bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the clonal origin of tumors: A review of experimental models
Authors: Iannaccone P. M. , Weinberg W. C. , Deamant F. D. 
Published: February 2007

AbstractA number of current models of carcinogenesis postulate that rare events are critical in the formation of malignant neoplasms. The most fundamental prediction of the hypothesis that these events are rare is the clonality of neoplasms. Evidence from spontaneous neoplasms supports the contention that such neoplasms are clonal. However, there are a number of reasons to believe that spontaneous neoplasms are derived from large numbers of cells. The issue can be resolved with experimental cancer models. In order to determine whether experimentally induced neoplasms are derived from the clonal expansion of single cells, a variety of benign and malignant tumors can be induced in mosaic rodents. These animals comprise 2 genetically distinguishable cell lineages. If the neoplastic tissues obtained from mosaic animals are composed entirely of progeny of one or the other of the 2 cell lineages, it may be concluded that they are clonal. If, on the other hand, the neoplasms began from the proliferation of many cells, then neoplastic masses would be expected to contain cells of both lineages. The results from a number of these experiments have led to the conclusion that chemically induced neoplasms are clonal. Furthermore, malignant neoplasms are generally believed to develop in a stepwise manner. If they were derived from a single cell, then each of the stages leading to the formation of the cancer should be clonal. A variety of stages thought to be necessary precursors of cancer have been analyzed in mosaic rodents. These preneoplastic lesions have been determined to be clonal in origin. Thus, theories of carcinogenesis must account for the rarity of the events critical to the formation of cancer.
In vitro susceptibility of different human T‐cell subpopulations and resistance of large granular lymphocytes to HTLV‐I infection
Authors: Macchi B. , Popovic M. , Allavena P. , Ortaldo J. , Rossi P. , Gallo R. C. , Bonmassar E. 
Published: February 2007

AbstractT4 subpopulation of T lymphocytes is the preferential target of infection with human T leukemia/lymphoma virus of subgroup I (HTLV‐I). In this study we attempt to determine whether different T‐cell subsets exbibit differences in susceptibility to virus infection. T cells from cord or peripheral blood were separated according to cell densities and T‐cell surface markers by Percoll gradient and Sepharose anti‐Fab immunoadsorbent affinity column (IAC), respectively. Separated T‐cell subpopulations were infected with HTLV‐I, by means of co‐cultivation with irradiated virus producer cell lines (MT‐2, TK). Percentages of HTLV‐I‐infected cells were assayed by immunofluorescence assay (IFA), using highly specific mouse monoclonal antibody (MAb) directed against HTLV‐I p19 core protein. The results showed that different T‐cell subpopulations separated either by Percoll or by IAC were susceptible to HTLV‐I infection with the exception of large granular lymphocytes (LGL), which exhibit high cell‐mediated natural cytotoxicity (CMNC). The susceptibility to HTLV‐I infection of T cells with CMNC activity was further studied on established cell clones with LGL morphology. The results showed again that these cells were resistant to the virus infection. The present studies indicate that different T‐cell subpopulations, irrespective of their size and of cell‐surface markers, are susceptible to HTLV‐I infection, with the exception of functionally mature LGL or of immortalized LGL clones.
Inhibition of murine lymphoma growth by adoptive transfer of lymphocytes sensitized to a xenogenized tumor variant
Authors: Bianchi R. , Romani L. , Puccetti P. , Fioretti M. C. 
Published: February 2007

AbstractLymphocytes immune to a highly immunogenic (“xenogenized”) variant of a murine lymphoma—which were shown to exert anti‐xenogenized tumor activity in a previously described model of tumor immunotherapy—were tested in the present study for possible suppressive effects on the growth of an i.c. graft of the original lymphoma. Remarkable tumor‐inhibitory effects followed the i.v. infusion of splenic lymphocytes sensitized or restimulated in vitro, or derived from animals immunized in vivo with the xenogenized tumor cells. The pattern of inhibition of the parental cells was apparently similar to that previously described for the xenogenized variant, but preliminary evidence suggests that the underlying mechanisms may be different.
The relationship of collagenolytic activity to stage of human colorectal carcinoma
Authors: Irimura Tatsuro , Yamori Takao , Bennett Stephen C. , Ota David M. , Cleary Karen R. 
Published: February 2007

