization of mTHF. mTHF retained hemolytic activity when reconstituted into stable phospholipid vesicles. Pre‐incubation of mTHF with red cell ghosts led to an abrogation of hemolytic activity. mTHF‐induced hemolysis consists of a 2‐stage phenomenon: an early binding step, followed by hemolysis after 4 hr.
Oncofetal mucin Ml epitope family: Characterization and expression during colonic carcinogenesis
Authors: Bara J. , Gautier R. , Mouradian P. , Decaens C. , Daher N.
Published: February 2007

The gastric mucin M1 antigens, markers associated with colonic carcinogenesis, have been characterized by new anti‐mucin monoclonal antibodies (MAbs). These MAbs, obtained against mucins isolated from a human ovarian mucinous cyst (MAbs 19M1, 21M1 and 45M1) and from a pancreatic adenocarcinoma (MAb 96RA), were compared with 5 other anti‐M1 mucin MAbs described previously, which characterized the a, b, c, d and e mucin M1 epitopes. Using immunoperoxidase, these new MAbs exclusively stained the surface gastric epithelium of normal human gastro‐intestinal tract and reacted with fetal, precancerous and cancerous colonic mucosa, but not with normal colon. Immunoradiofixation studies showed that these new MAbs are directed against 3 epitopes (f, g and h) which are different from the a, b, c, d and e mucin M1 epitopes, though present on the same a immunoreactive high‐molecular‐weight components (> 1,000 kDa) with a density of 1.4 by CsCl‐density‐gradient ultracentrifugation. M1 antigenicity is characterized by a family of 8 different M1 epitopes which were destroyed with β‐mercaptoethanol (except for the f epitope), sensitive to a 5 hr trypsin treatment and resistant to 5 mM periodate (except for the h epitope). Some epitopes (b, c and d) showed increasing immunoreactivity after 20 mM periodate treatment, suggesting cryptic location. In rat‐colon adenocarcinomas, M1 mucin epitopes were masked but could be decrypted using high periodate treatment, similar to normal rat gastric mucosa, thus suggesting the absence of drastic changes in the saccharide coat of the peptide mucin portion bearing M1 epitopes. Cryptic location, periodate resistance, sensitivity to protease and conformational behavior strongly suggest that the peptidic core of gastric (or fetal colonic) mucin plays a role in M1 immunoreactivity. Indeed, the resurgence of M1 antigens during colonic carcinogenesis is due to re‐expression of the peptide core of gastric (or fetal colonic) mucins.
Cigarette smoking and cancer of the pancreas: Evidence from a population‐based case‐control study in Toronto, Canada
Authors: Howe G. R. , Jain M. , Burch J. D. , Miller A. B.
Published: February 2007

Results are reported with respect to smoking data from a population‐based case‐control study of pancreatic cancer conducted in Toronto, Canada, between 1983 and 1986. Lifetime smoking histories were obtained for 249 cases and 505 controls. A statistically highly significant positive association was observed between lifetime cigarette consumption and risk of pancreatic cancer. There was a rapid decrease in risk with time for those who quit cigarette smoking, the risk for ex‐smokers being the same as for lifetime non‐smokers between 10 and 15 years after quitting. Limiting exposure to the 15 years prior to diagnosis considerably strengthens the association and leads to a much more clearly defined dose‐response relationship with relative risks of 1.88, 4.61, and 6.52 for tertiles of consumption for current cigarette smokers compared with lifetime non‐smokers (p trend < 10−5). We conclude that the current data, together with those from previous studies, strongly support a causal relationship between cigarette smoking and risk of pancreatic cancer, and indicate that cessation of smoking is likely to prove a rapidly effective preventive measure for this major type of cancer.
Correlation between cytogenetic data and ganglioside pattern in human meningiomas
Authors: Berra B. , Papi L. , Bigozzi U. , Serino D. , Morichi R. , Mennonna P. , Rapelli S. , Cogliati T. , Montali E.
Published: February 2007

