Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acquired resistance to doxorubicin and other anti-cancer drugs is generally dependent on gene amplification of a specific nucleotide sequence, the MDR1 gene. Verapamil, cyclosporin and other drugs have been used to circumvent the resistance in experimental models in vitro and/or in vivo. We have attempted to reverse the MDR phenotype by treating human adenocarcinoma resistant cells with 20 mers of synthetic unmodified oligodeoxynucleotide MDR1 antisenses. Five ODNs towards different mRNA regions and three different schedules of ODN antisense administration were tested. We found that FCS concentration greatly influenced the stability of ODN, whereas heat-inactivated FCS had no effect. The kinetics of ODN cellular uptake suggest the presence of a saturable receptor. Among the five antisense ODNs used, the most efficient was the oligomer (ODN-1) complementary to 20 bases upstream of the AUG initiation codon. No effect was observed with antisense complementary to the nucleotide binding sites. Administration of ODN-1 every 12 hr for 72 hr partially reversed the MDR phenotype. Approximately 60% of the cells lost their resistance to doxorubicin and did not form colonies in the presence of the drug. The MDR1 mRNA was transiently down-regulated so that the level of gp170 was slightly reduced. The incomplete switch off of MDR1 gene expression may be ascribed to the large abundance and great stability of MDR1 messenger RNA. Moreover, the inactivity of the two ODNs complementary to the NBS protein domains suggests that translation inhibition is ineffective. It is likely that ODN-4 and ODN-5 complement a large number of mRNAs competing for duplex formation, because these sequences are highly conserved among many proteins.
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PMID:An oligomer complementary to the 5' end region of MDR1 gene decreases resistance to doxorubicin of human adenocarcinoma-resistant cells. 144 3

Between 1982 and 1990, 2388 bronchoscopic examinations were carried out in patients with cancer in our hospital. A diagnosis of endobronchial metastasis was established in 30 patients (2.09%), with the following primary tumors in descending order of frequency: breast, large bowel, melanoma, neuroblastoma, leiomyosarcoma and endometrial. Despite the rarity of endobronchial metastases secondary to colon adenocarcinoma, we were able to study 3 cases from our Center. In one case the diagnosis of endobronchial metastasis was simultaneous with that of the primary tumor, and in the other 2 this metastatic complication occurred 16 and 42 months, after the original diagnosis. When this complication occurred, the stage of the disease was advanced in all 3 cases: 2 were Dukes' stage C and one stage D. Although this metastatic location usually implies a very negative prognosis as regards life expectancy, it did not seem to significantly reduce the latter in our patients.
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PMID:Endobronchial metastases in colorectal adenocarcinoma. 146 85

Adenocarcinoma arising in Barrett's esophagus has recently been described in two children aged 11 and 14 years. The long-term follow-up of Barrett's esophagus in children is not well described. We evaluated 16 cases of Barrett's esophagus in children treated at this institution during the last 16 years. Ages ranged from 1.2 to 16 years (mean, 10.3 years). There were 11 boys and 5 girls. Barrett's esophagus was documented by endoscopy in 14 instances and at autopsy in 2 patients with secretory diarrhea and tetralogy of Fallot who died of sepsis. Two children had cancer (neuroblastoma, leukemia) and died of their malignant disease. Five patients had cerebral palsy, 1 esophageal atresia, 1 Fanconi's anemia, and 5 were otherwise normal children. Six were treated medically. Eight patients underwent Nissen fundoplication for complications of gastroesophageal reflux (GER). Five patients were available for follow-up endoscopy (mean, 2 years; range, 1.1 to 5.4 years). Endoscopy was performed on a yearly basis, obtaining biopsy specimens from multiple levels of the esophagus. Four children had satisfactory clinical response to an antireflux procedure including the resolution of a stricture in one case. However, in all 5 cases persistent metaplastic epithelium was documented and showed no evidence of regression. Although there has been speculation that Barrett's esophagus in children may be more likely to revert to normal squamous epithelium than in the adult, there has been only one case of regression in 180 cases of Barrett's esophagus occurring in children described in 37 reports in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Persistence of Barrett's esophagus in children after antireflux surgery: influence on follow-up care. 156 27

