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Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 73 records · Page 4Linked to original sources
PubMed2000

Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA.

OBJECTIVES: To determine the frequency of cervicovaginal lavage and plasma HIV-1 RNA levels that are below detectable levels (< 400 copies/ml) among women on highly active antiretroviral therapy (HAART), non-HAART and on no therapy. To compare the effect of initiating HAART on the timing of HIV-1 RNA suppression in the blood plasma and genital tract among antiretroviral-naïve women. METHODS: Data were obtained from 205 HIV-infected women with paired plasma and cervicovaginal lavage viral load measurements. Seven antiretroviral-naïve women starting HAART had viral load measurements performed daily for one week, at 2 weeks and at 1 month after initiating therapy. Viral load quantification was carried out by nucleic acid sequence-based amplification assay. The lower limit of detection was 400 copies/ml. RESULTS: Plasma and cervicovaginal HIV-1 RNA was detectable in 71 and 26% of the women, respectively. Among women with plasma viral loads less than 400, 400-9999, and 10,000 copies/ml or over, genital tract HIV-1 RNA was detected in 3, 17 and 48%, respectively (P < 0.001). Fifty-one per cent of the women with CD4 cell counts of less than 200/mm3 had detectable cervicovaginal viral loads compared with 18% among women with CD4 cell counts of 200/mm3 or over (P < 0.001). Cervicovaginal HIV-1 RNA was less than 400 copies/ml in 85% of those on HAART, 69% of those on non-HAART and 69% of those on no therapy (P < 0.045). In seven antiretroviral-naïve women initiating HAART, cervicovaginal HIV-1 RNA decreased by 0.7-2.1 log10 within 1-14 days of starting therapy. CONCLUSION: The cervicovaginal HIV-1 RNA level was positively correlated with plasma HIV-1 RNA and negatively with the CD4 cell count. The use of HAART was significantly associated with below-detectable levels of HIV-1 RNA in both plasma and the genital tract. HIV-1 RNA suppression in the genital tract may occur rapidly after initiating therapy.

Adult↗
PubMed2000

Cardiotocography only versus cardiotocography plus PR-interval analysis in intrapartum surveillance: a randomised, multicentre trial. FECG Study Group.

BACKGROUND: There is a need to improve the sensitivity and specificity of fetal monitoring during labour. We compared the gold standard, cardiotocography, with cardiotocography plus time-interval analysis of the fetal electrocardiogram in fetal surveillance. The aim was to find out whether time-interval analysis decreased the need for operative intervention due to fetal distress. METHODS: We did a randomised, prospective trial in five hospitals in the UK, Hong Kong, the Netherlands, and Singapore. 1038 women undergoing high-risk labours were randomly assigned fetal monitoring by cardiotocography alone, or cardiotocography plus fetal electrocardiography (ECG). Outcomes measured were rates of operative intervention, and neonatal outcome. Analysis was by intention to treat. FINDINGS: 515 women were assigned management by cardiotocography, and 523 cardiotocography plus fetal ECG. There was a trend towards fewer operative interventions for presumed fetal distress in the time-interval analysis plus cardiotocography group (63 [13%] vs 78 [16%]), but this was not significant (relative risk 0.80 [95% CI 0.59-1.08], p=0.17). There was no significant difference between groups in the proportion of babies who had an umbilical arterial pH of 7.15 or less (51 [11%] vs 49 [11%]; 1.01 [0.7-1.47]), or in the frequency of unsuspected acidaemia (42 [9%] vs 35 [8%]; 1.17 [0.76-1.79]). INTERPRETATION: The addition of time-interval analysis of the fetal electrocardiogram during labour did not show a significant benefit in decreasing operative intervention. There was no significant difference in neonatal outcome.

Cardiotocography↗
PubMed2000

Isolation and expression of a novel alternatively spliced mu opioid receptor isoform, MOR-1F.

The MOR-1 gene is large, with a recent study reporting nine exons spanning 250 kb which combine to yield six different mu opioid receptor splice variants. We now report the isolation of exon 10, which is contained within yet another splice variant, MOR-1F, which is composed of exons 1, 2, 3, 10, 6, 7, 8 and 9. Exon 10 comprises 186 bp which predict a unique 58 amino acid sequence extending beyond exon 3. It has been mapped between exons 4 and 6 and has flanking consensus splice sequences. On Northern blot analysis, the MOR-1F mRNA is smaller than the other MOR-1 mRNAs. When expressed in CHO cells, MOR-1F binds the mu opioid radioligand [3H]DAMGO with high affinity (K(D) = 1.04+/-0.03 nM). Competition studies demonstrated the selectivity of the variant for mu opioid ligands, supporting its classification within the mu opioid receptor family.