Partial or total loss of chromosome 22 is often associated with tumors of the central nervous system and in particular with meningiomas. As in the case of other tumors, the ganglioside pattern is modified in transformed tissues. Cytogenetic analysis of 30 human meningiomas has been performed and the results compared to biochemical analysis of ganglioside distribution on the membrane surface. The meningiomas were divided into 2 groups on the basis of the presence or absence of chromosome 22. Thirteen tumors exhibited partial or total monosomy of the chromosome, whereas 17 were normal or showed other chromosomal anomalies. The GM3 and GD3 content of the meningiomas belonging to the 2 groups revealed a significant correlation between amount and reciprocal ratio of these 2 gangliosides and cytogenetic data. Tumors with monosomy 22 had a higher content of ganglioside GD, than samples without monosomy 22, where the main ganglioside was GM3. Other gangliosides such as GM1, GD1a, GD1b and GT were present in various amounts in the 2 groups. Considering the biosynthetic pathway of gangliosides, we hypothesize the involvement of a gene located on chromosome 22 in the regulation of the enzymes which catalyze either GD3 synthesis (sialyltransferase 2, SAT‐2) or its degradation to GM3 (neuraminidase).
Quantitative measurement of monoclonal antibody distribution and blood flow using positron emission tomography and 124iodine in patients with breast cancer
Authors: Wilson C. B. , Snook D. E. , Dhokia B. , Taylor C. V. J. , Watson I. A. , Lammertsma A. A. , Lambrecht R. , Waxman J. , Jones T. , Epenetos A. A.
Published: February 2007

The uptake and in vivo quantitation of monoclonal antibodies (MAbs) has been measured non‐invasively using positron emission tomography (PET) and 124iodine in 9 patients with breast ductal carcinoma. Blood‐flow measurements were also made using 15oxygen‐labelled water and PET to evaluate antibody delivery; 7 patients were studied with HMFGI antibody and 2 patients with a non‐specific antibody. Tumour uptake ranged from 2‐7.7 × 10−3% of injected dose per gram of tissue. Values for normal tissue including liver, lung and bone were also obtained. In 2 out of 7 patients studied with the specific antibody, uptake was greater than that seen with the non‐specific antibody. There was no correlation between antibody uptake and blood flow. This report exemplifies the potential of PET for the non‐invasive and accurate quantitative assessment of targeted antibody which is a prerequisite to therapy.
Bilateral ovarian carcinoma: Cytogenetic evidence of unicentric origin
Authors: Pejovic Tanja , Heim Sverre , Mandahl Nils , Elmfors Bengt , Furgyik Stefan , Flodérus Ulla‐Maria , Helm GÖRan , Willén Helena , Mitelman Felix
Published: February 2007

Cytogenetic analyses were performed on the tumors from both ovaries in 15 patients with bilateral ovarian carcinoma. In 4 of them, omental implants were also examined. Abnormal karyotypes were detected in 11 cases. The baseline karyotypes in the 2 tumorous ovaries were identical in each patient, indicating that bilateral ovarian cancer develops by metastatic spreading. There was no clear‐cut evidence of differences in the clonal evolution between the tumors of the 2 ovaries, and hence the side harboring the primary tumor could never be determined. The metastatic nature of the omental implants was proved by the fact that their karyotypes were indistinguishable from those of the ovarian tumor tissue.
Expression of the gastrin‐releasing peptide gene in carcinomas of the breast
Authors: Pagani A. , Papotti M. , Sanfilippo B. , Bussolati G.
Published: February 2007

Expression of gastrin‐releasing peptide (GRP), the mammalian homologue of the amphibian bombesin, has been investigated at gene and protein level in a series of 28 primary breast carcinomas, in 6 mammary cancer cell lines and in one transplantable rat mammary carcinoma. Moderate to strong expression of GRP mRNA was detected in 5 breast carcinomas by Northern blot analysis with a pre‐pro‐GRP probe; 4 other cases were weakly reactive. Two of these cases also gave a specific immunocytochemical reaction for GRP, controlled with absorption experiments. Correlation with NE differentiation [as shown by chromogranins (Cg) and/or NSE and/or Grimelius positivity] was low, since only one case of breast carcinoma co‐expressed GRP and Cg mRNAs. Breast cancer cell lines and a rat carcinoma gave negative results. GRP production in breast cancer did not appear to bear prognostic implications, but longer follow‐up periods are needed to confirm these data. As shown in small‐cell lung cancer, GRP might be involved in autocrine growth control mechanisms of a group of breast carcinomas.
Squamous‐cell carcinoma antigen (SCC‐A) values related to clinical outcome of pre‐invasive and invasive cervical carcinoma
Authors: Brioschi P. A. , Bischof P. , Delafosse C. , Krauer F.
Published: February 2007