We developed a new approach for detecting the gene amplification of cancer DNAs with restriction landmark genomic scanning (RLGS). In cancer research, much effort has been made to find the amplified loci of cancer DNAs, because many lines of evidence indicate association between oncogene amplification and carcinogenesis. Conventionally, such gene amplification has been detected by using Southern hybridization with DNA probes. However, only the information of one locus can be obtained by one hybridization procedure, and analysis of many loci throughout the genome is too laborious and time consuming, even if only several candidate genes are investigated. On the other hand, the "in-gel renaturation method" was reported as another alternative for detection of amplified regions. However, even though this method is much improved, it is difficult to detect less than 7-fold amplification, which is often higher than the amplification of many cancer cases. To overcome these limitations and, in addition, to locate the amplified DNA two dimensionally, we applied RLGS for analysis of DNA amplification in cancer tissues, such as breast cancer (infiltrative tubuloadenocarcinoma), neuroblastoma, meningioma (endotheliomatous meningioma), and thyroid cancer (papillary adenocarcinoma). In some cases of breast cancer, several amplified spots located on the same amplicon were detected. In thyroid cancer, in which no amplification has yet been reported, low-grade amplification was also detected. In this report, we demonstrated that RLGS allows us to screen 2000-3000 restriction landmarks distributed on the genome simultaneously, and even low-grade amplification could be detected effectively. Thus, RLGS has proven to be a very useful method in detecting DNA amplification.
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PMID:New approach for detection of amplification in cancer DNA using restriction landmark genomic scanning. 161 37

The expression of "tissue" transglutaminase (tTG) in two human tumor cell lines (the cervix adenocarcinoma line HeLa-TV and the neuroblastoma cells SK-N-BE-2) was found to be in correlation with the rate of physiological cell death (apoptosis) in culture. We investigated the effect of retinoic acid (RA) and alpha-difluoromethylornithine (DFMO) in order to elucidate the relationship between tTG expression and apoptosis. RA led to a 6-fold increase of tTG activity in HeLa-TV cells and to a 12-fold increase in SK-N-BE(2) cells, which was paralleled in both cell lines by a proportional increase in the number of apoptotic bodies recovered from the cultures. On the contrary, DFMO determined a dramatic reduction of tTG expression and of the apoptotic index. Immunohistochemical analysis using an anti-tTG antibody showed that the enzyme was accumulated in both cell lines within typical apoptotic bodies. Immunocytochemistry and cell cloning of SK-N-BE(2) line demonstrated that tTG was absent in cells showing neurite outgrowth, indicating that the enzyme expression is not associated with neural differentiation, even though both phenomena are elicited by retinoic acid. On the whole, these data indicate that also in tumors tTG activation takes place in cells undergoing apoptosis. The enzyme is activated in apoptotic cells to form cross-linked protein envelopes which are insoluble in detergents and chaotropic agents. The number of insoluble protein envelopes as well as the N,N-bis(gamma-glutamyl)polyamine cross-links is related with both tTG expression and apoptotic index, strongly suggesting the participation of the enzyme in the apoptotic program.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The expression of "tissue" transglutaminase in two human cancer cell lines is related with the programmed cell death (apoptosis). 167 9

Melanoma and lung adenocarcinoma may be amenable for radiotherapy if it were possible to increase the presently used total dose. In order to investigate this, spheroids from two cell lines of human origin, one obtained from a BRO melanoma and one from an NCI-H125 lung adenocarcinoma were exposed to graded doses (3-9 Gy) of radiation with 18-MV photons. Radiation was applied either as a single dose or as split doses with an interval of 6 h to determine the extent of sublethal damage repair. Radiation response was quantified in terms of spheroid cure and specific growth delay. Both cells lines have previously been shown to be less sensitive than a neuroblastoma and a squamous cell carcinoma cell line grown as spheroids. Data obtained from the growth delay analysis were used to calculate the extent of split-dose recovery. Repaired dose for BRO spheroids did not increase after 7 Gy, whereas in NCI-H125, the repaired dose showed a steady increase. Recovery ratios did not differ between the two cell lines, but were lower than reported for normal tissues. Both cell lines revealed a low repair capacity was expressed by the beta-value of the linear-quadratic (LQ) equation. However, repair capacity for sublethal damage as expressed by the dose repaired and the beta-value of the LQ equation was not different from values reported earlier by us for neuroblastoma and squamous cell carcinoma when grown as spheroids. This indicates that the low radiosensitivity for the cell lines used in this study is determined by the alpha-value of the LQ equation. Our results support the clinical finding that the application of increased total radiation doses in the treatment of melanoma and lung adenocarcinoma may be feasible if radiation is applied in multiple small fractions to ensure normal tissue sparing.
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PMID:Sublethal damage repair in two radioresistant human tumor cell lines irradiated as multicellular spheroids. 187 10