AbstractCollagenolytic enzymes produced by tumor cells are believed to play a significant role in the destruction of surrounding normal tissue and, in certain experimental animal systems, the ability of tumor cells to degrade type‐IV collagen (basement membrane collagen) correlates positively with those cells' metastatic capacity. We measured collagenolytic activity levels of extracts from freshly excised colorectal carcinoma tissues and of conditioned media from primary organ culture (total of 114 tissues from 53 patients) by using purified radio‐labelled type‐1 (rat tail) and type‐IV (mouse Engelbreth‐Holm‐ Swarm [EHS] sarcoma) collagens. Both type‐IV and type‐l collagenolytic activity levels of extracts from tumor and adjacent mucosa ranged from < I to 80 ng/hr/mg wet tissue, and no significant differences between mucosa and carcinoma tissues were observed. In conditioned media, the type‐IV collagenolytic activity was low for normal mucosa and benign tumors and slightly higher for carcinoma than for mucosa. In 5 of 32 primary tumors, collagenolytic activity levels were 2–5 times higher than in the rest of the tumors and mucosal tissues. There were no significant differences in collagenolytic activity levels of conditioned media and tissue extract from colorectal carcinoma of different Dukes' stages. Deep and superficial areas of primary tumors released similar type‐IV collagenolytic activity levels, suggesting that there was little intratumoral heterogeneity in the release of this enzyme.
Human tumor cell lines with pleiotropic drug resistance are efficiently killed by interleukin‐2 activated killer cells and by activated monocytes
Authors: Allavena P. , Grandi M. , D'Incalci M. , Geri O. , Giuliani F. C. , Mantovani A. 
Published: February 2007

AbstractTwo human cell lines, the colon carcinoma Lovo and the transformed intestinal 1–407, and their variants (Lovo/Dx and l‐407/Dx), with pleiotropic resistance to cancer chemothera‐peutic drugs, were examined for their susceptibility to human lnterleukin‐2‐activated killer cells and to activated mono‐cytes. These non‐specific or broadly specific effector cells expressed cytotoxicity levels on pleiotropically resistant tumor cells comparable to those of the parental cell populations. This finding provides a rationale for immunological approaches designed to eradicate residual tumor cells surviving and resistant to cytotoxic chemotherapy.
Monoclonal integration of HTLV‐I proviral DNA in patients with strongyloidiasis
Authors: Nakada K. , Yamaguchi K. , Furugen S. , Nakasone T. , Nakasone K. , Oshiro Y. , Kohakura M. , Hinuma Y. , Seiki M. , Yoshida M. , Matutes E. , Catovsky D. , Ishii T. , Takatsuki K. 
Published: February 2007

AbstractThe relationship between strongyloidiasis and HTLV‐I was investigated in Okinawa, an area where both conditions are endemic. Thirty‐six patients with strongyloidiasis were sero‐positive for HTLV‐I and suffered from several related clinical complications. Fourteen of these patients (39%) were shown to have monoclonal integration of HTLV‐I proviral DNA in their blood lymphocytes, a condition designated as “smouldering” adult T‐cell leukaemia (ATL). Monoclonal integration of proviral DNA correlated with an increased CD4/CD8 ratio and the presence of abnormal lymphocytes in the peripheral blood, and with a trend for greater severity of the parasitic infection. Although the immunodeficiency caused by HTLV‐I could predispose to hyper infestation by Strongyloides, it is also possible that both the parasitic and the retroviral infestations are important co‐factors leading to the development of ATL.
Clonal rearrangements of T‐cell receptor and immunoglobulin genes and immunophenotypic antigen expression in different subclasses of Hodgkin's disease
Authors: Griesser Henrik , Feller Alfred C. , Mak Tak W. , Lennert Karl 
Published: February 2007

