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T An

Publications and source records attributed to T An.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effect of transfection of a Drosophila topoisomerase II gene into a human brain tumour cell line intrinsically resistant to etoposide.

The human brain tumour cell line HBT20 is intrinsically resistant to etoposide and does not express mdr-1 mRNA. These studies were conducted to determine whether transfecting a Drosophila (D) topoisomerase II (topo II) gene into HBT20 cells could increase their sensitivity to etoposide. A D-topo II construct in a pMAMneo vector under the control of a mouse mammary tumour virus (MMTV) promoter was transfected into HBT20 cells. The gene is inducible by dexamethasone (Dex). The growth rate of the transfected cells and percentage of the cells in G1, S and G2M was no different than the parental cells. Survival after etoposide exposure (10 microM x 2 h) was measured by colony formation. Parental cells and cells transfected by pMAMneo vector alone showed no enhanced etoposide sensitivity after 24 h of Dex stimulation. By contrast, D-topo II transfected cells were sensitised 3-fold when etoposide treatment was preceded by 24 h Dex stimulation. Northern blotting and Western blotting confirmed that Dex had induced D-topo II expression in the sensitised cells. However, in D-topo II-transfected cells increasing the duration of Dex stimulation to 48 h eliminated the sensitisation to etoposide although increased MMTV promoter activity and expression of the D-topo II gene persisted. Measurement of endogenous human topo-II mRNA and protein revealed a decrease after Dex exposure of greater than 24 h. At these distal times, the total cellular topo II levels (endogenous + exogenous) may be decreased, which may explain why increased sensitivity to etoposide could no longer be demonstrated. This model suggests that D-topo II gene transfection can sensitise de novo resistant HBT20 cells to etoposide but that the time frame of that sensitisation is limited.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Transfection of a human topoisomerase II alpha gene into etoposide-resistant human breast tumor cells sensitizes the cells to etoposide.

The etoposide-resistant human breast cancer cell line MDA-VP was derived from MDA-parent cells by sequential selection in increasing concentrations of etoposide. MDA-VP cells express a lower amount of topoisomerase II alpha mRNA than the MDA-parent does, have mutations in topoisomerase II alpha (topo II) cDNA, and show cross-resistance to doxorubicin and amsacrine. We investigated whether transfer of a normal human topoisomerase II alpha (H-topo II) gene into MDA-VP cells could overcome their resistance to etoposide. H-topo II in a mammalian expression vector containing a glucocorticoid-inducible mouse mammary tumor virus (MMTV) promoter (pMAMneo) was transfected into MDA-VP cells (MDA-VP-hTOP2MAM). These H-topo II-transfected cells showed increased H-topo II mRNA expression and protein levels compared with MDA-VP parental cells or with MDA-VP cells transfected with the control pMAM vector (MDA-VP-MAM). Following cell exposure to dexamethasone, DNA-protein cleavable complex formation and cytotoxicity induced by etoposide, doxorubicin, and amsacrine were increased in the MDA-VP-hTOP2MAM cells compared with MDA-VP-MAM cells. However, these changes were short-lived, and by 24 h, cytotoxicity, cleavable DNA-protein complex formation, and H-topo II protein levels returned to baseline values. These results indicate that sensitivity of MDA-VP cells correlated with changes in cellular H-topo II. The gene transfer of a normal H-topo II gene can sensitize MDA-VP cells to the actions of multiple antineoplastic agents that target topo II.

Amsacrine↗
PubMed1995

Synovial thickening detected by MR imaging in osteoarthritis of the knee confirmed by biopsy as synovitis.

