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Yuan Ji

Publications and source records attributed to Yuan Ji.

At least 37 records · Page 2Linked to original sources

Bayesian dose-finding in phase I/II clinical trials using toxicity and efficacy odds ratios.

A Bayesian adaptive design is proposed for dose-finding in phase I/II clinical trials to incorporate the bivariate outcomes, toxicity and efficacy, of a new treatment. Without specifying any parametric functional form for the drug dose-response curve, we jointly model the bivariate binary data to account for the correlation between toxicity and efficacy. After observing all the responses of each cohort of patients, the dosage for the next cohort is escalated, deescalated, or unchanged according to the proposed odds ratio criteria constructed from the posterior toxicity and efficacy probabilities. A novel class of prior distributions is proposed through logit transformations which implicitly imposes a monotonic constraint on dose toxicity probabilities and correlates the probabilities of the bivariate outcomes. We conduct simulation studies to evaluate the operating characteristics of the proposed method. Under various scenarios, the new Bayesian design based on the toxicity-efficacy odds ratio trade-offs exhibits good properties and treats most patients at the desirable dose levels. The method is illustrated with a real trial design for a breast medical oncology study.

Antineoplastic Combined Chemotherapy Protocols↗

RefSeq refinements of UniGene-based gene matching improve the correlation of expression measurements between two microarray platforms.

Matching genes across microarray platforms is a critical step in meta-analysis. Standard practice uses UniGene to match genes. Numerous studies have found poor correlations between platforms when using UniGene matching. We profiled samples from 33 breast cancer patients on two different microarray platforms (Affymetrix and cDNA) and investigated gene matching. Our results confirmed that UniGene-based matching led to poor correlations of gene expression between platforms. Using RefSeq, a database maintained by the National Center for Biotechnology Information (NCBI), we developed and implemented a new method to refine gene matching. We found that the correlations between gene expression measurements were substantially higher after the RefSeq matching. Our approach differs from previously reported sequence-matching approaches and retains useful expression measurements. It is a sensible approach for matching probes across platforms. We conclude that UniGene alone is insufficient to match genes across platforms. Refined matching based on RefSeq significantly improves the quality of matches.

Breast Neoplasms↗

Solitary fibrous tumor of the liver.

BACKGROUND: Solitary fibrous tumor of the liver is a rare neoplasm. So far, 23 cases have been described in the English literature. We reported an additional case. METHODS: A 46-year-old woman presented with abdominal mass for 2 weeks. Both abdominal sonography and CT scan showed a solid mass occupying the right lobe of the liver. Right lobectomy was performed and the tumor was resected. RESULTS: Pathological examination showed spindle cell and fibroblast-like cells within the collagenous troma. On immunohistochemical staining, these spindle tumor cells showed diffusely CD34 positive reactivity. The post-operative course was uneventful. The patient recovered smoothly, and was alive half a year without evidence of disease recurrence. CONCLUSIONS: The proper diagnosis was depended on CD34 immunohistochemical study. The number of solitary fibrous tumor of the liver reported to date is too limited to confirm the definite prognosis of the tumor.

Adult↗

[Diagnosis and differential diagnosis of intraductal papillary mucinous neoplasm of pancreas].

OBJECTIVE: To study the clinicopathologic features of intraductal papillary mucinous neoplasm (IPMN) and its distinction from mucinous cystic neoplasm of pancreas. METHODS: The clinical, radiologic and histologic features of 17 cases of IPMN and 13 cases of mucinous cystic neoplasm (MCN) were reviewed. Mucin profiles (MUC1, MUC2 and MUC5AC) were studied by histology (HE) and immunohistochemistry (EnVision). RESULTS: 10 of the 17 cases of IPMN were males. 13 cases of the IPMN were located in head of pancreas. Communication with the main pancreatic duct was demonstrated in 15 cases. Histologically, there were mild to severe papillary ingrowths of dysplastic epithelial cells, associated with intervening normal or atrophic pancreatic parenchyma. Ovarian-like stroma was not seen. Ancillary investigations showed that MUC2 and MUC5AC were detected in tumor cells of 9 and 4 cases respectively. The 4 cases with invasive component showed MUC1 positivity. On the other hand, 11 of the 13 cases of MCN occurred in middle-aged to elderly females and were located in the body and tail of pancreas. Ovarian-like stroma was commonly seen and there was no connection with the main pancreatic duct. All non-invasive MCN, regardless of the degree of cytologic atypia, were positive for MUC5AC (but not MUC2). In the 2 cases with invasive component, MUC1 expression was observed, as in IPMN. CONCLUSIONS: The age and sex of patients, tumor location, absence of ovarian-like stroma, communication with main pancreatic duct and characteristic mucin profiles represent useful parameters in distinguishing IPMN from MCN of pancreas. The tumor cells of IPMN express mainly MUC2, while those of MCN express MUC5AC. MUC1 may also be a useful marker in demonstration of stromal invasion in these tumors.

