bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of monoclonal antibody 3H‐1 reactivity with squamous‐cell head‐and‐neck cancers
Authors: Kearsley John H. , Leonard J. Helen , Takahashi Hiroyuki , Battistutta Diana , Parsons Peter G. , Moss Denis J. 
Published: February 2007

AbstractWe report the reactivity of a novel murine IgM monoclonal antibody (MAb), 3H‐1, in formalin‐fixed tissue from a series of 44 patients with squamous‐cell cancers (SCCs) of the upper aerodigestive tract. The antigen detected by 3H‐1 MAb is not expressed in simple squamous epithelia and only rarely in non‐squamous malignancies. The following staining patterns were found to be associated with a progressively unfavourable prognosis: membranous, diffuse cytoplasmic and focal cytoplasmic/nil staining. There were no statistically‐significant associations between focal cytoplasmic/nil staining and traditionally used prognostic parameters such as tumour size, nodal involvement or pathologic grade. However, multivariate analyses demonstrated that focal or nil staining was a significant independent prognostic factor for survival (p< 0.001) and was the only significant prognostic factor for relapse (p< 0.001). The converse applied to tumours with predominantly membranous staining (p= 0.004). 3H‐I MAb, with the advantage of relying on the pattern rather than the intensity of staining, makes it possible to identify different cellular phenotypic sub‐populations more accurately than by conventional means, and may ultimately improve our understanding of the mechanisms underlying transformation from a benign or proliferative state to a malignant one.
Case‐control study on stomach cancer in Germany
Authors: Boeing H. , Frentzel‐Beyme R. , Berger M. , Berndt V. , Göres W. , Körner M. , Lohmeier R. , Menarcher A. , Männl H. F. K. , Meinhardt M. , Müller R. , Ostermeier H. , Paul F. , Schwemmle K. , Wagner K. H. , Wahrendorf J. 
Published: February 2007

AbstractA multicentric hospital‐based case‐control study was simultaneously performed in a high‐risk and a low‐risk area for stomach cancer in Germany, 143 patients with incident stomach cancer and 579 controls completing a retrospective interview about life style aspects. Periods of non‐centralized water supply or well water as the only source compared to life‐long central water supply, and preservation of meat by smoking it with spruce compared to no home smoking of meat, were significantly associated with an increased stomach cancer risk. Use of a refrigerator at home for 30 and more years compared to 24 years or less showed an inverse relationship, whereas salt intake estimated by questionnaire showed no relationship to stomach cancer risk. Tobacco smoking was negatively associated with risk for current smokers of cigarettes compared to non‐smokers but was presumably not causally related. After adjustment for other food constituents, only increased vitamin C consumption showed an inverse relation to risk. For food groups, increased consumption of fruit, citrus fruit, cheese and whole‐meal bread were associated with decreased risk. A similar effect was also seen for increased consumption of raw vegetables. Total vegetable consumption was not particularly associated with risk. Increased consumption of processed meat and of beer showed a positive association with risk whereas increased wine and liquor consumption showed a significant negative association. The association of alcoholic beverages with stomach cancer risk may reflect a particular life style rather than being causally related to risk.
The immunoscintigraphic use of Tc‐99m‐labelled monoclonal anti‐CEA antibodies (BW 431/26) in patients with suspected primary, recurrent and metastatic breast cancer
Authors: Lind Peter , Smola Michael G. , Lechner Peter , Ratschek Manfred , Klima Gert , Költringer Peter , Steindorfer Peter , Eber Otto 
Published: February 2007