Previous studies have established the value of magnetic resonance imaging (MRI) in detecting articular changes characteristic of osteoarthritis (OA) of the knee. We have observed some MRI features in OA of the knee presumably indicating synovial thickening. To determine whether these MR features represent chronic synovial inflammation, we studied the knees of nine patients at the mild end of the spectrum of OA of relatively short duration (89%: < or = 4 yr), who were selected because MRI showed anatomical abnormalities compatible with synovial thickening. The painful knee was examined using conventional and weight-bearing radiographs, MRI, and arthroscopy. MR images suggestive of synovial thickening typically appeared in or near the intercondylar region of the knee, in the infrapatellar fat pad, or in the posterior joint margin. The site of an arthroscopic biopsy of the synovial membrane was guided by MRI to the area thought to represent synovial thickening for each patient knee. Pathological examination of these synovial membrane biopsies showed a mild chronic synovitis, and thus a correspondence with the synovial thickening detected by MRI. Our results suggest that MRI can be used to evaluate the extent of synovitis, observed as synovial thickening, in patients with early OA of the knee.

Arthroscopy↗
PubMed1994

Liposomal muramyl tripeptide up-regulates interleukin-1 alpha, interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 gene expression in human monocytes.

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a new biologic agent presently in clinical trials for metastatic osteosarcoma and melanoma. The mechanism of L-MTP-PE antitumor activity is linked to its activation of monocyte tumoricidal function. The purpose of this study was to determine whether L-MTP-PE affected the expression of cytokine genes in monocytes. Monocyte interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha expression were all up-regulated after a 2-h incubation with L-MTP-PE. The increased expression of IL-1 alpha, IL-1 beta, IL-6 and IL-8 persisted up to 72 h. Increased TNF-alpha expression declined by 24 h. The kinetics of cytokine expression stimulated by L-MTP-PE were different from those seen after lipopolysaccharide (LPS) stimulation. Lipopolysaccharide stimulation caused a rapid increase in cytokine expression followed by a rapid decline. L-MTP-PE did not affect the expression of these cytokines in lymphocytes, nor did L-MTP-PE upregulate IL-2 expression in lymphocytes. The early up-regulation of all five cytokines was due to an increase in the transcriptional activity. Modification of mRNA stability was not detected at 2 h but was seen after a 24-h exposure to L-MTP-PE. The subsequent production and secretion of these cytokine proteins may play a role in L-MTP-PE antitumor activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Effect of Adriamycin on liposomal muramyl tripeptide's ability to up-regulate monocyte cytokine expression.

Liposomal muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) is a biological agent in phase I and II trials for osteosarcoma and melanoma. Its mechanism of action has been linked to its ability to activate monocyte tumoricidal function and to stimulate monocyte production of tumor necrosis factor (TNF) and interleukins(IL)-1, -6, and -8. Our ultimate goal is to combine L-MTP-PE with chemotherapy. The purpose of this study was to determine whether doxorubicin (Adriamycin) interfered with the ability of L-MTP-PE to activate monocyte cytokine production. Human monocytes were cultured with or without 5-500 ng/ml of Adriamycin for 3 h and washed before being exposed to 2 micrograms/ml L-MTP-PE for 16 h. Cultured supernatants were collected and assayed for TNF, IL-1, IL-6, and IL-8. The messenger RNA expression of IL-1 alpha, IL-1 beta, TNF alpha, IL-6, and IL-8 was quantified with northern blot analysis. Adriamycin did not suppress the up-regulation of any of these cytokines. We concluded that combination therapy with L-MTP-PE and Adriamycin is feasible and that this combination warrants further investigation in a clinical setting.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1993

Cytokine production and immune cell activation in melanoma patients treated with liposomal muramyl tripeptide (CGP 19835A lipid).

