bluuebunny/crossref_metadata_2025 huggingface dataset:
Unique patterns of brain metastasis produced by different human carcinomas in athymic nude mice
Authors: Schackert G. , Price J. E. , Bucana C. D. , Fidler I. J.
Published: February 2007

The purpose of this study was to develop an in vivo model to study the growth pattern and biological behavior of brain metastases produced by different human carcinomas. To do so, human tumor cells from 8 different carcinomas of the colon, breast, kidney and lung were injected into athymic nude mice either by a direct intracerebral route or into the internal carotid artery. All carcinoma cells invaded through the blood‐brain barrier and produced progressively growing lesions in the brain parenchyma. Unique patterns of growth were discernible among the carcinomas. Human colon carcinomas produced multiple lesions that spread by extension. Lung carcinoma cells produced widespread lesions throughout the brain. A very high degree of vascularization was associated with lesions produced by renal‐cell carcinoma. The influence of estrogen on the growth of estrogen‐receptor‐positive human breast carcinoma cells was well demonstrated in this model. We conclude that the athymic nude mouse can be a useful model for studies of the biology and perhaps therapy of brain metastases produced by human carcinoma cells.
Clustering of discrete cell properties essential for tumorigenicity and metastasis. II. Studies of syrian hamster embryo fibroblasts transformed by rous sarcoma virus
Authors: Deichman G. I. , Kashleva H. A. , Kluchareva T. E. , Matveeva V. A.
Published: February 2007

Tumorigenic and metastasizing activities (TGA; MA) and susceptibility, or resistance to H202 and PGE‐releasing activity (H2OR2 + PGEs+ phenotype) have been examined in 6 Syrian hamster embryo cell strains transformed in vitro with Rous sarcoma viruses (Schmidt‐Ruppin and Prague strains). Early observations of extremely high level of TGA and even MA of RSV‐SR‐transformants never selected in vivo have been confirmed. The correspondence of these properties with a high level of expression of H2OR2 + PGEs+ phenotype and its clustering character were demonstrated in 4 RSV‐SR trans‐formants, while significantly lower expression of all these characteristics, including TGA, was observed in 2 RSV‐Prague transformants. High level of spontaneous MA was noticed in some RSV‐SR transformants. A tumor cell line induced in vivo by RSV‐SR did not differ from the cell strain transformed in vitro by RSV‐SR. inhibition of H2OR2 + PGEs+ phenotype in one of RSV‐SR transformants was obtained with non‐toxic doses of BCNU and indomethacin, leading to a marked decrease of TGA.
Diacylglycerols and the protein kinase inhibitor H‐7 suppress cell polarity and locomotion of walker 256 carcinosarcoma cells
Authors: Keller H. U. , Zimmermann A. , Niggli V.
Published: February 2007

We show that diacylglycerols, like phorbol myristate acetate (PMA), suppress cell polarity and locomotor activity of Walker carcinosarcoma cells in a dose‐dependent fashion in vitro. OAG and diC8 show significant activity at concentrations above 3 × 10−5 M. The inhibitory effect on locomotion is due to a reduction in the proportion of locomoting cells rather than gradual lowering of the speed of individual cells. Measurement of protein kinase C (PKC) activity in isolated fractions showed a substantial reduction of the total cellular PKC activity and of the activity in the cytosolic fraction following incubation of cells with 10−8 M PMA for 30 min. In contrast, the total and relative PKC activity associated with the membrane fraction was increased by PMA. The effect of H‐7, an inhibitor of PKC as well as of cAMP‐dependent kinase, has been tested. H‐7 suppressed cell polarity of “unstimulated” control cells (ID50 = 6.5 μ.M H‐7), colchicine‐stimulated cells (ID50 = 92 μM H‐7) or cells treated with both PMA and colchicine (ID50 = 15 μM H‐7), in a dose‐dependent fashion. The locomotor activity of the cells was also suppressed. LTB4 had no clearcut activity in this system. Our findings suggest that diacylglycerols and H‐7 are of interest as physiological or pharmacological stop signals for tumor‐cell locomotion. Contrary to our expectations, PMA and diacylglycerols vs. H‐7 did not produce opposing or antagonistic effects on cell polarity and locomotion. This similarity may be due to down‐regulation of PKC by PMA and inhibition of PKC by H‐7. However, the mechanisms underlying these novel effects of diacylglycerols and of H‐7 on cell polarity and locomotion may be even more complex; they require further studies.
Human glioma cell lines expressing the common acute lymphoblastic leukemia antigen (cALLa) have neutral endopeptidase activity
Authors: Monod Léonard , Disekens Annie‐Claire , Jongeneel C. Victor , Carrel Stefan , Ronco Pierre , Verroust Pierre , de Tribolet Nicolas
Published: February 2007

Several established human glioma cell lines have been previously shown to express the common acute lymphoblastic leukemia antigen (cALLa, CD 10), an important marker in the diagnosis of human acute lymphocytic leukemia (ALL). The amino acid sequence of cALLa is identical to that of neutral endopeptidase (NEP,E.C.3.4.24.11), and cALLa expressed on leukemia and melanoma cell lines is enzymatically active NEP. In the present study, we investigated whether cALLa expressed on glioma cell lines is active NEP. We detected cALLa on 10 out of 13 glioma cell lines using 2 different anticALLa MAbs (A12‐G4 and FAH99). NEP antigen, as detected by immunostaining with an anti‐NEP MAb (135A3), was expressed on the same 10 lines. cALLa‐positive, but not cALLa‐negative ceil lines displayed an endopeptidase activity. This activity could be blocked by phosphoramidon, a specific inhibitor of NEP. Furthermore, mRNAs hybridizing to an NEP‐specific probe were present in cALLa‐positive glioma cells but not in cALLa‐negative cells. Taken together, the results provide strong evidence that cALLa‐positive glioma cell lines express endopeptidase activity on the cell surface.
Cytogenetic abnormalities in benign lymphoid hyperplasia: A dual‐parameter study using chromosome analysis and flow cytometry
Authors: Grace J. , Hall B. E. , Lew M. , Singh S. , Pittman S. , Palmer A. A. , Zbroja R. , Wass J. , Vincent P. C.
Published: February 2007

