bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical and immunological properties of the human carcinoma antigen car‐5 defined by the monoclonal antibody BD‐5
Authors: Prat Maria , Medico Enzo , Garrino Cristina , Comoglio Paolo M.
Published: February 2007

The monoclonal antibody (MAb) BD‐5 reacts with an epitope (CAR‐5) expressed in 83% of the gastric carcinomas and in 51% of the ductal pancreatic carcinomas. This MAb reacts also with epithelial cells of colorectal mucosa, but does not react at all with normal adult gastric mucosa or normal adult pancreas. We report the biochemical and immunochemical characterization of CAR‐5‐bearing molecule. The epitope was found to be carried on a mucin of more than 400 kDa with a density of 1.45 g/ml, metabolically labelled with 35S‐sulfate, 3H‐glucosamine, 3H‐mannose and 35S‐methionine. Antigenicity survived metaperiodate oxidation and alkalinization, while it was fully destroyed by pronase or papain. Trypsin, although cleaving the molecule, did not affect its antigenic activity. CAR‐5 epitope is thus carried on the protein moiety of a sulfo‐mucin. On the basis of its biochemical properties, the antigen was purified by a 3‐step procedure, consisting of perchloric acid extraction, molecular sieving on Sepharose CL‐4B and affinity chromatography on wheat‐germ agglutinin coupled to Sepharose 4B. Cross‐competition experiments, together with the chemical properties displayed by the different epitopes, clearly indicate that CAR‐5 is different from all previously characterized carcinoma‐associated determinants. Cross‐DDIRMA experiments performed with different “catcher” and “tracer” antibody combinations showed that CAR‐5 epitope may be expressed on the same mucin bearing CA 19‐9, MOv2, DU‐PAN‐2, Lewisa and Lewisb epitopes.
Alcohol consumption in a case‐control study of breast cancer in southern france
Authors: Richardson Sylvia , Vincenzi Isabelle De , Pujol Henri , Gerber Mariette
Published: February 2007

The effect of alcohol consumption on breast cancer risk was investigated in a hospital‐based, case‐control stud/ of 808 patients (349 cases and 459 controls) in Montpellier (France). Semi‐quantified diet history including beverage consumption as well as relevant medical and personal characteristics were assessed by interview. A dose‐rate relationship for total alcohol consumption was found with unadjusted odds ratios ranging from 1.8 (95% Cl 1.2‐2.8) for 1 to 2 drinks per week to 3.5 (95% Cl 2.0‐6.1) for more than 17 drinks per week, in comparison with less than I drink per week. Confounding by known or suspected determinants of breast cancer, smoking, use of oral contraceptives, lipid and vitamin consumption was looked into. Significant interactions were found with level of education and lipid consumption, with a higher risk for alcohol in women having had less schooling or consuming less fat. Adjustment with respect to the other risk factors did not modify the relationship. There was a significant risk increase both for wine and stronger drinks. Along with several other studies, our results give support to the hypothesis that alcohol is a risk factor in breast carcinogenesis.
Partial transcription map of Marek's disease herpesvirus in lytically infected cells and lymphoblastoid cell lines
Authors: Schat K. A. , Buckmaster A. , Ross L. J. N.
Published: February 2007

Marek's disease herpesvirus (MDV) can cause either a productive‐restrictive or lytic infection, a latent infection or can transform thymus‐derived lymphocytes. RNA was extracted from infected chicken embryo fibroblasts (CEF) or from lym‐phoblastoid tumour cell lines. Some of the infected CEF were treated with 200 μg/ml cycloheximide to identify immediate early (IE) transcripts, and others with I μM l‐(2‐fluoro‐2‐deoxy‐B‐D‐arabinofuranosyl)‐5‐methyluracil (FMAU), an inhibitor of herpesvirus DNA synthesis to identify early transcripts. An extensive Northern blot analysis was carried out using DNA probes spanning almost the complete MDV genome. In the lytically infected CEF at least 66 discrete transcripts were detected, ranging in size from 9.1 kb to 0.6 kb. Eleven IE transcripts were identified, of which 8 were mapped in the genome segment consisting of the IRL, IRs, Us and TRs. Six transcripts were identified as early genes. In the MD lym‐phoblastoid cell lines MDCC‐HPI, a non‐producer cell line, and MDCC‐CU4I, a non‐expression cell line, 4 and 7 transcripts were detected, respectively. These RNAs were transcribed from IE genes located mainly in the repeat sequences flanking UL and Us and in Us. Treatment of the lymphoblas‐toid cell lines with 20 μ.g/ml 5‐iodo‐2‐deoxyuridine resulted in the additional transcription of I RNA species in HP I and 9 in CU41. Most of the transcripts present in lytically infected cells were also detected in MDCC‐CU36, a cell line with a high percentage of antigen‐positive cells (expression cell line).
Cytomegalovirus enhances lysis of HIV‐infected T lymphoblasts
Authors: Casareale D. , Fiala M. , Chang Cm. , Cone L. A. , Mocarski E. S.
Published: February 2007

A T4+ T lymphoblastoid cell line (CR‐10) persistently infected with the human immunodeficiency virus (HIV) and designated CR‐1O/NIT was superinfected with cytomegalovirus (CMV) isolated from peripheral blood mononuclear cells of a patient with AIDS. A productive CMV cycle in the CR‐1O/NIT lymphoblasts was demonstrated by fluorescent antibody staining (IF) using a monoclonal antibody (MAb) to the 150‐kDa major capsid protein, by infectivity assays and by electron microscopy (EM). Two‐color IF analysis showed that a small percentage of the CR‐1O/NIT cells were producing both CMV and HIV at any one time. EM studies revealed that all doubly infected cells were lysed whereas most cells infected only with HIV appeared intact. Cell lysis appeared 24 hr after superinfection of the CR‐1O/NIT cells with CMV and progressed to complete destruction of the cell culture between days 9 and 10. Our results suggest that CMV may convert a mildly cytopathic HIV infection of T lymphoblasts into a highly lytic process.
Reversal of drug resistance by erythromycin: Erythromycin increases the accumulation of actinomycin d and doxorubicin in multidrug‐resistant cells
Authors: Hofsli Eva , Nissen‐meyer Jon
Published: February 2007