Adult↗

Human phenylethanolamine N-methyltransferase pharmacogenomics: gene re-sequencing and functional genomics.

Phenylethanolamine N-methyltransferase (PNMT, EC2.1.1.28) catalyzes the N-methylation of norepinephrine to form epinephrine. As a step toward understanding the possible contribution of inheritance to individual variation in PNMT-catalyzed epinephrine formation, we 're-sequenced' the entire human PNMT gene, including the three exons, the introns and approximately 1 kb of the 5'-flanking region (5'-FR), using DNA samples from 60 African-American (AA) and 60 Caucasian-American (CA) subjects. Within the 3.5 kb re-sequenced, 18 single nucleotide polymorphisms (SNPs) were observed, including four non-synonymous coding SNPs (cSNPs) that resulted in the following alterations in encoded amino acid sequence: Asn9Ser, Thr98Ala, Arg112Cys and Ala175Thr. When constructs for the non-synonymous cSNPs were transiently expressed in COS-1 cells, the Ala98 allozyme displayed significantly lower levels of both activity and immunoreactive protein (p < 0.002) than did the wild-type (WT) enzyme due, at least in part, to accelerated protein degradation by a proteasome-mediated process. Luciferase reporter gene constructs were also created for the six common PNMT 5'-FR haplotypes observed. Significant differences were observed among haplotypes in their ability to drive transcription. These observations raise the possibility of inherited variation in the ability to form epinephrine from norepinephrine as a result of variant PNMT polymorphisms and haplotypes.

Animals↗

Factors controlling the drop evaporation constant.

In this paper, we discuss the factors affecting drop evaporation. We found that the droplet morphology at a specific temperature was controlled by the physical properties of the liquid itself, such as the molecular weight, density, diffusion coefficient in air, and heat of vaporization. Two processes are included in drop evaporation: diffusion of liquid molecules into the air (diffusion part) and flow of the liquid molecules from inside the drop to the free outer shell liquid layer within the liquid-vapor interface (evaporation part). The diffusion part remained steady during drying and was not sensitive to the variation of temperature. The evaporation part, however, was an active factor and determined the differences in drop evaporation behaviors.

Journal Article↗

Tools and strategies for physiological genomics: the Rat Genome Database.

The broad goal of physiological genomics research is to link genes to their functions using appropriate experimental and computational techniques. Modern genomics experiments enable the generation of vast quantities of data, and interpretation of this data requires the integration of information derived from many diverse sources. Computational biology and bioinformatics offer the ability to manage and channel this information torrent. The Rat Genome Database (RGD; http://rgd.mcw.edu) has developed computational tools and strategies specifically supporting the goal of linking genes to their functional roles in rat and, using comparative genomics, to human and mouse. We present an overview of the database with a focus on these unique computational tools and describe strategies for the use of these resources in the area of physiological genomics.

Animals↗

Applications of beta-mixture models in bioinformatics.

SUMMARY: We propose a beta-mixture model approach to solve a variety of problems related to correlations of gene-expression levels. For example, in meta-analyses of microarray gene-expression datasets, a threshold value of correlation coefficients for gene-expression levels is used to decide whether gene-expression levels are strongly correlated across studies. Ad hoc threshold values such as 0.5 are often used. In this paper, we use a beta-mixture model approach to divide the correlation coefficients into several populations so that the large correlation coefficients can be identified. Another important application of the proposed method is in finding co-expressed genes. Two examples are provided to illustrate both applications. Through our analysis, we also discover that the popular model selection criteria BIC and AIC are not suitable for the beta-mixture model. To determine the number of components in the mixture model, we suggest an alternative criterion, ICL-BIC, which is shown to perform better in selecting the correct mixture model. SUPPLEMENTARY INFORMATION: http://odin.mdacc.tmc.edu/~yuanj/highcorgeneanno.html.