Alternative Splicing↗
PubMed2000

Development and validation of sensitive assays to quantitate gene expression after p53 gene therapy and paclitaxel chemotherapy using in vivo dosing in tumor xenograft models.

SCH58500 (ACN53) is a replication-deficient, type 5 adenovirus (Ad) expressing human wild-type p53 tumor suppressor. It is currently undergoing clinical trials as a cancer therapeutic. Many SCH58500 clinical trials incorporate an arm comparing traditional chemotherapy against chemotherapy combined with SCH58500. Paclitaxel was chosen for combination therapy in the preclinical study reported here due to its extensive use as a first-line therapy in ovarian cancer, its synergy with SCH58500 in preclinical cancer models, and its activation of p53-independent apoptosis, which might result in a "lowered threshold" for tumor cell death. SCID mice bearing human tumor xenografts were dosed with intratumoral vehicle, control Ad vector, or SCH58500, with or without paclitaxel. Real-time quantitative reverse transcriptase polymerase chain reaction assays were developed and validated to quantitate expression of p53, the p53 downstream effector gene p21, and the apoptosis-related genes, bax, bcl-2, and survivin. Protein expression was confirmed using immunohistochemical assays for p53 and p21. Only tumors injected with SCH58500 had detectable levels of exogenous p53 DNA and mRNA. After SCH58500 treatment, 3-11-fold elevations of p21 expression were observed in tumor xenografts containing nonfunctional p53 (MDA-MB-468, MDA-MB-231, MIAPaCa2, DU-145, and SK-OV-3), but no change in p21 mRNA in wild-type p53 PA-1 tumors. Immunohistochemical assays confirmed induction of p21 protein in MDAMB-468 and SK-OV-3 cells, but not in PA-1 cells. Ad vector alone or paclitaxel alone had no effect on p21 mRNA levels in most tumors. However, paclitaxel suppressed p21 expression induced by SCH58500 4-fold in DU-145 and SK-OV-3 tumors. Paclitaxel also affected expression of the housekeeping gene gapdh. There was no consistent pattern to the changes in bax, bcl-2, or survivin after SCH58500 treatment with or without paclitaxel between tumor types, although there were consistent responses within individual tumor lines. The mRNA ratios for bax/bcl-2 and bax/survivin were also not informative across tumor types. Of the genes examined, only p21 gave a predictable response 24 hours after p53 gene therapy and therefore, p21 expression may be useful for confirming SCH58500 activity in human tumor biopsies.

Adenoviridae↗
PubMed2000

Detailed deletion mapping at chromosome 11q23 in colorectal carcinoma.

Loss of heterozygosity (LOH) is frequent at the chromosomal region 11q22-q23 in several types of tumours of diverse cell origin. Previous investigations of LOH at this chromosomal region in colorectal carcinoma have been contradictory in their findings, and have only included between 1-4 loci. In order to define any regions of LOH on 11q23, we investigated 16 loci between D11S940 and D11S934 on the long arm of chromosome 11 using microsatellite analysis. Of 57 colorectal carcinomas specimens, 36 (63.2%) demonstrated LOH at one or more marker, with the highest frequencies of LOH at D11S1340 (41.0%), located between 105.13-111.97 Mb from the centromere, and D11S924 (37.1%) and D11S4107 (40.5%), both located approximately 113 Mb from the centromere. No statistically significant associations between LOH and age-of-presentation or Dukes' stage were found. LOH was observed in colorectal tumours of all Dukes' stages, including Dukes' stages A and B, suggesting that the inactivation of a tumour suppressor gene(s) on 11q23 occurs in the early stages of colorectal carcinoma. These results confirm the presence of putative tumour suppressor gene(s) at chromosome 11q23, involved in the carcinogenesis of colorectal carcinoma, and will facilitate future identification of candidate genes.

Adenocarcinoma↗
PubMed2000

An endosome-to-plasma membrane pathway involved in trafficking of a mutant plasma membrane ATPase in yeast.