Development of resistance to one type of lipophilic chemo‐therapeutic drug often leads to resistance to other, structural!/ unrelated, lipophilic drugs. This suggests that non‐toxic lipophilic agents may interfere with and reverse drug resistance by saturating the pathway through which multidrug‐resistant (MDR) cells protect themselves against cytotoxic drugs. The lipophilic antibiotic, erythromycin, can significantly reverse the resistance of MDR WEHI 164 murine fibrosarcoma cells to the chemotherapeutic drugs, doxorubicin and actinomycin‐D. The MDR cells showed an approximately 10‐fold higher expression of the P‐glycoprotein than the drug‐sensitive parental cells from which the resistant cells were derived. The accumulation of actinomycin‐D and doxorubicin was much lower in the drug‐resistant cells than in the sensitive parental cells. The concentrations of erythromycin which reversed the drug resistance of the MDR cells increased the accumulation of actinomycin‐D and doxorubicin in these cells to a level comparable to that observed in the sensitive parental cells. Our data suggest that erythromycin reverses drug resistance by saturating the drug‐binding sites on the P‐glycoprotein, thereby reducing the capacity of this protein to pump drugs out of resistant cells. Some of our MDR cells have also become more resistant to tumour necrosis factor (TNF). However, erythromycin did not reverse TNF resistance, suggesting that the mechanisms of multi‐drug and TNF resistance are different. TNF did not influence drug accumulation in MDR cells.
Up‐regulation by granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) of induction of lymphokine (IL‐2)‐activated killer (LAK) cells by human blood monocytes
Authors: Singh Sukh Mahendra , Sone Saburo , Inamura Noriaki , Ogura Takeshi
Published: February 2007

The role of recombinant granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in monocyte‐mediated up‐regulation of lymphokine‐activated killer (LAK) ell induction by IL‐2 was examined. Treatment of blood mononuclear cells (MNC) of healthy donors with GM‐CSF for 4 days in the presence of IL‐2 resulted in a significant increase in LAK activity against natural killer (NK)‐resistant Daudi cells, as assessed by the 4 hr 5lCr‐release assay. For determination of the role of GM‐CSF in LAK induction, highly purified lymphocytes (>99%) and monocytes (>90%) were isolated from MNC by counter‐flow centrifugal elutriation (CCE). Pre‐treatment of monocytes for 4 days with GM‐CSF before addition of lymphocytes plus IL‐2 resulted in a significant dose‐dependent increase in monocyte‐mediated up‐regulation of LAK induction, but in the absence of monocytes GM‐CSF had no effect on LAK cell induction. Similarly, GM‐CSF augmented the proliferative response of lymphocytes to IL‐2 in the presence of monocytes as assessed by 3H‐TdR uptake. Treatment with anti‐GM‐CSF antibody completely abolished up‐regulation of LAK induction by GM‐CSF‐treated monocytes. When blood monocytes were separated into 5 fractions by CCE, GM‐CSF‐responding monocytes were found to be responsible for up‐regulation of LAK induction. These results suggest that GM‐CSF may be important in monocyte‐mediated upregulation of LAK cell induction in vivo.
Development of an animal model to study the biology of recurrent colorectal cancer originating from mesenteric lymph system metastases
Authors: Schackert H. K. , Fidler I. J.
Published: February 2007

We developed an animal model to study the biology and therapy of local‐regional recurrent colorectal cancer. Syngeneic tumor cells or human colon carcinoma cells, respectively, were injected into the lymphoid follicle of the cecum of conventional mice or athymic nude mice. The cecum was resected (at a distant site) at various time points after the injection. Recurrent disease at the site of resection and in regional mesenteric lymph nodes was found in most of the injected mice, even in those whose cecum was resected 10 min after injection. The injection of tumor cells into the lymphoid follicle of the cecum introduces tumor cells into the lymph system of the cecum and the draining mesenteric lymph nodes, and these few cells, which cannot be detected at the time of operation, are the source of recurrent disease. This new animal model should allow us to study the biology and therapy of local and regional colorectal cancer.
The ma le factor in the etiology of cervical cancer among sexually monogamous women
Authors: Brinton Louise A. , Reeves William C. , Brenes Maria M. , Herrero Rolando , Gaitan Eduardo , Tenorio Francisco , de Britton Rosa C. , Garcia Mariana , Rawls William E.
Published: February 2007

To address the hypothesis that male sexual behavior may affect the etiology of invasive cervical cancer, a case‐control study was undertaken in Panama, Costa Rica, Colombia and Mexico. The study enrolled husbands of those women with invasive cervical cancer and of those age‐matched controls who reported only one lifetime sexual partner. A total of 204 case and 485 control husbands (78% and 72%, respectively, of identified husbands) were interviewed, clinically examined, and had penile swabs taken for papillomavirus assays. Risk increased significantly (p = 0.005) with the number of sexual partners reported by the husband (RR = 2.0 for 26+ vs. <6 partners). Low educational status of the husband was also an important predictor of risk, possibly indicating the role of unmeasured aspects of sexual behavior. Visits to prostitutes, circumcision status and sexually transmitted disease histories were not important predictors of risk, but evidence from clinical examination indicated that poor genital hygiene may be involved. Human papillomavirus (HPV) expression as defined by filter in situ hybridization was detected in 20‐23% of subjects and, except in the small group with both HPV types 6/11 and 16/18, was not related to risk. This may reflect sampling problems in the male or the importance of host factors which enhance viral carcinogenicity in the female.
Re‐targeting of human lymphocytes expressing the T‐cell receptor gamma/delta to ovarian carcinoma cells by the use of bispecific monoclonal antibodies
Authors: Ferrini Silvano , Prigione Ignazia , Mammouti Serafina , Colnaghi Maria Ines , Ménard Sylvie , Moretta Alessandro , Moretta Lorenzo
Published: February 2007