Animals↗

The Rat Genome Database (RGD): developments towards a phenome database.

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms.

Animals↗

Impact of donor gender on male rat recipients of small-for-size liver grafts.

The aim of this study was to assess the impact of donor gender on small-for-size (SFS) liver transplantation in male recipients using a rat model. Adult female or male Lewis rats were used as donors and male Lewis rats as recipients. Size-matched (SM) and SFS liver grafts from either male or female donors were transplanted into male recipients. Animals receiving SFS grafts were sacrificed at postoperative week 1, week 4, and week 12, respectively (n = 6-8 per group), those receiving SM grafts after 3 months. The cumulative survival rate (SVR) in the female-to-male (F-M) SFS group was significantly lower (62%; 13 of 21) compared with the male-to-male (M-M) group (90%; 18 of 20) (P < 0.05). Spontaneous death occurred in the F-M SFS combination either in the early postoperative period (<3 weeks) in animals with confluent hepatic necrosis or in the late postoperative period (>8 weeks) in animals with biliary obstruction. In contrast, no death was observed in the early posttransplantation period after M-M liver transplantation. The relative graft size in the SM F-M group was significantly higher (graft-to-recipient weight ratio [GRWR] 2.40% +/- 0.8%) than in the SFS M-M group (GRWR 1.35% +/- 0.2%; P < 0.001). Regardless of graft size, the outcome was worse in terms of SVR as well as regarding the incidence and severity of biliary complications in F-M compared with M-M liver transplantation. In conclusion, male recipients of female livers had a less favorable outcome irrespective of graft size. Confluent hepatic necrosis as well as biliary obstruction were perceived as consequence of a severe perfusion problem in F-M liver transplantation, which was possibly related to an enhancement of ischemia-reperfusion (I/R) injury by the lack of estrogen in male recipients of female grafts.

Animals↗

Preliminary investigation of mitoxantrone coating on stent-grafts to inhibit neointimal proliferation.

PURPOSE: To investigate the inhibition of neointimal proliferation induced by a stent-graft loaded with mitoxantrone. METHODS: Stent-grafts with and without mitoxantrone loading (150 microg per device) were inserted into the carotid artery of 7 and 6 rabbits, respectively. After an observation period of 28 days, the animals were sacrificed, and a detailed morphological and morphometric workup of the stented vessels was performed. RESULTS: Uncoated stent-grafts induced a thick neointima (median diameter 97+/-99 microm), whereas no neointima formed in mitoxantrone-loaded stent-grafts. However, the loaded devices were not fully covered by an endothelial layer. The underlying media was significantly thinner (31.8+/-5.6 versus 48.6+/-3.3 microm, p=0.002) and showed a widespread loss of smooth muscle cells. CONCLUSIONS: Mitoxantrone loading of a stent-graft inhibited the formation of a neointima. However, important regenerative processes were prevented as well, indicating a local overdose. More experiments using lower doses are warranted.

Animals↗

Pancreatic primary lymphoma: a case report and review of the literature.

BACKGROUND: Primary pancreatic lymphoma is a rare but treatable malignancy (less than 1% of pancreatic tumors) that may be clinically confused with pancreatic adenocarcinoma. METHODS: In a patient with upper abdominal pain, ultrasonography and CT detected a mass in pancreatic head, which compressed the common bile duct. The patient received a Whipple's operation and intraoperative frozen sections of the mass showed an anaplastic carcinoma. Immunohistochemical staining was used to indicate the origin and prognosis of tumor. RESULTS: Grossly the tumor involved the pancreatic head, soft in consistence and invaded part of the gastric wall. Histologically, the tumor was composed mainly of large and moderate neoplastic cells, which were diffusely positive for CD20 and Bcl-6 antigens, indicating the features of diffusely large B cell lymphoma. CONCLUSIONS: The proper diagnosis of the tumor should be made with CD20 and Bcl-6 immunohistochemical study. Radical surgery is indicated for resectable carcinoma but not for a chemosensitive lymphoma.

Diagnosis, Differential↗

A novel means of using gene clusters in a two-step empirical Bayes method for predicting classes of samples.