The plasma membrane ATPase, encoded by PMA1, is delivered to the cell surface via the secretory pathway. Previously, we characterized a temperature-sensitive pma1 mutant in which newly synthesized Pma1-7 is not delivered to the plasma membrane but is mislocalized instead to the vacuole at 37 degrees C. Several vps mutants, which are defective in vacuolar protein sorting, suppress targeting-defective pma1 by allowing mutant Pma1 to move once again to the plasma membrane. In this study, we have analyzed trafficking in the endosomal system by monitoring the movement of Pma1-7 in vps36, vps1, and vps8 mutants. Upon induction of expression, mutant Pma1 accumulates in the prevacuolar compartment in vps36 cells. After chase, a fraction of newly synthesized Pma1-7 is delivered to the plasma membrane. In both vps1 and vps8 cells, newly synthesized mutant Pma1 appears in small punctate structures before arrival at the cell surface. Nevertheless, biosynthetic membrane traffic appears to follow different routes in vps8 and vps1: the vacuolar protein-sorting receptor Vps10p is stable in vps8 but not in vps1. Furthermore, a defect in endocytic delivery to the vacuole was revealed in vps8 (and vps36) but not vps1 by endocytosis of the bulk membrane marker FM 4-64. Moreover, in vps8 cells, there is defective down-regulation from the cell surface of the mating receptor Ste3, consistent with persistent receptor recycling from an endosomal compartment to the plasma membrane. These data support a model in which mutant Pma1 is diverted from the Golgi to the surface in vps1 cells. We hypothesize that in vps8 and vps36, in contrast to vps1, mutant Pma1 moves to the surface via endosomal intermediates, implicating an endosome-to-surface traffic pathway.

Biological Transport↗
PubMed2000

Physiological regulation of uteroglobin/CCSP expression.

Uteroglobin/CCSP is expressed specifically in the Clara cells. This allows the gene to be used as a marker to identify the elements regulating the physiologic and cell-specific expression of this gene. The regulation of UG/CCSP by IFN-gamma was shown to be at the level of the proximal promoter by the upregulation of HNF3 beta. This has allowed the determination of the factors responsible for the expression of UG/CCSP.

Animals↗
PubMed2000

Reduction of aortic wall motion inhibits hypertension-mediated experimental atherosclerosis.

Hypertension is a well-known risk factor for coronary artery disease and carotid and lower extremity occlusive disease. Surgically induced hypertension in hypercholesterolemic animals results in increased aortic wall motion and increased plaque formation. We tested the hypothesis that reduction in aortic wall motion, despite continued hypertension, could reduce plaque formation. New Zealand White rabbits (n=26) underwent thoracic aortic banding to induce hypertension and were fed an atherogenic diet for 3 weeks. In 13 rabbits, a segment of aorta proximal to an aortic band was externally wrapped to reduce wall motion. All animals were fed an atherogenic diet for 3 weeks. Four groups were studied: 1, coarctation control (no wrap, n=7); 2, coarctation with loose wrap (n=6); 3, coarctation with firm wrap (n=7); and 4, control (noncoarcted, n=6). Wall motion, blood pressure, and pulse pressure were measured at standard reference sites proximal and distal to the coarctation by use of intravascular ultrasound. Quantitative morphometry was used to measure intimal plaque. Mean arterial pressure and cyclic aortic wall motion were equally increased proximal to the aortic coarctation in all 3 coarcted rabbit groups compared with the control group (P:<0.001). Wall motion in the segment of aorta under the loose and firm wraps was no different from the control value. The external wrap significantly reduced intimal thickening in the 4 groups by the following amounts: group 1, 0.30+/-0.03 mm(2); group 2, 0.06+/-0.02 mm(2); group 3, 0. 04+/-0.02 mm(2); and group 4, 0.01+/-0.01 mm(2) (P:<0.001). Localized inhibition of aortic wall motion in the lesion-prone hypertensive aorta resulted in significant reduction in intimal plaque formation. These data suggest that arterial wall cyclic motion may stimulate cellular proliferation and lipid uptake in experimental atherosclerosis.

Animals↗
PubMed2000

Luminescence studies of the phagocyte response to endotoxin infusion into normal human subjects: multiple discriminant analysis of luminescence response and correlation with phagocyte morphologic changes and release of elastase.