TcR gamma/delta+ lymphocytes represent a small subset homogeneously composed of cytolytic T cells displaying unique motility and homing properties. Since the lytic machinery of these cells can be efficiently triggered by monoclonal antibodies (MAbs) directed to the TcR gamma/delta, such MAbs were used for the construction of bispecific MAbs in conjunction with an MAb specific for ovarian carcinoma cells. Hybrid hybridomas were obtained by fusing the Mov19 MAb (IgG2a)‐producing hybridoma with either GI (IgG2a) or A13 (IgG1) hybridomas, secreting MAbs specific for 2 peripheral blood subsets of TcR gamma/delta+ lymphocytes. Hybrid hybridomas producing bispecific MAbs were screened according to their ability to induce ovarian carcinoma (IGROVI) target cell lysis by GI+ or A13+ T cell clones, respectively. The Gl‐derived GM33.9 bispecific MAb induced selective lysis of Mov19+ ovarian carcinoma target cells only by GI+ clones, whereas the A13‐derived AM 18.4 MAb was effective only in combination with A13+ clones. Neither the anti‐TcR gamma/ delta nor the Mov19 parental MAbs (used alone or in combination) induced target‐cell lysis. The hybrid nature (IgG1/ lgG2a) of the AM 18.4 bispecific MAb was indicated by 2‐color immunofluorescence experiments. Thus, both ovarian carcinoma and A13+ effector cells were double stained by AM18.4 bispecific MAb followed by PE‐conjugated anti‐IgG1 and FITC‐conjugated anti‐IgG2a second reagents. Polyclonal TcR gamma/delta+ cells were obtained by direct stimulation of peripheral blood mononuclear cells with Sepharose bead‐conjugated anti‐TcR gamma/delta MAbs and IL‐2. The lines so obtained contained more than 90% of TcR gamma/delta+cells after 4 weeks of culture, with an increase in TcR gamma/ delta+ cell numbers ranging from 200 to 1,000‐fold. These TcR gamma/delta+ cell lines efficiently lysed ovarian carcinoma target cells in the presence of bispecific MAb and may therefore represent a suitable source of effector cells for induction of ovarian carcinoma cell lysis.
Establishment of human malignant mesothelioma cell lines
Authors: Versnel Marjan A. , Bouts Monique J. , Hoogsteden Henk C. , Van Kwast Theodorus H. Der , Delahaye Mick , Hagemeijer Anne
Published: February 2007

Seventeen human malignant mesothelioma cell lines were isolated from 61 samples (46 effusions, 9 biopsies and 6 tumors obtained at autopsy) collected from patients with a confirmed malignant mesothelioma. The method used is given in detail. Cytogenetic analysis of growing cultures is the best indicator to determine whether the observed proliferation concerns malignant or normal mesothelial cells. The addition of epidermal growth factor (EGF) and hydrocortisone (HC), or EGF alone, to the culture medium increases the chances of successful isolation of a malignant mesothelioma cell line.
Time‐dependent toxicity of drugs used in cancer chemotherapy: Separate and combined administration
Authors: Peleg L. , Ashkenazi I. E. , Carlebach R. , Chaitchik S.
Published: February 2007

Time‐dependent toxicity of 3 anti‐cancer drugs was demonstrated in BALB/c mice. Cisplatinum, adriamycin and cyclophosphamide were injected at 4 different circadian stages, either together (combined injection) or separately, to different groups of mice. Toxicity was evaluated by body‐weight changes, mortality and white blood cell counts. Maximal body‐weight loss was caused by the administration of either Cisplatinum or the combination of all 3 drugs at 15.00 hr and 21.00 hr, i.e., 9 and 15 hr after fight on (HALO). Only moderate body weight loss was induced when adriamycin was injected at 09.00 hr or at 21.00 hr (3 and 15 HALO). In contrast to Cisplatinum and adriamycin, cyclophosphamide induced no significant change in body weight when injected at either time. The highest level of mortality was caused by the injection of all 3 drugs together at 21.00 hr (15 HALO). No death occurred when drugs were administered separately. The rate of recovery (as assessed by weight regain) also exhibited dependence upon the time of drug administration and was the slowest after injections at 21.00 hr (15 HALO). It appears, therefore, that the time‐dependence modes of toxicity and recovery (as assessed by body‐weight change) are different. The decrease in white blood cell count also exhibited a time‐dependence pattern which differed from that of weight loss and death.
Characterization of a newly established, TA‐4‐producing squamous carcinoma cell line derived from metastatic tongue carcinoma
Authors: Nakano Shuji , Nakayama Masaaki , Ichinose Ichiro , Mitsugi Kenji , Nagafuchi Seiho , Niho Yoshiyuki
Published: February 2007

