p63 expression is useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations.

Human trophoblast is composed of a heterogeneous population of cells, which give rise to a variety of trophoblastic tumors and tumor-like lesions. In this report, we analyzed the expression pattern of the p63 gene, a transcription factor belonging to the p53 family, in different trophoblastic subpopulations and in trophoblastic lesions. p63 has various isoforms that are classified into two groups designated TA and DeltaNp63 isoforms.

Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis.

The pathogenesis of ovarian carcinoma, the most lethal gynecological malignancy, is unknown because of the lack of a tumor progression model. Based on a review of recent clinicopathological and molecular studies, we propose a model for their development. In this model, surface epithelial tumors are divided into two broad categories designated type I and type II tumors that correspond to two main pathways of tumorigenesis.

MicroRNA-directed cleavage of HOXB8 mRNA.

MicroRNAs (miRNAs) are endogenous approximately 22-nucleotide RNAs, some of which are known to play important regulatory roles in animals by targeting the messages of protein-coding genes for translational repression. We find that miR-196, a miRNA encoded at three paralogous locations in the A, B, and C mammalian HOX clusters, has extensive, evolutionarily conserved complementarity to messages of HOXB8, HOXC8, and HOXD8. RNA fragments diagnostic of miR-196-directed cleavage of HOXB8 were detected in mouse embryos.

Molecular genetic analysis of ovarian serous cystadenomas.

Ovarian serous cystadenomas are common ovarian lesions that may be precursors of serous borderline tumors, which can in turn progress to low-grade serous carcinomas. It has been shown that low-grade serous carcinoma and serous borderline tumors are characterized by frequent mutations in BRAF or KRAS genes, but the mutational status of these genes in serous cystadenomas and the clonal nature of serous cystadenomas have not been fully investigated. We isolated cyst-lining epithelium from 30 consecutive serous cystadenomas, and analyzed their BRAF and KRAS mutational status.

Complications mimicking lupus flare-up in a uremic patient undergoing pegylated liposomal doxorubicin therapy for cervical cancer.

Patients with systemic lupus erythematosus (SLE) have an increased risk for malignancy and end-stage renal disease itself might further augment the risk. Treating uremic patients with cervical cancer by cisplatin-based chemotherapy combined with radiation is hampered by the reduced renal excretion of cisplatin. Doxorubicin, a potential radiosensitizer with an established effect on carcinomas that arise in the ovary, uterine cervix and endometrium, might be applied in these cases.

Profiling the activity of G proteins in patient-derived tissues by rapid affinity-capture of signal transduction proteins (GRASP).

The next phase in molecular medicine will require the ability to identify signal transduction events inside a cell, in the biologic context of the disease-host interface and at a given point in time. New technologies are needed to profile the activity of these signaling pathways in patient tissue rather than cultured cell lines since the tumor-host microenvironment influences the cellular proteome. We introduce such a technology, rapid affinity capture of signaling proteins (GRASP), to investigate the activity of signaling pathways from patient-derived carcinomas and benign epithelial surfaces and apply it to studying important signaling events in ovarian carcinoma.

Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients.

Resistance to chemotherapy is a major cause of mortality in advanced cancer patients. In this study, digital karyotyping was used to search for genomic alterations in liver metastases that were clinically resistant to 5-fluorouracil (5-FU). In two of four patients, we identified amplification of an approximately 100-kb region on 18p11.

Biomedical applications of chemically and microbiologically synthesized poly(glutamic acid) and poly(lysine).

This review article deals with the synthesis, physiochemical properties, and potential biomedical applications of two homo-poly amino acids. Poly-alpha-glutamic acid (alpha-PGA) and poly-alpha-lysine (alpha-PL) were synthesized by chemical synthesis. poly-gamma-glutamic acid (gamma-PGA) and poly-epsilon-lysine (epsilon-PL) were naturally occurring bio-materials that were produced by microbial fermentation.

Principle and applications of digital PCR.