A blood luminescence system (BLS) was employed to analyze blood phagocyte function in response to infusion of endotoxin (4 ng Escherichia coli lipopolysaccharide (LPS)/kg body weight) into 7 healthy human subjects. The subjects were closely monitored clinically, and extensive chemical, hematological and coagulation measurements were taken during the pretreatment, early (symptomatic, 1-8 h post-LPS), and late (asymptomatic, 12-48 h post-LPS) phases of acute inflammation. BLS assessment included measurement of basal and PMA-stimulated phagocyte oxidase and myeloperoxidase (MPO) activities, and also included measurement of circulating (COR) and PAF-primed maximum (MOR) opsonin receptor-dependent phagocytic activities. Basal oxidase activity peaked at T + 1 h and showed an additional peak at T + 24 h post-LPS. The COR activity also peaked at 1-2 h, but remained elevated through T + 24 h post-LPS, while the basal MPO activity peaked only once at T + 1 h. We concluded that while MPO evidence of phagocyte respiratory activation returned to baseline by T + 4 h, COR evidence of receptor expression (receptor alert) remained elevated through T + 24 h. During this early (0-8 h) period, elastase/alpha 1AT complex concentration peaked at T + 3-4 h and again at T + 8 h. Peak numbers of circulating polarized and vacuolated phagocytes also appeared at T + 3 h and 7 h. We concluded that there was biochemical and morphological evidence of continuing phagocyte activity beyond T + 4 h to T + 8 h, and that this corresponded with the period during which the subjects were symptomatic. In addition, the appearance of a second peak of basal oxidase activity at T + 24 h, multiple discriminant analyses of all the luminescence data, and the sustained elevation of lactate suggested that there was a later second stage (T + 12 h to 48 h) of the human response to endotoxin, during which time the subjects were asymptomatic.

Adult↗
PubMed2000

Multi-institutional phase I/II trial of paclitaxel, cisplatin, and etoposide with concurrent radiation for limited-stage small-cell lung carcinoma.

PURPOSE: To determine the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP) and thoracic radiotherapy. PATIENTS AND METHODS: Thirty-one patients were enrolled onto this study. During the phase I section of this study, the dose of paclitaxel was escalated in groups of three or more patients. Cycles were repeated every 21 days. For cycles 1 and 2, paclitaxel was administered according to the dose-escalation schema at doses of 100, 135, or 170 mg/m(2) intravenously over 3 hours on day 1. Once the maximum-tolerated dose (MTD) of paclitaxel (for cycles 1 and 2, concurrent with radiation) was determined, that dose was used in all subsequent patients entered onto the phase II section of this study. For cycles 3 and 4, the paclitaxel dose was fixed at 170 mg/m(2) in all patients. On day 2, cisplatin 60 mg/m(2) was administered for all cycles. On days 1, 2, and 3, etoposide 60 mg/m(2)/d (cycles 1 and 2) or 80 mg/m(2)/d (cycles 3 and 4) was administered. Chest radiation was given at 9 Gy/wk in five fractions for 5 weeks beginning on day 1 of cycle 1. Granulocyte colony-stimulating factors were used during cycles 3 and 4 only. RESULTS: Twenty-eight patients were assessable. The MTD of paclitaxel was 135 mg/m(2), with the dose-limiting toxicity being grade 4 neutropenia. Cycles 1 and 2 were associated with grade 4 neutropenia in 32% of courses, with fever occurring in 7% of courses and grade 2/3 esophagitis in 13%. Cycles 3 and 4 were complicated by grade 4 neutropenia in 20% of courses, with fever occurring in 6% of courses and grade 2/3 esophagitis in 16%. The overall response rate was 96% (complete responses, 39%; partial responses, 57%). After a median follow-up period of 23 months (range, 9 to 40 months), the median survival time was 22.3 months (95% confidence interval, 15.1 to 34.3 months) CONCLUSION: The MTD of paclitaxel with radiation and EP treatment is 135 mg/m(2) given over 3 hours. In this schedule of administration, a high response rate and acceptable toxicity can be anticipated.

Adolescent↗
PubMed1999

Eps1, a novel PDI-related protein involved in ER quality control in yeast.