The serum concentration of squamous‐cell carcinoma antigen (SCC‐A), a subfraction of tumour antigen, was determined by RIA from healthy donors (control group) and from patients with malignant cervical disease. Ninety‐six percent (173/180) of the healthy patients had squamous‐cell carcinoma antigen serum levels below 2ng/ml. Ten of 70 (14.3%) patients with CIN III, 53.8% (34/62) of patients with invasive squamous‐cell carcinoma stage 1, 85.8% (30/35) with stage II and 96.5% (27/28) with stage III/IV had squamous‐cell carcinoma antigen serum levels above 2ng/ml. We observed that 22.5% (11/49) of patients with a tumour volume below 10ml and 92.6% of patients with a tumour volume greater than 10ml had squamous‐cell carcinoma antigen levels above 2ng/ml (p < 0.005). SCC‐A was correlated with recurrence or progressive disease in 90.0% of cases. Other risk factors such as depth of invasion, microscopic parametrial involvement, lymphatic and/or vascular space permeation and histological grade were not correlated with squamous‐cell carcinoma antigen. Furthermore, this marker increased 4.3 ± 2.7 months before clinical evidence of recurrence or progressive disease. We conclude that serial serum levels of squamous‐cell carcinoma antigen provide a means for early detection of recurrence or progressive disease. This tumour marker might also be useful for monitoring the treatment effects and has some prognostic value.
Changes in cell kinetics induced by primary chemotherapy in breast cancer
Authors: Daidone Maria Grazia , Silvestrini Rosella , Valentines Barbara , Ferrari Laura , Bartoli Cesare
Published: February 2007

Changes in the 3H‐thymidine labelling index (3H‐TdR LI) of primary tumor induced by cytoreductive chemotherapy were evaluated in 26 patients with locally advanced breast cancer subjected to mastectomy after different systemic therapies. A significant reduction of 3H‐TdR LI by primary chemotherapy was observed in 11 cases. Changes in cell kinetics were related to the pretreatment proliferative activity: significant increases were observed in 70% of tumors with a very low 3H‐TdR LI (<2.5%) and significant decreases in 100% of tumors with a very high 3H‐TdR LI (>7.0%). There was no correlation between pretreatment 3H‐TdR LI and the objective clinical response, which was conversely related to post‐treatment cell kinetics. The 2‐year progression rate was lower for patients whose residual tumors after treatment had remained (2/7) or become (1/8) slowly proliferating than for patients whose tumors had remained (5/7) or become (4/4) rapidly proliferating.
Coffee and alcohol as determinants of risk of pancreas cancer: A case‐control study from toronto
Authors: Jain M. , Howe G. R. , St. Louis P. , Miller A. B.
Published: February 2007

Results are reported from a population‐based study of 249 cases of pancreas cancer and 505 controls carried out in Toronto, Canada, between 1983 and 1986. Lifetime consumption of coffee and alcohol and medical histories were assessed by personal interviews. No evidence of any association was found with different types of coffee or alcohol after adjusting for smoking, calories and fibre intake. There was a significant increased risk associated with a history of diabetes mellitus within 5 years of cancer development. A protective effect of a history of some allergic conditions, hay fever, eczema and asthma, was observed, although the relative risks were not significant (p value > 0.10).
Inhibition by neurotensin of azaserine‐induced carcinogenesis in rat pancreas
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Nakaizumi Akihiko
Published: February 2007

The effect of neurotensin on pancreatic carcinogenesis induced by azaserine was investigated in Wistar rats. Rats were given weekly injections of 10 mg/kg body weight of azaserine for 25 weeks and 200 μg/kg body weight of neurotensin in depot form every other day for 62 weeks. Carcinogen‐induced pancreatic lesions were examined by histochemical techniques, and were classified as ATPase‐positive or ATPase‐negative. In week 62, quantitative histological analysis showed that prolonged administration of neurotensin significantly reduced the volume (as percent of parenchyma) of ATPase‐positive pancreatic lesions, which are closely correlated with the ultimate development of pancreatic cancer. Histologically, pancreatic adenocarcinomas occurred at a significantly lower rate in rats treated with neurotensin than in untreated rats. Administration of neurotensin also significantly decreased the labelling indices of carcinogen‐induced pancreatic lesions, but not of the surrounding acinar cells. These findings indicate that neurotensin inhibits pancreatic carcinogenesis, and that this may be related to the reduction of ATPase‐positive lesions and to the inhibition of cell proliferation in neoplastic lesions of the pancreas.
Differential role of transforming growth factor‐α in two human colon‐carcinoma cell lines
Authors: Watkins Linda F. , Levine Alan E.
Published: February 2007

