bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human T‐cell recognition of epstein‐barr virus‐induced replication antigen complexes
Authors: Pothen Susan , Richert John R. , Pearson Gary R. 
Published: February 2007

AbstractCellular immune responses to Epstein‐Barr Virus (EBV)‐associated antigens play an important role in the control of EBV‐immortalized B lymphocytes. The nature of the antigens that serve as targets for these responses remains largely unknown. The purpose of the experiments reported here was to determine if virus‐replication‐associated antigens might function as targets for T‐cell immunity with the emphasis on EBV‐induced early antigen (EA) complex. Activated T‐cell populations directed against this group of antigens would theoretically be effective in controlling the production of new virus progeny. Our results demonstrate that polypeptides associated with the EA complex do, in fact, induce the proliferation of memory T‐cells from EBV‐infected individuals irrespective of their serological status to the EA complex. The major polypeptide associated with the diffuse component of EA (EA‐D) was notably effective in inducing a strong proliferative T‐cell response. Cell lines established from EBV‐infected individuals following continuous exposure to either p17 or p50 components of the EA complex over a 10‐ to 12‐week period were composed primarily of CD4‐positive T‐cells, although CD8‐positive cells also persisted for up to 9 weeks in culture. The data suggest that components of the EA complex might function as important target antigens in the immunosurveillance of EBV‐infected cells.
Contribution of glutathione and glutathione‐dependent enzymes in the reversal of adriamycin resistance in colon carcinoma cell lines
Authors: Lai Gi‐Ming , Moscow Jeffrey A. , Alvarez Manuel G. , Fojo Antonio T. , Bates Susan E. 
Published: February 2007

AbstractFour human colon cancer cell lines (SW620, LS 180, DLD‐I, and HCT‐15) and sub‐lines isolated in vitro by selection with Adriamycin were studied for reversal of intrinsic and acquired Adriamycin resistance, using buthionine sulfoximine (BSO) to deplete cellular glutathione alone and in combination with the P‐glycoprotein antagonist verapamil. GSH levels varied among the parental cell lines but did not increase with resistance. In the parental SW620, DLD‐1 and HCT‐15 and their drugresistant derivatives, there was no relation between the effect of the glutathione‐depleting agent BSO, the mRNA expression of both selenium‐dependent glutathione peroxidase (GPx) and glutathione S‐transferase pi (GSTπ), bulk glutathione S‐trans‐ferase (GST) activity, and the degree of resistance. However, in LS 180 and its derivative sub‐lines, which do not principally rely on P‐glycoprotein (Pgp) for Adriamycin resistance, treatment with BSO demonstrated a relatively diminished GSH depletion and enhanced recovery. In comparison with the other acquired cell lines, BSO specifically reversed acquired resistance in the LS 180 Adriamycin‐resistant subline (LS 180 Ad 150) after short‐term drug exposure. Furthermore, the LS 180 Ad 150 cells demonstrated an increase in both GPx and GSTπ mRNA expression. These observations suggest that glutathione‐mediated detoxification of Adriamycin may play a role in the resistance of this sub‐line. Verapamil enhanced Adriamycin cytotoxicity 1.2‐ to 12‐fold in the intrinsically resistant cells and as much as 15‐fold in cell lines with acquired resistance. Combination of BSO with verapamil resulted in additive, but not synergistic, reversal of resistance. The results underscore the complex nature of Adriamycin resistance, and suggest a role for drug‐resistance‐modulating agents in the treatment of colon carcinoma.
Interferon‐gamma interrupts autocrine growth mediated by endogenous interleukin‐6 in renal‐cell carcinoma
Authors: Gruss H.‐J. , Brach M. A. , Mertelsmann R. H. , Herrmann F. 
Published: February 2007

AbstractCells of the renal‐cell carcinoma line ACHN constitutively produce IL‐6, express the IL‐6 receptor and use IL‐6 in an autocrine fashion to augment their growth. Growth arrest of ACHN cells can be achieved by exposure of cells to neutralizing monoclonal antibody (MAb) to recombinant human (rh) IL‐6. Treatment of ACHN cells with rh IFN‐γ also leads to inhibition of proliferation of these cells in a dose‐dependent manner, that can be reversed by exogenous rh IL‐6, while IFN‐α, IL‐2, IL‐4 and vinblastine or 17‐β‐estradiol has no effect on growth (3H‐thymidine uptake) of ACHN cells and IL‐6 expression. Studies on the mechanism of action of IFN‐γ revealed that IFN‐γ was acting by inhibiting the autocrine IL‐6‐mediated loop generated by ACHN.
Cell proliferation and vascularization in human breast carcinomas
Authors: Monschke F. , Müller W.‐U. , Winkler U. , Streffer C. 
Published: February 2007

