bluuebunny/crossref_metadata_2025_split huggingface dataset:
An idiotypic replica of carcinoembryonic antigen inducing cellular and humoral responses directed against human colorectal tumours
Authors: Durrant L. G. , Denton G. W. L. , Jacobs E. , Mee M. , Moss R. , Austin E. B. , Baldwin R. W. , Hardcastle J. D. , Robins R. A. 
Published: February 2007

AbstractA monoclonal anti‐idiotypic antibody (anti‐Id MAb) 708 (IgG2b), which inhibited the binding of NCRC23 (IgG1) MAb to CEA and prevented radiolabelled CEA from binding to MAb NCRC23, was produced. No recognition of 3 other anti‐CEA antibodies, 3 other IgG1 or 2 IgM MAbs was observed with this anti‐idiotypic antibody. When an immunoblotting technique was used, 708 anti‐Id MAb failed to bind to isolated heavy or light chains of MAb NCRC23, whereas binding was observed with intact antibody. Mouse, rat and human lymphocytes (in vitro) were immunized with 708 anti‐Id MAb and the resultant Ab3 antibodies all inhibited binding of labelled 708 anti‐Id MAb to MAb NCRC23 and also reacted with CEA, showing that 708 anti‐Id MAb induced anti‐CEA antibody responses. Similarly, mice immunized with 708 anti‐Id MAb could be restimulated in vitro with either CEA or tumour cells expressing CEA which induced specific T‐cell proliferative responses. Human tumour‐infiltrating lymphocytes isolated from colorectal tumours or peripheral blood T cells from cancer patients were stimulated in vitro with 708 anti‐Id MAb or an irrelevant IgG2b antibody. Six days later both sets of lymphocytes were restimulated with CEA, and lymphocytes primed to 708 anti‐Id MAb proliferated in response to CEA. These results suggest that 708 anti‐Id MAb can act as an idiotypic replica of CEA and stimulate cellular and humoral anti‐CEA immune responses. It is therefore of great interest as an idiotypic vaccine against colorectal cancer.
Cellular heterogeneity of DNA/total‐protein content in human lung tumors, as determined by flow cytometry
Authors: Teodori L. , Trinca M. L. , Salvati F. , Berettoni L. , Storniello G. , Göhde W. 
Published: February 2007

AbstractWith the aim of distinguishing neoplastic cell sub‐populations of different prognostic and diagnostic significance, dual‐parameter measurements (DNA/protein) have been simultaneously determined in a (256, 256) channel matrix in lung samples derived from 110 patients affected by neoplastic and non‐neoplastic lung diseases. Biparametric analysis demonstrated that cells with abnormally high red fluorescence (i.e., protein content), which is indicative of unbalanced growth, were often observed in malignant tumors as compared with normal lung samples. Furthermore, the dual‐parameter analysis allowed recognition of additional aneuploid tumor‐cell lines, indicating that the frequency of cytometrically determined diploid tumor is lower than that previously described by DNA monoparametric analysis. The recognition of aneuploid sub‐populations by dual‐parameter analysis in clinically and histologically negative one‐parameter flow‐cytometric “diploid” samples assumes important diagnostic value. The results have also shown the presence of multiple protein sub‐populations in clones with the same ploidy value, indicating a higher level of cellular heterogeneity than demonstrated by DNA monoparametric measurements.
Human breast cancer: Concerted role of diet, prolactin and adrenal C19‐Δ5‐steroids in tumorigenesis
Authors: Adams John B. 
Published: February 2007

AbstractThe low incidence of breast cancer in japan disappears within 2 generations in migrant Japanese in the USA. This is of fundamental importance if we are to understand, and perhaps reverse, the high rate seen in Western countries. Diet is the most likely factor involved, and a review of the topic of diet, body mass index, and gain in adult body mass, supports a relationship between these factors and breast‐cancer risk in post‐menopausal, but not pre‐menopausal, women. A direct link between nutritional factors and secretion of the hormones prolactin and dehydroepiandrosterone sulfate is proposed. An estrogen 5‐androstene‐3p, 17p‐diol is formed peripherally from the latter steroid, and in Western women attains a blood concentration at which it is biologically active. Thus diet/fat provides factors, viz., fatty acids, prolactin and estrogen, which in concerted fashion provide a milieu conducive to mammary tumorigenesis.
p53 expression and prognosis in gastric carcinoma
Authors: Martin Hilary M. , Filipe M. Isabel , Morris Richard W. , Lane David P. , Silvestre Frederico 
Published: February 2007

