bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlative study on neuro‐endocrine differentiation and presence of somatostatin receptors in breast carcinomas
Authors: Papotti M. , Macri L. , Bussolati G. , Reubi J. C. 
Published: February 2007

AbstractTo correlate the expression of neuro‐endocrine (NE) markers with the presence of somatostatin receptors (SSR) in human breast cancer, a series of 100 cases was stained with the Grimelius silver procedure, by immunocytochemistry with specific NE markers (i.e., chromogranin A and B and synaptophysin) and by autoradiography for SSR. Nine cases were positive for at least one NE marker, while 4 cases were positive for all of them. SSR were detected in 17 cases, either with low (10 cases) or with high receptor density (7 cases). A highly significant correlation was established between the expression of NE markers and high SSR density. Our findings are additional evidence of the existence of a group of breast cancers showing morphological and cytochemical similarity with neuro‐endocrine tumors present in other organs. The identification of this type of breast cancer is of biological and potential therapeutic interest.
Pathologic prognostic factors for cutaneous malignant melanoma: The western canada melanoma study
Authors: Worth Ann J. , Gallagher Richard P. , Mark Elwood J. , Yang Paul C. , Lamb Charles , Spinelli John J. , Wood William S. , Threlfall William J. , Hill Gerry B. 
Published: February 2007

AbstractAn analysis of data for histopathologic factors influencing survival was conducted on 798 cases of invasive cutaneous malignant melanoma. On univariate analysis, a number of factors influenced survival; however, when these factors were examined using a proportional‐hazards model, sex and log of depth of penetration were the only factors governing survival. Moreover, these factors were only important in patients with lesions up to 4 mm in depth with no evidence of other disease. For patients with solitary lesions deeper than 4 mm, or patients with regional or distant disease, none of the factors examined in our study was of predictive value for survival assessment.
Increased serum ferritin in chronic liver disease: A risk factor for primary hepatocellular carcinoma
Authors: Hann Hie‐Won L. , Kim Chung Yong , Thomas London W. , Blumberg Baruch S. 
Published: February 2007

AbstractPrevious studies from this laboratory support the view that increased serum ferritin levels are associated with an increased risk of primary hepatocellular carcinoma (PHC). We have tested this hypothesis in a population of Korean patients with chronic liver disease followed for development of PHC. Serum ferritin levels were measured over time in 249 patients with liver diseases (mostly chronic) followed for 2 to 17 years in Seoul, Korea. Most of the patients were chronically infected with hepatitis B virus. During the first 8 months of follow‐up, there were no cases of PHC and no deaths. During this same period, no patient had a serum ferritin level initially below 300 ng/ml and rising above 300 ng/ml, but some patients with ferritin levels above 300 ng/ml experienced decreases to below 300 ng/ml. Therefore, patients were grouped by ferritin level during the first 8 months of follow‐up into 3 categories according to the above criteria. Multivariate analysis showed that consistently elevated ferritin levels (category 3) were significantly associated with the development of PHC. Men were more likely to have elevated ferritin levels than women and were at higher risk of developing PHC. Men who were chronically infected with HBV and had ferritin levels above 300 ng/ml had a 50% chance of developing PHC during the follow‐up period, compared with a 20% risk of PHC for men with lower ferritin levels (categories 1 and 2). This elevated risk of PHC in men with elevated ferritin levels was confined to the first 3 years of follow‐up.
Expression of transforming growth factor alpha messenger rna in the normal and neoplastic gastro‐intestinal tract
Authors: Malden L. T. , Novak U. , Burgess A. W. 
Published: February 2007

AbstractThe presence of TGFα mRNA has been reported previously to occur in primary colon cancers. We report the expression of the normal 4.5 kb TGFα transcript in the mucosa of the normal human gastro‐intestinal tract from oesophagus through to colon. The highest levels of human TGFα mRNA occurred in the duodenum but significant levels were present in all of the mucosa. Similarly, in the rat gastro‐intestinal tract, TGFα transcripts were detected in the lower gastro‐intestinal tract mucosa. The relative abundance of the TGFα mRNA appeared to decrease in distal regions of the gastrointestinal tract. The level of the TGFα mRNA was similar in both the normal and the neoplastic colon tissue. Similarly, in 2 patients with carcinomas, the TGFα mRNA was expressed at similar levels in the tumour and in adjacent mucosa. Although TGFα mRNA is associated with transformed cells from the gastro‐intestinal tract, the presence of this mRNA at equivalent concentrations in normal mucosa suggests that over‐production of TGFα is not an essential feature of carcinomas in the gastro‐intestinal tract.
Sensitivity to genotoxic effects of bleomycin in humans: Possible relationship to environmental carcinogenesis
Authors: Hsu T. C. , Johnston Dennis A. , Cherry Lorraine M. , Ramkissoon Dindyal , Schantz Stimson P. , Jessup John M. , Winn Rodger J. , Shirley Linda , Furlong Cynthia 
Published: February 2007