Digital PCR represents an example of the power of PCR and provides unprecedented opportunities for molecular genetic analysis in cancer. The technique is to amplify a single DNA template from minimally diluted samples, therefore generating amplicons that are exclusively derived from one template and can be detected with different fluorophores or sequencing to discriminate different alleles (e.g.

Prediction of mammalian microRNA targets.

MicroRNAs (miRNAs) can play important gene regulatory roles in nematodes, insects, and plants by basepairing to mRNAs to specify posttranscriptional repression of these messages. However, the mRNAs regulated by vertebrate miRNAs are all unknown. Here we predict more than 400 regulatory target genes for the conserved vertebrate miRNAs by identifying mRNAs with conserved pairing to the 5' region of the miRNA and evaluating the number and quality of these complementary sites.

Antifreeze activities of poly(gamma-glutamic acid) produced by Bacillus licheniformis.

Various enantiomeric isomers, metals salts and molecular sizes of poly(gamma-glutamic acid), gamma-PGA, produced by Bacillus licheniformis CCRC 12826, were prepared and their antifreeze activities were studied by differential scanning calorimetry. The antifreeze activity of gamma-PGA increased as its molecular weight decreased but was indifferent to its D/L-glutamate composition. The antifreeze activity was cation dependent decreasing in the order Mg2+ >> Ca2+ approximately Na+ >> K+ which follows that of inorganic chlorides in that high ionic charge leads to high antifreeze activity.

HLA-G is a potential tumor marker in malignant ascites.

Purpose: Molecular approaches as supplements to cytological examination of malignant ascites may play an important role in the clinical management of cancer patients. HLA-G is a potential tumor-associated marker and that one of its isoforms, HLA-G5, produces a secretory protein. This study is to assess the clinical utility of secreted HLA-G levels in differential diagnosis of malignant ascites.

Identifying tumor origin using a gene expression-based classification map.

Identifying the primary site in cases of metastatic carcinoma of unknown origin has profound clinical importance in managing cancer patients. Although transcriptional profiling promises molecular solutions to this clinical challenge, simpler and more reliable methods for this purpose are needed. A training set of 11 serial analysis of gene expression (SAGE) libraries was analyzed using a combination of supervised and unsupervised computational methods to select a small group of candidate genes with maximal power to discriminate carcinomas of different tissue origins.

Increased plasma DNA integrity in cancer patients.

Tumor-released DNA in blood represents a promising biomarker for cancer detection. It has been postulated that tumor necrosis causes release of DNA of varying sizes, which contrasts apoptosis in normal tissue that releases smaller and more uniform DNA fragments. To test the hypothesis that increased DNA integrity, i.

Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma.

Activating mutations in KRAS and in one of its downstream mediators, BRAF, have been identified in a variety of human cancers. To determine the role of mutations in BRAF and KRAS in ovarian carcinoma, we analyzed both genes for three common mutations (at codon 599 of BRAF and codons 12 and 13 of KRAS). Mutations in either codon 599 of BRAF or codons 12 and 13 of KRAS occurred in 15 of 22 (68%) invasive micropapillary serous carcinomas (MPSCs; low-grade tumors) and in 31 of 51 (61%) serous borderline tumors (precursor lesions to invasive MPSCs).

Mel-CAM (CD146) expression in parotid mucoepidermoid carcinoma.

Mel-CAM (CD146) is a cell-cell adhesion protein found in normal and tumoral tissues. The aim of this study was to analyse Mel-CAM expression in mucoepidermoid carcinoma (MEC), and assess its importance in prognosis and its utility in differentiating high-grade MEC from squamous cell carcinoma (SCC). Immunohistochemical expression of Mel-CAM in 41 parotid MEC was correlated with clinical parameters.

Calcifying odontogenic cyst: clinicopathological features and immunohistochemical profile of 10 cases.

Background: Calcifying odontogenic cyst (COC) is an uncommon odontogenic lesion with few studies describing its immunohistochemical profile and proliferative activity reported in the literature.