AbstractCell proliferation and vascularization were studied in 10 human breast carcinomas by an immunoenzyme technique. The monoclonal antibody (MAb) Ki‐67 was used as a marker for proliferating cells and a polyclonal antibody directed against human von‐Willebrand factor to identify blood vessels. The proportion of Ki‐67‐labelled cells varied from 1% to 20%, the number of small blood vessels from 4.4/mm2 to 57.6/mm2. Within single histological sections of individual tumours the percentage of proliferating cells was not related to the number of small blood vessels. However, after evaluation of 5 sections of each tumour, the average values showed that tumours with high grade of vascularization had a higher percentage of Ki‐67‐positive cells than poorly vascularized samples. The influence of vascular density on cell proliferation was investigated in a selected area of one of the tumours (in 2‐dimensions) and with regard to the over‐ and underlying sections (in 3‐dimensions). After 2‐dimensional evaluation, distances from proliferating cells to the closest blood vessel between 10 and 390 μm were observed, and after 3‐dimensional evaluation none of the proliferating cells measured was located more than 130 μm away from the closest vessel.
Human allogeneic melanoma‐reactive T‐helper lymphocyte clones: Functional analysis of lymphocyte‐melanoma interactions
Authors: Radrizzani M. , Benedetti B. , Castelli C. , Longo A. , Ferrara G. B. , Herlyn M. , Parmiani G. , Fossati G. 
Published: February 2007

AbstractLymphocyte clones were isolated from CD4+ peripheral‐blood lymphocytes (PBL) of melanoma (Me) patient 9923 (HLA‐DR7, DQw2, w6), co‐cultured for 30 days with autologous accessory cells, allogeneic Me (Me 1811) (HLA‐DR7, DQwl, w2), IL‐1 β (2 U/ml) and IL‐2 (15 IU/ml). The 55 clones tested displayed a CD3+, CD4+, CD8−, T‐cell receptor (TCR) cu/p+, y/8‐ phenotype. Twenty clones were assayed for proliferation the presence of Me 1811 and B‐lymphoblastoid cell line (LCL) 1811, both expressing HLA‐class‐1 and ‐11 (DR7 and DQw2 shared with patient 9923), intercellular adhesion molecule‐I (ICAM‐ 1) and lymphocyte‐function‐associated antigen‐3 (LFA‐3) molecules. Eight clones were found t o be reactive to Me 1811 but not to LCL 1811. Specificity analysis of these 8 clones revealed that each of them proliferated only to Me 1811, not to other 14 Me and 12 different LCL, suggesting recognition of melanoma‐associated antigen (MAA) expressed on the stimulating Me. One clone (103) was analyzed in more detail. A wider specificity analysis showed that it reacted to Me 1811 but not to 10 other Me expressing or not HLA‐DR7, 5 normal melanocyte cultures (2 of them typing HLA‐DR7‐positive when exposed to interferon‐γ ‐ IFN‐γ), 4 tumors other than Me and 20 different LCL. Clones did not show proliferation in the presence of autologous Me cells. Clone proliferation in response to Me 1811 was significantly inhibited by monoclonal antibodies (MAbs) directed to CD3, TCR α/β, TCR β chain V12, CD4 and HLA‐DR. Moreover, following stimulation with Me 1811, clone 103 showed increased surface expression of CD25 (IL‐2 receptor) and CD71 (transferrin receptor) and produced significant amounts of IL‐2 and IFN‐γ. The supernatant taken from co‐culture of clone 103 with Me 1811 augmented the cytotoxicity of PBL 9923 and other allogeneic PBL against K562 and Me 1811. Thus, the lymphocyte clone 103 is a CD4+ Th clone which uses its CD3/TCR α/β complex to recognize an MAA in conjunction with HLA‐DR7. Availability of this type of reagent may prove useful to identify and characterize MAA recognized by lymphocytes.
Cell kinetic analysis of human brain tumors by in situ double labelling with bromodeoxyuridine and iododeoxyuridine
Authors: Hoshino Takao , Ito Satoyuki , Asai Akio , Shibuya Makoto , Prado Michael D. , Dodson Barbara A. , Davis Richard L. , Wilson Charles B. 
Published: February 2007