AbstractResponses to the genotoxic effect of bleomycin in lymphocytes of blood cultures, expressed as the average number of chromatid breaks per cell (b/c), varied from less than 0.20 to more than 2.00 in 335 normal individuals. More than 11% of the subjects tested showed a b/c rate above 1.00 and more than 22% showed a b/c rate above 0.80. These individuals are considered sensitive to this radiomimetic drug. The distributional profile of bleomycin responses of the control individuals appears to be representative of the normal human population. In patients with cancers of the colon (83), upper aerodigestive tract (head/neck) (77), and lung (71), the frequencies of subjects in the hypersensitive class were found to be between 40 and 50%, and the response profiles were distinctly different from those of the control population. On the other hand, in a group of elderly cigarette smokers, who exhibited no symptoms of lung cancer, the bleomycin sensitivity profile was significantly skewed toward the more resistant stratum, with only one hypersensitive case among 56 individuals tested (1.78%). The sensitivity profile of patients with breast cancer (82) was similar to that of the control population. Our data suggest that: (1) mutagen sensitivity may play an important role in carcinogenesis of organs and tissues that have direct contact with the external environment (respiratory, digestive, and integumentary systems); (2) it appears to have no significant influence on carcinogenesis of tissues that are not directly exposed to the environment (e.g., breast, brain); and (3) it also has little impact on carcinogenesis in individuals with a hereditary predisposition to cancer (e.g., retinoblastoma, Gardner's syndrome). Development of more effective and precise test systems for carcinogen sensitivity is highly desirable for identification of persons at risk.
Histocompatibility antigens in primary and metastatic squamous cell carcinoma of the larynx
Authors: Esteban F. , Concha A. , Huelin C. , Pérez‐ayala M. , Pedrinaci S. , Ruiz‐Cabello F. , Garrido F. 
Published: February 2007

AbstractA series of 38 primary laryngeal and hypopharyngeal tumours, 15 lymph‐node metastases and normal tissue were evaluated in frozen sections for the expression of MHC class I and II antigens, using monomorphic monoclonal antibodies (MAbs) to HLA‐ABC, β2‐microglobulin, DR, DP, DQ, HLA‐B and polymorphic HLA‐ABC antigens. Normal distant mucosa of larynx reacted to anti‐class I antibodies but not to anti‐class II. In 9 primary tumours (23.7%) HLA class I antigens were not observed. The remaining 29 showed a strong reaction to anti‐HLA‐ABC (heavy chain) and anti‐β2‐microglobulin, although in 3 cases out of 29 no staining was observed with anti‐HLA‐B locus‐specific MAbs. These selective losses were confirmed using the corresponding anti‐HLA polymorphic MAbs. For HLA class II molecules, only DR was observed in 3 of 38 cases. Defective HLA class I expression statistically correlates with high scores according to Jakobsson's criteria for histopathological tumour grading. Loss of HLA‐ABC antigens was most frequent among the cases with poor differentiation (6/8 cases). On the contrary, class II antigen expression was correlated with a well differentiated pattern and a more favourable prognosis (p < 0.001). We have found differences in HLA class I expression when comparing primary tumours and autologous metastases (3/9 cases). Immunoprecipitation and SDS‐PAGE of class I antigens, Northern and Southern blot analyses of MHC class I genes were performed. We have not detected class I gene rearrangement using HLA coding and locus‐specific non‐coding probes. However, we have found a class I transcription defect that corresponds with a class‐I‐negative phenotype.
Effects of propranolol and cimetidine on cysteamine inhibition of gastric carcinogenesis induced in wistar rats by n‐methyl‐n′‐nitro‐n‐nitrosoguanidine
Authors: Tatsuta Masaharu , Iishi Hiroyasu , Baba Miyako , Mikuni T. , Taniguchi Haruo 
Published: February 2007