AbstractTwenty‐two cases of Hodgkin's disease (HD), representing the 4 different subclasses, were studied by immunophenotypic and immunogenotypic analysis. Quantitative immunophenotypic analysis of HD infiltrates showed a predominance of CD3‐positive T cells in all subtypes except the lymphocytic depletion (HDLD) subtype. Only 5 samples of HD [2 of lymphocytic predominance (HDLP), 2 of mixed cellularity (HDMC), and one of nodular sclerosis type (HDNS)] were found to have both their Ig and T‐cell antigen receptor (TcR) genes in the germ‐line configuration. The remaining patients with HDLP (3 cases), HDNS (5 cases), and HDMC (4 cases), all exhibited rearrangements of either TcRγ or TCRγ and TcRβ genes, while all 5 cases of HDLD had either TCRγ or immunoglobulin heavy‐chain gene rearrangement. These results substantiate the view that Hodgkin's lymphomas contain clonal lymphocyte populations and that different rearrangement patterns may be associated with different subclasses of HD.
Trends in incidence of ocular malignant melanoma in Denmark 1943–1982
Authors: Østerlind Anne 
Published: February 2007

AbstractAll records of ocular malignant melanoma notified to the Danish Cancer Registry between 1943 and 1982 were re‐coded, and 1,624 out of 1,650 cases were verified and included in this investigation. The annual number of incident cases increased from about 30 to 50, but the age‐standardized incidence rate remained stable at 0.75 per 100,000 in males and 0.60 In females. There was no predilection for one or the other eye in either sex. About 80% of the tumours were located in the choroid, 10% in the ciliary body and iris, 5% in the conjunctiva, and 5% in “multiple regions”. The histopathology of the tumours was: epithelioid cell type in 12%, spindle‐cell type in 36%, and mixed‐cell type in 51%. The stable incidence rates of ocular malignant melanomas were in marked contrast to the 5‐to 6‐fold increase observed for cutaneous melanomas during the same time period. Possible differences in risk factors are discussed. Similarities and differences between the present data and results from other countries are highlighted.
Autologous mixed lymphocyte‐tumor reaction and autologous mixed lymphocyte reaction. I. Proliferation of two distinct T‐cell subsets
Authors: Uchida Atsushi , Moore Michael , Klein Eva 
Published: February 2007

AbstractIn patients with carcinomatous pleural effusions blood T lymphocytes proliferated in vitro in response to autologous, freshly isolated effusion tumor cells in the autologous mixed lymphocyte‐tumor culture (AMLTC) and to autologous blood non‐T cells in the autologous mixed lymphocyte culture (AMLC). Treatment of the stimulator cells with the anti‐HLA‐DR monoclonal antibody (MAb) abrogated the stimulatory capacity in AMLC, but not in AMLTC. A subset of T cells that formed rosettes with autologous erythrocytes showed proliferative response to autologous non‐malignant cells, whereas this subset did not respond to autologous tumor cells. Non‐adherent lymphocytes were fractionated by centrifugation on discontinuous Percoll density gradients. Medium‐sized T lymphocytes were excellent responders in AMLC, but were weak responders in AMLTC. Small T lymphocytes proliferated preferentially in AMLTC, but responded poorly in AMLC. Large granular lymphocytes (LGL) did not proliferate in mixed cultures of either type. Instead, LGL suppressed the T‐cell proliferation in AMLTC. The same suppressor LGL, however, had no inhibitory effect on AMLC. Elimination of the CD4 subset reduced or abolished proliferative response in AMLC in all cases, whereas it was ineffective in diminishing the reaction in 6 of 8 AMLTC. In contrast, removal of the CD8 subset decreased or eliminated T‐cell proliferation in 4 of 8 AMLTC, but in none of the AMLC. These results indicate that the auto reactive T lymphocytes detectable in response to tumor cells and non‐malignant non‐T cells differ in several characteristics. Thus, the reaction in the AMLTC is not due to contaminating non‐malignant cells in the stimulator population and may be a tumor‐induced prolixferative response.
Aberrant ribonucleotide pattern in lymphoid cells from patients with chronic lymphocytic leukaemia or non‐Hodgkin lymphoma
Authors: De Korte Dirk , Haverkort Willem A. , Roos Dirk , Van Gennip Albert H. 
Published: February 2007