We conducted a pilot study using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) preoperatively in patients with stage III or IV resectable melanoma who were at high risk for recurrence. Patients received L-MTP-PE for 1 month before surgery and then 5 months postoperatively. Several immune parameters were monitored during preoperative therapy to search for correlations with clinical (tumor) response. The 18 patients were classified into three groups according to their responses and disease-free intervals: no evidence of disease (NED) at week 24 of therapy, relapse during therapy and progressive disease on therapy noted at the time of surgery. Six of nine patients in the NED group demonstrated increased monocyte tumoricidal activity (MTA) during week 1 of therapy. MTA increased in three of the six patients in the relapse group. MTA did not increase in the three patients who had progressive disease on therapy. Plasma neopterin levels were elevated by 72 h following the first L-MTP-PE dose in all 18 patients. Circulating levels of tumor necrosis factor were elevated in 15 of 16 patients tested, and IL-6 levels were elevated in all 18 patients. Melanoma cells from all three patients with progressive disease at the time of surgery proliferated well in vitro, whereas tumor cells from 10 of the 15 patients in the other two groups did not proliferate. There were no discernible differences among the three groups in the magnitude of IL-2-induced proliferation of tumor infiltrating lymphocytes. However, IL-2-activated TILs from the NED group exhibited cytotoxicity against autologous tumor cells in vitro. In summary, whereas L-MTP-PE stimulated several immunologic responses in all patients, the only two parameters that correlated with clinical status were MTA and the tumor proliferation assay. These two biologic assays could serve to distinguish potential responders from nonresponders early in the course of treatment.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Cellular distribution of a colonic adenoma-associated antigen as defined by monoclonal antibody Adnab-9.

Adenomatous colonic polyps constitute a precursor for colorectal cancer. Antibodies to these precancerous lesions might identify specific early tumor antigens. Adnab-9 is a murine monoclonal antibody raised against membranes of colonic adenomas. Adnab-9 binding in colonic washings (effluent) correlates with the presence of colorectal cancer. Immunohistochemical staining with Adnab-9 shows cytoplasmic reactivity in scattered cells in 4 of 31 adenomatous tissue sections, 0 of 14 sections of colorectal cancer cells, and 1 of 8 normal-appearing colonic mucosa specimens examined. Adnab-9 recognized a dominant M(r) 87,000 protein species in tissue extracts in the membrane-bound fraction of effluent by Western blotting. Adnab-9 binding by enzyme-linked immunosorbent assay in adenomatous extracts is higher than cancer or normal tissue, is membrane-bound, and is absent from established colorectal cancer cell lines. This distribution and nature of immunostaining suggest that Adnab-9 recognizes a determinant associated with the membrane component of a subpopulation of adenoma cells which may have a role in early colorectal neoplasia.

Adenoma↗
PubMed1992

Proteoglycans from osteoarthritic human articular cartilage influence type II collagen in vitro fibrillogenesis.

Collagen fibrils were formed in the presence of dermatan sulfate (DSPG) and high density (HDPG) proteoglycans isolated from human adult knee femoral articular cartilage. Eroded cartilage had a higher percentage of DSPGs in the extracted proteoglycans than normal cartilage (p = .018). The dermatan sulfate proteoglycans (DS-PGI and DS-PGII) were detected in normal and osteoarthritic cartilage. DSPGs compared to HDPG inhibited in vitro collagen fibrillogenesis producing a longer lag phase (p less than .05) and a slower rate of fibril formation (p less than .05). DSPGs from eroded osteoarthritic cartilage alone or in combination with HDPG produced a longer lag phase than DSPGs from normal cartilage alone or in combination with HDPG (p less than .05). The inhibition of fibrillogenesis by DSPGs suggests that collagen fibril formation in vivo may be abnormal due to the influence of molecular changes in proteoglycan as well as an increased proportion of DSPGs occurring in osteoarthritic cartilage. Abnormal fibril formation may produce a weakened cartilage matrix, thus contributing to an accelerated process of cartilage degeneration in osteoarthritis.

Cartilage, Articular↗
PubMed1990

Immunohistochemical study of melanocytic nevus and malignant melanoma with monoclonal antibodies against S-100 subunits.

