Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA content and sensitivity of DNA in situ to denaturation by acid were analyzed by flow cytometry of cell nuclei freshly isolated from the bladder tumors of 32 patients and were compared with normal urothelium of 8 subjects. DNA sensitivity to denaturation was assessed in RNase treated cells by acridine orange metachromasia following partial denaturation with hydrochloric acid; the extent of denatured DNA is given as an index (alpha t), representing the ratio of single stranded to total DNA per nucleus. Of the low stage tumors (papillomas, Ta, Tis, T1) 11 of 18 (61%) were aneuploid. Of the high stage tumors (T2 and T3a) 11 of 14 (79%) were aneuploid. DNA in nuclei of normal transitional epithelium was very sensitive to denaturation, as was papilloma, characterized by nuclear alpha t indices of 0.73 +/- 0.01 (SD) and 0.73 +/- 0.04, respectively. Nuclear DNA of noninvasive carcinomas (Ta, Tis) was significantly more resistant to denaturation (alpha t = 0.69), and DNA of invasive carcinomas was most resistant, ranging from alpha t = 0.61 (T1 tumors) to alpha t = 0.59 (T2 tumors) to alpha t = 0.57 (T3 tumors). High stage tumors as a group (T2, T3) had significantly different (lower) alpha t values than low stage tumors (Ta, Tis, T1). In model cell culture systems it is known that a decrease in alpha t index, i.e., greater resistance to denaturability, occurs as cells transit from resting phase into the cell cycle. Whether the alpha t index can be used to estimate resting vesus cycling cells of human tumors is still speculative; changes in DNA denaturability also are known to occur with changes in chromatin structure during cell differentiation and in transformation. However, the empirical relationship between alpha t index and tumor stage, of itself, may prove clinically useful in identifying more advanced and perhaps more aggressive tumors.
 ...
PMID:DNA in situ sensitivity to denaturation in bladder cancer and its correlation with tumor stage. 225 31

Activated macrophages kill several types of tumor cells in vitro, whereas non-activated macrophages lack this capacity. We, however, observed that non-activated macrophages efficiently kill F9 teratocarcinoma as well as other teratocarcinoma cell lines. Dexamethasone, a glucocorticoid known to prevent macrophage activation, did not perturb the killing of F9 teratocarcinoma cells. Neither tumor necrosis factor alpha, nor the reactive oxygen intermediates, i.e. hydrogen peroxide, superoxide anion, and hydroxyl radical, nor serine proteases participated in this killing, shown by employing various agents which interfere with their production, secretion, or function. Using acridine orange/ethidium bromide vitality staining, the F9 teratocarcinoma cells were shown to be phagocytized alive by macrophages and subsequently killed intracellularly. Intact lysosomal function is required for the killing of F9 cells, as the lysosomotropic drugs chloroquine and ammonium chloride markedly inhibited this killing without perturbing their engulfment. The signal transduction pathway induced in the macrophages upon interaction with F9 teratocarcinoma cells seems to differ from that induced by macrophage activation. Neither the protein kinase C inhibitors polymyxin B and H-7 [1-(5-isoquinolinylsulfonyl)-2-methyl piperazine] nor the protein kinase C activator phorbol 12-myristate-13-acetate affected the killing of F9 cells. However, chlorpromazine (a powerful inhibitor of calmodulin), dibutyryl cAMP (a cAMP analog), and prostaglandin E2 inhibited the macrophage-mediated killing of F9 cells. In vivo studies indicate that an increased number of macrophages at the F9 tumor inoculation site (the peritoneal cavity) as a result of elicitation by thioglycollate prevents F9 tumor development. Our findings indicate that non-activated macrophages kill teratocarcinoma cells using a mechanism which differs from that employed by activated macrophages in the killing of other tumor cells.
 ...
PMID:Engulfment and intracellular killing of F9 teratocarcinoma cells by non-activated murine macrophages. 227 89

Fluorescent in situ hybridization (FISH) with biotinated chromosome-specific repetitive DNA probes was used for the cytogenetic study of ten gastric adenocarcinomas. All tumors (eight male, two female patients) were histologically moderately or poorly differentiated and nine of ten had metastasized to regional lymph nodes. The authors applied a set of satellite DNA probes, specific for chromosomes 1, 7, 17, X, and Y in order to detect numerical chromosome aberrations in freshly isolated tumor cell nuclei. Normal diploid human lymphocyte nuclei and, in a number of cases, normal gastric mucosa served as controls. Parallel with the hybridization experiments DNA flow cytometric study of acridine orange (AO)-stained tumor cells was carried out. By means of FISH the authors found seven cases to be aneuploid, the other three cases appeared diploid. This was confirmed by DNA flow cytometric analysis with AO. Furthermore, loss of the Y chromosome in a high percentage of cells was seen by FISH in six of eight tumors from male patients. In the other two male samples a possible loss was observed in a small proportion of cells (15%). In three patients from whom the authors had normal gastric mucosa the Y loss was restricted to the tumor cells. These data indicate that in situ hybridization with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of solid human tumors, at least with respect to the detection of numerical chromosome abnormalities.
 ...
PMID:Targeted cytogenetic analysis of gastric tumors by in situ hybridization with a set of chromosome-specific DNA probes. 236 62