A human squamous carcinoma cell line was established from the pleural effusion of a patient with recurrent squamous carcinoma of the tongue. The cell line, designated HST‐I, has been passaged 82 times over a period of 4 years. The cells have been shown by light and electron microscopy to be of the squamous epithelial type. Immuno‐histochemical staining was positive for keratin. When these cells were transplanted into athymic nude mice, tumors developed at the site of inoculation, which on histological examination were shown to be well‐differentiated squamous carcinomas. Karyotypic analysis of cells from the cell line demonstrated an aneuploid human type with a modal chromosome number of 71, with both numerical and structural aberrations. HST‐I cells produce and secrete TA‐4, a squamous‐cell carcinoma‐related antigen, in vitro in culture and in vivo in nude mice bearing the tumors produced by inoculation of cultured cells. Thus, the HST‐I cell line represents a new human tongue squamous carcinoma producing TA‐4. This cell line appears useful for facilitating therapeutic investigations as well as biological studies on the association between cancerous growth and circulating TA‐4 levels.
Development of splenic natural suppressor (NS) cells in ehrlich tumor‐bearing mice
Authors: Subiza Jose L. , Vinuela Juan E. , Rodriguez Rosa , Gil Juana , Figueredo M. Angeles , de la Concha Emilio G.
Published: February 2007

Spleen cells from C57BL/6J mice bearing Ehrlich carcinoma growing as a solid tumor show progressive unresponsiveness to concanavalin A (Con A) and lipopolysaccharide (LPS) mitogens. This is accompanied by striking spleen enlargement with marked hematopoietic activity. Lymphoproliferative assays of normal spleen cells in co‐culture with tumor‐bearing spleen cells (TBSC) show that: (a) TBSC contain non‐specific suppressor cells able to abrogate both Con A and LPS responses, or mixed lymphocyte reaction, of normal spleen cells and (b) suppression by TBSC is MHC‐unrestricted, non‐prostaglandin‐mediated and greatly enhanced by Con A su‐pernatants. Suppressor cells associated with TBSC are large, low‐density cells without markers of mature B or T lymphocytes or of the mononuclear phagocyte system. Most appear to be asialo‐GM,‐negative, as suppression was only partially inhibited by treatment with anti‐asialo‐GM, and complement. Since NK activity is lacking in TBSC, our data strongly suggest that these “null” suppressor cells are related to the natural suppressor (NS) cells found described in normal bonemarrow and neonatal spleens, or induced in adult spleens by total lymphoid irradiation, graft‐vs.‐host disease, or cyclophosphamide treatment.
The accelerating role of abelson murine leukemia virus in murine plasmacytoma development: in vitro infection of spleen cells generates donor‐type tumors after transfer to pristane‐treated BALB/c mice
Authors: Sugiyama Hiroyuki , Weber Günther , Silva Santiago , Babonits Magda , Wiener Francis , Klein George
Published: February 2007

The role of Abelson murine leukemia virus (A‐MuLV) in the accelerated development of murine plasmacytomas (PCs) (Potter et al., 1973: Science, 132, 592‐594) was studied in a new experimental system. Spleen cells from pristane‐treated or untreated BALB/c mice carrying Robertsonian 6;I5 fusion chromosomes were infected in vitro with helper‐free A‐MuLV overnight and subsequently transplanted into the peritoneal cavity of pristane‐treated or untreated BALB/c mice. Donor‐derived PCs developed in 4 out of 76 pristane‐treated recipients [latent periods: 38‐82 (mean 51) days] that had received spleen cells from pristane‐treated donors, and also in 2 out of 41 pristane‐treated recipients that had received untreated donor‐derived spleen cells (latent periods: 65 and 120 days). Three of the PCs in the former and both PCs in the latter group were tested for integration and expression of the v‐abl gene, with positive results. This indicates that the spleen contains PC‐precursor cells that can be activated by A‐MuLV even before the impact of pristane. All 6 donor‐origin PCs carried a translocation involving chromosone 15, band D2/3. Four of these corresponded to a typical 12; 15 translocation, one was a variant 6; 15 translocation and the 6th may represent a previously unidentified translocation between chromosome 15 and the λ gene‐carrying chromosome 16. No PCs developed among 29 pristane‐untreated recipients that had received pristane‐treated donor‐derived spleen cells. In addition to PCs, monocytic tumors developed in 37 (26%) of all recipients. Their development was independent of pristane treatment of recipients but was particularly frequent in those who had received spleen cells from pristane‐treated donors.
Increased CMP‐NeuAc:Galβ1,4GlcNAc‐R α2,6 sialyltransferase activity in human colorectal cancer tissues
Authors: Olio Fabio Dall , Malagolini Nadia , di Stefano Giuseppina , Minni Francesco , Marrano Domenico , Serafini‐Cessi Franca
Published: February 2007

The sialyltransferase activities of 10 human colorectal specimens were compared with those of the corresponding adjacent normal mucosa. Using asialofetuin as an acceptor we found, in tumor tissues of 9 out of 10 patients, an increased sialyltransferase activity towards the N‐linked chains as determined upon peptide‐N4‐(N‐acetyl‐β‐glucosaminyl)aspara‐gine amidase (PNGase) treatment. On the contrary, the activity towards the O‐linked chains was not significantly changed. When the specificity of the sialyltransferase acting on N‐linked chains was investigated by using N‐acetyl‐lactosamine (Galβ1,4GlcNAc) as an acceptor, we found that the α2,6 sialyltransferase activity expressed by both normal and tumor colorectal tissues was far higher than the α2,3‐activity and that α2,6 was the only sialyltransferase activity increased in tumor tissues. Kinetic analysis revealed that normal and tumor α2,6 sialyltransferases have the same apparent Km for the acceptor substrate (469 and 465 μ,M), but normal enzyme has a higher Km for CMP‐NeuAc (303 μM) than the tumor enzyme (50 μM). The higher affinity of tumor enzyme for the nucleotide‐sugar might partially explain its increased activity in tumor tissues. In addition, tumor tissues contain a lower amount of sialic acid despite the increase in α2,6 sialyltransferase activity.
Sera of children with renal tumours contain low‐molecular‐mass hyaluronic acid
Authors: Kumar S. , West D. C. , Ponting J. M. , Gattamaneni H. R.
Published: February 2007