AbstractThe discrepancy between serum CEA levels and CEA tissue expression in patients with breast cancer is well known. Whereas immunohistochemistry shows positive CEA expression in 70‐90%, the serum CEA levels are often within the normal range. We performed immunoscintigraphy and SPECT with a Tc‐99m labelled anti‐CEA monoclonal antibody (MAb BW 431/26) in 46 women with suspected breast cancer or recurrence. The results of anti‐CEA immunoscintigraphy, mammography, serum CEA levels and immunohistochemistry were evaluated according to the histology of the tumor. Histology verified breast cancer or recurrence (pT1 [n = 7], pT2 [n = 17], pT3 [n = 3], pT4 [n = 3]) in 30 out of 46 patients; benign breast disease such as fibrocystic disease, fibroadenoma, fatty necrosis or chronic mastitis was responsible for suspicious mammographic findings in 16 patients. Immuno‐SPECT showed 25 true‐positive, 5 false‐negative, 11 true‐negative and 5 false‐positive findings (sensitivity 83%, specificity 69%). Anti‐CEA immuno‐SPECT of 2 patients with bone metastasis showed all lesions previously detected by bone scintigraphy to be CEA‐expressing metastases. In contrast, serum CEA levels were slightly elevated in only 5 out of 30 patients with histologically verified breast cancer (sensitivity 17%). The results of immuno‐histochemistry were surprising; tissue CEA expression could be demonstrated in only 5 patients with breast cancer. According to our experiences with this Tc‐99m labelled anti‐CEA MAb, immuno‐SPECT is a suitable additional method for the diagnosis of breast cancer and especially of recurrence. Pre‐operative serum CEA levels give no support for the differentiation between benign and malignant breast tumors.
Tumor‐promoting activity of epstein‐barr‐ virus‐inducing factor transforming growth factor type beta (EIF/TGF‐β) is due to the induction of irreversible transformation
Authors: Bauer Georg , Götschl Michaela , Höfler Petra 
Published: February 2007

AbstractEBV‐inducing factor/transforming growth factor type beta (EIF/TGF‐β) exhibits tumor‐promoting activity for C3H‐10T1/2 mouse fibroblasts in vitro. Treatment of C3H 10 T 1/2 fibroblasts seeded at low density with initiating doses of UV light, followed by culture in the presence of EIF/TGF‐β leads to the appearance of foci of stably transformed cells that have the potential to grow in soft agar. The promoting effect depends both on the dose of EIF/TGF‐β applied and its continuous presence for 2 to 3 weeks. In addition to its pro‐carcinogenic effect in tumor promotion, EIF/TGF‐β exhibits a strong negative effect on transformed cells surrounded by normal cells, indicating a dual role of EIF/TGF‐β in carcinogenesis. The lack of completely transformed individual cells in the initiated cell population and the negative effect of EIF/TGF‐β on transformed cells in contact with normal cells exclude any possible explanation of the tumor‐promoting effect of EIF/TGF‐β as being the result of a selection process due to the establishment of growth advantages for cells transformed by the initiator. The data, in fact, indicate that tumor promotion by EIF/TGF‐β implies the stable acquisition of distinct qualitative changes by the cells.
Anti‐drug monoclonal antibodies antagonize toxic effect more than anti‐tumor activity of doxorubicin
Authors: Balsari A. , Ménard S. , Colnaghi M. I. , Ghione M. 
Published: February 2007

AbstractMonoclonal antibodies (MAbs) able to bind epitope(s) of drug molecule can interfere with the biologic action of the drug. This is known and already exploited in some instances of practical relevance, as in the reversal of the digoxin effect. Similar antidotal action is exhibited by MAbs reacting with a cytotoxic antibiotic, doxorubicin (DXR), and in such a way as to induce differential neutralization of drug action. Indeed, within certain limits, the cytotoxic action of DXR in vitro as well as in vivo is more effectively neutralized on normal than on tumor cells, with consequent increase in therapeutic index.
Therapeutic efficacy of two‐route chemotherapy using cis‐diamminedichloroplatinum(II) and its antidote, sodium thiosulfate, combined with the angiotensin‐II‐induced hypertension method in a rat uterine tumor
Authors: Kobayashi Hiroaki , Hasuda Keitaro , Taniguchi Shun'Ichiro , Baba Tsuneo 
Published: February 2007