This is a prospective study of lymphoid tissue showing benign reactive hyperplasia (18 lymph nodes and 2 tonsils), using cytogenetic analysis of cells stimulated with T‐ or B‐cell mitogens. The reason for this study was the detection of an abnormal chromosomal population in cells from an enlarged lymph node excised from a 7‐year‐old female who on further investigation was found to be clinically well and after one year's close follow‐up had not developed any further signs or symptoms of malignancy. In addition, DNA content was measured by flow cytometry (FCM) on fresh cell suspensions in 17 cases and fixed cell suspensions in 3 cases. Structural and numerical clonal chromosome abnormalities were found in 9 of the 20 samples, but no common specific defect was identified. FCM showed an abnormal DNA content in 10 of the 20 samples studied; 3 of these showed clonal chromosome abnormalities. Surface membrane immunoglobulin studies were carried out on 15 of the 20 samples using cell suspensions and frozen tissue sections. In 5 of the 15 cases, monoclonal surface immunoglobulin was detected. There was no direct correlation between the surface membrane immunoglobulin studies and the chromosome and FCM analyses. We conclude that aneuploidy is a common feature in reactive lymphoid tissue, but both cytogenetics and FCM are needed to identify it.
The copenhagen case‐control study of renal pelvis and ureter cancer: Role of analgesics
Authors: Jensen O. M. , Knudsen J. B. , Tomasson H. , Sørensen B. L.
Published: February 2007

Analgesic intake was investigated for 96 patients with cancer of the renal pelvis and ureter (including papillomas) and 294 hospital controls. In comparison with persons who never used analgesics, increased relative risks (RR) were seen for users of phenacetin‐containing drugs after adjustment for smoking and high‐risk occupational exposure (men: RR = 2.4; women: RR = 4.2). A significant relative risk for aspirin use among women was also observed. There was an indication of a dose‐effect relationship for both types of analgesics. The influence of phenacetin and aspirin on the development of renal pelvis and ureter tumours could not be separated since in this study the two compounds occurred so frequently in the same formulation. Experimental studies and phenacetin metabolism makes it biologically most relevant to attribute the observed association in the present study to the phenacetin component of the drugs.
The subcellular localization of the neu protein in human normal and neoplastic cells
Authors: De Potter C. R. , Quatacker J. , Maertens G. , Van Daele S. , Pauwels C. , Verhofstede C. , Eechaute W. , Roels H.
Published: February 2007

We have examined the subcellular localization of the neu protein by immunohistochemistry and immuno‐electron microscopy, associated with immunoblotting of normal and neoplastic tissues with 2 monoclonal antibodies (MAbs). Immunoelectron microscopy clearly reveals that neu protein resides only on the lateral plasma membrane of the simple epithelium of the breast and on the plasma membrane of malignant breast cells. It is also found on the membranes of the microvilli and the apical vacuoles of the cells of the proximal convoluted tubule of the kidney. In the cytoplasm, the only immunoreactivity detected with both antibodies was on the membrane of the mitochondrial cristae of normal and malignant cells. Immunoblotting reveals that the molecular weight of the membrane protein is I85 and 155 kDa for the mitochondrial protein. The cell membrane staining pattern can be revealed by light microscopic immunohistochemistry only in malignant cells and is therefore specific for malignancy. The membrane expression in normal cells cannot be visualized in this way. The mitochondrial reactivity appears as a cytoplasmic granular staining when examined under the light microscope. Similar cytoplasmic staining has been described previously in other studies with other antibodies against the neu protein and has lead to speculation about its function in normal and malignant cells. However, it is demonstrated in this study that it is not the known neu‐oncogene product.
Ki67 and 4F2 antigen expression as well as dna synthesis predict survival at relapse/tumour progression in low‐grade B‐cell lymphoma
Authors: Holte Harald , De Lange Davies Catharina , Beiske Klaus , Stokxe Trond , Marton Per F. , Smeland Erlend B. , Høie Johan , Kvaløy Stein
Published: February 2007

Previous work has shown that parameters of cell activation studied on lymphoma biopsies can be used to discriminate between low‐grade and high‐grade non‐Hodgkin's lymphomas and to predict prognosis in the low‐grade malignancy group alone. We have now examined expression of several activation antigens and indicators of DNA synthesis in 29 patients with low‐grade malignant B‐cell lymphomas at the time of primary diagnosis and later at relapse and/or tumour progression. At both times, the level of 4F2 antigen expression examined by flow cytometry on cells in suspension as well as the number of Ki67 antigen‐positive cells examined by immunohistochemistry were predictive of patient survival. DNA synthesis estimated by (3H‐TdR) thymidine incorporation was of prognostic value at the second biopsy only. These parameters were more sensitive than histological demonstration of morphological transformation in secondary high‐grade lymphomas in identifying high‐risk patients at repeated biopsy. We propose that Ki67 or 4F2 expression or a marker of DNA synthesis (such as 3H‐TdR incorporation or labelling index) should be evaluated when repeated biopsies are performed, in order to select patients for whom aggressive chemotherapy may be considered.
Patterns of familial transmission of HBV and the risk of developing liver cancer: A case‐control study in the Philippines
Authors: Muñoz Nubia , Lingao A. , Lao J. , Estève Jacques , Viterbo G. , Domingo E. O. , Lansang M. A.
Published: February 2007