The molecular mass of hyaluronic acid (HA) rather than its serum concentration alone may be a hallmark of certain types of malignancy. A radiometric assay was used to measure HA levels in 35 children with renal tumours [33 Wilms' tumours and 2 bone metastasizing renal tumours of childhood (BMRTC)] and 20 normal siblings of children with cancer. The HA level in the sera of normal children was barely detectable and had a molecular mass of 1–5 × 105. In both Wilms' and BMRTC patients, very high levels of HA were found in preoperative serum samples; these fell dramatically following surgical excision of the tumours. A novel finding of our study was the presence of low‐molecular‐mass HA (similar to the angiogenic fragments of HA) in the sera of BMRTC patients. In contrast, high‐molecular‐mass HA (which is not angiogenic) was found in the sera of Wilms' patients (2 × 106 kDa). Following surgery in BMRTC patients, not only did serum HA levels fall to a value within normal ranges, but also the HA which remained was of high molecular mass.
Insulin receptor expression in burkitt lymphoma cell lines
Authors: Newman Julie D. , Harrison Leonard C.
Published: February 2007

The specific binding of insulin to 7 different Burkitt lymphoma cell lines containing chromosomal translocations t(8; 14), t(8;2) and t(8;22) was markedly decreased when compared to binding to lymphoblastoid cells of normal karyotype derived from Burkitt lymphoma patients or the human IM‐9 lymphoblastoid line. The number of insulin‐binding sites on intact Burkitt cells was decreased by >90% compared to lymphoblastoid cells, with no change in affinity. This decrease in binding was paralleled by reduced amounts of insulin receptor α (Mr 130,000) and β (Mr 95,000) subunits detected by cell‐surface‐labelling and insulin receptor mRNA transcripts, indicating that transcription of receptor mRNA is decreased in Burkitt cells compared to lymphoblastoid cells and/or that receptor mRNA is less stable. Burkitt cells displayed negligible insulin‐stimulated β subunit auto‐phosphorylation, which could reflect either their decreased number of receptors or a defect in signal transduction. Structural analysis also revealed that the Burkitt cells had an increase in a precursor form (Mr210,000) of the receptor, suggesting that decreased expression of the receptor may be associated with defective processing. Four Burkitt cell lines with t(8;l4) also had reductions of 45–100% in expression of class‐l major histocompatibility (MHC) antigens. The expression of insulin receptors in both Burkitt and lymphoblastoid cells correlated with the expression of class‐l MHC antigens. There was also an inverse correlation between the expression of c‐myc and both insulin receptors and class‐l MHC antigens. As the insulin receptor is absent on resting B cells and is induced after cell activation, the decrease in receptor expression on Burkitt cells may reflect their less activated phenotype compared to lymphoblastoid cells.
Discrepancy in the abilities of lymphokines and bacteria to mediate tumor protection in vivo and/or tumoricidal activity by macrophages in vitro
Authors: Keller R. , Keist R. , Schwendener R. A.
Published: February 2007

In the present study, the ability of lymphokines (MAF and IFNγ) and microbial agents (CP and LM) to induce and maintain tumoricidal activity in BMMP in vitro and to enhance local resistance to the DA rat D‐12 ascites tumor in vivo was assessed comparatively. Under standard conditions in vitro, i.e., when present during the 24‐hr induction and the 36‐hr effector phase, both lymphokines and microbes were similarly potent for eliciting tumoricidal activity in BMMP. When the activating agents were present only during the induction phase, and effector cells were interacted with tumor targets after a 24‐hr interval, clear differences were observed: BMMP which had been incubated with lymphokines had largely if not completely lost their tumoricidal activity; in contrast, BMMP which had been incubated with microbes still manifested considerable tumoricidal activity. Experiments performed to assess the in vivo significance of the discrepancy established in vitro have shown that resistance to the D‐12 ascites tumor was markedly enhanced after local inoculation of microbes but was affected very little or not at all by soluble lymphokines. The causes responsible for the discrepancy in the antitumor potential of lymphokines vs. microbes are probably manifold. Extensive attempts to improve the efficacy of lymphokines by repeated administration or by incorporation into liposomes were not successful.
Integrin‐receptor‐mediated differentiation and growth inhibition are enhanced by transforming growth factor‐β in colorectal tumour cells grown in collagen gel
Authors: Pignatelli Massimo , Bodmer Walter F.
Published: February 2007

We have studied the role of cell‐matrix interactions and the modulating effect on these of transforming growth factor‐βs (TGF‐βs) in controlling differentiation and proliferation in a series of human colorectal carcinoma cell lines. Two (SW1222 and SW480) out of 7 cell lines specifically bound type‐1 collagen, via integrin‐like (SW1222) and non‐integrin‐like (SW480) collagen receptors. Binding of these receptors may be responsible for regulating the degree of epithelial differentiation of the cells when grown in a 3‐dimensional (3D) collagen gel. We have also shown that TGF‐βs enhance the binding of SW1222 cells to collagen and that this is accompanied by greatly increased crypt‐like glandular differentiation and inhibition of cell proliferation. Inhibition of cell proliferation was only seen when cells were grown in 3D collagen gel and were thus expressing a fully differentiated phenotype. The enhanced collagen binding induced by TGF‐βs was partially inhibited by an Arg‐Gly‐Asp (RGD)‐containing peptide which is a cell recognition signal for collagen binding. This suggests that TGF‐βs mediate their effects on differentiation of SW1222 cells specifically by modulating the expression of the integrin‐like collagen receptor. The other colorectal carcinoma cell lines which lack this integrin‐like receptor either failed to bind collagen or, in the case of SW480 binding, exhibited differentiation and proliferation which were not affected by TGF‐βs. This suggests that cell responsiveness to TGF‐βs may depend, at least in part, upon the cell‐matrix interaction.
Localization and imaging of radiolabelled monoclonal antibody against squamous‐cell carcinoma of the head and neck in tumor‐bearing nude mice
Authors: Quak J. J. , Balm A. J. M. , Brakkee J. G. P. , Scheper R. J. , Haisma H. J. , Braakhuis B. J. M. , Meijer C. J. L. M. , Snow G. B.
Published: February 2007