AbstractTo enhance the therapeutic effect of conventional TRC using intra‐arterial (i.a.) DDP plus simultaneous i.v. STS, we combined the AT‐II‐induced hypertension method with TRC and evaluated its efficacy for a rat uterine tumor, using the simulation of intra‐arterial chemotherapy for human uterine tumors. During interruption of arterial blood flow by vascular manipulations, DDP plus AT‐II were injected for 10 min through the abdominal aorta in the direction of the uterus. Then STS was administered i.v. for a further 5 min and all the arterial restrictions were released. This modified TRC using AT‐II showed a much higher anti‐tumor effect than that seen in conventional TRC without AT‐II and was free from DDP‐induced renal damage. On the other hand, severe nephrotoxicity was unavoidable in the rats given the delayed i.v. administration of STS to i.a. DDP alone. The feasibility of post‐administration of STS without obvious nephrotoxicity in modified TRC was explained by transient inhibition of DDP delivery to the kidney during the AT‐II‐induced hypertension. The loss of body weight and the decrease in the number of leukocytes after this therapy were tolerable. Modified TRC showed a higher anti‐tumor effect and a lower nephrotoxicity compared with other treatments, as follows: DDP i.a. with or without AT‐II; i.v. infusion of DDP alone. Such a superior anti‐tumor effect of modified TRC consists of the following 2 factors: (i) the post‐administration of STS leading to the delayed neutralization of DDP at the tumor site; (ii) the selective enhancement of DDP delivery to the tumor tissue during AT‐II‐induced hypertension.
Intra‐thecal treatment of leptomeningeal lymphoma with immunotoxin
Authors: Urch Catherine E. , George Andrew J. T. , Stevenson George T. , Bolognesi Andrea , Stirpe Fiorenzo , Weller Roy , Glennie Martin J. 
Published: February 2007

AbstractAn animal model has been established to investigate the effect of intra‐thecal (i.t.) immunotoxins in the treatment of leptomeningeal metastases of acute lymphoblastic leukaemia (ALL). Direct inoculation of L2C lymphoma cells into the cisterna magna of guinea‐pigs gives rise to a leptomeningeal pattern of growth, similar to that of human ALL, and to a systemic leukaemia which develops in approximately 14 days. In our model the systemic disease could be controlled with cyclophosphamide while the meningeal disease progressed and provided a target for i.t. immunotoxin. The immunotoxin used consisted of an anti‐idiotypic antibody disulphide‐bonded to the ribosome‐inactivating protein saporin. It was highly cytotoxic to L2C cells in vitro, being around 30,000 times more potent than a control immunotoxin at inhibiting protein synthesis. In vivo, the maximum tolerated dose of i.t. immunotoxin was 10 μg. From the rate at which radiolabeled immunotoxins appeared in the plasma following i.t. injection, we were able to estimate that its half‐life in the cerebrospinal fluid (CSF) was between 1° and 2 hr. Intrathecal treatment of guinea‐pigs with immunotoxin I day after inoculation of L,C cells into the cisterna magna had a remarkable therapeutic effect. All guinea‐pigs treated with 0.5 or 5 μg of immunotoxin survived, and remained tumour‐free for more than 100 days after treatment, while control animals given cyclophosphamide alone or an irrelevant immunotoxin had a mean survival time of 28 days. Provided concerns over toxicity can be overcome, these results indicate that i.t. immunotoxins offer an alternative, highly specific form of treatment in leptomeningeal neoplasia.
Expression of dipeptidyl aminopeptidase IV during enterocytic differentiation of human colon cancer (Caco‐2) cells
Authors: Yoshioka Masahiro , Erickson Roger H. , Matsumoto Hisashi , And Elizabeth Gum , Kim Young S. 
Published: February 2007