AbstractThe intracellular purine and pyrimidine ribonucleotide concentrations were determined in lymphoid cells from peripheral blood of 16 patients with chronic lymphocytic leukaemia (CLL) and from peripheral blood and/or lymphoid tissue of 18 patients with non‐Hodgkin lymphoma (NHL). Compared to normal peripheral lymphocytes, the lymhoid cells from CLL patients contained lower, and those from NHL patients higher amounts of nucleotides. The lymphoid cells of NHL patients showed an imbalance in the nucleotide pool compared to either normal resting peripheral or proliferating tonsillar lymphocytes. The lymphoid cells of patients with CLL showed an imbalance only when compared to normal, resting peripheral lymphocytes. The abnormalities in the nucleotide pools involved decreased ratios of purine:pyrimidine, adenine:guanine and uracil:cytosine nucleotides. Lymphocytes from CLL and NHL patients contained increased amounts (relative and/or absolute) of UDP sugars, and NHL lymphocytes also showed a changed composition of the UDP sugars. Analysis of the ribonucleotides in the lymphoid cells provides useful information for the differential diagnosis of patients suspected of having CLL or NHL, and may be valuable for the design of new chemotherapeutic regimens.
Conversion of the lymphoma line “BJAB” by Epstein‐Barr virus into phenotypically altered sublines is accompanied by increased C‐myc mRNA levels
Authors: Wennborg Anders , Åman Pierre , Saranath Dhananjaya , Pear Warren , Sümegi Janos , Klein George 
Published: February 2007

AbstractThe steady‐state level of c‐myc proto‐oncogene mRNA was investigated in the EBV‐negative human B‐lymphoma line BJAB and 2 sublines that have been converted by EBV into stable EBV‐genome‐carrying and EBNA‐positive status. The EBV‐converted sublines expressed c‐myc at a 2‐to 6‐fold higher level than the original BJAB during exponential growth. The EBV‐positive BJAB lines are known to differ from the parent line in several phenotypic characteristics, including increased agarose clonability, lower serum requirements and, in one case, increased tumorigenicity in nude mice. The pattern of increased c‐myc expression accompanying EBV conversion was not observed in the myc/lg translocation‐carrying Burkitt lymphoma line RAMOS or in 2 of its EBV‐converted sublines.
Differential effects of retinoic acid on the in vitro growth and cell‐surface glycoconjugates of 2 human head and neck squamous‐cell carcinomas
Authors: Lotan Reuben , Sacks Peter G. , Lotan Dafna , Hong Waun K. 
Published: February 2007