Nude mice carrying human squamous‐cell carcinoma xenografts were given i.v. injections of radiolabelled monoclonal antibodies (MAbs). MAb E 48, which reacts with squamous‐cell carcinomas, was labelled with 131l,while a second control MAb of similar immunoglobulin subclass was labelled with 125l. Both antibodies were injected simultaneously, then the mice were scanned with a gamma camera or their tissues were removed and antibody uptake was calculated as a percentage of the injected dose. Uptake of E 48 reached a peak value of 16%/g on day 3, while uptake of the control antibody was less than 1.8%/g. By 24 hr after injection tumor could be visualized without subtraction techniques. At days 3 and 7, only xenografts were visible on imaging. These findings suggest that E 48 is capable of high specificity in targeting isotopes to squamous‐cell carcinomas in an experimental setting.
Doxorubicin resistance in P388 leukemia—evidence for reduced drug influx
Authors: Ramu Avner , Pollard Harvey B. , Rosario Luis M.
Published: February 2007

Multi‐drug resistance (MDR) in cancer cells is associated with reduced drug accumulation. Although intensively studied, the mechanism of this process remains ill‐defined. We have now developed a new, rapid and quantitative method of measuring uptake of doxorubicin by these cells, in which the fluorescence of accumulated drug is rapidly quenched by DNA in the cell nucleus. Pre‐treatment of cells with deoxyribonuclease eliminates DNA from non‐viable, permeable cells, and this obviates the spurious fluorescence quenching that made previous application of this technique useless. Our data strongly suggest that the drug passively diffuses into cells. The rate of this diffusion into drug‐resistant cells is considerably lower than that found in drug‐sensitive cells. The ratio of the rates of drug entry in these cell types could fully account for the differences between the cell lines in doxorubicin growth‐inhibitory activity. In these experiments no evidence for the previously proposed active efflux mechanism was found in either cell line.
Differential modulation by tumor necrosis factor and immune interferon of HLA class‐II antigens expressed by melanoma cells
Authors: Maio Michele , Gulwani Beena , Morgano Anna , Ferrone Soldano
Published: February 2007

Tumor necrosis factor (TNF‐α) was compared to immune interferon (IFN‐γ) for its ability to modulate the expression and shedding of HLA antigens, of intercellular adhesion molecule I (ICAM I) and of high‐molecular‐weight melanomaassociated antigen (HMW MAA) by a panel of melanoma cell lines. The latter included the melanoma cell line MeWo and its metastatic variant MeM 50–10, which display differential susceptibility to modulation of HLA class‐ll antigens by IFN‐γ and the cell lines SK‐MEL‐93‐DX‐2 and SK‐MEL‐93‐DX‐3, which originated from anatomically distinct metastases in patient DX. TNF‐α enhanced the expression of HLA class‐l antigens on all 7 melanoma cell lines tested, although to a lower extent than IFN‐γ and the combination of IFN‐γ and TNF‐α. TNF‐α displayed a differential effect on the expression of HLA class‐ll antigens by the 7 melanoma cell lines: it enhanced it on 3 out of the 4 cell lines with constitutive expression of HLA class‐ll antigens and induced them on I of 3 cell lines without detectable expression of these antigens. The effects of IFN‐γ were different since it enhanced HLA class‐ll antigens on the 4 cell lines with constitutive expression of these antigens and induced them on 2 out of the remaining 3 lines. Interestingly, both TNF‐α and IFN‐γ enhanced the expression of HLA class‐ll antigens by SK‐MEL‐93‐DX‐3 cells. On the other hand only TNF‐α induced the expression of HLA class‐ll antigens by MeWo cells and only IFN‐γ induced such expression by MeM 50–10 cells and by SK‐MEL‐93‐DX‐2 cells. The effect of the combination of TNF‐α and IFN‐γ was similar to that of the individual cytokines. Both TNF‐α and IFN‐γ displayed a differential effect on the expression of the gene products of the HLA‐D region by the melanoma cell lines. Northern blot analysis with HLA‐DR β‐, DQ β‐ and DP β‐specific probes suggests that the modulation of HLA class‐ll antigens by both cytokines reflects transcriptional and posttranscriptional events. TNF‐α enhanced the expression of ICAM‐I on all the melanoma cell lines, although to a lower extent than IFN‐γ and the combination of IFN‐γ and TNF‐α. Lastly, neither TNF‐α nor IFN‐γ displayed a marked effect on the expression of HMW‐MAA by the melanoma cell lines tested.
Neural cell adhesion molecule (NCAM) is the antigen recognized by monoclonal antibodies of similar specificity in small‐cell lung carcinoma and neuroblastoma
Authors: Patel K. , Moore S. E. , Dickson G. , Rossell R. J. , Beverley P. C. , Kemshead J. T. , Walsh F. S.
Published: February 2007