AbstractThe effects of propranolol and cimetidine on inhibition by cysteamine (2‐aminoethanethiol hydrochloride) of gastric carcinogenesis induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) and on gastric acid secretion, serum gastrin level, and labelling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received alternate‐day injections of cysteamine (25 mg/kg body weight) with or without propranolol (dl‐propranolol hydrochloride) (2 mg/kg bw) or cimetidine (50 mg/kg bw) in depot form after 25 weeks of oral treatment with MNNG. Prolonged administration of cysteamine significantly reduced the incidence of adenocarcinoma of the glandular stomach. A combination of cysteamine and propranolol significantly accelerated the inhibitory effect of cysteamine on gastric carcinogenesis. However, with concomitant administration of cysteamine and cimetidine, the incidence of adenocarcinoma was slightly but not significantly increased as compared to that after treatment with cysteamine alone. Administration of cysteamine caused a significant increase in gastric acid secretion and serum gastrin level, and a significant decrease in the labelling index of the antral mucosa. A combination of cysteamine and propranolol significantly increased gastric acid secretion by cysteamine alone and significantly decreased the labelling index of the antral mucosa. With this treatment, the serum gastrin level was significantly higher than the basal level, but the stimulated serum gastrin level was significantly lower than observed that after administration of cysteamine alone. In contrast, concomitant administration of cysteamine and cimetidine caused a significant decrease in gastric acid secretion and a significant increase in the serum gastrin level as compared to the levels seen after treatment with cysteamine alone, but had no influence on the labelling index of the antral mucosa. These findings indicate that hypersecretion of acid, but not hypergastrinemia associated with hyposecretion of acid or achlorhydria, exerts a protective effect against gastric carcinogenesis, and that this effect may be related to its activity in decreasing proliferation of the antral mucosa.
Immunodetection of cathepsins b and l present in and secreted from human pre‐malignant and malignant colorectal tumour cell lines
Authors: Maciewicz Rose A. , John Wardale R. , Etherington David J. , Paraskeva Christos 
Published: February 2007

AbstractPre‐malignant and malignant human colorectal tumour epithelial cell lines both secreted precursor forms of the 2 cysteine proteinases, cathepsins B and L. The amount of proteinases secreted by these cell lines varied according to the cell density. Comparison at similar cell densities showed that the pre‐malignant, adenoma‐derived cell line (PC/AA) secreted as much, or more, of both cathepsin B and L precursors as did the malignant, carcinoma‐derived cell line (PC/JW/FI). However, mature forms of cathepsins B and L were detected in the culture media of only the carcinoma‐derived cell line, thus indicating that the invasive potential of a tumour may be related to its ability to process extracellularly the secreted precursor enzyme to a mature and consequently active enzyme, rather than to the amount of proteinase synthesized and/or secreted. Similar results were obtained using 2 other epithelium‐derived tumour cell lines, HT/29 (carcinoma) and SP/AN (adenoma). Immunolocation studies showed that cathepsin B was lysosomal while cathepsin L appeared to have a distribution more consistent with a plasma membrane association. Purified human cathepsins B and L (mature form) were capable of solubilizing an isolated basement membrane matrix (bovine anterior lens capsule) In vitro, thus indicating that the secreted mature enzymes and the membraneassociated cathepsin L could potentially degrade basal laminae or sub‐endothelial basement membranes in vivo.
Circumvention of adriamycin resistance by dipyridamole analogues: A structure‐activity relationship study
Authors: Ramu Nili , Ramu Avner 
Published: February 2007

AbstractDipyridamole restores sensitivity to Adriamycin (ADR) in drug‐resistant cells. In an effort to elucidate the relationship between activity and chemical structure of dipyridamole, the ability to enhance the growth inhibitory effect of ADR, in multidrug‐resistant (MDR) P388 murine leukemia cells, was determined for 43 derivatives and related compounds. Since both substituted pyrimidopyrimidines and pteridines enhanced the growth‐inhibitory effect of ADR in drug resistant cells, the core skeleton may not be directly involved and rather serve as a carrier for the substituents connected with this activity. The exact positions of the active substituents on the core skeleton did not seem to be critical for exertion of the activity. Activity was dependent on the presence of 3 tertiary amine groups. However, not all tertiary amines showed the same potency which might be related to the degree of basicity and/or the spatial structure of these groups. The most active derivatives carried piperidine and pyrrolidine groups while derivatives with thiomorpholine, 3‐hydroxypiperidine or dimethylamine groups had low activity. Activity was also dependent on the presence of a substituent with partial electronegative charges as found in a diethanolamine group. However, this function could be carried out, with even higher efficiency, by a substituent containing 6π electrons.
Biological activities and cellular uptake studies of fluorescent derivatives of indole alkaloid tumor promoter teleocidin
Authors: Irie Kazuhiro , Okuno Shigenori , Koshimizu Koichi , Tokuda Harukuni , Nishino Hoyoku , Iwashima Akio 
Published: February 2007