AbstractAbnormalities of the p53 gene have been identified in many malignancies, with reports of aberration in over half of colorectal, lung, breast and hepatocellular carcinoma cases. The normal gene acts as a recessive oncogene, while mutations change the apparent function to that of a dominant oncogene.In this investigation a 3‐layered immunoperoxidase technique was applied to routinely fixed and paraffin‐embedded tissue sections from 125 gastric carcinomas, using a polyclonal anti‐p53 antibody (CM‐1).We found that 57% of these carcinomas expressed high levels of p53 protein (positive nuclear staining). Survival analysis revealed a strong association between p53 status of the tumour and patient survival time after diagnosis (p = 0.02, Mantel‐Cox Test); odds ratio of death, 2.09 (95% confidence interval 1.02 to 4.25). The 5‐year survival of patients with p53‐expressing tumours was 24%, compared with 56% for those non‐p53‐expressing tumours (the median survival times were 13 and 102 months, respectively).
Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in epstein‐barr‐virus‐positive nasopharyngeal carcinoma cells
Authors: Busson Pierre , Zhang Qin , Guillon Jean‐Michel , Gregory Christopher D. , Young Lawrence S. , Clausse Bernard , Lipinski Marc , Rickinson Alan B. , Tursz Thomas 
Published: February 2007

AbstractUndifferentiated nasopharyngeal carcinoma (NPC) is a remarkable entity among human tumors because of its constant association with the Epstein‐Barr virus (EBV). Malignant epithelial cells harbor the EBV genome and often express at least 2 species of latent EBV protein (EBNA1 and LMP1). Despite the massive presence of tumor‐infiltrating lymphocytes, NPC cells obviously escape immune surveillance directed to EBV antigens. Previous investigations carried out on EBV‐positive Burkitt lymphoma (BL) cells have shown that this fact may be partially accounted for by a lack of expression of ICAM1 (CD54) and LFA3 (CD58). ICAM1 and LFA3 have therefore been investigated in fresh NPC biopsies and transplanted NPCs. With only I exception out of 9 cases, NPC cells appear to express high levels of ICAM I and low levels of LFA3. This is a complete inversion of the pattern observed in normal epithelial cells in vivo. Additional investigations will be required to determine to what extent these characteristics affect T‐cell interactions with NPC cells, specially in the process of EBV‐antigen recognition.
Cancer mortality after iodine‐131 therapy for hyperthyroidism
Authors: Hall Per , Berg Gertrud , Bjelkengren Göran , Boice John D. , Ericsson Ulla‐Britt , Hallquist Arne , Lidberg Monika , Lundell GÖRan , Tennvall Jan , Wiklund Kerstin , Holm Lars‐Erik 
Published: February 2007

AbstractCancer mortality was studied in 10,552 Swedish hyperthyroid patients treated with 131l between 1950 and 1975. The patients were matched with the Swedish Cause‐of‐Death Register and the cases of 977 patients who died from cancer or leukemia were studied. The patients had been followed up for an average of 15 years (range 0 to 35 years), and the overall standardized mortality ratio (SMR) was 1.09 [95% confidence interval (CI) = 1.03 to 1.16], with a higher risk for women. The highest mortality was seen during the first year after exposure (SMR = 1.15) and decreased for the following 9 years (SMR = 1.04). The risk of dying from a cancer in the digestive tract and respiratory organs was significantly elevated more than 10 years after exposure, as was the overall cancer mortality (SMR = 1.14). No increased risk was seen for leukemia, bladder cancer or breast cancer. Younger patients and those receiving 131I at higher activity had higher SMRs than older patients and those receiving lower activity. Patients with toxic nodular goiter had higher risk than those with Graves' disease. The lack of increasing mortality over time and with increasing activity of 131I administered argues against a carcinogenic effect of 131I. However, in the case of cancers of the stomach, the 131I exposure could have contributed to the excess mortality from these cancers.
Oral contraceptives and risk of benign proliferative epithelial disorders of the breast
Authors: Rohan Thomas E. , L'Abbé Kristan A. , Cook Martin G. 
Published: February 2007