The present case‐control study was carried out in the Philippines to determine the risk of developing hepatocellular carcinoma (HCC) in relation to different HBV serological profiles of parents and sibs of HCC cases and controls. The HBV serological profiles of parents and sibs of 33 patients with HCC were compared with those of 2 types of community control: 33 general population controls matched for sex and age (CI controls) and 33 asymptomatic HBsAg carriers also matched for sex and age (C2 controls). When cases were compared with CI controls, increased risks were associated with the fact of having an HBsAg‐positive mother (RR = 2.5, 95% CI = 0.4–26.3) and older sibs positive for HBsAg (RR = 2.0, 95% CI = 0.5–9.1), but the increased risk was not statistically significant. However, a significantly increased risk was associated with the fact of having a mother (95% CI = 3.5–∞) or father (RR =11, 95% CI = 1.6–473) who had been exposed to HBV. On the other hand, when cases were compared with C2 controls, a non‐significant 2‐fold increase was associated with the fact of having an HBsAg‐positive mother, but no differences were observed in the HBV serological profiles of their fathers and older sibs. These results suggest that, in the Philippines, the fact of having a mother or father who has been infected in the past with HBV increases the risk of developing HCC but that the contribution of the mother to this increase in risk is not as important as hitherto believed.
Expression of the ras‐related rap genes in human tumors
Authors: Culne Stèphane , Olofsson Birgitta , Gosselin Sylvette , Honore Nicole , Tavitian Armand
Published: February 2007

The expression of the recently described rap genes, closely related in the effector region to the ras proto‐oncogenes, was examined by Northern blot analysis in 41 primary human tumors. The structural and in vitro biological properties of the rap gene products suggest their possible antagonistic action in the same effector pathway as the ras proteins. In order to determine whether a deregulation in the rap transcription levels could be involved per se in the multistep carcinogenic process, we chose to analyze tumors for which the ras mutation rate was previously reported to be extremely rare or unknown, i.e., non‐Hodgkin's lymphomas, certain types of carcinoma, sarcomas, germinal neoplasms of the testes and various tumors of the nervous system. A severe decrease in the expression of the rapl A gene was shown in the fibrosarcomas and the adenocarcinoma of the salivary gland studied, as compared to their normal counterparts, whereas no rap2 expression was found in the polyadenylated RNA of sarcoma samples.
Cell‐mediated immune responses—prognostic indicators of survival from breast cancer
Authors: Cannon Grace B. , Pomerantz Robin
Published: February 2007

The prognostic significance of cell‐mediated immunity measured by a single post‐operative in vitro lymphoproliferation assay with an autologous tumor hypotonic membrane preparation (HMP) and in the mixed leukocyte culture (MLC) is shown in white and black breast cancer patients followed for as long as 14 years. Nine of 16 white patients and 6 of 11 black patients who did not respond to their tumor but who had a normal MLC died of systemic breast cancer as compared to I of 20 white and 2 of S black patients who responded to the HMP and/or had a depressed MLC. When high‐risk clinical variables (nodal status, tumor size and cell differentiation) were combined with high‐risk immunological risk factors in white patients, the prognostic values of both the immunological and clinical categories were enhanced. Seven of 9 concordant high‐risk white patients died from systemic breast cancer. These results point to the necessity of immunological testing as an aid in clinical staging of breast cancer patients.
Resident macrophages specifically inhibit DNA synthesis in the nuclei of transformed cells in heterokaryons
Authors: Prudovsky Igor A. , Gumeniuk Raphilja R. , Yegorov Yegor E. , Zelenin Alexander V.
Published: February 2007

DNA synthesis in heterokaryons of mouse peritoneal macrophages and various proliferating cultured cells was analyzed. Macrophages did not inhibit replication in the nuclei of non‐immortalized and spontaneously immortalized cells (rat fibroblasts and macrophages, mouse pre‐macrophages, NIH3T3 cells). On the contrary, the percentage of DNAsynthesizing nuclei of malignant HeLa cells was drastically reduced in heterokaryons. The transformation of NIH3T3 cells with c‐Ki‐ras oncogene and that of rat chondrocytes with p53 oncogene made these cells sensitive to the replication‐inhibiting activity of macrophages in heterokaryons. Our observation represents a kind of “intracellular” cytotoxic activity of macrophages directed against transformed cells.
Tissue norepinephrine depletion as a mechanism for cysteamine inhibition of colon carcinogenesis induced by azoxymethane in wistar rats
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Taniguchi Haruo
Published: February 2007

The effects of cysteamine (2‐aminoethanethiol hydrochloride) on the incidence, number and histology of colon tumors induced by azoxymethane (AOM), and on the norepinephrine concentration in the colon wall tissue and the labelling indices of colon mucosa and colon cancers were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body weight of AOM and alternate‐day subcutaneous injections of 25 mg/kg of cysteamine in 0.9% NaCI solution until the end of the experiment. At week 40, prolonged administration of cysteamine significantly reduced the incidence and number of colon tumors. Histologically, the adenocarcinomas that did develop in rats treated with cysteamine exhibited high mucin‐producing activity. Administration of cysteamine caused significant decreases in the norepinephrine concentration in colon tissue and in the labelling indices of colon mucosa and cancers. Our findings indicate that cysteamine inhibits the development of colon tumors. This action may be related to its effect in decreasing norepinephrine concentration in the colon wall tissues and subsequently in decreasing proliferation of colon cancer cells.
Transforming activity of nasopharyngeal carcinoma DNA detectable in mouse JB6 cells
Authors: Colburn N. H. , Raab‐Traub N. , Becker D. , Cao Y. , Winterstein D.
Published: February 2007