AbstractTo investigate the interaction between tumor promoters and their cellular targets, 6 new fluorescent derivatives of indole alkaloid tumor promoter teleocidin were synthesized from (–)‐indolactam V, and examined for induction of Epstein‐Barr virus, binding ability to the TPA receptor on mouse skin and activation of protein kinase C. (–)‐7‐(2‐N‐Dansylaminoethyl)indolactam V (dansyl‐ILV) had strong activities and proved to be a potent tumor promoter in a 2‐stage carcinogenesis experiment. (–)‐2‐Formyl‐7‐decanoylindolactam V (FD‐ILV) showed a weak but significant activity. The other 4 derivatives had little activity. Treatment of HeLa cells with dansyl‐ILV and FD‐ILV resulted in intense fluorescence in the entire cytoplasm and on the nuclear membrane. Inactive or less active derivatives with hydrophobicity similar to that of dansyl‐ILV showed significant cytoplasmic fluorescence, and those far less hydrophobic than dansyl‐ILV or far more hydrophobic than FD‐ILV showed little fluorescence. This suggested that hydrophobicity rather than biological activity determines the cellular uptake of these fluorescent probes.
Effect of erythromycin and tumour necrosis factor on the drug resistance of multidrug‐resistant cells: Reversal of drug resistance by erythromycin
Authors: Hofsli Eva , Nissen‐Meyer Jon 
Published: February 2007

AbstractWEHI 164 murine fibrosarcoma cells were rendered multidrug‐resistant (MDR) by culture in the presence of actinomycin D. In addition to resistance to actinomycin D, the cells acquired resistance to doxorubicin, mitomycin, vincristine and cycloheximide. The fact that development of resistance to one type of lipophilic chemotherapeutic drug also results in resistance to other structurally unrelated lipophilic drugs suggests that non‐toxic lipophilic agents may interfere with drug resistance by saturating the pathway by which MDR‐cells inhibit drug cytotoxicity. We show that the antibiotic erythromycin significantly reverses the resistance of MDR WEHI 164 cells to doxorubicin and actinomycin D. In addition to crossresistance to chemotherapeutic drugs, 3 out of 4 actinomycin D‐resistant WEHI 164 cell lines also showed higher resistance to tumour necrosis factor (TNF) than the parental WEHI 164 cells. However, whereas verapamil, a calcium antagonist known to reverse multidrug‐resistance, rendered resistant cells more sensitive to chemotherapeutic drugs, it protected the cells from killing by TNF, suggesting that drug resistance and TNF resistance may not be directly connected. A synergistic cytotoxic effect of TNF and actinomycin D was obtained on both the parental and the MDR cells. However, higher concentrations of TNF and actinomycin D were required to obtain a cytotoxic effect in the MDR cells, reflecting actinomycin D and TNF resistance in these cells.
Limiting dilution cloning of B cells from patients with multiple myeloma: Emergence of non‐malignant B‐cell lines
Authors: Clofent G. , Klein B. , Commes T. , Vincent C. , Ghanem N. , Lenoir G. , Lefranc M. P. , Bataille R. 
Published: February 2007