PMA1 is an essential gene encoding the yeast plasma membrane [H(+)]ATPase. A pma1-D378N mutant has a dominant-negative effect on cell growth because both newly synthesized mutant and wild-type Pma1 molecules are retained and degraded in the endoplasmic reticulum (ER). Like other substrates for ER-associated degradation, Pma1-D378N is stabilized in mutants defective in components of the ubiquitination machinery. A genetic selection was performed for eps (ER-retained pma1 suppressing) mutants in which the growth defect caused by the D378N allele is suppressed. In an eps1 mutant, both mutant and wild-type Pma1 molecules are allowed to travel to the plasma membrane; however, normal retention of resident ER proteins Shr3 and Kar2 is not perturbed. Eps1 is a novel membrane protein belonging to the protein disulfide isomerase (PDI) family, and Eps1 co-localizes with Pma1-D378N in the ER. In the absence of Pma1-D378N, ER export of wild-type Pma1 is not affected by eps1 deletion, but export of the plasma membrane protein Gas1 is delayed. Because Eps1 is required for retention and degradation of Pma1-D378N, we propose a model in which Eps1 acts as a novel membrane-bound chaperone in ER quality control.

Amino Acid Sequence↗
PubMed1999

Role of the integrin-associated protein CD9 in binding between sperm ADAM 2 and the egg integrin alpha6beta1: implications for murine fertilization.

CD9 is a tetraspan protein that associates with several beta1 integrins, including alpha6beta1. Because alpha6beta1 is present on murine eggs and interacts with the sperm-surface glycoprotein ADAM 2 (fertilin beta), we first asked whether CD9 is present on murine eggs and whether it functions in sperm-egg binding and fusion. CD9 is present on the plasma membrane of oocytes in the ovary as well as on eggs isolated from the oviduct. The anti-CD9 mAb, JF9, potently inhibits sperm-egg binding and fusion in vitro in a dose-dependent manner. JF9 also disrupts binding of fluorescent beads coated with native fertilin or a recombinant fertilin beta disintegrin domain. (Both ligands bind to the egg via alpha6beta1.) Immunohistochemistry showed that CD9 is undetectable in the uterine epithelium, appears basolaterally and as prominent apical patches on the epithelium in the region between the uterus and the oviduct, and then persists apically in the oviduct. The integrin alpha6A subunit is found in similar apical patches in the region between the uterus and oviduct, but is confined to the basal aspect of the epithelium in the uterus and oviduct. Hence, alpha6A and CD9 both are expressed on the apical epithelial surface at the uterine-oviduct junction. These findings correlate with the observation that fertilin beta "knockout" sperm traverse the uterus but do not progress into the oviduct, contributing to the infertility of fertilin beta(-/-) male mice. Our results suggest that high-avidity binding between fertilin beta (ADAM 2) and alpha6beta1 requires cooperation between alpha6beta1 and CD9. Such cooperation may assist sperm passage into the oviduct as well as sperm-egg interactions.

ADAM Proteins↗
PubMed1999

Expression of oligodendrocyte progenitor cell antigens by gliomas: implications for the histogenesis of brain tumors.

The early events in neoplastic transformation can be understood only by comparison of the neoplastic cell with its nontransformed counterpart. The most common central nervous system gliomas traditionally are thought to arise from mature astrocytes and oligodendrocytes. We examined the possibility that gliomas arise from a population of glia that has properties of oligodendrocyte progenitors. These glial cells express the NG2 chondroitin sulfate proteoglycan and the alpha receptor of platelet-derived growth factor in vivo. We identified NG2 and the alpha receptor of platelet-derived growth factor expression in tissue from seven of seven oligodendrogliomas, three of three pilocytic astrocytomas, and one of five glioblastoma multiforme. These data provide evidence that glial tumors arise from glial progenitor cells. Molecules expressed by these progenitor cells should be considered as targets for novel therapeutics.

Antibodies, Monoclonal↗
PubMed1999

Pathogenesis of tissue injury in MS lesions.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system. The primary pathological target in multiple sclerosis is myelin. Most MS patients follow a relapsing-remitting (RR-MS) course for 10 to 15 years that transforms into a chronic or secondary progressive disease (SP-MS). This review summarizes studies from our laboratory that implicate activated microglia and astrocytes in early stages of myelin destruction in MS brain. In addition, we review evidence that indicates that axonal transection is a major pathological process in multiple sclerosis. Our data support the hypothesis that neurological disability in RR-MS is due to inflammatory demyelination while axonal loss plays a significant role in the irreversible neurological decline in SP-MS. Further elucidation of the pathological targets and pathological mechanisms of tissue destruction in MS brain will help identify new therapeutics.