A JB6 mouse epidermal recipient cell line has been used to detect nasopharyngeal carcinoma (NPC) DNA‐associated transforming activity that is not detectable in the NIH 3T3 focus assay. NPC DNA showed both transforming activity and activity for transferring sensitivity to tumor‐promoter‐induced neoplastic transformation, assayed in 2 different variants of mouse JB6 cells. Comparison of DNAs from various NPC sources that did or did not harbor EBV DNA and that varied in degree of differentiation showed similar transforming activities and similar activities for transferring promotion sensitivity. Thus both a NPC DNA‐associated promotion sensitivity and an oncogenic activity function independently of concurrent EBV gene expression.
Biodistribution and histological localization of anti‐human colon cancer monoclonal antibody (MAb) 1A3: The influence of administered MAB dose on tumor uptake
Authors: Fenwick J. R. , Philpott G. W. , Connett J. M.
Published: February 2007

Using a murine monoclonal antibody MAb 1A3, which binds to a lipid antigen found enriched in human colon cancer, and MOPC‐21 antibody, as a non‐specific control, we examined the effect of increasing doses of 125l‐labelled MAbs (5μg to 2,000μg) on tumor localization. Biodistribution studies in hamsters with small GW‐39 human colon carcinoma tumors [0.44g ± 0.014 (SEM)] demonstrated functional saturation of antigen binding sites in tumors when large doses of MAb 1A3 were used. The percentage injected dose bound per gram of tumor (ID/g tumor) remained constant for doses of intact MAb 1A3 > 100μg but decreased with doses > 100μg, suggesting that a population of antigen binding sites had been saturated. While the percentage ID/g tumor decreased for doses of MAb 1A3 > 100μg, the absolute amount specifically bound/ g tumor increased (up to the 1,000μg dose), suggesting that another population of less accessible 1A3 antigen could continue to bind MAb 1A3. In contrast, MOPC demonstrated a relatively constant percentage ID/g of tumor (2.26% ± 0.11) throughout the dose range which was 2–3 times lower than MAb 1A3 (6.8% ± 0.14) at plateau doses (5–100μg). These data suggested that specific saturation of tumor binding sites was a biphasic phenomenon. Blood and normal tissues did not show binding kinetics suggesting saturation. Results of dose response experiments using MAb 1A3 F(ab′)2 fragments (5μg to 1,000μg) closely paralleled those obtained with intact MAb 1A3, but with lower percentages of ID/g tumor, blood and non‐tumor tissues as in previous studies with MAb 1A3 and other MAb F(ab′)2 fragments. Histological examinations demonstrated that non‐specific binding of MOPC or MAb 1A3 to tumor or normal tissues was of such low affinity as to be largely undetected after histological procedures. In contrast, MAb 1A3 (but not MOPC) showed specific cell‐binding patterns to tumor but not normal tissues at all doses.
The influence of glucocorticoids on the growth of a human leiomyosarcoma cell line SK‐LMS‐1
Authors: Madsen Walter E. , Das Gupta Tapas K. , Walker Michael J.
Published: February 2007

A cell line derived from a human leiomyosarcoma, SK‐LMS‐I, has cystolic [Bmax 201.6 ± 39.7, x̄ ± SD, fM/mg cytosol protein KD 14.6 ± 7.8 nM (n = 8)] and nuclear [Bmax189.2 ± 87.3 fM/mg DNA, KD 4.8 ± 0.26 nM (n = 5)] glucocorticoid receptor, by Scatchard analysis of tumors grown in male athymic mice. Tumor growth of SK‐LMS‐I cells in male athymic mice is inhibited by daily s.c. injection of DEX 5 μg, DEX 25 μg, DEX 5 μg with 5 μ. RU‐486 and 5 μg RU‐486. In sharp contrast, in vitro, glucocorticoid markedly stimulates the growth (as determined by cell number) of SK‐LMS‐I cells, principally at higher cell densities (days 10‐21 of growth carried on over a 21‐ to 23‐day period), the greatest stimulation being seen with DEX 10−6 to 10−8 M, and no stimulation being seen with DEX 10−9 and 10−10 M. In vitro, glucocorticoids with higher affinity for the GR stimulate growth, steroids with lower affinity inhibit growth. No alterations in cell‐cycle distribution (percent G0G1 S, or G2/m) could be found by flow cytometric analysis of glucocorticoid‐stimulated asynchronously growing cultures. Single, isolated, untreated SK‐LMS‐1 cells form colonies in soft agar with an efficiency of 1.78 ± 0.10%. Pre‐treatment of cells with DEX 10−7 M increases this to 3.24 ± 0.17%, while cells pre‐treated with both DEX 10−7 M RU‐486 107 M form colonies with the same efficiency as untreated cells. Glucocorticoids have inhibitory effects on in vivo growth and stimulatory effects on in vitro growth of a GR‐positive human leiomyosarcoma cell line.
Intrinsic differences in the transplantability and outgrowth potential of DMBA‐induced rat mammary tumors
Authors: Rivera Evelyn M. , Alston‐Mills Brenda
Published: February 2007