AbstractFifty‐seven patients with brain tumors (29 gliomas, 23 meningiomas, 5 miscellaneous) received infusions of intravenous iododeoxyuridine (IUdR) and bromodeoxyuridine (BUdR) 1–5 hr apart shortly before tumor removal. Excised tumor specimens were stained sequentially for BUdR and IUdR. The percentage of BUdR‐labelled cells was determined to establish the labelling index (LI), or S‐phase fraction, and the ratio of cells labelled only with IUdR to cells labelled with BUdR or with BUdR and lUdR was determined to calculate the duration of S‐phase (Ts) and the potential doubling time (Tp) of each tumor. The BUdR LIs varied from < 1% to 20%, reflecting the malignancy of each tumor. Despite the difference in LIs, however, Ts was fairly uniform (mean ± so, 8.7 ± 2.0 hr). Tp varied from 2 days to more than 1 month and correlated closely with the BUdR LIs (Tp = 23/LI0.93; r2 = 0.91). Double‐labelling studies with IUdR and BUdR allow the S‐phase fraction, Ts and Tp to be determined from a single biopsy specimen and thus provide more useful information on the growth characteristics of individual tumors than can be obtained by single‐labelling studies with BUdR.
Lack of association between in vitro clonogenic growth of human cervical carcinoma and tumour stage, differentiation, patient age, host cell infiltration or patient survival
Authors: Davidson S. E. , West C. M. L. , Hunter R. D. 
Published: February 2007

AbstractBiopsies from 117 patients with cervical carcinoma were studied using a clonogenic assay to assess in vitro growth. Successful colony growth was achieved in 84 tumours (72%) with a mean colony‐forming efficiency (CFE), based on total viable nucleated cell counts, of 0.18 ± 0.49% (± 1 standard deviation). There was a wide range of values, from 0.003–4.28%, with a coefficient of variation of 272%. The relationship between clinical features of cervical carcinoma and in vitro colony formation was investigated. No significant association was demonstrated between in vitro growth and either clinical stage (r = 0.02), tumour differentiation (r = −0.08) or patient age (r = −0.12). There was no significant difference in tumour grade between the group of tumours which failed to grow in culture and those which grew well (p = 0.70). In addition, there was no correlation between CFE and the degree of macrophage (r = 0.001), lymphocyte (r = 0.12), or granulocyte (r = 0.08) infiltration. There was no significant difference between CFEs of tumours from patients who had died and from those who were alive and well after a minimum of 2 years' follow‐up after radiotherapy (p = 0.51). Ability to form colonies in agar was not associated with a worse prognosis (p = 0.49). Although CFE is an independent biological parameter, our results suggest that, for cervical carcinoma, it is not useful as a univariate prognostic factor.
Apparent fusion of basement membranes in colorectal carcinoma
Authors: Hewitt Robert E. , Powe Desmond G. , Holland Cathrine M. , Gray Trevor , Turner David R. 
Published: February 2007

AbstractPrevious studies on colorectal carcinomas indicate that consistent differences in epithelial basement membrane (EBM) integrity are present between the tumour centre and periphery. We report that within the tumour centre, EBM staining between back‐to‐back (BTB) neoplastic glands (i.e., adjacent glands in direct contact with no intervening connective tissue) generally follows a pattern different from that of EBM staining at the tumour:stromal interface (TSI). Such distinctions are important, since the factors responsible for EBM deficiencies may vary with intra‐tumoural location, as may the prognostic significance of these deficiencies. Analysis of paraffin sections from 130 colorectal carcinoma cases showed that EBM staining between BTB glands is generally weaker and more discontinuous than at the TSI, sometimes appearing as a linear array of immunostained granules on high‐resolution light microscopy. By double‐labelling immunofluorescence analysis of cryostat sections from 30 cases, a decrease in type‐IV collagen:laminin staining intensity ratio was found between BTB glands. Hence, the composition of EBM between BTB glands appears to be abnormal. As much recent evidence indicates that epithelial:mesenchymal interactions play an essential role in EBM formation, the demonstration of immunostained EBM fragments between BTB glands requires an explanation: We suggest that the synthesis of EBM between BTB glands involved previously intervening stromal (mesenchymal) cells, and that EBM fusion and dissolution occur between BTB glands following the displacement of these cells.
Haemopoietic cell kinetics in humans treated with rGM‐CSF
Authors: Lord Brian I. , Gurney Howard , Chang James , Thatcher Nicholas , Crowther Derek , Dexter T. Michael 
Published: February 2007