Astrocytes↗
PubMed1999

Provider-reported illness and absence due to illness among children attending child-care homes and centers in San Diego, Calif.

PURPOSE: To compare the incidence of provider-reported illness and absence due to illness among children attending small child-care homes, large child-care homes, and child care centers in a large metropolitan area. METHODS: From July 6, 1992, through January 28, 1994, we collected information from child-care providers on illness and absence due to illness at 64 small and 58 large child-care homes and 41 child-care centers. This included 113 446 child-weeks of information on 5360 children. RESULTS: Providers reported 14 474 illness episodes (6.6 episodes per child-year) and 8593 days of absence due to illness (3.9 days per child-year). The incidence of illness episodes was greatest in children who were younger than 1 year, white, or enrolled in small child-care homes. The incidence of absence due to illness was greatest in children who were 1 year of age, Hispanic, or enrolled in child-care centers. Respiratory symptoms were most commonly associated with illness episodes and absence due to illness. CONCLUSIONS: Children in child-care homes had a greater incidence of provider-reported illness than did those in centers. This risk varied by the type of facility and was greatest in small child-care homes. The increased risk for absence due to illness among children in child-care centers reflects exclusion and attendance patterns. It may be possible to reduce the incidence of absence due to illness and subsequent economic impact of child-care-associated illness by educating providers on exclusion guidelines.

Absenteeism↗
PubMed1999

The use of laser scanning cytometry to assess depth of penetration of adenovirus p53 gene therapy in human xenograft biopsies.

SCH58500 is an agent for gene therapy of cancer, consisting of a replication-deficient type 5 adenovirus (Ad5) expressing the human p53 tumor suppressor gene (Ad5/p53). An important question about the use of Ad5/p53 gene therapy is how to achieve the therapeutically effective delivery of an Ad5/p53 vector to the tumor. We wanted to determine the effective depth of penetration of an Ad5/p53 vector by dosing the vector in an experimental human xenograft/SCID model. To assess depth of penetration, we developed a novel methodology for scanning tissue sections by laser scanning cytometry (LSC). SCID mice were given intraperitoneal injections of either p53(null) SK-OV-3 human ovarian tumor cells or p53(mut) DU-145 human prostate tumor cells to establish xenograft solid tumors. Mice were then dosed once or twice at 24-hour intervals by intraperitoneal injection with SCH58500 (Ad5/p53), an adenovirus construct expressing beta-galactosidase (Ad5/beta-gal), or a buffer control. Additional groups of mice received a single intraperitoneal dose of 10 mg/kg paclitaxel either alone or coadministered with Ad5/p53. Twenty-four hours after each last dose, the human solid tumor xenograft and relevant mouse tissue were removed from each mouse for the analysis of Ad5/p53 penetration. Immunohistochemistry (IHC) for beta-galactosidase protein revealed a depth of penetration of between 1 and 10 cells from the tumor surface. In some mice, hepatocytes in the periportal regions of liver lobules were also positive, indicating systemic absorption of adenovirus from the peritoneal cavity. IHC staining for p53 and p21 proteins in SK-OV-3 solid tumor xenografts revealed similar Ad/p53 penetration. LSC was used to map and quantitate apoptosis in both tumor and liver tissue biopsies, with over 450,000 nuclei from liver tissue and 150,000 nuclei from tumor tissue being evaluated. LSC analysis demonstrated a high level of apoptosis in the tumors that had been removed from Ad5/p53-dosed mice (12.7-19.7%). This level of apoptosis was significantly higher (P < 0.05) than was observed for liver tissues taken from Ad5/p53-dosed mice (2.7-8.0%) or tumor tissues taken from either Ad5/beta-gal-dosed mice (3.0-6.4%) or buffer control-dosed mice (3.0-5.3%). Scan bit maps from the extensive LSC analyses confirmed that apoptosis was present to about the same depth (1-10 cells) as had been identified by IHC for beta-galactosidase, p53, and p21 proteins. Paclitaxel coadministered with Ad5/p53 had no effect on Ad5 penetration into solid tumors in vivo as measured by IHC for p53 or p21 protein. However, the combination therapy did cause an elevation in the number of tumor cells undergoing apoptosis.

Adenoviridae↗