Only a small proportion of DMBA‐induced rat mammary tumors are transplantable in cleared (gland‐free) mammary fat pads. To enhance their transplantability, several host factors were modified: age, parity, hormone levels, and tissue integrity of the fat pad. Our 2 important findings were that (1) there were individual differences between the tumors in their transplantability and potential to proliferate normal and hyperplastic outgrowths, and (2) these differences were determined by their inherent potential and not by their environment. These intrinsic differences among the tumors are consistent with the concept that properties of a given type of tumor are independently variable.
Histo‐blotting: Hybridization in situ detection of specific RNAs on tissue sections transferred on nitrocellulose
Authors: Gudkov A. V. , Kashkin K. N. , Zaitsevskaya T. E. , Troyanovsky S. M.
Published: February 2007

A simple and rapid variant of in situ hybridization on tissue sections (histo‐blotting) usable for detection of specific RNA distribution among tissues is proposed. Tissue sections prepared with a cryostatic microtome are placed on nitrocellulose and these “histo‐blots” are hybridized with labelled DNA or RNA probes under conditions of Northern‐blot hybridization without any particular pretreatment. Tissue specificity of the RNA distribution may be determined by comparison of autoradiograms with the histological structure of the stained section. Histological staining and light microscopy may be carried out after hybridization of histo‐blots. Hybridization in situ may be easily combined with immunostaining under conditions of immunoblotting. Application of the proposed method is shown for alfa‐fetoprotein (AFP) and endogenous provirus (ev‐3) RNA detection in rat and chicken embryos, respectively. Histo‐blotting results correlate with the distribution of given RNAs among tissues determined by independent methods. Sensitivity, specificity and resolution of histo‐blotting have been evaluated and discussed.
Monoclonal antibody UJ13A recognizes the neural cell adhesion molecule (NCAM)
Authors: Patel K. , Rossell R. J. , Bourne S. , Moore S. E. , Walsh F. S. , Kemshead J. T.
Published: February 2007

Monoclonal antibody (MAb) UJ13A, raised against 16‐week‐old human foetal brain, recognizes an antigen present on the majority of tissues of neuro‐ectodermal origin. The binding profile of this antibody is similar to the known distribution of the neural cell adhesion molecule (NCAM). Although detailed immunohistological and immuno‐cytochemical studies with the MAb have been published previously, we demonstrate here, through investigations of selected tissues and cell lines, that the binding profile of an anti‐NCAM antiserum is similar to UJ13A. Additional indirect evidence suggesting that UJ13A recognizes NCAM comes from Northern blot analysis of cell lines either binding or not binding UJ13A as determined by indirect immunofluorescence. Only those cell lines known to bind UJ13A express high levels of NCAM mRNA. Western blot analysis of extracts of human brain show that U J13A recognizes proteins of 180 and 140 kDa in addition to a very weak band of 120 kDa. This data corroborates the suggestion that UJ 13A recognizes NCAM as these 3 isoforms of the protein are identified in human brain. Final confirmation of the specificity of UJ 13A comes from the study of 3T3 fibroblasts transfected with a cDNA coding for the 125 kDa isoform of human muscle NCAM. UJ 13A selectively recognizes these transfectants and binds to a 125 kDa protein isolated from the cells by Western blot analysis. Thus we conclude from these immunological, biochemical and molecular studies that the antigen recognized by the UJ 13A MAb is the neural cell adhesion molecule.
Influence of cyclosporin a and α‐difluoromethylornithine, an inhibitor of polyamine biosynthesis, on two rodent T‐cell cancers in vivo
Authors: Smart L. M. , Maclachlan G. , Wallace H. M. , Thomson A. W.
Published: February 2007

We have examined the influence of cyclosporin A (CsA), administered together with the polyamine antimetabolite, a‐difluoromethylornithine (DFMO), on growth of the Roser acute T‐cell leukaemia in PVG rats and on growth of the EL4 lymphoma in C57BL/6 mice. CsA or DFMO alone, administered from the time of tumour injection, markedly reduced numbers of circulating lymphoblasts in leukaemic rats, although survival was prolonged only in those animals given DFMO. Drug combination further reduced blood‐borne tumour cells, but had no additional effects on tumour growth within organs or on host survival, compared to that achieved with DFMO treatment alone. Neither CsA nor DFMO, administered from the time of tumour‐cell injection, nor both drugs in combination, affected peritoneal growth of the EL4 lymphoma or organ infiltration. Host survival was prolonged by DFMO. As anticipated, DFMO inhibited polyamine synthesis in vivo, but the observed anti‐tumour effect of CsA was not accompanied by an alteration in polyamine biosynthesis. By reducing polyamine synthesis, however, DFMO may enhance the vulnerability of those malignant T cells which are susceptible to the as yet unexplained selective inhibitory action of CsA in vivo.
Increased drug cytotoxicity at reduced pH counteracts cyclophosphamide resistance in cultured rat mammary carcinoma cells
Authors: Jähde Fckhard , Geüsenkamp Karl‐Heinz , Rajewsky Manfred F.
Published: February 2007

