Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The level of sulfo-Lea (SO3-3Gal beta 1-3(Fuc alpha 1-4)GlcNAc) epitope recognized by monoclonal antibody (mAb) 91.9H in hepatic metastasis of colon carcinoma is known to be lower than at the primary sites. We examined 19 human colon carcinoma cell lines for their production of this epitope. Sixteen cell lines were found to produce high M(r) components that metabolically incorporated [35S]sulfate and were resistant to heparitinase I and chondroitinase ABC, and 8 of them were reactive with mAb 91.9H as shown by western blotting analysis. These were all of the 4 cell lines derived from well differentiated primary tumors (HCCP-2998, LS174T, GEO, and CBS), 2 of 10 cell lines (DLD-1 and HCT116) from moderately to poorly differentiated primary tumors, and 2 of 5 cell lines (SW480 and HCC-M1544) from metastases. Incubation of LS174T cells with benzyl-N-acetyl-alpha-D-galactosaminide abrogated the incorporation of [35S]sulfate and the reactivity of mAb 91.9H with high M(r) components in the cell lysates. Sodium chlorate, which inhibits the formation of 3'-phosphoadenosine 5'-phosphosulfate, also inhibited the [35S]sulfate incorporation and reactivity with mAb 91.9H. These treatments did not change the incorporation of [14C]threonine into high M(r) components. These results indicated that sulfo-Lea epitopes were expressed on O-linked carbohydrate chains in sulfomucins. Immunohistochemical studies of tumor tissues in nude mice indicated that sulfo-Lea was expressed at the site of orthotopic transplantation in the cecum. The expression appeared to be suppressed in liver metastatic foci in nude mice.
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PMID:Expression of mucin-associated sulfo-Lea carbohydrate epitopes on human colon carcinoma cells. 1008 87

We investigated the mechanism of adhesion of highly malignant ascites hepatoma AH66F cells to mesothelial cells. The adhesion rate of AH66F cells to mesentery-derived mesothelial cells (M-cells) was about 46% at 37 degrees C, but it decreased to about 27% at 4 degrees C. The adhesion rate of AH66F cells was about 25% in the presence of leukocyte function-associated antigen 1 (LFA-1) mAb at both 4 C and 37 C. When M-cells were treated with hyaluronidase, the AH66F/M-cell adhesion was decreased to half at 37 degrees C and had nearly disappeared at 4 degrees C. The residual adhesion of AH66F cells to M-cells treated with hyaluronidase almost disappeared in the presence of LFA-1 mAb. AH66F cells strongly adhered to a hyaluronate (HA)-coated plate, but not to a bovine serum albumin-coated plate. AH66F cells expressed a CD44 molecule (a HA receptor) in the plasma membrane, with a molecular size of about 85 to 90 kDa, corresponding to the CD44H isoform. These results indicated that the adhesion of AH66F cells to mesothelial cells is composed of pathways of CD44/HA and LFA-1/ICAM-1.
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PMID:Adhesive interaction of highly malignant hepatoma AH66F cells with mesothelial cells. 1044 75