This report describes a retrospective study of 23 patients with incidentally discovered adrenal masses. Two patients with subclinical cortisol secretion developed adrenal insufficiency after removal of benign adenomas. Another patient, who probably harbors an asymptomatic pheochromocytoma, developed a hypertensive crisis when a mass was palpated during aortic vascular surgery. Twelve patients underwent surgery. Seven benign adenomas, an angiomyolipoma, and a cyst were removed. Three patients had malignant masses that include an angiosarcoma, an adrenal adenocarcinoma, and a congenital neuroblastoma. We conclude that hormones, especially cortisol, may be secreted in subclinical amounts by incidentally discovered masses. We recommend a concise laboratory evaluation that includes an overnight dexamethasone suppression test. Based on our interpretation of the literature, we believe masses greater than 3 cm in size should be removed. Patients who do not undergo surgery should have computed tomographic scans repeated for one year and should be reassessed periodically for the development of hormone secretion.
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PMID:Incidentally discovered adrenal masses. 192 30

Human brain tumors (obtained as surgical specimens) and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using [3H]1,3-di-o-tolylguanidine (DTG), whereas opoid receptor subtypes were measured with tritiated forms of the following: mu, [D-ala2,mePhe4,gly-ol5]enkephalin (DAMGE); kappa, ethylketocyclazocine (EKC) or U69,593; delta, [D-pen2,D-pen5]enkephalin (DPDPE) or [D-ala2,D-leu5]enkephalin (DADLE) with mu suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels (pmol/mg protein) found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. kappa opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.
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PMID:Sigma and opioid receptors in human brain tumors. 197 2

Four human tumor lines were grown as xenografts in nude mice to determine whether xenografts derived from different types of tumors would show tumor-type dependent differences in response to single-dose irradiation, and whether these differences, paralleled clinical behavior. Xenografts from a neuroblastoma, a squamous cell carcinoma, a melanoma and a lung adenocarcinoma were studied in terms of growth delay and tumor control dose (TCD50). To exclude an immunoreaction of the host in the radiation response of the tumor xenografts, the tumor lines were tested for their growth in immunosuppressed Wistar rats. No differences in growth of xenografts in either immunodeficient mice or immunosuppressed rats were observed. Both growth delay and local tumor control as expressed by cure correlated well with clinical behavior of the tumor types of origin. This study demonstrates that radiosensitivity of different human tumor lines can be evaluated in terms of growth delay and tumor control dose50 when they are grown as xenografts. To exclude immune reactions, proper controls should be included. The sensitivities established from these evaluations parallel clinical behavior, thus offering a tool for analysis of human tumor radiosensitivity of histologically different tumor types.
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PMID:Radiosensitivity of different human tumor lines grown as xenografts determined from growth delay and survival data. 210 69

Two clones have been selected from a human fibroblast cDNA bank. By DNA sequencing the clones were shown to contain Alu elements located near the ends of the cDNA inserts. DNA of the clones was used for Northern blot hybridization analysis of a number of poly(A)-containing RNAs from normal human tissues (brain, stomach, uterus, spleen, fibroblasts) and tumors (neurinoma, glioma, neuroblastoma, liposarcoma, adrenal cortex adenocarcinoma). All RNA samples reveal a heterodisperse distribution of Alu transcripts with discrete bands in the region of 7-12 S RNA. The majority of these small poly(A)+ Alu+ RNAs contain Alu sequences only in one (canonical) orientation with functional signals including the split promoter for RNA polymerase III.
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PMID:Cloning of Alu-containing cDNAs from human fibroblasts and identification of small Alu+ poly(A)+ RNAs in a variety of human normal and tumor cells. 243 58


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