AbstractIn a case‐control study conducted in Adelaide, South Australia, we investigated the hypothesis that use of oral contraceptives is associated with increased risk of benign proliferative epithelial disorders (BPED) of the breast, conditions strongly associated with increased risk of breast cancer and thought to have pre‐malignant potential. The study was restricted to women with no prior history of breast biopsy, and involved 383 cases of biopsy‐confirmed BPED, 192 controls whose biopsy did not show epithelial proliferation, and 383 unbiopsied community controls individually matched to cases by age and socio‐economic grading of area of residence. When cases were compared with community controls, the adjusted odds ratio (OR) for the association between ever‐use of oral contraceptives and risk of BPED was 1.1 (95% CI 0.7 to 1.7), while when cases were compared with biopsy controls, the adjusted OR was 0.9 (95% CI 0.5 to 1.5). There was little variation in risk of BPED with total duration of use of oral contraceptives, and with duration of use before first pregnancy, while current users had a statistically significant 60% reduction in risk, irrespective of the control group used for comparative purposes. Also, there was little variation in risk with years since first and last use of oral contraceptives, and there was no trend in the association between ever‐use of oral contraceptives and risk of BPED by degree of cytological atypia.
in vitro and in vivo detection of somatostatin receptors in human malignant lymphomas
Authors: Reubi J. C. , Waser B. , Van Hagen M. , Lamberts S. W. J. , Krenning E. P. , Gebbers J.‐O. , Laissue A. J. 
Published: February 2007

AbstractA wide variety of primary and metastatic human neoplasms express somatostatin receptors (SS‐Rs). We evaluated the SS‐R status of malignant lymphomas that had been surgically removed from 31 patients, by use of in vitro SS‐R autoradiography with the SS analog 1251‐[Tyr3]‐octreotide as radioligand. Of 11 low‐grade‐malignancy B‐cell non‐Hodgkin's lymphomas, 10 were SS‐R‐positive, with a high receptor density restricted to the neoplastic follicles. All of the 8 intermediate‐grade lymphomas were SS‐R‐positive. Of the B‐cell lymphomas of high‐grade malignancy, 7 out of 10 were SS‐R‐positive, often with a high density of receptors. One T‐cell lymphoma and one Hodgkin's lymphoma were also positive. SS‐Rs were of high affinity (KD = 1.2 nM) and specific for bioactive SS analogs. In 4 patients, the lymphomas were localized in vivo by use of gamma‐camera scintigraphy after i.v. injection of the SS analog IIIIn‐[DTPA‐D‐Phe]‐octreotide. Hot spots, identified in all 4 patients, corresponded to SS‐R‐positive malignant‐lymphoma tissue, as confirmed by receptor autoradiography of the surgically removed tumors. Our data show that SS‐Rs are valuable pathobiochemical tissue markers and potentially useful in vivo diagnostic tools for human malignant lymphomas.
Oestrogen sulphatase activity in hormone‐dependent and hormone‐independent breast‐cancer cells: Modulation by steroidal and non‐steroidal therapeutic agents
Authors: Purohit A. , Reed M. J. 
Published: February 2007

AbstractOestrogen sulphatase may play an important role in providing intracellular oestrogens from E1S for the growth and maintenance of breast tumours. In this study, we characterized oestrogen sulphatase in the hormone‐dependent (ER/PR+) MCF‐7 and in the hormone‐independent (ER/PR ) MDA‐MB‐231 breast‐cancer cells and, furthermore, examined its modulation by MPA, 4‐OH‐A4, tamoxifen, danazol, ethinyloestradiol and DMAS in both these cell types. Our detailed study of oestrogen sulphatase activity as a function of incubation time, E1S concentration and numbers of MCF‐7 and MDA‐MB‐231 cells showed that more E1S was hydrolysed by MDA‐MB‐231 cells than by MCF‐7 cells at all time points and all substrate concentrations. Additionally, although the km values of E1S for oestrogen sulphatase in both MCF‐7 and MDA‐MB‐231 cells were similar, the Vmax values, and therefore the activity, differed greatly. The effect of various steroidal and non‐steroidal compounds also suggested differences in these 2 cell lines with respect to oestrogen sulphatase inhibition or stimulation. MPA significantly increased the hydrolysis of [3H]E1S in both cell lines, possibly through its effect on membrane fluidity. Tamoxifen increased E1S hydrolysis in MDA‐MB‐231 cells but not in MCF‐7 cells, whereas 4‐OH‐A4 inhibited E1S in MCF‐7 cells but not in MDA‐MB‐231 cells. Danazol (an isoxazol derivative of 17α‐ethinyltestosterone), 17α‐ethinyloestradiol and DMAS all significantly inhibited oestrogen sulphatase activity in both cell lines. Furthermore, danazol had a growth‐inhibitory effect on both MCF‐7 and MDA‐MB‐231 cells, although MCF‐7 cells appeared to be more sensitive to growth inhibition by danazol.
The mechanism of hepatic uptake of a radiolabelled monoclonal antibody
Authors: Boyle Catherine C. , Paine Alan J. , Mather Stephen J. 
Published: February 2007