To explore the potential role that ribonucleic acid (RNA) content analysis may have in the assessment of primary renal cell carcinomas (RCC), biparametric flow cytometric (acridine orange) measurements for DNA/RNA were obtained on 108 fresh neoplastic specimens. RNA content was divided into low and high groups, based on the average RNA content in normal kidney controls. High RNA content was significantly correlated with aneuploidy, high proliferative index, high nuclear grade, cytoplasmic granularity, and large tumor size. No correlation was found between RNA content and patients' sex, race, and clinical stage of the carcinomas. When diploid RCCs were separately analyzed, high RNA content was correlated with high nuclear grade, large tumor size, high clinical stage, and cytoplasmic granularity. There was no correlation between RNA content and the patient's sex or race or the neoplasm's proliferative index. Of the 16 patients that relapsed (5 diploid and 11 aneuploid), four of the diploid and all 11 aneuploid neoplasms displayed high RNA content. The authors' data show that RNA may be a valuable objective and quantitative parameter in the clinicopathologic assessment of RCC.
 ...
PMID:Acridine orange flow cytometric analysis of renal cell carcinoma. Clinicopathologic implications of RNA content. 238 96

EMT6 multicellular spheroids were introduced into the peritoneal cavities of mice and allowed to become vascularised, resulting in solid spherical tumours. The necrotic cores of the initially avascular spheroids were replaced by vascularised tumour tissue but the outer zones of the spheroids failed to become vascularised. The presence of both vascular and avascular components in each spheroid allowed the role of the vasculature in the antitumour action of flavone acetic acid (FAA) to be determined. Eighteen hours after treatment with FAA 0.8 mmol kg-1, the vascularised core became necrotic and haemorrhagic, while the outer avascular zone remained viable. Tumour cells which were infiltrating superficial sub-mesothelial fat did not become necrotic despite the presence of numerous thrombi in associated vessels. Injection of two fluorescent vascular markers, the first (Hoechst 33342) together with FAA, and the second (10-nonyl acridine orange) 4 h later, demonstrated that there is a marked loss of blood flow in the spheroids. These results provide further evidence that FAA kills blood vessel-dependent tumour cells by interrupting the tumour blood supply.
 ...
PMID:The use of vascularised spheroids to investigate the action of flavone acetic acid on tumour blood vessels. 238 39

Proliferation in total populations of thymocytes from control AKR mice or AKR mice injected intrathymically with MCF 69L1 virus was measured by flow cytometry of acridine orange-stained cells. Cell sorting experiments showed that the majority subpopulations of small cortical and medullary thymocytes in control mice were noncycling and were predominantly in the Go phase of the cell cycle. Of the 15 to 20% cycling thymic lymphoblasts, approximately 50% were in the G1 phase, 35% were in the S phase, and 15% were in the G2 + M phases of the cell cycle. Cycling cells appeared to consist of a major subpopulation with low RNA content and a minority subpopulation with high RNA content. In virus-injected mice, no changes in cell cycling were observed at stage I of leukemogenesis (30 to 40 days postinjection), at which time infection of thymocytes by MCF virus is maximum and constant but no clonality is evident. Thus, MCF virus infection of thymocytes per se does not appear to alter cell proliferation. Increased cell cycling and a shift in cell cycle distribution to more cells in G1 was observed at stage II of leukemogenesis (50 to 60 days postinjection), at which time a clonally expanded cell population is known to emerge in thymuses of injected mice. Acridine orange staining resolved these novel cycling cells from subpopulations of normal thymic lymphoblasts on the basis of intermediate RNA content. The transition from stage II to stage III (50 to 60 days postinjection) was accompanied by the outgrowth of a major cycling population with a distinct, often increased, RNA content. As a result, the residual "normal" background of cycling cells often observed in stage II was markedly reduced or completely absent by stage III. Populations of cycling blasts from mice with frank leukemia differed from those at stage III by a variability in mean RNA content and in cell cycle distribution indicative of individual tumor heterogeneity. In addition, thymomas often contained multiple populations of cycling blasts that could be resolved by their discrete RNA distributions. Simultaneous staining of DNA and RNA by acridine orange appears particularly well-suited for studying a heterogeneous population of cycling and noncycling cells represented by mouse thymus. This method has permitted a rapid and quantitative analysis of cell cycle parameters at progressive stages of viral leukemogenesis in AKR mice.
 ...
PMID:Changes in thymocyte proliferation at different stages of viral leukemogenesis in AKR mice. 241 23