AbstractAs a part of an assessment of the potential use of retinoids in preventive and adjuvant treatment of HNSCC, we examined the effects of β‐all‐trans retinoic acid (RA) on the growth and cell‐surface glycoconjugates of 2 HNSCC cell lines. These lines, designated 1483 and 183A, were established from an untreated patient with a well‐differentiated SCC of the re‐tromolar trigone and one with a poorly differentiated SCC of the tonsil. Whereas the 1483 cells were sensitive to RA in that their anchorage‐dependent growth, their colony growth on solid substratum, and their anchorage‐independent growth in semi‐solid agarose gel were all inhibited in a dose‐dependent fashion by RA concentrations in the range between I nM and 10 μM, the 183A cells were not inhibited by RA. Their anchorage‐dependent growth and colony formation were stimulated by RA, whereas their anchorage‐dependent colony formation was not altered. Cell‐surface glycoconjugates were modulated by RA in the sensitive 1483 cells but not in the 183A cells. Treatment of the 1483 cells resulted in a large increase in the cell‐surface labelling of high‐molecular‐weight (Mr > 400,000) galactoglycoconjugates and sialoglycoconjugates, as well as an Mr 280,000 sialoglycoconjugate. Glycoconjugates with similar electrophoretic mobilities in polyacrylamide gels were labelled intensely on the surface of the 183A cells even before RA treatment and only minor changes were noticed in their labelling after treatment. These results demonstrate that RA can exert different effects on different HNSCC lines, and suggest that correlations might exist between responsiveness to RA and the stage of differentiation of the HNSCC, and between modulation of cell growth and enhancement of cell‐surface glycoconjugate glycosylation by RA.
Combination tumor‐immunotherapy with recombinant tumor necrosis factor and recombinant interleukin 2 in mice
Authors: Nishimura Takashi , Ohta So , Sato Naoko , Togashi Yuji , Goto Makiko , Hashimoto Yoshiyuki 
Published: February 2007

AbstractRecombinant human tumor necrosis factor (r‐TNF) inhibits growth of various mouse tumor cell lines both in vitro and in vivo. Treatment of established tumor nodules with intratumoral (i.t.) injection of r‐TNF caused hemorrhagic necrosis of tumor and temporary disappearance of tumor mass. However, a small number of tumor cells remained and later formed fresh nodules. In striking contrast, combination therapy with r‐TNF and recombinant human interleukin‐2 (r‐IL‐2) resulted in a marked inhibition of regrowth of tumor cells. More than 60% of MBL‐2‐bearing mice were completely cured of tumor by treatment with r‐TNF and r‐IL‐2. Cured mice could also reject rechallenged MBL‐2 lymphoma cells, indicating the generation of anti‐tumor effector cells in vivo. However, lymphocytes obtained from mice cured of MBL‐2 showed no significant in vitro cytotoxic activity against MBL‐2 lymphoma cells. In contrast, in vitro sensitization of spleen cells from cured mice with mitomycin‐C‐treated MBL‐2 lymphoma cells resulted in the generation of cytotoxic cells against MBL‐2 lymphoma cells. Moreover, spleen cells from mice cured of MBL‐2 by treatment with r‐TNF and r‐IL‐2 revealed a strong anti‐tumor activity upon in vivo neutralization tests. These results strongly suggest that tumor‐bearing mice can acquire systemic immunological memory after combination therapy with r‐TNF and r‐IL‐2.
Phenotype versus immunoglobulin and T‐cell receptor genotype of Hodgkin‐derived cell lines: Activation of immature lymphoid cells in Hodgkin's disease
Authors: Falk Martin H. , Tesch Hans , Stein Harald , Diehl Volker , Jones David B. , Fonatsch Christa , Bornkamm Georg W. 
Published: February 2007