The sensitivity of a cyclophosphamide (CP)‐resistant MIR rat mammary carcinoma cell variant (MIRCPr) in monolayer culture towards the cytotoxic effect of mafosfamide (an analogue of “activated” CP) was measured as a function of extracellular pH (pHe). An inverse correlation was found between cell survival and the H+ ion concentration in the culture medium. At pHe 7.4, the fraction of clonogenic MIRCPrcells exposed to mafosfamide (7.S üg/ml) for 24 hr was 1 ± 10−1 in relation to untreated control cells. At pHe6.2, however, this value was reduced to 3 ± 10−4, i.e., a value equal to that for the CP‐sensitive parental MIR cells exposed to the same concentration of mafosfamide at pHe 7.4. Our data indicate complete compensation of CP resistance in MIRCPrcells at pHe 6.2. MIRCPr cells were not resistant to the cytotoxic effect of nornitrogen mustard. This suggests that resistance to CP in MIRCPr cells is due to enzymatic inactivation of the primary intermediates in CP bioactivation. The alkylating activity of nornitrogen mustard (and less so that of phosphoramide mustard) is strongly enhanced at low pH. In MIRCPr cells shifted to an acidic environment, therefore, a (putative) decrease in the intracellular concentration of alkylating CP metabolites may be counteracted by an enhancement of their alkylating activity (on a molar basis). By parenteral administration of glucose, the pH in malignant tumors of both animal and human origin can be lowered to values between 5.6‐6.6. Our data suggest that an upshift of H+ ion concentration in malignant tissues may at least partially counteract CP resistance in cancer cells in vivo.
Effects of disseminative route on the liver‐ and lung‐colonizing efficiencies of B16 melanoma and colon‐26 carcinoma in mice
Authors: Weiss L. , Ward P. M.
Published: February 2007

Tumor‐colony formation in the liver and lungs of mice was assessed, after delivery of equal numbers of B16 melanoma or colon‐26 carcinoma cells via the portal vein or the hepatic artery, and via the pulmonary artery or the bronchial artery. Significantly greater lung involvement occurred after delivery of both cell types Wa the bronchial artery than via the pulmonary artery. In the case of colon‐26 cells, liver colonization via the hepatic artery was more efficient than via the portal vein. In the case of B16 cells, no route‐dependent differences in liver colonization were detected. Our results indicate that during hematogenous metastasis, the vascular route taken by some cancer cells to the same target organ may considerably modify the efficiency with which they form metastases.
Anti‐tumor effects of interleukin‐2 and interleukin‐1 in mice transplanted with different syngeneic tumors
Authors: Belardelli F. , Ciolli V. , Testa U. , Montesoro E. , Bulgarinl D. , Proietti E. , Borghi P. , Sestili P. , Locardi C. , Peschle C. , Gresser I.
Published: February 2007

We have studied the anti‐tumor effects of human recombinant IL‐2, alone or in association with LAK cells, in mice transplanted subcutaneously (s.c.) with the following syngeneic tumors: highly metastatic Friend leukemia cells (FLC), non‐metastatic FLC, lymphoma RBL‐S cells and HeJ16 fibrosarcoma cells. In these tumor models, peri‐tumoral injections of IL‐2 were more effective in inhibiting tumor growth than a systemic treatment. Although s.c. IL‐2 treatment resulted in marked inhibition of tumor growth in mice injected s.c. with highly metastatic FLC, it was not effective in inhibiting growth of FLC in the liver and spleen. IL‐2 therapy was more effective at increasing survival time in mice transplanted with non‐metastatic FLC or with RBL‐5 cells. In mice transplanted wth HeJ16 fibrosarcomas, s.c. IL‐2 treatment resulted in highly significant anti‐tumor effect and survival of 70% of tumor‐injected mice. No general correlation was found between in vitro sensitivity or resistance to the cytolytic activity of LAK cells and the anti‐tumor effects observed in vivo. Subcutaneous injection of IL‐1β in mice transplanted with highly metastatic FLC resulted in a marked increase in survival time and inhibition of metastatic tumor growth in liver and spleen. Combined treatment of IL‐1β and IL‐2 produced a synergistic anti‐tumor effect: 60% of mice injected with highly metastatic FLC survived. Combined IL‐1/IL‐2 treatments exerted no anti‐tumor activity either in DBA/2 mice injected with antibody to Thy 1.2 antigen or in nude mice, indicating that T cells play important roles during IL‐1/IL‐2 therapy. In vitro treatment of FLC with IL‐1β resulted in a slight inhibition of cell multiplication, whereas even high doses of IL‐2 did not affect FLC multiplication. Our results indicate that local combined treatments with IL‐1 and IL‐2 can induce potent, host‐dependent (T cell‐mediated) anti‐tumor effects against highly malignant tumors.
Cytogenetic analysis of eight human papillomavirus immortalized human keratinocyte cell lines
Authors: Smith Patricia P. , Bryant Eileen M. , Kaur Pritinder , McDougall James K.
Published: February 2007

Cytogenetic analysis was performed on human papillomavirus (HPV)‐immortalized cell lines. Lines were established by co‐transfection of primary human keratinocyte cells with HPV type 16 or 18 DNA and pSV2neo. The resulting clonal lines contained integrated HPV DNA and exhibited extended life spans in culture but were non‐tumorigenic in nude mice. Two HPV16‐immortaiized lines (FEPEIL8 and FEPEIL9) and 4 HPV18‐immortalized lines (FEA, FEH18L, FEP18‐5 and FEP18‐11) were established. Two additional lines were derived by subsequent treatment of the FEA line with TPA and by further transfection with HSVII DNA. Cytogenetic analysis revealed that all lines were abnormal, containing a variety of numerical and structural aberrations. Six of the 8 lines were hyper‐triploid and 2 were near‐diploid. Examination of lines FEA, FEH18L and FEP18‐II at multiple passages in culture revealed that the lines were clonal and chromosomally stable over extended passage in culture. Structural rearrangements were most common in chromosomes 1 and 3 but also occurred in chromosomes 5, 7, 8, 12, 16 and 22. Marker chromosomes were present in all cell lines. A small metacentric marker, possibly an isochromosome for the short arm of chromosome 5, was consistently present in the FEA line and its derivatives (FEAB10 and FEAT) as well as the FEH 18L line. A loss or reduction in copy number of chromosome 13 was seen in 5 of the 8 cell lines.
Use of monoclonal antibodies to human breast‐tumor‐associated antigens in the diagnosis of fine‐needle aspirates of breast nodules: Results of a multicenter study
Authors: Natali P. G. , Mottolese M. , Perrone Donnorso R. , Buffa R. , Bussolati G. , Coggi G. , Corradi G. , Coscia‐Porrazzi L. , Ferretti M. , Rondanelli E. , Castagna M. , Vecchione A. , Siccardi G. A.
Published: February 2007