AbstractClinical and experimental scintigraphic studies have found that radiolabelled antibodies are not only taken up by tumour (s) but also by normal liver. The accumulation of radio nuclides in this organ poses a major problem to the use of radiolabelled antibodies as diagnostic and therapeutic tools. In an attempt to understand the mechanism of hepatic uptake and clearance of radiolabelled antibodies, the intrahepatic biodistribution of an 111In‐labelled MAb (HMFGI), was determined following i.v. administration to normal male rats. Two hours after administration the liver contained 15% of the injected dose, with most of the remaining radioactivity in the blood. The hepatic burden of the 111 In MAb remained constant over the next 72 hr in the face of decreasing blood levels of radioactivity as well as its urinary and faecal excretion. At 2 and 72 hr after injection, 50% and 10% respectively of the hepatic radiolabel was due to blood borne antibody. Following a collagenase‐cell isolation procedure, only 23% of the amount remaining in the liver at 2 hr was found to be cell‐associated; 66% was lost during the cell isolation and purification procedure. Cellular uptake increased with time so that, by 72 hr after administration, 58% was cell‐associated and 29% freely removable. At all timepoints, the parenchymal cells contained more activity than non‐parenchy‐mal cells. No evidence of antibody‐receptor interactions could be obtained either in vivo or in cultures of hepatic parenchymal and non‐parenchyma) cells. Our data suggest that the bulk of the hepatic burden of 111In MAb results from extra vascular pooling of the antibody.
Post‐transcriptional regulation of urokinase plasminogen activator gene expression occurs in the nucleus of BC1 rat mammary tumor cells
Authors: Henderson B. R. , McDonald D. A. , Kefford R. F. 
Published: February 2007

AbstractThe regulation of urokinase plasminogen activator (uPA) expression was investigated in 2 highly metastatic rat mammary adenocarcinoma cell lines, BCI and MAT 13762. BCI cells were observed to synthesize, on average, 10 times less uPA enzyme and mRNA than MAT 13762 cells; however this difference was not accounted for by differences in uPA gene copy number/ structure or in the rate of uPA gene transcription in the cell lines studied. Moreover, Northern blot analysis of invasive sub‐populations derived in vitro from the BCI cell line revealed levels of uPA expression similar to those of the parent, but a 3‐fold elevation in expression of the metalloprotease gene, transin. Further investigation showed that treatment of BCI cells with either of the protein synthesis inhibitors, cycloheximide or anisomycin, increased the level of both nuclear and cytoplasmic uPA RNA 6‐ to 18‐fold in 4 hr, whilst inducing a maximum 2.6‐fold increase in the rate of uPA gene transcription. This increase in uPA gene expression may therefore reflect, in part, an increase in the stability and/or processing of nuclear uPA transcripts. These results suggest that the degree of uPA gene expression does not correlate directly with BCI tumor‐cell invasion in vitro, and that the uPA gene is down‐regulated, at least in part, post‐transcriptionafly in the nucleus of BCI mammary tumbr cells.
Mesothelioma in rats following intrapleural injection of chrysotile and phosphorylated chrysotile (chrysophosphate)
Authors: Van Der Meeren A. , Fleury J. , Nebut M. , Monchaux G. , Janson X. , Jaurand M. C. 
Published: February 2007