AbstractWe have investigated the kinetics of myeloid cell proliferation in the marrow of patients with small‐cell lung cancer and treated with 10 daily subcutaneous injections of granulocyte/macrophage colony‐stimulating factor (GM‐CSF). Bone marrow, obtained before and during treatment with the growth factor, was labelled in vitro with tritiated thymidine (3H‐TdR). A 3rd bone‐marrow sample was obtained I hr following an intravenous injection of 3H‐TdR. Subsequent daily blood samples were also collected, and 3H‐TdR labelling was assessed on these and the marrow preparations by autoradiography. GMCSF treatment increased the peripheral granulocytic cells nearly 5‐fold, but this included significant eosinophilia, so that the neutrophilic granulocytes increased only 3.3‐fold. These cells were released from the marrow over a normal time scale, but their peripheral half‐life was about 6 times longer than normal and they were probably functionally defective. Furthermore, significant numbers of immature cells were released from the marrow. Neutrophil production stimulated by GM‐CSF was thus overestimated by measurement of the apparent peripheral granulocytosis. Increased labelling indices and grain counts in the proliferating granulocytic cells of the marrow indicate shortened cell‐cycle times, and the excess granulocyte production appears to be the result of extra amplification divisions in the proliferative compartments.
Stefins and lysosomal cathepsins B, L and D in human breast carcinoma
Authors: Lah Tamara T. , Kokalj‐Kunovar Majda , Štrukelj Borut , Pungerčar Jože , Barlič‐Maganja Darja , Drobnič‐Košorok Marina , Kastelic Lili , Babnik Joža , Golouh Rastko , Turk Vito 
Published: February 2007

AbstractIn the study of 50 matched pairs of breast carcinoma and normal breast tissue, the activities of cysteine proteinases (CPs), cathepsin (Cat) B and Cat L in tumors were increased on average by 18.5‐fold and 52.5‐fold respectively. The differences in activity of cysteine proteinase inhibitors (CPIs) between tumor and control breast tissues was also observed: in approximately two thirds of carcinomas, lowered CPI activity was measured (group‐I patients), while similar or higher tumor CPI activity was measured in the remaining samples (group‐II patients). Relative increases in specific activity of Cat B and Cat L in group I were significantly higher than in group II. In group I more patients with histopathological tumor grade III and negative estrogen (ER) and progesteron receptor (PR) levels were found, but the metastatic involvement of regional lymph nodes was similar in both groups. A 2‐year follow‐up study showed a significant inverse correlation between disease‐free survival and increased Cat L activity, but the differences in group I and group II patients were not significant in this short time interval. In 20 matched pairs of breast carcinoma and normal breast tissue, the mean activity of Cat D was 5.8‐fold higher in tumors compared with controls. The hypothesis that elevated Cat D activity increased CP activity and/or lowered tumor CPI activity due to post‐translational proteolytic modification appeared less likely, since no correlations between corresponding activities were observed. We suggested that lowered CPI might rather reflect changes in transcription of intracellular CPIs, the stefins. Immunoassay and Northern blot analysis showed that the average value of stefin A protein and mRNA content respectively in the majority of investigated breast carcinoma samples were lowered, suggesting the possible value of stefin A in diagnosis and/or prognosis of the disease.
Cancer control programme in india: Opportunities for implementation and evaluation
Authors: Sankaranarayanan R. , Nair M. Krishnan , Mathew Babu , Wesley Remani , Mayadevi S. 
Published: February 2007

AbstractCancer is now being appreciated in India as an emerging public health problem. Approximately 600,000 new cancer cases occur in India every year, and the absolute number of new cancer patients will increase considerably, due to growth in the size of the population and an increase in the proportion of elderly persons due to improved life expectancy following control of communicable diseases. This emerging problem has received the attention of the Government of India, and some state governments within the Indian Federation have formulated National and State Cancer Control Programmes to deal with the situation. In the event of these programmes being implemented, consideration should be given now to measures of evaluation of the activities, as many of the indices, used to monitor programmes in developed countries, such as 15% reduction from peak cancer mortality, or in peak mortality from specific cancers, are not applicable in developing countries like India. Factors such as the pattern of tobacco habits in the community, knowledge, attitude and practice (KAP) patterns regarding cancer in the general population, referral practices, and the national pattern of extent of disease at presentation, gain considerable importance from the evaluation point of view. Our article mainly deals with the sources and the quality of baseline data for such factors and the realistic quantitative goals which could be set for the above factors.
MCF‐7 breast cancer cells grown as multicellular spheroids in vitro: Effect of 17β‐estradiol
Authors: Olea Nicolás , Villalobos Mercedes , De Almodóvar J. Mariano Ruiz , Pedraza Vicente 
Published: February 2007