A multidimensional slit-scan flow system was developed for the automated recognition of abnormal cells derived from cancer of the uterine cervix and its precursors. It provides great sensitivity in both its ability to recognize cellular abnormality and to deal with the myriad potential causes of false alarms in an automated flow system. While its initial application was the automated recognition of the spectrum of neoplasia in gynecologic cytology samples, a preliminary study was carried out using specimens obtained from the urinary bladder. Cellular material was collected by bladder irrigation and stained with the fluorochrome acridine orange. One hundred fifty-three bladder irrigation specimens, including 115 abnormal specimens containing cells derived from neoplastic lesions of the bladder epithelium, were analyzed. For the purposes of this study, abnormal specimens from the urinary bladder included specimens containing cells derived from the following lesions of the urothelium: dysplasia (atypical hyperplasia), carcinoma-in-situ, and transitional cell carcinoma, grades 1-3. Approximately 50,000 cells were analyzed for most specimens. Of the 38 presumed normal specimens (specimens containing only normal urothelial components), four were instrument classified abnormal. For the 69 specimens containing cells derived from transitional cell carcinoma, grade 1, 1-2, 2, 66 were correctly classified as abnormal while three were classified as normal.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Multidimensional slit-scan detection of bladder cancer. Preliminary clinical results. 241 61

Ehrlich cancer cells and inflammatory cells in mouse ascitic fluid were hydrolyzed and stained with acridine orange (AO). The AO hydrolysis curves for G1/G2 + M phase cancer cells and inflammatory cells were differentially determined using flow cytometry by monitoring the metachromatic red-shifted fluorescence of the fluorochrome bound to the single-stranded DNA produced by acid hydrolysis. By computer fitting of the Bateman function to the hydrolysis curves, the kinetic parameters k1 (rate constant for the production of single-stranded DNA), k2 (rate constant for the degradation of the produced single-stranded DNA), and y0 (theoretical value of the single-stranded DNA present initially) were determined. It was found that the k2 value, which reflects the degree of DNA instability, was much higher for cancer cells in both the G1 and G2 + M phases than for inflammatory cells. This finding led us to develop a method for the differential AO staining of cancer cells and non-cancerous cells utilizing the different degree of DNA instability at acid hydrolysis. AO staining after hydrolysis with 2N HCl at 30 degrees C for 8.5 min was found to be the optimal method. In the 60 cases of human malignant epithelial and nonepithelial tumors tested, all of the malignant tumor cells emitted metachromatic red fluorescence, while all of the nonmalignant tumor cells (5 cases of benign tumor) and normal cells emitted orthochromatic green fluorescence when observed with a violet excitation light under a fluorescence microscope. This new technique can be a useful tool for the screening of malignancy in exfoliative cytology and also for basic cancer research.
 ...
PMID:Different instability of nuclear DNA at acid hydrolysis in cancerous and noncancerous cells as revealed by fluorescent staining with acridine orange. 242 70

A series of metalloporphyrins linked through basic chains to certain DNA interactive groups has been synthesized. Several of these agents reproduce the characteristic properties of the antitumor glycopeptide bleomycin, including the oxygen-mediated scission of DNA in the presence of thiols, antibiobic activity under aerobic conditions, and activity against human and animal tumor models. Initial screening by scission of PM2-CCC-DNA identified six of the compounds, including those bearing acridine and acodazole intercalating groups, as the most active. The specificity of the oxygen-mediated scission of a 139 base pair HindIII/NciI restriction fragment of pBR322 by these six selected agents was then determined and compared with the action of pancreatic DNase by densitometric scans. All six of these compounds produce uniform base and sequence neutral cleavage of the restriction fragment at each base site. The six active compounds bear either of two types of intercalators, 6-chloro-2-methoxyacridine or acodazole, and with linkages to the ferric binding domain of -NH(CH2)2-, -NH(CH2)3-, -NH(CH2)4-, or -NH(CH2)3NH(CH2)3- and either porphyrin or deuteroporphyrin moieties. Comparison of the Kassoc values for binding to calf thymus DNA suggests that the enhanced binding observed with the linker -NH(CH2)3NH(CH2)3- contributes to the efficiency of sequence neutral DNA scission and may be a factor in the relative anticancer activities of these agents. The iron porphyrins give no evidence of the production of base propenals in DNA degradation, and the autoradiograms clearly indicate that a phosphate group is attached to the 5' end of the oligomer. The scission is partially suppressible by catalase and superoxide dismutase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Deoxyribonucleic acid cleavage specificity of a series of acridine- and acodazole-iron porphyrins as functional bleomycin models. 242 95

We propose a method for visually enhancing residual cutaneous carcinoma in excision sites using topical stains. Utilizing nude mice, topical stains were applied to fresh wound beds containing partially resected human squamous cell carcinoma xenografts. Fifteen of 18 tumors were visually enhanced using topical 1% acridine orange and ultraviolet light, while none of the seven tumors stained with 0.25% dihematoporphyrin ether and ultraviolet light were enhanced. Of the stains tested, only acridine orange proved to visually enhance tumor tissue in a fresh wound bed. This study establishes the concept of direct wound staining as an aid in the excision of cutaneous cancers.
 ...
PMID:Topical vital staining of human squamous cell carcinoma xenografts in nude mice. 245 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>