We describe reagents from 2 workshops which had been identified as recognizing the same or very similar antigens based on their tissue reactivity. Examination of their tissue specificity led us to the conclusion that this was similar to the expression of the neural cell adhesion molecule (NCAM). We also describe the use of a transfection‐based assay to show that these reagents do recognize NCAM. 3T3 cells were trans‐fected with a full‐length clone of human NCAM. Indirect immunofluorescence studies showed binding of all related antibodies to the transfectants, but not to the control 3T3 cells. In addition, biochemical analysis using certain antibodies in the cluster confirm that they detect NCAM in the transfectants. Our study shows the benefits of using workshops to compare monoclonal antibodies and a molecular approach to define the antigens recognized by such reagents.
Increase in murine monoclonal‐antibody‐defined urinary antigens in patients with bladder cancer and benign urogenital disease
Authors: Masuko Takashi , Sugahara Kunio , Kamiya Takashi , Hashimoto Yoshiyuki
Published: February 2007

Monoclonal antibodies (MAbs) were obtained from hybrid‐oma clones established by cell fusion between P3X63Ag8.653 mouse myeloma cells and spleen cells of mice or rats hyper‐immunized against human bladder cancer tissue or BC47 rat bladder cancer cells. RBS‐31 and RBS‐85 mouse MAbs and RBA‐1 rat MAb were raised against BC47 cells and HBP‐1 MAb was raised against human bladder cancer tissues. Urinary antigens detected by these MAbs were quantitatively assayed by means of ELISA using 50 μ1 of 1:2 diluted urine samples. The cut‐off value of the assay was set up as the mean + 4 × SD of the mean using data from the healthy individual urine samples. The reactivity of all healthy control urine samples were under the cut‐off value (negative). By contrast, urine from bladder cancer patients reacted positively with the RBS‐31 MAb at 72%, with the RBS‐85 MAb at 63%, with the RBA‐1 MAb at 51% and with the HBP‐1 MAb at 35%. The urine samples from some patients with renal calculi, acute cystitis or complicated urinary tract infections showed only a weak reactivity with our MAbs. As for extra‐bladder cancers, some patients with renal, renal pelvis, prostate or ureter cancer, but no patients with esophageal, gastric, colon or liver cancer or leukemia, had reactive urinary antigens.
Diet and pharyngeal cancer
Authors: Rossing Mary Anne , Vaughan Thomas L. , McKnight Barbara
Published: February 2007

A population‐based case‐control study was conducted to examine the effect of ingestion of vitamin C, carotenoids and retinol on risk of pharyngeal cancer. Data were available from 166 cases of pharyngeal cancer or their next‐of‐kin, and from 547 controls similar in age and sex to the cases. Odds ratios (ORs) relating consumption of vitamin C, carotenoids and retinol from foods and vitamins C and A from supplements to risk of pharyngeal cancer were calculated using multiple logistic regression analysis. After adjustment for smoking and alcohol consumption, a significant increase in risk associated with low intake of vitamin C from foods was observed. Compared to the highest quartile, the OR for the lowest quartile of intake was 2.5 (95% confidence interval, 1.5‐4.2). No overall effect of dietary carotenoid or retinol consumption was noted after adjustment for smoking and alcohol. Decreasing use of either vitamin C or vitamin A supplements was associated with increasing cancer risk among the case group as a whole. However, the effect of vitamin C supplement use was substantially lower when next‐of‐kin respondents were excluded from analysis. Also, the OR for use of vitamin A supplements is based on a very small number of cases reporting use, and must be viewed with caution. The results of our study suggest that intake of vitamin C may be protective against pharyngeal cancer, and are consistent with the results of previous studies which reported a decreased risk of pharyngeal cancer associated with intake of fruits and vegetables.
Tobacco and bladder cancer in males: Increased risk for inhalers and smokers of black tobacco
Authors: Clavel J. , Cordier S. , Boccon‐Gibod L. , Hemon D.
Published: February 2007

Relationships between risk of bladder cancer and tobacco smoking were assessed from a hospital‐based case‐control study conducted in France from 1984 to 1987. Smoking history was analyzed for 954 male patients (477 cases and 477 controls). The odds ratio (OR) of bladder cancer was estimated at 3.95 for all smokers vs. non‐smokers. The risk increased with duration of smoking and with average daily cigarette consumption, but there was a significant interaction between these 2 parameters, since the risk only increased with average daily consumption when the duration exceeded 20 years. Black tobacco consumption and inhaling were both found to double the risk when analyzed separately, but their respective effects appeared to interact, and an elevated risk for smokers of black tobacco was only observed among inhalers. Smokers of black and blond tobacco also differed in the way in which the risk evolved with time after cessation of smoking. The OR decreased faster after cessation of smoking among smokers of black tobacco than among smokers of blond tobacco, but the residual risk was higher 15 years after cessation among the former than among the latter.
A case‐control study of gastric cancer and diet in Italy
Authors: Buiatti Eva , Palli Domenico , Decarli Adriano , Amadori Dino , Avellini Claudio , Bianchi Simonetta , Biserni Roberta , Cipriani Francesco , Cocco Pierluigi , Giacosa Attilio , Marubini Ettore , Puntoni Riccardo , Vindigni Carla , Fraumeni Joseph , Blot William
Published: February 2007