AbstractTo obtain multicellular spheroids from MCF‐7 human breast cancer cells we adhered to the following procedure: (a) limiting the adherence of cell to the substratum; (b) seeding more than the minimum number of cells; (c) guaranteeing the presence of estrogens in the culture medium. Charcoal‐dextran (CO)‐ treated sera seemed to inhibit spheroid formation. A reduction in the concentration of CD‐human sera (from 10% to 5%) added to phenol‐red‐free medium facilitated progress from cellular aggregates to multicellular spheroids. Once the spheroids became initiated, size increased at a rate that showed a good fit to a Gompertzian equation (A = 0.368 ± 0.067 α = 0.065 ± 0.013, r range = 0.890–0.989). Three different patterns of spheroid morphology and proliferative kinetic were defined: (a) spheroids with diameter < 200 μm had a constant pattern of heterogeneity in the distribution of 3H‐TdR‐labelled cells and in the expression of estrogen receptors; (b) spheroids 250 to 700 μm in diameter showed a decrease in the proportion of 3H‐TdR‐labelled cells accompanying inward progression (50% in the outer shell, less than 10% in a cell layer located at a depth of 150 μm) while, at a depth of 170 μm, of signs of concurrent cellular degeneration and death were apparent; and (c) spheroids with a diameter of > 750 μm showed a crust of viable cells uniformly labelled with thymidine without impairment of the proportion of labelled cells when progressing inward from the spheroid crust. The larger the spheroid volume, the lower its growth fraction and the longer its volume doubling time. The hormone‐dependence of MCF‐7 cells in forming multicellular spheroids represents a unique experimental model for assessing estrogen action on cell organization and proliferation.
Detection of human papillomavirus dna sequences in tongue squamous‐cell carcinoma utilizing the polymerase chain reaction method
Authors: Shindoh Masanobu , Sawada Yukiharu , Kohgo Takao , Amemiya Akira , Fujinaga Kei 
Published: February 2007

AbstractTwenty‐four cases of tongue squamous‐cell carcinoma (SCC) were analyzed for human papillomavirus (HPV) DNAs by the polymerase chain reaction (PCR) method and the dot‐blot hybridization technique. HPV DNAs were detected in 8 cases. One specimen histopathologically diagnosed as poorly differentiated grade‐III SCC contained both HPV‐16 and HPV‐18 DNA, and 7 other cases contained HPV‐16 DNA.
Localized formation of micronuclei in the oral mucosa and tobacco‐specific nitrosamines in the saliva of “reverse” smokers, khaini‐tobacco chewers and gudakhu users
Authors: Stich Hans F. , Parida Bibhuti B. , Brunnemann Klaus D. 
Published: February 2007

Abstract“Reverse”‐cigar smokers (who hold the burning end of cigars within the mouth), dippers (who place a mixture of Khaini‐tobacco and slaked lime into the lower gingival groove) and users of tobacco‐containing toothpaste (gudakhu) in Orissa, India, were examined for precancerous oral lesions, the frequency of micronucleated cells at 3 different intra‐oral sites, and levels of tobacco‐specific nitrosamines (TSNA) in the saliva. Among reverse‐cigar smokers, a high incidence of leukokeratosis nicotina palati, an elevated frequency of micronucleated cells in the palate (2.5% as compared to 0.6% in non‐smokers and non‐chewers of tobacco) and tongue (2.1 %) from which carcinomas preferentially develop, and up to 5890 ppb nitrosonomicotine and up to 1880 ppb N‐nitrosoanatabine in the saliva were found. Among Khaini‐tobacco chewers, the frequency of micronucleated cells was elevated to 2.1 % in the gingival groove, and up to 1580 ng N‐nitrosonornicotine, 690 ng N‐nitrosoanatabine, 90 ng N‐nitrosoanabasine, and 180 ng 4‐(methyl‐N‐nitrosamino)‐I‐(3‐pyridyl)‐1‐butanone per ml of saliva were observed. The localized elevation of the frequency of micronuclei and cancer development is probably due to a synergistic effect of hyperthermia and tobacco‐related carcinogens among reverse‐cigar smokers, and to the close, prolonged contact between the mucosa and tobacco among Khaini‐tobacco/slaked lime dippers. Neither pre‐cancerous lesions nor an elevated frequency of micronuclei were seen in the oral mucosa of users of gudakhu, a tobacco‐containing toothpaste, which may be due to the low amount of TSNA released from the gudakhu and the short exposure time, which is restricted to the period of tooth brushing.