Diffusion-weighted (Dw) imaging has for a number of years been a diagnostic tool in the field of neuroradiology, yet only since the end of the 1990s, with the introduction of echoplanar imaging (EPI) and the use of sequences capable of performing diffusion studies during a single breath hold, has it found diagnostic applications at the level of the abdomen. The inherent sensitivity to motion and the magnetic susceptibility of Dw sequences nonetheless still create problems in the study of the abdomen due to artefacts caused by the heartbeat and intestinal peristalsis, as well as the presence of various parenchymal-gas interfaces. With regard to focal liver lesions, a review of the literature reveals that Dw imaging is able to differentiate lesions with high water content (cysts and angiomas) from solid lesions. With regard to the latter, although there are differences between benign forms [focal nodular hyperplasia (FNH), adenoma] and malignant forms [metastasis, hepatocellular carcinoma (HCC)] in their apparent diffusion coefficient (ADC) in the average values for histological type, there is a significant overlap in values when lesions are assessed individually, with the consequent problem of their correct identification. One promising aspect is the possibility of quantifying the degree of fibrosis in patients with chronic liver disease and cirrhosis given that the deposit of collagen fibres "restricts" the motion of water molecules and therefore reduces ADC values. However, even in this field, studies can only be considered preliminary and far from real clinical applications. The retroperitoneum is less affected by motion artefacts and similarly deserves the attention of Dw imaging. Here it is possible to differentiate mucin-producing tumours of the pancreas from pseudocystic forms on the basis of ADC values even though the limited spatial resolution of Dw imaging does not enable the identification of small lesions. Dw imaging may be applied to the study of the kidney to differentiate hydronephrosis from pyonephrosis and with regard to tumours, solid from pseudocystic forms. In addition, given that renal parenchyma has significantly variable ADC values on the basis of the anatomic section and physiological conditions, the possibility of assessing functional alterations is currently being studied. Indeed, a good correlation has been found between ADC values and glomerular filtration rate. With regard to musculoskeletal applications, the absence of motion artefacts in the regions studied has enabled the development of sequences less sensitive to magnetic susceptibility and with greater spatial resolution than EPI. Attempts have therefore been made to use Dw imaging in the characterization of soft-tissue tumours although the findings so far have been disputed. Greater agreement has been found regarding sensitivity of the technique in assessing response of these tumours to chemotherapy: tumour necrosis is thought to increase ADC whereas the persistence of vital neoplastic tissue tends to lower it. One of the most promising applications of Dw imaging is without doubt the assessment of vertebral collapse where a high ADC has been shown to be associated with an osteoporotic cause and a low ADC with a neoplastic cause. Nonetheless, even here, a moderate overlap between ADC values of the two types has been encountered. Dw imaging has also been used in the assessment of bone marrow cellularity: areas of tightly packed cells show a higher ADC value than hypocellular areas. In particular, no significant difference in ADC is noted between normal hypercellular bone marrow and hypercellular bone marrow secondary to lymphomatous infiltration whereas this difference is significant between hypocellular, normocellular and haematopoietic hypercellular bone marrow. With regard to the study of joints, the limited structure dimensions, particularly cartilage, creates technical difficulties related to spatial resolution and an adequate signal-to-noise ratio, problems that can only be solved by further technological developments. Lastly, a significant difference in ADC values between degenerative and inflammatory effusion has been found, a fact that may be explained as the result of the activity of hyaluronidase present in inflammatory forms, which causes a reduction in the concentration of hyaluronic acid with a consequent decrease in viscosity.
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PMID:Magnetic resonance diffusion-weighted imaging: extraneurological applications. 1668 86

In recent years, cancer treatment has been facing the challenge of increasing antitumor efficiency and avoiding severe adverse effects simultaneously. In this study, we designed a controlled release drug delivery system, doxorubicin (Dox)-loaded and hyaluronic acid (HA)-modified PEGylated gold nanocages (AuNCs), which was designated as PEG-HAn-AuNCs/Dox (n represented 10n HA repeating units were modified on each AuNC). In this system, AuNCs were applied as the photothermal cores, Dox was employed as the model drug, HA was applied as the tumor-microenvironment responsive switch to achieve controlled release, and poly (ethylene glycol) (PEG) was used as the stealth polymer to prolong systemic circulation time. Firstly, we evaluated the physical and chemical properties of the PEG-HAn-AuNCs/Dox with different ratios of HA to AuNC and found that PEG-HA4-AuNCs/Dox was the optimal. Secondly, PEG-HA4-AuNCs/Dox revealed the feature of controlled release, namely, the drug release was triggered by hyaluronidase (HAase) and accelerated by the acidic pH and near-infrared (NIR) irradiation. And then PEG-HA4-AuNCs/Dox could be effectively delivered to a cultured SMMC-7721 cell line in vitro and the tumor tissues of the subcutaneous mouse models of hepatocellular carcinoma (HCC) in vivo. Finally, the results demonstrated the synergetic therapy, namely the combination of chemotherapy and photothermal therapy (PTT) (defined as chemo-photothermal therapy) mediated by PEG-HA4-AuNCs/Dox, could efficiently inhibit the tumor growth both in vitro and in vivo. Therefore, the advantages of PEG-HA4-AuNCs/Dox endowed it as a great potential candidate for HCC treatment.
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PMID:PEGylated hyaluronidase/NIR induced drug controlled release system for synergetic chemo-photothermal therapy of hepatocellular carcinoma. 3077 81


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