Immunohistochemical localization of S-100 protein alpha and beta subunits in the cells of melanocytic nevi and malignant melanomas was studied by using monoclonal antibodies directed against each subunit. Although polyclonal anti-S-100 reactivities have been demonstrated uniformly in all nevus cells and melanoma cells, monoclonal anti-S-100 alpha and anti-S-100 beta reactivities were either absent or rarely found in ordinary junctional nevi or junctional nests of ordinary compound nevi. However, in the junctional nests of dysplastic junctional nevi and junctional components of dysplastic compound nevi, monoclonal anti-S-100 alpha reactivity become more frequent, whereas monoclonal anti-S-100 beta reactivity remains negative. In the superficial variety of melanomas such as superficial spreading melanoma and lentigo maligna melanoma, monoclonal anti-S-100 beta is nonreactive until vertical growth or invasiveness begins. Most nodular melanomas are positively stained with both monoclonal anti-S-100 alpha and anti-S-100 beta. It is suggested that monoclonal anti-S-100 alpha can be an indicator of active junctional nevus of melanocytic nevi and the reactivity with monoclonal anti-S-100 beta may be related to vertical progression of superficial spreading melanomas and lentigo maligna melanomas.

Antibodies, Monoclonal↗
PubMed1990

Efficacy of liver wound healing by secondary intent.

Nonoperative treatment of liver injury raises questions about liver wound healing (LWH) when the edges are not approximated by primary intent. The efficacy of LWH was studied in 18 dogs and 18 pigs with a total of 108 standard 6-cm injuries. The 36 injuries in six dogs and six pigs were compressed for hemostasis and then allowed to heal by second intent. LWH in these animals was compared to 36 liver wounds in six dogs and six pigs following primary closure (hepatorrhaphy) and 36 liver wounds after omental buttress plus hepatorrhaphy in six dogs and six pigs. Average wound breaking strength (WBS) of liver wounds was studied at 3 weeks (54 wounds) and 6 weeks (54 wounds) with a Chatillon tensiometer and microscopic analysis. The WBS of liver wounds was also compared to normal uninjured liver WBS. The porcine WBS at 3 weeks after healing by second intent (0.31 kg/cm2) was similar to the WBS at 3 weeks after healing by hepatorrhaphy (0.30 kg/cm2) and omental buttress (0.25 kg/cm2). Porcine WBS at 6 weeks after healing by second intent was significantly greater than WBS at 6 weeks after hepatorrhaphy or omental buttress. The canine WBS at 3 weeks after healing by second intent exceeded WBS at 3 weeks after hepatorrhaphy or omental buttress. Canine WBS at 6 weeks after healing by second intent exceeded WBS at 6 weeks after omental buttress and was similar to WBS at 6 weeks after hepatorrhaphy. WBS in all groups paralleled the extent of fibrosis seen on microscopic analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Articular cartilage defects of the knee: correlation between magnetic resonance imaging and gross pathology.

Magnetic resonance imaging (MRI) of the knee articular cartilage is possible owing to the contrast provided by different signal intensities of adjacent menisci and subchondral bone. The objective of this study was to determine the accuracy of MRI in quantitatively detecting thinning and focal defects of articular cartilage in vivo. High resolution MRI was performed followed by dissection of the knee within one hour of amputations above the knee of eight patients (62-89 years) with peripheral vascular disease. Articular cartilage was examined for erosions, surface irregularities, and appearance. Mean thicknesses of femoral and tibial articular cartilage sagittal sections from MRI were statistically indistinguishable from matched gross thicknesses. In those joints in which cartilage erosions, thinning, or irregularities were detected by MRI the same defects were apparent by gross examination. Cartilage that appeared normal by MRI had a normal gross appearance by gross examination. Thus high resolution MRI can accurately predict gross articular cartilage appearance and thickness, allowing an objective, quantitative, noninvasive assessment of eroded cartilage.

Aged↗
PubMed1987

In situ quantitation of inflammatory mononuclear cells in ductal infiltrating breast carcinoma. Relation to prognostic parameters.