Fine‐needle aspiration (FNA) cytology is being increasingly employed in conjunction with physical examination and mammography in the pre‐surgical diagnosis of breast nodules. In the present study, we have submitted to multicenter validation an immunocytochemical test which employs monoclonal antibodies (MAbs) to breast‐tumor‐associated antigens (BTAA) for the diagnosis of breast cancer. The results of this analysis, which has evaluated 846 FNAs, show that the immunological test has a sensitivity of 88.62%, a specificity of 97.9% and an accuracy of 92.4%. The predictive value of a positive and a negative finding were 98.4% and 85.57% respectively. Comparison between the cytological and immunocytochemical diagnosis displayed a higher sensitivity, accuracy and predictive value of a negative result with the latter method (p <0.01). Our findings clearly indicate that immunocytochemical methods can complement and improve the diagnostic accuracy of FNA cytology of breast nodules.
Frequency and degree of aneuploidy in benign and malignant thyroid neoplasms
Authors: Schelfhout Lodewijk J. D. M. , Cornelisse Cees J. , Goslings Bernard M. , Hamming Jacob F. , Kuipers‐Dijkshoorn Nel J. , van de Velde Cornelis J. H. , Fleuren Gert Jan
Published: February 2007

The frequency and degree of aneuploidy in 44 benign and 124 malignant thyroid neoplasms were analyzed by DNA flow cytometry. Single aneuploid cell populations were found in 72% of the undifferentiated carcinomas, 64% of the follicular carcinomas, 24% of the papillary carcinomas and in 24% of the follicular adenomas. Multiple aneuploid cell populations were detected in 4% of the papillary and in 36% of the follicular carcinomas but not in undifferentiated carcinomas. A low degree of aneuploidy was found in well differentiated papillary carcinomas (mean DNA index of aneuploid populations; DI =1.17; SD ± 0.09). Significantly higher values were found for aneuploid moderately differentiated papillary carcinomas (DI =1.46; SD ± 0.29), well and moderately differentiated follicular carcinomas (DI =1.61; SD ± 0.33 and DI =1.60; SD ± 0.30, respectively) and undifferentiated carcinomas (DI =1.72; SD ± 0.19). High DNA indices were also found in several follicular adenomas (DI =1.49; SD ± 0.22). Comparison of the 10‐year survival rates of patients with moderately versus well differentiated papillary carcinoma (79 vs. 98 months, respectively) indicates that loss of differentiation and progression of aneuploidy in this tumour type is associated with more aggressive clinical behaviour. Similarly, the high frequency and degree of aneuploidy in undifferentiated carcinomas is in agreement with the very poor survival rate (0% at 10 years) in this group of patients. However, the occurrence of highly aneuploid adenomas and (near)‐diploid undifferentiated carcinomas does not point to a direct causal relationship between DNA‐ploidy changes and clinical behaviour of these thyroid tumours.
Human papillomavirus (HPV) DNA in esophageal precancer lesions and squamous cell carcinomas from China
Authors: Chang Fuju , Syrjänen S. , Shen Qiong , Ji Hongxiu , Syrjänen K.
Published: February 2007

A series of 51 biopsies derived from the same number of patients with established invasive squamous‐cell carcinoma of the esophagus in Linxian, a high‐risk area for esophageal cancer in China, were analyzed histologically and by in situ DNA hybridization to demonstrate human papillomavirus (HPV) infection. Epithelial changes suggesting HPV infection within or adjacent to the carcinoma lesions were found in 25 cases (49.0%). Esophageal lesions with HPV morphology showed both flat (25 cases) and inverted condylomas (2 cases) resembling those found in the genital tract. HPV 6, 11, 16 or 18 DNA sequences were detected in 22/51 (43.1%) of the esophageal specimens. HPV DNA was most frequently localized in epithelium adjacent to carcinomas in areas showing either epithelial hyperplasia (36.1%) or dysplasia (22.2%). Of the lesions with morphological HPV changes, 64% (16/22) were shown to contain HPV DNA. In 2 specimens, HPV DNA was found in frankly malignant cells. High‐risk types HPV 16 and/or 18 DNA sequences were found in 16 of the 22 HPV DNA‐positive cases (72.7%). Our results confirm previously reported HPV involvement in esophageal squamous‐cell lesions, and support the hypothesis of HPV as a possible etiological agent in esophageal carcinogenesis.
Lack of benefit from semi‐annual screening for cancer of the lung: Follow‐up report of a randomized controlled trial on a population of high‐risk males in czechoslovakia
Authors: Kubik A. , Parkin D. M. , Khlat M. , Erban J. , Polak J. , Adamec M.
Published: February 2007

Cigarette‐smoking males (6,364), aged 40–64, were randomized into an intervention group which received 6‐monthly screening by chest X‐ray and sputum cytology, and a control group which received no asymptomatic investigation. After 3 years, both groups entered a follow‐up period during which they received annual chest X‐rays. Lung cancer cases detected by screening were identified at an earlier stage, more often resectable, and had a significantly better survival than “interval” cases diagnosed mainly because of symptoms. Comparison of the 2 groups showed a higher incidence of lung cancer in the intervention group, despite the follow‐up period when both groups received annual examinations. There was no significant difference in mortality between the 2 groups.
Prognostic significance of dna‐ploidy in a series of 690 primary breast cancer patients
Authors: Beerman H. , Kluin Ph. M. , Hermans J. , Van de Velde C. J. H. , Cornelisse C. J.
Published: February 2007