AbstractThree Hodgkin‐derived cell lines (L428, L540, and CO) were studied for rearrangements and expression of immunoglobulin and T‐cell receptor genes, and their genotype was compared to the phenotype. As far as the genotype is concerned, all 3 cell lines have characteristics of lymphoid cells; L428 of B, and L540 and CO of T‐cell origin. L428 cells have one Ig heavy chain allele rearranged to Cγ and transcribed into RNA, while the second is deleted. Furthermore, L428 cells show an unusual immunoglobulin kappa light chain gene rearrangement involving deletion of the kappa constant gene in one allele, while the remaining kappa and lambda loci are in germ‐line configuration. L540 and CO have, in contrast to L428 cells, the immunoglobulin genes in germline and T‐cell receptor genes rearranged. The T‐cell receptor β and γ genes are rearranged in both L540 and CO, whereas a rearrangement in the a locus was detected in L540 cells only. RNA of the size of functional β chain transcripts was found in CO cells and of the size of functional α chain transcripts in L540 cells. All 3 cell lines are classified as immature lymphoid cells with respect to the limited expression of B‐and T‐cell antigens, respectively, and to the incomplete expression of their antigen receptor. The immaturity of lymphoid differentiation contrasts with the expression of activation antigens, i.e. Ki‐1, Ki‐24, HLA‐DR, and IL‐2 receptor. The immaturity of the cells excludes the possibility that the cells were activated along the physiological pathway, i.e. by interaction of the cell with antigen. The results obtained on the cell lines are in accordance with in vivo studies and suggest that Hodgkin and Sternberg‐Reed cells are immature lymphoid cells which are activated by a still unknown mechanism.
Epidemiology of respiratory cancers related to nickel mining an refining in New Caledonia (1978–1984)
Authors: Goldberg M. , Goldberg P. , Leclerc A. , Chastang J. F. , Fuhrer R. , Brodeur J. M. , Segnan N. , Floch J. J. , Michel G. 
Published: February 2007

AbstractThe incidence rate of respiratory (lung and upper respiratory tract) cancer related to the nickel industry was sudied in the male population of New Caledonia over a 7‐year period (1978–1984). The findings show no excess incidence of lung or upper respiratory tract (larynx, pharynx, nasal cavities) cancer cases in the population of nickel workers compared with the rest of the male population in New Caledonia. This result was corroborated by a case‐control study which does not indicate any particular role of hazards specific to the nickel mining and refining industry. Our findings, which may be specific 1 or the type of ore processed in New Caledonia, must nevertheless be confirmed by extending the study to a total of 10 years (1978–1987). The incidence rate of male respiratory cancer in New Caledonia was also compared to that of cancers of this type reported in certain regions of industrialized countries (Australia, France, U.K., USA). Such findings are very similar to those observed in New Caledonia, thereby confirming a predominant role of tobacco and alcohol consumption in a territcry which, despite certain characteristics of a developing country, has life‐style habits similar to those of industrialized countries.
Specific uptake of alpha‐fetoprotein by malignant human lymphoid cells
Authors: Laboida Jorge , Naval Javier , Allouche Michèle , Calvo Miguel , Georgoulias Vassilis , Mishal Zohair , Urkl José 
Published: February 2007

AbstractWe have studied the ability of human B‐and T‐lymphoblastcid cell lines, as well as of peripheral lymphoid cells from leukemia patients, to take up alpha‐fetoprotein (AFP) and other serum proteins. Two technical approaches have been employed, both using fluorescent protein derivatives (FITC‐proteins): microscopic examination of labelled cells using epifluorescent illumination and quantitation of endocytosed proteins by fluorescence‐activated cell sorting (FACS). Compared to human resting T‐lymphocytes, all T‐and B‐cell lines tested exhibited positive staining for fluoresceinated AFP and transferrin (Tf) and a significant increase, up to 100‐fold, of the number of AFP and Tf molecules endocytosed per cell. Labeling was prevented or strongly diminished by a 100‐fold excess of unlabelled protein. Preliminary results with peripheral lymphoid cells harvested from leukemia patients showed the presence of AFP‐and Tf‐positive cells in the blood of all patients examined. Intensity of labelling was related to the type of leukemia cells and/or the degree of cell maturation. Host cell lines exhibited positive staining for alpha2‐macroglobulin (α2M) and also, to a lesser extent, for serum Vitamin D3 binding protein (DBP). In contrast, no labelling was observed with FITC‐serum albumin (FITC‐Alb) or FITC‐ovalbumin (FITC‐OVA). Comparative uptake of several FITC‐protcins by a single cell population revealed significant quantitative and qualitative differences.