Antibodies to epidermal‐growth‐factor receptor (EGF) and transforming growth factor‐α (TGF‐α) were used to determine the role of endogenous TGF‐α in the growth of 2 human colon‐carcinoma cell lines. Both the GEO and HCT 116 colon‐carcinoma cell lines secrete similar levels of TGF‐α and have similar numbers of low‐affinity binding sites for EGF. However, the HCT 116 cells lack the high‐affinity EGF binding site present on the GEO cells. The anti‐EGF receptor antibodies effectively blocked the binding of 125I‐EGF to the GEO and HCT 116 cell lines. Growth of the GEO cell line was inhibited 50‐80% by the anti‐EGF receptor and anti‐TGF‐α antibodies. When the same antibodies, in sufficient amounts to block binding of TGF‐α to the cells, were added to the HCT 116 cell line, no effect on growth was seen. These results suggest that while the GEO cell line utilizes TGF‐α in an autocrine manner, the TGF‐α secreted by the HCT 116 cells apparently does not play a role in the growth of these cells.
Retinoic‐acid‐induced differentiation prevents gene amplification in teratocarcinoma stem cells
Authors: Lücke‐Huhle Christine , Herrlich Peter
Published: February 2007

In an attempt to study the regulatory properties of cells required for gene amplification, the capacity for amplification of the dehydrofolate reductase gene (dhfr) was determined in F9 teratocarcinoma stem cells during differentiation. By stepwise selection of surviving cells exposed to progressively increasing concentrations of methotrexate (MTX) up to 1000 μm within 4 months, non‐differentiated F9 cells reached a more than 40‐fold amplification of their dhfr gene, elevated levels of dhfr mRNA and a 5‐log increase in MTX resistance. Exposure to 5 Gy of 40Co‐gamma‐irradiation accelerated the process of amplification. In contrast, F9 cells that had been differentiated to endodermal cells by treatment with retinoic acid (RA) did not grow in MTX concentrations above 0.1 μm, either with or without radiation pretreatment and did not amplify the dhfr gene to any measurable extent over the same period of time. Upon treatment of methotrexate‐resistant (F9‐MTXr) cells with retinoic acid, loss of the amplified DNA in the absence of selection was significantly retarded. The ability to amplify the dhfr gene was correlated with the occurrence of origin binding activity in vitro (early domain of SV40 minimal origin of replication). These data indicate an increase in genomic stability and rigorous control of origin activity by differentiation.
Differential influence of organ site on three subpopulations of a single mouse mammary tumor at two distinct steps in metastasis
Authors: Aslakson Cheryl J. , Rak Janusz W. , Miller Bonnie E. , Miller Fred R.
Published: February 2007

Tumor subpopulations 66c 14, 168FARN, and 4T07 are drug‐resistant variants selected from sister subpopulations derived from a single mouse mammary tumor. These subpopulations are heterogeneous in their capacities to form experimental metastatic growth in the lungs and liver. Initial survival kinetics of arrested cells, determined by the clearance of 125IUdR‐labelled cells, and subsequent growth rates, determined by sequential recovery of clonogenic tumor cells from occult metastases, both correlated with organ‐colonizing potential as determined by necropsy. The growth rates of these 3 subpopulations were determined in vitro in monolayer and in situ in the subcutis, in the liver following intrasplenic injection, and in the lung following intravenous injection. Clonogenic potential of all 3 lines was similar in vitro (54‐59%). Growth rates in vitro (population doubling times 16.5‐21 hr) and in the subcutis (tumor volume doubling times 5.2‐7.4 days) were similar for the 3 subpopulations, but differed significantly in the liver and lungs. For line 4T07, the most metastatic line to both lung and liver, population doubling times in vitro and in the lung and liver were similar, ranging from 17 to 26 hr. For lines 66c 14 and 168FARN, the growth rates in lungs and livers were much slower than in vitro. Line 66c14, which is relatively more metastatic to the lungs, grew much faster in the lung (39 hours) than in the liver (91 hr), but line 168FARN, which is relatively more metastatic to the liver, grew at a faster rate in the liver (37 hr) than in the lung (63 hr). Thus, 3 tumor subpopulations (seeds) derived from a single tumor were differentially affected by host organ factors (soil) at 2 distinct stages in the metastatic process.