Flow cytometric DNA‐ploidy measurements were performed on paraffin‐embedded and fresh tumor specimens from 690 patients with Stage I‐III breast cancer. The conventional classification of DNA‐ploidy (diploid versus aneuploid) was compared with a division of tumor ploidy into 5 classes based on DNA index (DI) range. The DI‐classification showed a better correlation with tumor size and TNM stage than the conventional classification. Aneuploidy was associated with an impaired survival and distant relapse‐free survival (p =0.02) but the DI‐classification improved the discrimination between different prognostic groups of patients. In general, this indicated a more aggressive phenotype for tumors evolved via polyploidization. Hyper‐tetraploidy (DI >2.10) indicated a very poor prognosis in pre‐menopausal patients. No prognostic effect of aneuploidy and DI‐class was found in node‐negative and TI patients. Cox multivariate regression analysis showed that aneuploidy was an additional prognostic factor to nodal status (1 < N < 3, N > 3 vs. N =0) and tumor size (T2‐4 vs. T1) for overall and distant relapse‐free survival. Subdivision according to DI‐class did not improve the prognostic power of DNA‐ploidy due to stronger correlations with established prognostic factors.
Two new human papillomavirus types (HPV54 and 55) characterized from genital tumours illustrate the plurality of genital HPVs
Authors: Favre Michel , Kremsdorf Dina , Jablonska Stefania , Obalek Slavomir , Pehau‐Arnaudet GÉRard , Croissant Odile , Orth GÉRard
Published: February 2007

The genomes of two new human papillomavirus (HPV) types, named HPV54 and HPV55, were cloned from penile lesions of 2 patients. HPV54 was isolated from a verrucous carcinoma (Buschke‐Löwenstein tumour) together with fulllength HPV6 genomes and HPV6 DNA molecules with a deletion of about 0.3 kb located in the non‐coding region. HPV55 was isolated from a condyloma acuminatum. No crosshybridization was observed between HPV54 DNA and the DNAs of the known cutaneous and genital HPVs by blot hybridization experiments performed under stringent conditions. In contrast, significant cross‐hybridization was detected between HPV55 DNA and the DNA of HPV13, associated with benign oral lesions, and, to a lesser extent, with the DNAs of HPV6, 11, and 44, associated with benign genital proliferative lesions. The DNA sequence homology between HPV55 and HPV6, 11, and 13 was estimated at 12%, 12%, and 20%, respectively, by hybridization in liquid phase at saturation, followed by nuclease SI analysis. The physical maps of HPV54 and 55 were aligned with the genetic maps of HPV16 and 11, respectively, by heteroduplex mapping and partial DNA sequencing. HPV54 is thus only weakly related to the known HPVs, while HPV55 represents an additional HPV6‐related HPV type. HPV54 and HPV55 are uncommon genital HPV types since, in a survey of a large series of specimens of benign, pre‐malignant or malignant anogenital and orolaryngeal tumours, HPV54 was not detected, and HPV55 was found in another case of condyloma acuminatum.
The neu‐oncogene protein as a predictive factor for haematogenous metastases in breast cancer patients
Authors: De Potter Christian R. , Beghin Catherine , Makar Amin P. , Vandekerckhove Dirk , Roels Hendrik J.
Published: February 2007

In a prospective study with a median follow‐up of 13 months on a series of 71 breast cancer patients, 9 developed haematogenous metastases. The neu protein was found on the cell membranes in 27 of the 71 carcinomas (38%) by an immunohistochemical technique using a monoclonal antibody (MAb). Eight of the 9 patients with haematogenous metastases showed overexpression of the neu protein. Immunohistochemical staining of the cell membrane was inversely correlated with the oestrogen and the progesterone receptor status. There was no correlation with lymph‐node involvement. The immunohistochemical detection of the neu protein in breast adenocarcinomas is an independent factor in predicting the patients at risk for haematogenous tumour spread and is therefore correlated with unfavourable prognosis.
A population‐based case‐control study of colorectal cancer in majorca. I. Dietary factors
Authors: Benito E. , Obrador A. , Stiggelbout A. , Bosch F. X. , Mulet M. , Muñoz N. , Kaldor J.
Published: February 2007

A population‐based case‐control study was conducted between July 1984 and February 1988 in the Spanish island of Majorca; 286 incident colorectal cancer cases, 295 population controls and 203 hospital controls were interviewed using a food frequency questionnaire. In a multivariate analysis, an increased risk of colon cancer was found for high consumption of fresh meats (RR =2.87) while a high consumption of cruciferous vegetables afforded protection (RR =0.48). For rectal cancer an increased risk was associated with dairy products (RR =3.08) while a protection was afforded by consumption of cruciferae (RR =0.50). For colorectal cancer, the cereal food group also showed an increase in risk (RR =1.92). When cases were compared to hospital controls, the effects of cruciferae in colon and rectum and those of dairy products in rectal cancer remained. The magnitude of the RR estimates was decreased for most comparisons, although in general terms the direction of the associations was the same. In addition, univariate analyses of food groups also suggested significant increases in risk of colorectal cancer for increasing consumption of cereals, potatoes, pastry, eggs and number of meals per day. An indication was found of a reduction in risk for consumers of coffee. An analysis based on risk scores was also conducted and a 4‐fold increase in the risk of colorectal cancer and a highly significant statistical trend was found for high consumption of fresh meat, dairy products and cereals combined with low consumption of cruciferae.