The authors examined inflammatory mononuclear cells in 10 fibroadenomas and 56 ductal infiltrating type carcinomas of the breast to see whether the distribution of various subpopulations of the mononuclear cells were correlated with known histologic, biochemical, and clinical parameters of the cancers. T cells, B cells, natural killer cells, and macrophages were quantitated on frozen tissue sections, which were stained with monoclonal antibodies, as demonstrated by the immunoperoxidase technique. The carcinomas had significantly higher numbers of T cells, Leu-3+ helper-inducer cells, T8+ cytotoxic-suppressor cells, M5+ macrophages, and T6+ Langerhans cells than the fibroadenomas. There were no significant differences in the distribution of natural killer cells. Among these mononuclear subsets, helper-inducer T cells were the primary cell type in both benign and malignant neoplasms. Estrogen receptor-positive carcinoma had significantly fewer numbers of T cells and the subgroup of Leu-3+ helper-inducer cells. Clinical Stage 3 cancers had significantly fewer numbers of T cells and natural killer cells than both fibroadenomas and Stage I and II neoplasms. Prominent infiltration of T cells, specifically helper-inducer cells, is not associated with estrogen receptor positivity, which is known to be a favorable prognostic marker of breast carcinoma. The findings of fewer T cells and natural killer cells in Stage 3 carcinomas are intriguing but unexplained.

Adenofibroma↗
PubMed1984

Augmented gastrin responses in diabetic patients with vagal neuropathy.

We evaluated serum gastrin responses to a test meal in normal subjects and diabetic patients with or without vagal neuropathy. Vagal neuropathy was defined as a heart rate variation during deep breathing of less than 9 beats/min. Forty-three percent (54 out of 124) of the diabetic patients had abnormal heart rate variation, compared with 5% (3 out of 53) of the normal subjects. Serum gastrin responses to a test meal were examined in 17 normal subjects, 20 out of 70 diabetic patients without vagal neuropathy and 17 out of 54 diabetic patients with vagal neuropathy. Meal-stimulated gastrin levels were significantly higher in the diabetic patients with vagal neuropathy than in the normal subjects, while the findings in the diabetic patients without vagal neuropathy were similar to those in normal subjects. These data suggest that augmented gastrin responses are due to vagal denervation induced by autonomic neuropathy.

Diabetic Neuropathies↗
PubMed1984

Breast carcinoma with osseous metaplasia: an electron microscopic study.

A breast carcinoma containing osseous metaplasia was examined with electron microscopy. The heterologous components were intermingled closely with the usual infiltrating ductal type of a breast carcinoma. Ultrastructurally, carcinoma cells were distinguished clearly from the various mesenchymal cells composed of active fibroblasts, osteoblasts, and osteoclasts. No intermediate cells were present between the two distinct cell populations. Our findings are consistent with the stromal cell origin of the heterologous components and are discussed with relation to their histogenesis in breast carcinoma.

Aged↗
PubMed1984

Are Fc gamma receptors naturally clustered on normal human B lymphocytes?

The Fc gamma receptor (FcR) on normal human B lymphocytes was studied by using electron-microscopic monovalent ligands made of one ferritin (Fer) and one rabbit IgG anti-Fer. The binding of ligands was ascertained with the modified Coombs mixed antiglobulin reaction. The receptors were found clustered at 0 degree C, which was not affected even by examining the coated cells without washing away excess of the ligand solution, or by cross-linking bound ligands with a second antibody. The clusters varied in length, measuring up to 220 nm. Most of them were less than 110 nm long, and were seen as spots. When lymphocytes were preincubated with both cytochalasin B and colchicine, the clustering of FcR was not affected. Our findings show that FcR on B lymphocytes are naturally aggregated, which is not primarily mediated with the cytoskeletons made of actin microfilaments and microtubules.

Animals↗
PubMed1983

Hyaline globules and intracellular lumina in a hepatocellular carcinoma.

The authors report ultrastructural findings on the morphogenesis of hyaline globular inclusions (HG) of a moderately well-differentiated hepatocellular carcinoma, with the features of a fibrolamellar variant. Pale blue cytoplasmic inclusions (pale bodies) of the tumor cells were shown to be intracellular lumina lined with numerous microvilli. Our findings suggest that HG were formed apparently by the successive deposition of fine granular materials in the lumina. Small accumulations were present in the intracellular lumina, which were seen on light microscopy as central hyaline cores of pale inclusions. Larger globular deposits, corresponding to HG and presumably mature ones, were lined closely with membranes devoid of microvilli that were probably shed intraluminally. Our observation was discussed with relation to the previous findings on the inclusions.

Adult↗