Methods: Clinical and histological features and immunohistochemical expression of cytokeratins, Mel-CAM (CD146), bcl-2, PCNA and ki-67, in 10 cases of COC were studied.

Results: All 10 cases affected the maxilla, eight intraosseous and two peripheral.

Mutational analysis of K-ras segregates ovarian serous carcinomas into two types: invasive MPSC (low-grade tumor) and conventional serous carcinoma (high-grade tumor).

We previously proposed a dualistic model for ovarian serous carcinogenesis. One pathway involves the stepwise development of invasive micropapillary serous carcinoma (MPSC) from serous borderline tumor (atypical proliferative serous tumor) to noninvasive and then invasive MPSC. The carcinomas that develop in this fashion are characterized by low-grade nuclei and frequent K-ras mutations.

Inverse transposition by the RAG1 and RAG2 proteins: role reversal of donor and target DNA.

The lymphoid-specific proteins RAG1 and RAG2 initiate V(D)J recombination by introducing DNA double-strand breaks at the recombination signal sequences (RSSs). In addition to DNA cleavage, the versatile RAG1/2 complex is capable of catalyzing several other reactions, including hybrid joint formation and the transposition of signal ends into a second DNA. Here we show that the RAG1/2 complex also mediates an unusual strand transfer reaction, inverse transposition, in which non-RSS DNA is cleaved and subsequently transferred to an RSS sequence by direct transesterification.

Proteomic approaches to tumor marker discovery.

Context: Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids.

Objective: To determine whether protein profiles of plasma can be used to identify potential biomarkers that improve the detection of ovarian cancer.

The role of chromosomal instability in tumor initiation.

Chromosomal instability (CIN) is a defining characteristic of most human cancers. Mutation of CIN genes increases the probability that whole chromosomes or large fractions of chromosomes are gained or lost during cell division. The consequence of CIN is an imbalance in the number of chromosomes per cell (aneuploidy) and an enhanced rate of loss of heterozygosity.

Assessment of plasma DNA levels, allelic imbalance, and CA 125 as diagnostic tests for cancer.

Background: Allelic imbalance (AI), the loss or gain of chromosomal regions, is found in many cancers. AI can be detected in genomic tumor DNA released into the blood after necrosis or apoptosis. We evaluated plasma DNA concentration, allelic status in plasma DNA, and serum CA 125 level as screening tests for ovarian and other cancers.

The Role of E-cadherin in the Motility and Invasion of Implantation Site Intermediate Trophoblast.

During early pregnancy, intermediate (extravillous) trophoblast infiltrates the basal plate and invades the spiral arteries, a physiological process required to establish the maternal-fetal circulation. Immunostaining studies have shown that differentiation of trophoblast into this invasive subpopulation is associated with down-regulation of E-cadherin expression. To study the function of E-cadherin in trophoblast in vitro, we restored E-cadherin expression in an E-cadherin negative human implantation site intermediate trophoblastic cell line, IST-1, using a recombinant adenovirus, E-cad/Ad5 which constitutively expresses E-cadherin.

Cutaneous lymphocytic vasculitis as the presenting feature of acute lymphoblastic leukemia.

The authors describe a patient with precursor B-cell acute lymphoblastic leukemia who presented with a 3-week history of indurated or ulcerative, purpuric lesions distributed mainly on her legs. A skin biopsy demonstrated a T-cell-mediated lymphocytic vasculitis. After the patient started chemotherapy, the skin lesions abated but she became febrile and a blood culture revealed cryptococci.

Genotype analysis using human hair shaft.

Analysis of genotypes for genetic predisposition of diseases has profound and widespread clinical application and has become a fundamental tool in the study of molecular epidemiology. In this study, we report a convenient and completely noninvasive approach to perform genotyping using terminal cephalic hair shaft. The average and median DNA amounts purified from the hair shaft are 112 +/- 180 (1 SD) pg/mg and 66 pg/mg of hair shaft, respectively.