AbstractMultiple myeloma (MM) is a B‐cell malignancy characterized by the accumulation of slowly proliferating malignant plasma cells in the bone marrow (BM). Several reports have shown the existence of an abnormal B‐cell compartment including proliferative idiotypic B cells (i.e., B cells bearing the same idiotypic determinants as the myeloma protein) in the BM and peripheral blood (PB) of patients with MM. In order to study whether this abnormal compartment can be grownin vitro, we cultured the PB and BM of 23 patients with MM using limiting dilution methods. Our purpose was to restrict the effect of suppressor cells and the possible overgrowth of the cultures by the more rapidly growing B cells, which occurs in bulk cultures. Spontaneously growing cells were obtained only from patients seropositive for the Epstein‐Barr virus (EBV) and all the cultures were composed of B cells carrying the EBV genome. Thus, positive cultures were generated only in the presence of B cells latently infected with EBVin vivo. The mean frequency of these B cells (1 in 25,000 B cells) was as low in MM patients as in healthy donors. This low frequency indicated that malignant cells do not bear the EBV genomein vivoand that thein vivoregulation of the EBV infection is unaffected in patients with MM. No Ig‐gene rearrangements, specific of the autologous myeloma cells, were found in the cell lines obtained from BM or PB. Thus, the putative malignant B cells or myeloma cells were not able to generate cell linesin vitro, either spontaneously or after endogenous infection with EBV.
Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. III. Defective interleukin‐2 production by t‐helper and natural killer cells
Authors: Chang Weng‐Cheng , Fujimiya Yoshiaki , Casteel Nancy , Pattengale Paul 
Published: February 2007

AbstractEven though they possess normal to increased numbers of circulating natural killer (NK) cells, patients with chronic myelogenous leukemia (CML) have a functional NK‐cell deficiency which is restorable in vitro in the presence of recombinant IL‐2. We therefore measured the level of IL‐2 production by both T‐helper and NK cells from CML patients as compared to normal controls using PHA‐stimulated peripheral blood mononuclear cells (PBMs) as well as FACS‐sorted CD4+ (OKT4+) lymphoid cells and FACS‐sorted CD16+(B73.1+) lymphoid cells. Peripheral blood mononuclear cells from CML patients demonstrated markedly defective IL‐2 production as compared to normal controls (4.0 ± 1.6 and 5.9 ± 1.4 units/ml after 24 hr of 5 and 10 μg/ml PHA stimulation as compared with 40.7 ± 10.3 and 69.3 ± 15.1 units/ml for normal subjects). In addition to the decreased relative percentage of CD4+ (OKT4+) lymphoid cells in CML patients, FACS‐sorted CD4+ (OKT4+) cells also demonstrated a significant defect in IL‐2 production, (10.8 ± 3.6 units/ml as compared to 39.0 ± 5.8 units/ml after 24 hr stimulation with 10 μg/ml PHA). FACS‐sorted CD16+ (B73.1+) lymphoid cells from CML patients also demonstrated significantly decreased IL‐2 production after 24 hr incubation with increasing concentrations of PHA or with the NK‐sensitive target K562 as compared to normal controls. Defective IL‐2 production by PBMs, CD4+(OKT4+), and CD16+(B73.1+) cells from CML patients was also evident after 48 hr of PHA stimulation. Although the percentages of both T4+2H4+ and T4+4B4+ subsets are significantly decreased in CML patients, CML patients have normal ratios of T4+4B4+/T4+2H4+ subsets as compared to normal controls. These and previous results support the hypothesis that decreased IL‐2 production by both T‐helper and NK cells from CML patients may be mechanistically related to the observed NK‐cell immunodeficiency in CML patients.
Milk drinking, other beverage habits, and lung cancer risk
Authors: Mettlin Curtis 
Published: February 2007

AbstractThe reported beverage habits of 569 lung cancer patients and 569 control patients admitted to Roswell Park Memorial Institute (RPMI) were studied, 355 male cases and 214 female cases being matched to controls within strata of age and residence. Smoking history and an index of vitamin A from vegetables had significant, dose‐response associations with risk. Animal fat intake as measured by an index of animal fats from meats showed elevated risks which were not significant. Three vegetables rich in vitamin A and 3 meats contributing to the animal fat index were, individually, associated with lung cancer risk. Frequency of consumption of milk, coffee, tea, soft drinks and alcoholic beverages was studied in multiple logistic regression analyses which controlled for smoking history, intake of vitamin A from vegetables and education level. Subjects reporting consumption of whole milk 3 or more times daily had a 2‐fold increase in lung cancer risk compared to those who reported never drinking whole milk (RR = 2.14). The same frequency of intake of reduced‐fat milk was associated with a significant protective effect (RR = .54). Significant risk variations were observed for other beverages but, with the exception of frequencies of reported diet cola and decaffeinated coffee intake, dose‐response patterns were not evident.