AbstractPathological effects of asbestos are probably dependent on the size and surface properties of the fibers. Surface‐modified chrysotile fibers were injected into the pleural cavity of rats to investigate the potency of the fiber to induce mesothelioma. Chrysotile fibers were modified by a phosphorylation process, resulting in the presence of phosphorus at the fiber surface. Phosphorylated samples were characterized by enhanced durability and reduced affinity for biological macromolecules. Five samples were tested: I untreated and 4 phosphorylated. ChrP1, ChrP2 and ChrP3 corresponded to phosphorylated samples obtained by first, second and third passages through an Alpine classifier; Pm was defibrillated ChrP1. The number of fibers per microgram and the size distribution were determined by transmission electron microscopy and classified in 4 size groups. Groups of 35 rats were inoculated with 20 mg of fibers suspended in 0.9% NaCl solution. No mesothelioma was found in the saline controls. All fiber samples were proficient in producing mesothelioma; the percentages were different between groups and untreated chrysotile but not significantly so. The differences may be explained on the basis of the number of fibers injected which were > 8 μm in length and < 0.25 μm in diameter. The findings of a proficiency of long fibers to produce mesothelioma, previously reported by others for glass fibers, could be applied to chrysotile.
Use of multi‐cell spheroids of ovarian carcinoma as an intraperitoneal radio‐immunotherapy model: Uptake, retention kinetics and dosimetric evaluation
Authors: Bardiès Manuel , Thedrez Philippe , Gestin Jean‐Francois , Marcille Berthe‐Marie , Guerreau Dominique , Faivre‐Chauvet Alain , Mahe Marc , Sai‐Maurel Catherine , Chatal Jean‐François 
Published: February 2007

AbstractThe purpose of this study, using multi‐cell spheroids as an in vitro model of micrometastases of ovarian carcinoma for i.p. radio‐immunotherapy, was to measure the uptake and retention kinetics of 'In‐labeled F(ab')2 fragments of OCI25 monoclonal antibody (MAb) in spheroids of the NIH:OVCAR‐3 cell line and to estimate absorbed doses with beta‐emitting radionuclides (kinetics was assumed to be similar to that of indium‐111). With 0.2‐mm‐diameter spheroids at different MAb concentrations the highest binding value was determined. Retention kinetics showed a biological half‐life of 50 hr. These data were used to calculate absorbed doses by integration of Berger's latest‐point kernels. Mean absorbed doses when spatial distribution was considered to be uniform at the surface (no penetration) or throughout the spheroid (total penetration) were, respectively, 247 and 417 Gy with 153Sm, and 90 and 135 Gy with 90Y. Thus, the use of a similar MAb concentration and specific activity in patients should lead to high absorbed doses in i.p. radio‐immunotherapy of micrometastases.
Diet and gastric cancer. A case‐control study in Belgium
Authors: Tuyns Albert J. , Kaaks Rudolf , Haelterman Margareta , Riboli Elio 
Published: February 2007

AbstractA case‐control study was carried out in 2 Belgian provinces with contrasting gastric‐cancer mortality. The results were analyzed for the total study group and also separately in each of the 4 sub‐groups: men and women in each province. Only risks which appeared consistently in at least 3 of these 4 sub‐groups were retained in the discussion. Consumption of most vegetables, either cooked or raw, and of fresh fruit was found to be protective. There was an increased risk associated with meal and flour products, including white bread. Added sugar also increased the risk of gastric cancer. Consumption of lean meat was associated with a decreased risk. There was no clear effect for most sources of fat, but for oils with a high P/S ratio there was a decreased risk. Together with our earlier finding on salt, these results are to a large extent similar to those of other recent studies on gastric cancer.
Treatment of intracranial human glioblastoma by direct intratumoral administration of 131I‐labelled anti‐tenascin monoclonal antibody BC‐2
Authors: Riva P. , Arista A. , Sturiale C. , Moscatelli G. , Tison V. , Mariani M. , Seccamani E. , Lazzari S. , Fagioli L. , Franceschi G. , Sarti G. , Riva N. , Natali P. G. , Zardi L. , Scassellati G. A. 
Published: February 2007

AbstractTen patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC‐2, raised against tenascin and labelled with 131I. Tenascin, the BC‐2‐recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti‐tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq of 131I) was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC‐2 uptake was 4.9% per gram and its effective half‐life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected 131I was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission (>50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after 11 months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection.