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Biomedical subjects

Q Peng

Publications and source records attributed to Q Peng.

At least 19 recordsLinked to original sources

Isolation and characterization of the major form of human MUC18 cDNA gene and correlation of MUC18 over-expression in prostate cancer cell lines and tissues with malignant progression.

Ectopical expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the development and malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. We cloned and characterized the human MUC18 (huMUC18) cDNA gene from three human prostate cancer cell lines and three human melanoma cell lines. The cDNA sequences from the six human cancer cell lines were identical except differences in one to five nucleotides. The deduced amino acid sequences of the longest ORF were 646 amino acids that were identical in these cDNAs except for one to three amino acid residues. The amino acid sequences of all our huMUC18 cDNA genes are similar to that cloned by other group (GenBank access #M28882) except differences in the same seven amino acids. We conclude that huMUC18 cDNA gene reported here represents the gene product from a major allele. The MUC18 mRNA and protein was expressed in three metastatic prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one non-metastatic prostate cancer cell line (LNCaP.FGC). The expression of huMUC18 in these four cell lines is positively related to their extent of in vitro motility and invasiveness and in vivo metastasis in nude mice. HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from cultured primary normal prostatic epithelial cells and the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas, and in cells of a perineural invasion, a lymph node, and a lung metastases compared to that in normal or benign hyperplastic epithelium (BPH). We therefore conclude that MUC18 expression is increased during prostate cancer initiation (high grade PIN) and progression to carcinoma, and in metastatic cell lines and metastatic carcinoma. Increased expression of MUC18 is implicated to play an important role in developing and malignant progression of human prostate cancer. Furthermore, the lacking of predominant cytoplasmic membrane expression of MUC18 appeared to correlate with malignant progression of prostate cancer.

Amino Acid Sequence↗

Selective distribution of porphyrins in skin thick basal cell carcinoma after topical application of methyl 5-aminolevulinate.

Topical photodynamic therapy (PDT) of superficial basal cell carcinoma (BCC) with 5-aminolevulinic acid (ALA) has achieved promising clinical results. However, the efficacy of this therapy for thick BCC is dramatically decreased by a limited diffusion of hydrophilic ALA into the tumor. Lipophilic esters of ALA may enhance their penetration into the lesion. In this randomized, open clinical study, microscopic fluorescence photometry incorporating a light-sensitive thermo-electrically cooled charge-coupled device (CCD) camera was employed to investigate the penetration of methyl 5-aminolevulinate-induced porphyrin fluorescence in thick BCC lesions. Both the distribution pattern and the amount of porphyrins in 32 lesions of 16 patients were studied after topical application of 16, 80 or 160 mg/g of methyl 5-aminolevulinate for 3 or 18 h. A highly selective and homogeneous distribution of methyl 5-aminolevulinate-induced porphyrin fluorescence was seen in all lesions studied, with much less fluorescence in the adjacent normal skin tissues. In lesions of up to 2 mm thickness the application of 160 mg/g methyl 5-aminolevulinate for 3 h showed the highest ratio of porphyrin fluorescence depth to tumor depth (0.98+/-0.04), thus providing a biologic rationale for a clinical PDT trial with this regimen.

Administration, Topical↗

Evaluation of protoporphyrin IX production, phototoxicity and cell death pathway induced by hexylester of 5-aminolevulinic acid in Reh and HPB-ALL cells.

Production of protoporphyrin IX (PpIX) in human B-cell leukemia cell line (Reh) and T-cell lymphoma cell line (HPB-ALL) was studied by flow cytometry after incubation with 5-aminolevulinic acid (ALA) or its hexylester in vitro. Cell survival and cell death pathway were also investigated in these two cell lines by cell growth curves, flow cytometry, and electron microscopy after ALA hexylester-mediated photodynamic therapy. Both ALA and its hexylester could induce PpIX production in the two cell lines, but ALA hexylester was about 100 times more efficient than ALA. Reh cells appear to be more sensitive than HPB-ALL cells to ALA hexylester-mediated phototoxicity. Apoptosis was the major cell death pathway of Reh cells, while necrosis played a major role in the case of HPB-ALL cells.

Aminolevulinic Acid↗

Antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy can be enhanced by the use of a low dose of photofrin in human tumor xenografts.

Practically all of the exogenous photosensitizers used for clinical photodynamic therapy (PDT) target mainly vasculature. Although effective in tumor destruction, they also, unavoidably, induce phototoxicity of normal tissues. Porphyrins synthesized endogenously from 5-aminolevulinic acid (ALA) accumulate within cells. Tumor eradication would be more efficient if both cellular components and vascular stroma of a tumor could be targeted. Thus, PDT with a mixture of ALA and Photofrin (Pf, a vessel-targeted sensitizer) may simultaneously destroy the two elements. Using chemical extraction assays, pharmacokinetics of ALA and ALA-induced porphyrins were studied in the plasma and tumors of nude mice bearing human WiDr and KM20L2 colonic carcinomas after an i.p. injection of 250 mg/kg body weight of ALA. Subsequently, PDT efficacy of the two tumor models with ALA, Pf, or with the two drugs in combination was evaluated. The phototoxic effects on tumor cells in vitro with the combined drugs was also determined. Moreover, histological and ultrastructural alterations of the treated tumors were investigated, and tumor cell clonogenicity was assessed as a function of time after in vivo PDT using an in vitro colony formation assay. Finally, the photosensitivity of normal skin tissue treated according to various protocols was compared. The amounts of ALA peaked at 0.5 h after administration in both plasma and WiDr tumor. The rates of ALA clearance seemed to follow a one-compartment model with half-lives of approximately 18 and 58 min in the plasma and tumor, respectively. About 100 and 60 times higher concentrations of ALA were needed to induce a given concentration of porphyrins in the plasma and tumor, respectively, although the plasma porphyrins may not only be released from blood cells but also from other organs. Similar kinetics of distribution patterns of ALA- and ALA methylester-induced porphyrins were found in the plasma and tumors, and the elimination rates were consistent with a two-compartment model. ALA induced much more porphyrins than ALA methylester in both plasma and tumors. Tumors PDT-treated with ALA plus Pf at a low dose (1 mg/kg) grew significantly more slowly than those treated with either of the drugs in both WiDr and KM20L2 models. However, the enhanced antitumor effect was not found in the tumor cells under in vitro conditions. Morphological studies demonstrated that PDT with the combined regimen resulted in necrosis of neoplastic cells and severe disruption of tumor microvasculature. This was supported by the findings obtained from the studies of in vivo PDT and in vitro clonogenic assay that showed a progressive reduction in tumor cell viability with times following PDT. Such a combined PDT protocol did not induce any phototoxicity in normal skin tissue. These data indicate that targeting both neoplastic cells and stroma with ALA and Pf (a low dose) can potentiate antitumor PDT effect with no risk of prolonged skin photosensitivity.

Adenocarcinoma↗

[Complication profiles of posterior chamber intraocular lenses IOL). An analysis of 586 foldable and 2077 rigid explanted intraocular lenses].

BACKGROUND: Foldable intraocular lenses (IOL) have become increasingly preferred choice for IOL implantation after cataract removal. However, both foldable as well as rigid IOLs are not yet complication-free and may need explanation. MATERIAL AND METHODS: A total of 2663 explanted posterior chamber IOLs (PCIOLs) were accessioned at the Center for Research on Ocular Therapeutics and Biodevices between January 1988 and September 2000. The lenses were examined grossly using a Leitz/Wild M-8-Zoom stereomicroscope. The clinical reasons for explanation were documented for foldable as well as for rigid lenses. RESULTS: Of a total of 2663 explanted PCIOLs, 586 were foldable lenses and 2077 were rigid PMMA lenses The most frequent reason for explantation of all 2663 IOLs studied was decentration/dislocation. Optic and haptic damage and posterior capsule rupture were significantly more often a reason for explantation in several foldable designs compared to rigid PCIOLs. Whereas rigid designs lead more often to corneal decompensation. The percentage of explanted IOLs because of inflammatory reactions decreased significantly from 1994 to 2000. CONCLUSIONS: The complication profiles of rigid and foldable IOLs revealed some apparent differences due to the nature of the IOL biomaterials and designs. IOL optic/haptic damage was a common complication for foldable IOLs, whereas it was only discovered in single digits for rigid PMMA IOLs. The possible explanation for this is, that the soft and flexible biomaterials, from which all the foldable IOLs were manufactured, are easier to be damaged during folding, unfolding and insertion procedure. In our opinion this relative disadvantage of foldable IOLs is by far outweighed by the numerous advantages of the small incision cataract surgery. The decreasing inflammatory reactions can be explained by advances in surgical techniques, especially the secure in-the-bag fixation of IOLs.

Humans↗

Eradication of posterior capsule opacification: documentation of a marked decrease in Nd:YAG laser posterior capsulotomy rates noted in an analysis of 5416 pseudophakic human eyes obtained postmortem.

OBJECTIVE: (1) To report the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy rate (%) of eight rigid and foldable intraocular lens (IOL) designs in a series of 5416 pseudophakic human eyes obtained postmortem, accessioned in our center between January 1988 and January 2000. (2) To identify factors that are instrumental in reducing the incidence of posterior capsule opacification, (PCO, secondary cataract) and hence the need for Nd:YAG laser posterior capsulotomy. DESIGN: Comparative autopsy tissue analysis. PARTICIPANTS: A total of 5416 globes with posterior chamber intraocular lens (PC-IOLs) obtained postmortem received from Lions Eye Banks between 1988 and 2000. METHODS: Miyake-Apple posterior photographic technique. Special reference was given to the presence or absence of Nd:YAG laser posterior capsulotomy orifice on the posterior capsule of each eye. MAIN OUTCOME MEASURES: The Nd:YAG laser posterior capsulotomy rate (%) as of January 2000 was documented. In addition, the Nd:YAG laser posterior capsulotomy rate for each lens was plotted on a monthly basis for the same period, creating a computerized trend or "timeline" for each IOL style. RESULTS: Relatively high Nd:YAG laser posterior capsulotomy rates ranging from 20.3% to 33.4% were noted with four relatively older designs (high incidence of implantation between 1988 and the early 1990s). Four modern foldable IOLs manufactured from silicone and acrylic materials had significantly lower Nd:YAG laser posterior capsulotomy rates ranging from 0.9% (Alcon Acrysof) to 17.1%. The difference in Nd:YAG rates among the eight IOL designs was found to be significant (P < 0.0001, chi-square test). Comparing foldable versus rigid designs, the foldable IOLs were associated with a much lower Nd:YAG laser posterior capsulotomy rate (14.1% vs. 31.1%). CONCLUSIONS: By use of the six factors regarding surgical technique and IOL choice described in this article, we strongly believe that the overall incidence of PCO and hence the incidence of Nd:YAG laser posterior capsulotomy is now rapidly decreasing from rates as high as 50% in the 1980s to early 1990s. Surgical tools and IOLs are now available to bring these rates down to single digits. Careful application and use of these tools by surgeons can genuinely lead in the direction of virtual eradication of secondary cataract, the second most common cause of visual loss worldwide.

Cataract↗

Dilation of Schlemm's canal in viscocanalostomy: comparison of 2 viscoelastic substances.

PURPOSE: To study the injection of viscoelastic material into Schlemm's canal adjacent to and 6.0 mm from the scleral flap during viscocanalostomy in an autopsy eye model. SETTING: Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Viscocanalostomy was performed in 8 postmortem human globes. Sodium hyaluronate (Healon GV or Healon5) was injected into 1 side of Schlemm's canal, with the other side serving as a control in some eyes. The eyes were prepared for light microscopic analysis, and serial pathologic sections were taken adjacent to the flap and 6.0 mm circumferentially from the flap. The area of Schlemm's canal was calculated and compared using t tests. RESULTS: Injecting viscoelastic material enlarged the area of Schlemm's canal adjacent to and 6.0 mm from the flap significantly more than not injecting viscoelastic material. While there was no difference between the viscoelastic materials in dilating Schlemm's canal at the flap, with Healon5 there was a small but statistically significantly greater dilation 6.0 mm from the flap. No full-thickness breaks in the trabecular meshwork were noted adjacent to or 6.0 mm from the flap. CONCLUSION: Injecting viscoelastic material significantly increased the cross-sectional area of Schlemm's canal and may play a role in the success of viscocanalostomy. Further study is needed to elucidate the mechanism of this procedure.

Anterior Eye Segment↗

Effect of heparin surface modification in reducing silicone oil adherence to various intraocular lenses.

PURPOSE: To evaluate surface properties of various intraocular lenses (IOLs), including a newly fabricated heparin-surface-modified (HSM) silicone IOL, with special reference to their efficiency in reducing potential silicone oil adherence to the IOL optics. SETTING: Center for Research on Ocular Therapeutics and Biodevices, Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Five groups of rigid and foldable IOLs were analyzed in an in vitro test for the percentage of silicone oil adherence: a single-piece foldable hydrophilic-acrylic IOL (n = 9); a single-piece rigid poly(methyl methacrylate) (PMMA) IOL with HSM coating of the lens optic (n = 9); a 3-piece foldable silicone optic IOL with HSM coating of the optic (n = 10); a single-piece standard rigid PMMA IOL (n = 7); and a standard 3-piece foldable silicone optic IOL (n = 9). After the IOLs were immersed in water and then in silicone oil, gross photographs taken. Image analysis was performed to evaluate the percentage of silicone oil coverage of the anterior and posterior surfaces of each IOL optic. RESULTS: The mean silicone oil coverage of the hydrophilic-acrylic IOLs was 5.6% +/- 2.5% (SD); of the HSM PMMA IOLs, 6.2% +/- 4.3%; of the HSM silicone optic IOLs, 6.7% +/- 3.2%; and of the standard PMMA IOLs, 20.3% +/- 13.3%. The mean silicone oil coverage was greatest on the standard silicone optic IOLs, 98.2% +/- 3.1%. CONCLUSIONS: Intraocular lenses with a hydrophilic optic have less tendency toward adherence to silicone oil than more hydrophobic designs. A foldable silicone IOL with heparin surface modification can significantly reduce potential silicone oil adherence, comparable to the level achievable with the rigid HSM PMMA designs. Two new foldable IOL styles, the HSM silicone IOL and IOLs in the general class of hydrophilic-acrylic, were highly efficacious in reducing silicone oil adherence. There is now a real choice of foldable lenses for patients with actual or potential vitreoretinal diseases.

Acrylic Resins↗

Linkage analysis of the 5q31-33 candidate region for asthma in 240 UK families.

Atopy and asthma are complex genetic diseases resulting from the interactions of a number of genetic and environmental factors. We had previously reported allelic association between the IL9 marker on chromosome 5q31-33 and atopy. In order to further investigate the role of susceptibility genes on 5q31-33 in the development of atopy and asthma we have studied 240 UK families comprising 131 families selected at random, 60 multiplex families with affected sib pairs, and 49 single proband nuclear families. Polymorphic markers on 5q31-33 were genotyped and both single and multipoint linkage analysis was undertaken using the BETA program. We have used both affection status and quantitative scores for atopy and asthma for phenotypic variables, combining data into scores for asthma and atopy. The strongest suggestion of linkage using multipoint analysis was centred around D5S410 with a maximum Lod of 1.946 at location 171.3 cM and a standard error of 3.3 for the asthma quantitative score. There was no evidence of linkage with atopy, the atopy quantitative score or total serum IgE.

Asthma↗

[Influence of surgery-related factors on the Nd:YAG laser capsulotomy rates of 3-piece silicone IOLs - analysis of 457 pseudophakic human globes obtained post mortem].

BACKGROUND: The purpose of this study was to analyze any possible surgical reasons which may have had caused posterior capsule opacification in 3-piece silicone IOLs that had required Nd:YAG laser treatment. Special attention was given to 1) quality of cortical clean up, 2) type of haptic fixation, and 3) continuous curvilinear capsulorhexis (CCC) size and shape. MATERIALS AND METHODS: Human eyes obtained post-mortem implanted with 3-piece silicone optic - PMMA haptic (SI 40 NB) and 3-piece silicone optic - Prolene haptic (SI 30 NB) designs IOLs, accessioned between January 1993 and December 2000 were evaluated by gross examination from behind under an operating microscope using the Miyake-Apple posterior photographic technique. The area and intensity of Soemmerring's ring and type of fixation was studied in 457 eyes. The mean diameter of the CCC and relation of the CCC edge to the optic rim were analyzed in 221 eyes. RESULTS: 1) The amount of Soemmerring's ring formation was significantly larger in the group of IOLs requiring Nd:YAG capsulotomy in both the SI 40 NB and SI 30 NB design than in the IOLs without capsulotomies. 2) The percentage of not in-the-bag fixated IOLs in both the SI 40 NB and SI 30 NB design was larger in the "Nd:YAG groups", without being statistically significant. 3) The "Nd:YAG groups" showed a significant higher amount of non overlapping clock hours of the CCC edge in relation to the optic rim. CONCLUSION: 1) The data confirm the clinical assumption that the incidence of PCO is correlated with the cortical clean up. 2) Our findings also support the clinical assumption, that poor IOL fixation increases the risk of PCO. 3) This study also verifies the relation of the CCC to PCO, namely a relatively small CCC covering the entire optic rim is best to reduce the Nd:YAG laser rate.

Cataract↗

[Postoperative opacification of posterior chamber intraocular lenses - a review].

Postoperative opacification of intraocular lenses (IOLs) is a very unpleasant complication for the ophthalmic surgeon and the patient. We report on our experiences with opacification of different foldable IOL designs and rigid poly (methyl methacrylate) (PMMA) posterior chamber lenses.1. Snowflake degeneration of PMMA IOLs: This condition is an unanticipated and surprising late postoperative finding 8 to 15 years after implantation. In our opinion, this complication is probably not related to the PMMA biomaterial itself, but rather it appears to represent a manufacturing problem that has affected a selected, albeit large number of lenses manufactured in the 1980s-mid 1990s.2. Degeneration of UV absorber material and calcium deposits within the optic of hydrophilic IOLs: Two years postoperatively degenerations of UV absorber material and calcium deposits within the optic of single piece hydrophilic acrylic lenses SC60B-OUV manufactured by MDR (Medical developmental research Inc. Clearwater FL, USA) can occur. Although the precise mechanism is not fully known, it was assumed that these opacifications are due to premature aging of the UV blocking agent incorporated in the lens biomaterial and calcification.3. Calcification on the surface of the Bausch & Lomb Hydroviewtrade mark IOLs: Twelve to 15 months postoperatively granular surface calcifications in Hydroviewtrade mark IOLs occured. The mechanism is not fully understood. According to Bausch and Lomb studies, part of the components of the packaging contained silicone, which may have come off the packaging onto the lens optic, where it then appears to be a catalyst for calcium precipitation. The manufacturer has correlated a change in packaging with the appearance of the opacification. The manufacturer now believes that this problem has been solved. However, final verification will require a careful 1 - 2 years clinical study.4. Glistenings in the hydrophobic acrylic AcrySoftrade mark IOLs: The time frame of glistenings in the AcrySoftrade mark IOLs is highly variable. It has been suggested that the occurrence of glistenings may be related to variations in the temperature of the lens just prior to and or during insertion into the eye. Formation of vacuoles may occur within the submersed acrylic polymer when there is a transient increase and then decrease in temperature during the surgical procedure. "Glistenings" may then subsequently form by ingress of anterior chamber fluid. Contrast sensitivity can been decreased in some patients, but clinically significant decrease of visual acuity has been rare.

Biocompatible Materials↗

[Millenniums update on posterior capsule opacification (PCO) scores, centration, biocompatibility and fixation of foldable intraocular lenses (IOL) - an analysis of 1,221 pseudophakic post mortem globes].

BACKGROUND: The ongoing and fast evolution of foldable IOL designs established the necessity to evaluate the different abilities of each lens style. The large IOL database (over 16,500 specimens) acquired in our laboratory, has permitted us to perform a clinico-pathological analysis on pseudophakic autopsy globes provided from sources worldwide, especially many Lions Eye banks in the United States. MATERIAL AND METHODS: We analyzed 6 foldable IOL styles commonly implanted in the United States, using one type of rigid IOL design (1-piece design rigid PMMA optics) as a comparison group. Posterior capsule opacification (PCO) score, decentration, fixation, presence or absence of a Nd:YAG laser posterior capsulotomy and area and intensity of Soemmerring's ring formation was discerned by examination under an operating microscope using the Miyake-Apple posterior photographic technique. RESULTS: The four lenses with the lowest rates ranging between 3.8 % and 21.7 % are modern designs, mostly implanted after 1992. The two lenses with the higher rates ranging between 23.1 % and 30.4 %, were all older designs, already prevalent prior to 1992. IOL fixation with both haptics in the capsular bag showed the best centration values and PCO scores. Our studies to date have shown in a preliminary fashion that the AcrySoftrade mark IOL displays the the lowest (best) biocompatibility score. CONCLUSIONS: Entering the new millenium, with evolution of modern surgical techniques and IOL designs, the incidence of the two major complications of cataract surgery, decentration and PCO are now finally diminishing.

Autopsy↗