A case‐control study was conducted in high‐ and low‐risk areas of Italy to evaluate reasons for the striking geographic variation in gastric cancer (GC) mortality within the country. Personal interviews with 1,016 histologically confirmed GC cases and 1,159 population controls of similar age and sex revealed that the patients were more often of lower social class and resident in rural areas and more frequently reported a familial history of gastric (but not other) cancer. After adjusting for these effects, case‐control differences were found for several dietary variables, assessed by asking about the usual frequency of consumption of 146 food items and beverages. A significant trend of increasing GC risk was found with increasing consumption of traditional soups, meat, salted/ dried fish and a combination of cold cuts and seasoned cheeses. The habit of adding salt and the preference for salty foods were associated with elevated GC risk, while more frequently storing foods in the refrigerator, the availability of a freezer and use of frozen foods lowered risk. Reduced GC risk were associated with increasing intake of raw vegetables, fresh fruit and citrus fruits. Lowered risk was also related to consumption of spices, olive oil and garlic. Neither cigarette smoking nor alcoholic beverage drinking were significantly related to GC risk. The case‐control differences tended to be consistent across geographic areas, despite marked regional variations in intake levels of certain foods. The high‐risk areas tended to show higher consumption of food associated with elevated risk (traditional soups, cold cuts) and lower consumption of foods associated with reduced risks (raw vegetables, citrus fruits, garlic). Our findings indicate that dietary factors contribute to the regional variation of stomach cancer occurrence in Italy, and offer clues for further etiologic and prevention research.
Presence on a human melanoma of multiple antigens recognized by autologous CTL
Authors: Van Eynde B. Den , Hainaut P. , Hérin M. , Knuth A. , Lemoine C. , Weynants P. , Van Bruggen P. Der , Fauchet R. , Boon T.
Published: February 2007

We derived from blood lymphocytes of a melanoma patient a large number of cytolytic T‐cell clones directed against a cell line of the autologous tumor. Three distinct groups of antigens were recognized by these CTL on the autologous melanoma cells: group A consisted of stable antigens present on all sublines, whereas antigens B and C appeared unstable and were expressed by distinct sublines. In vitro immunoselec‐tions with various anti‐A CTL clones were applied to the melanoma cells and variants resistant to 3 different CTL clones were obtained. These variants remained sensitive to other anti‐A CTL clones, indicating that group A comprises at least 4 different antigens (D, E, F and A). From a total of 76 CTL clones obtained from lymphocytes collected from the patient at various times, we found that 45 were anti‐B, 17 were anti‐C, 2 were anti‐D, 9 were anti‐E, 2 were anti‐F and I was anti‐A′. It is therefore likely that the 6 antigens identified by these CTL clones represent all or nearly all the transplantation antigens recognized by autologous CTL on this human melanoma.
Coexistence of delta sleep‐inducing peptide and serotonin in midgut carcinoid tumour cells in vivo and in vitro
Authors: Ahlman H. , Åhlund L. , Nilsson O. , Dahlström A. , Bjartell A. , Ekman R.
Published: February 2007

By immunocytochemistry, delta sleep‐inducing peptide (DSIP) was demonstrated to coexist with serotonin (5‐HT) in a majority of midgut carcinoid tumour cells studied in biopsies and long‐term cell cultures. Tumour cell colonies were characterized ultrastructurally and by confocal laser microscopy. The cultures produced several DSIP‐like peptides chromato‐graphically separated from culture media. DSIP has not yet proved to be a useful tumour marker clinically. Provocation with pentagastrin in patients with midgut carcinoid syndrome resulted in increased peripheral levels of 5HT, but not of DSIP.
Epidermal growth factor responsiveness of a new human neuroblastoma cell line
Authors: Suardet L. , Gross N. , Gaide A.‐C. , Beck D. , Eliason J. F.
Published: February 2007

A human neuroblastoma cell line, CA‐2E, has been established from a bone‐marrow aspirate of a 16‐month‐old boy with progressive disease. The karyotype and antigen pheno‐type of the cells correspond to those of a neuroblastoma. This cell line grows well in liquid cultures supplemented with 5% fetal calf serum; conversely, colony formation in semi‐solid medium by cells from early passages is dependent upon exogenous EGF. With time in continuous culture, the cloning efficiency in the absence of EGF increases, but the line remains sensitive to EGF, as evidenced by an enhancement of the number and size of colonies. A relative dependence upon EGF in liquid cultures has also been clearly demonstrated by limiting the concentration of serum. Long‐term (over 2 weeks) treatment with EGF results in a decreased rate of proliferation, a decreased proportion of clonogenic cells, and the appearance of flat, epithelial‐type cells. In some experiments, EGF also has a remarkable effect in inducing neurite outgrowth and process branching. Our results suggest that EGF may have both proliferation‐ and differentiation‐inducing effects on this neuroblastoma cell line. We have also shown that EGF induces increased proliferation in 7 out of 8 other human neuroblastoma cell lines. Functional response of neuroblastoma cells to EGF appears to be a general phenomenon which may be related to a block in the normal maturation pathway of the neural crest cells from which this tumor originates.
Effect of ethanol on hepatocarcinogenesis initiated in rats with 3′‐methyl‐4‐dimethylaminoazobenzene in the absence of liver injuries
Authors: Yanagi S. , Yamashita M. , Hiasa Y. , Kamiya T.
Published: February 2007

In this study special care was taken to discriminate between the direct effect of ethanol on hepatocarcinogenesis and secondary effects such as choline deficiency or fatty liver. Rats were divided into 2 groups, D and N. Group D was initiated using 3′‐Me‐DAB, while the control group N was not initiated. Groups N and D were divided into 4 sub‐groups. Each subgroup was given, in the drinking water, one of the following ethanol solutions: 0, 5, 10 or 15% for 45 weeks. Liver tumors were induced only in D groups. Evidence obtained indicates that: (a) in the N group, ethanol did not cause any apparent disorders in histology and lipid metabolism, and (b) in the D group no significant differences were observed in the incidence of HCCs and other liver lesions. Ethanol thus does not appear to enhance hepatocarcinogenesis, at least in the absence of liver injury.