AbstractThe human colon cancer cell line Caco‐2 spontaneously differentiates to an enterocyte‐like cell after confluence under standard culture conditions. This is characterized by polarization of the cell monolayer with the appearance of tight junctions, a brush border membrane and expression of brush‐border‐membrane‐associated hydrolases. Studies have shown that differentiated Caco‐2 cells express relatively high levels of dipeptidyl aminopeptidase IV (DPP IV) when compared with other enzymes. However, the biochemical mechanisms involved in the expression of DPP IV in differentiated cells are currently unknown. Therefore, the biosynthesis and expression of membrane‐associated DPP IV in undifferentiated (0 day confluent) and differentiated (14 day confluent) Caco‐2 cells were examined. Though levels of DPP IV activity in differentiated cells was 5‐ to 6‐fold higher than undifferentiated cells, there was only a 1.6‐fold difference in the synthetic rate. Post‐translational processing of newly synthesized DPP IV occurred at a slower rate in differentiated cells, though there were no major differences in the type or degree of glycosylation. A comparison of the degradation rates revealed that they were similar with a half‐life of approximately 8 to 10 days. We conclude that the high levels of DPP IV expressed in differentiated Caco‐2 cells is primarily due to an increase in enzyme synthesis. In addition, accumulation of the enzyme is aided by its slow turnover rate.
Selection of monoclonal antibodies which induce internalization and phosphorylation of P185HER2 and growth inhibition of cells with HER2/neu gene amplification
Authors: Tagliabue Elda , Centis Filippo , Campiglio Manuela , Mastroianni Antonio , Martignone Stefania , Pellegrini Rita , Casalini Patrizia , Lanzi Cinzia , Ménard Sylvie , Colnaghi Maria I. 
Published: February 2007

AbstractIn order to obtain further information on the biological role of the HER2/neu oncoprotein monoclonal antibodies (MAbs) were produced against the p185 extracellular domain. To immunize the mice and screen the hybridoma supernatants we selected a lung adenocarcinoma cell line (Calu‐3), which demonstrated an over‐expression of p185HER2 measured as the reactivity with polyclonal rabbit serum to the 14‐amino‐acid carboxy‐terminal‐HER2/neu. Two MAbs, designated MGR2 (IgG,) and MGR3 (IgG2), selected for reactivity on Calu‐3 and negativity on A431 live cells, the reference target cell for EGF receptor expression, were found to immunoprecipitate a 185‐kDa molecule. Immunodepletion experiments with the polyclonal antiserum and cross‐competition experiments indicated that the 2 reagents recognized 2 different epitopes located on the pl85HES2 molecule. One of the 2 MAbs, MGR3, was found to internalize, induce p185HER2 phosphorylation and inhibit tumor cell growth in vitro. These results indicate that MGR3 is directed against a determinant located in the p185HER2 ligand binding site and may compete with the p185HER2 ligand, but is incapable of inducing a complete mitotic signal.
Effects of tyrosine kinase inhibitor, erbstatin, on cell growth and growth‐factor/receptor gene expression in human gastric carcinoma cells
Authors: Takekura Naoki , Yasui Wataru , Kyo Eikai , Yoshida Kazuhiro , Kameda Takashi , Kitadai Yasuhiko , Abe Kaoru , Umezawa Kazuo , Tahara Eiichi 
Published: February 2007

AbstractThe effect of tyrosine kinase inhibitor, erbstatin, on cell growth and mRNA expression of growth‐factor/receptor system was examined in 6 human gastric‐carcinoma cell lines. Erbstatin inhibited both EGF‐induced and serum‐stimulated cell growth of all 6 cell lines (TMK‐1, MKN‐1, −7, −28, −45, −74) in a dose‐dependent manner. 3H‐thymidine incorporation by TMK‐I cells was also suppressed by erbstatin. Erbstatin inhibited protein kinase activity of EGF receptor, p185ERBB2 and pp60c‐src in TMK‐I cells. The expression of mRNA of EGF receptor gene and ERBB‐2 by TMK‐1 cells was not changed by erbstatin treatment, whereas that of c‐src was slightly decreased. Interestingly, erbstatin decreased membrane‐bound TGF‐α precursor as measured by anti‐TGF‐α antibody‐binding assay, although mRNA expression for TGF‐α was not altered by erbstatin. Our findings suggest that erbstatin may act as a growth inhibitor for human gastric‐carcinoma cells and may not only inhibit tyrosine kinase activities but also negatively modulate the post‐transcriptional step of TGF‐α expression.
Indirect immunotargeting of CIS‐PT to human epidermoid carcinoma KB using the avidin‐biotin system
Authors: Schechter B. , Arnon R. , Wilchek M. , Schlessinger J. , Hurwitz E. , Aboud‐Pirak E. , Sela M. 
Published: February 2007

AbstractCis‐diamminedichloroplatinum (II) (cis‐Pt) complexed to a carboxymethyl dextran‐avidin conjugate was targeted to biotin‐monoclonal antibody 108 (b‐MAb108). This MAb recognizes the extracellular domain of the epidermal growth factor receptor (EGF‐R) on human epidermoid carcinoma (KB) cells over‐expressing EGF‐R. Cis‐Pt‐carboxymethyl‐dextran‐avidin (Pt‐dex‐Av) containing 60–90 M cis‐Pt/M avidin was administered 24 hr following b‐MAb108 containing 3–5 M biotin/ M MAb. This treatment was potentially more effective in suppressing the growth of established KB tumor xenografts, or in inhibiting the development of lung metastases in nude mice, than free MAb 108, free drug or MAb 108 followed by drug. Replacing b‐MAb108 by unbiotinylated antibody or by b‐MAb of a different specificity also yielded lower suppressive effects. The sequential administration of Pt‐dex‐Av following b‐MAb was more effective than Introduction, of the Pt‐dex‐Av when already complexed to b‐MAb 108. The results presented in this preliminary investigation suggest that Pt‐dex‐Av is specifically removed from the circulation by b‐MAb 108 concentrated at the tumor site.
Oral contraceptive (OCP) use increases proliferation and decreases oestrogen receptor content of epithelial cells in the normal human breast
Authors: Williams Gerard , Anderson Elizabeth , Howell Anthony , Watson Robert , Covne John , Roberts Stephen A. , Potten Christopher S. 
Published: February 2007

AbstractThe effect of ingestion of oral contraceptives (OCP) on cell proliferation and oestrogen (ER) and progesterone receptor (PR) expression of the epithelial cells of the normal human breast was compared with findings in controls not taking OCPs. Histologically normal breast tissue was removed during operation for fibroadenoma or reduction mammoplasty in 216 women whose mean age was 28.1 ± 8.5 years (±SD range 14–53 years). During natural cycles the mean proportion of cells expressing ER was 3.94 ± 3.71 (% mean ±SD, range 0–20.8, n = 51), while of those expressing PR it was 12.1 ± 7.1% (range 3.0–36.1, n = 47). There was a significant decline in ER during the menstrual cycle [p = <0.001 by multiple linear regression (MLR)], but there was no significant change in the proportion which expressed PR. The mean proportion of proliferating cells (LI) was 2.50 ± 2.42 (range 0–11.5, n = 147). There was a significant increase of LI during the cycle (p = <0.001, MLR) and a significant inverse relationship between LI and ER (r = −0.29, p < 0.01). Use of the OCP significantly reduced the number of cells which expressed ER and increased the LI earlier in the cycle. No effect of OCP use on the number of PR+ cells was detectable. We conclude that significant changes in the proportions of ER+ and proliferating cells occur during natural menstrual cycles. These changes are perturbed by ingestion of OCPs, so that there is greater suppression of ER and a longer period of high proliferation during the menstrual cycle. These results may explain the relationship between OCP use and the possible risk of breast cancer.
Differential expression of isopeptide bonds Nϵ(γ‐glutamyl) lysine in benign and malignant human breast lesions: An immunohistochemical study
Authors: Roch Anne‐Marie , Noel Patrick , Alaoui Said El , Charlot Carole , Quash Gérard 
Published: February 2007

AbstractNϵ(γ‐glutamyl) lysine isopeptide bonds were detected situ in histological sections from benign and malignant human breast tissue using the monoclonal antibody (MAb) 8 ID Ic2. On cryostat sections of fresh‐frozen mammary tissue post‐fixed in acetone, or on paraffin sections also from mammary tissue fixed in Bouin's solution, the MAb reacted preferentially with glandular epithelial cells and staining was restricted to the nuclei. In 41 out of 44 benign lesions examined, staining was strong or moderate, while in 25 out of 33 malignant lesions no staining was observed. In the 8 remaining lesions of this group, staining was positive but weak. The difference in reactivity of this MAb with the 2 types of lesions highly significant (p < 0.0005) according to the χ2 test.
Bispecific monoclonal antibodies directed to CD16 and to a tumor‐associated antigen induce target‐cell lysis by resting NK cells and by a subset of NK clones
Authors: Ferrini Silvano , Prigione Ignazia , Miotti Silvia , Ciccone Ermanno , Cantoni Claudia , Chen Qi , Colnaghi Maria Ines , Moretta Lorenzo 
Published: February 2007

AbstractCD 16 surface antigens represent activatory molecules in CD3–16+ NK cells. In order to target NK cells against relatively NK‐resistant ovarian carcinomas, we used an anti‐CD 16 monoclonal antibody (MAb) (VD4), together with an anti‐ovarian carcinoma‐associated antigen (MOV19), to construct biMAbs. To this end, hybrid hybridomas were generated by fusing a TK‐deficient VD4 hybridoma mutant with a HGPRT‐deficient MOV19 hybrid. Supernatants from hybrid hybridomas that had been selected in HAT medium were screened for their ability to induce a CD3–16+ NK clone to lyse an MOV19+ ovarian carcinoma cell line in a 4‐hr 31Cr‐release assay. The NMB.45 hybrid hybridoma secreted a biMAb which triggered lysis of MOV19+ but not of MOV19‐target cells. Some degree of target cell lysis was also observed with MOV19 MAb (due to ADCC mechanisms), while the VD4 MAb was ineffective. HPLC fractionation of MAbs secreted by the hybrid hybridoma made it possible to identify 4 different peaks, one of which appeared to contain functional biMAb molecules. HPLC‐purified biMAb (100 ng/ml) induced resting PBL to lyse the “NK‐resistant” IGROVI ovarian carcinoma cell line. Fresh MOV19+ tumor cells were also lysed, although with lower efficiency. When IL‐2‐activated lymphocytes were used as a source of effectors, biMAb caused only minor increases in the IL‐2‐induced cytolytic activity. Further analyses of the effect of biMAb were performed at the clonal level. Among CD3–16+ NK cell clones, a clear enhancing effect could be observed only in GL183+ but not in GL183‐clones. In CD3+ cytotoxic clones a triggering effect could be detected in one out of 4 TCR γ/δ+ clones but not in TCR α/β+ clones.
Isolation and partial characterization of a soluble oncofetal antigen from murine and human amniotic fluids
Authors: Barsoum Adel L. , Coggin Joseph H. 
Published: February 2007

AbstractA soluble (cell‐free) oncofetal antigen (OFA) was detected in murine and human amniotic fluids by immunostaining with the murine monoclonal antibody (MAb 115) produced by syngeneic immunization with mid‐gestational mouse fetal cells. OFA was purified from the amniotic fluids by ammonium sulfate precipitation at 30–70% saturation, followed by successive gel chromatography of the OFA‐containing fraction on Sephacryl‐S300 HR, Q‐and S‐Sepharoses and lentil lectin agarose. The fraction eluted from the lentil lectin column gave a single band on SDS‐PAGE of the same molecular weight as the membrane‐bound OFA found on both fetal and tumor tissues of humans and several rodents. Both soluble and membrane‐bound OFAs share several chemical characteristics, including binding to lentil lectin and wheat‐germ agglutlnin, molecular weight (44 kDa) and pI (6.8). Mild Periodate oxidation of OFA did not affect its binding to MAb 115 in an enzyme‐linked immunosorbent assay, indicating that the reactive epitope is a peptide.