MOTIVATION: The classification of samples using gene expression profiles is an important application in areas such as cancer research and environmental health studies. However, the classification is usually based on a small number of samples, and each sample is a long vector of thousands of gene expression levels. An important issue in parametric modeling for so many gene expression levels is the control of the number of nuisance parameters in the model. Large models often lead to intensive or even intractable computation, while small models may be inadequate for complex data. METHODOLOGY: We propose a two-step empirical Bayes classification method as a solution to this issue. At the first step, we use the model-based cluster algorithm with a non-traditional purpose of assigning gene expression levels to form abundance groups. At the second step, by assuming the same variance for all the genes in the same group, we substantially reduce the number of nuisance parameters in our statistical model. RESULTS: The proposed model is more parsimonious, which leads to efficient computation under an empirical Bayes estimation procedure. We consider two real examples and simulate data using our method. Desired low classification error rates are obtained even when a large number of genes are pre-selected for class prediction.

Algorithms↗

Capecitabine inhibits postoperative recurrence and metastasis after liver cancer resection in nude mice with relation to the expression of platelet-derived endothelial cell growth factor.

PURPOSE: This study was to investigate the effect of capecitabine on recurrent tumor and metastasis after curative resection of liver cancer, xenograft of a highly metastatic human hepatocellular carcinoma (HCC) tumor (LCI-D20), with special reference to the expression of platelet-derived endothelial cell growth factor (PD-ECGF). EXPERIMENTAL DESIGN: LCI-D20 and LCI-D35 (a low metastatic human HCC model) liver tumors were orthotopically implanted in 96 nude mice and divided into a treatment group (24 LCI-D20 mice and 24 LCI-D35 mice) and a prevention group (48 LCI-D20 mice). In the prevention group, curative resection of liver tumors was done 10 days after the orthotopic implantation of LCI-D20 tumor. Arabic gum (control), 5-fluorouracil (5-FU), and capecitabine were administrated respectively to all of the 96 mice. RESULTS: In the treatment group, tumor volume was 468 +/- 138, 442 +/- 81, and 240 +/- 119 mm3 (P<0.01) in the control, 5-FU, and capecitabine subgroups, respectively, in LCI-D20 mice, whereas it was 168 +/- 35, 164 +/- 23, and 144 +/- 21 mm3 (P>0.05), respectively, in LCI-D35 mice. In the prevention group, incidence of liver recurrence in the control, 5-FU, and capecitabine subgroups was 100, 100, and 50%; lung metastasis being 100, 100, and 17%; and life span being 31 +/- 5, 37 +/- 5, and 77 +/- 19 days, respectively. PD-ECGF was highly expressed in HCC and its metastatic tissues in LCI-D20 mice and hardly expressed in HCC tissues in LCI-D35 mice. CONCLUSIONS: Capecitabine inhibits tumor growth and metastatic recurrence after resection of HCC in highly metastatic nude mice model. The effect of capecitabine may be attributed to the high expression of PD-ECGF in tumors.

Animals↗

Role of tumor metastasis suppressor gene KAI1 in digestive tract carcinomas and cancer cells.

The KAI1 gene is identified as a tumor metastasis suppressor gene in many types of cancer. We examined KAI1 gene and its protein KAI1/CD82 expression by in situ hybridization and immunohistochemical analysis, and found that KAI1 mRNA and protein expression were inversely correlated with lymph node and distant metastasis in digestive tract carcinomas, but not with age and gender of the patient, or with tumor differentiation. Moreover, KAI1/CD82 protein expression positively reflected the survival outcome of patients. Western blot analysis showed that VP-16 increased KAI1/CD82 protein expression obviously in various cancer cell lines, especially in those that were highly metastatic. This increased KAI1/CD82 expression was associated with its translocation from the cytomembrane to the nucleus, in which it interacted with nuclear p53 protein, forming a strong complex, observed by confocal microscopy and co-immunoprecipitation, respectively. In nude mice, after feeding with VP-16, the number of tumors metastasized from spleen to liver was obviously reduced, and KAI1/CD82 protein expression became stronger in those metastatic tumors. Accordingly, this demonstrated that KAI1 might be used as an indicator for predicting the clinical outcome, and VP-16 may be clinically considered as a promising candidate for anti-metastasis with regard to its potential to upregulate KAI1 expression.

Animals↗