Mesothelin as a target for cervical cancer therapy.

Purpose: The cell surface glycoprotein Mesothelin is overexpressed in several tumor entities and novel immune-based therapies are currently under the early clinical evaluation for the treatment of malignant pleura mesothelioma, ovarian cancer, and pancreatic cancer. Cervical cancer has not been recognized as a suitable target for Mesothelin-directed immune therapies so far.

Methods: To exploit a possible role of Mesothelin in cervical cancer treatment, we analysed Mesothelin expression in 79 cervical carcinomas and aligned expressions patterns with tumor growth parameters.

Validity of the colposcopic criteria inner border sign, ridge sign, and rag sign for detection of high-grade cervical intraepithelial neoplasia.

Objective: To evaluate the association of three pathognomonic criteria, inner border, ridge sign, and rag sign with high-grade cervical intraepithelial neoplasia (CIN) using video exoscopy.

Methods: Retrospective evaluation of video recordings of 335 patients, referred for diagnostic colposcopy, who underwent cervical biopsies, and, if indicated loop excisions, was performed. The most severe histologic diagnosis was recorded.

Evaluation of the VITOM in digital high-definition video exocolposcopy.

Objective: : Our aim was to present our initial clinical experience using a novel exoscopically based colposcopy system (VITOM) for the evaluation of cervical, vulvar, and vaginal diseases.

Materials And Methods: : Women referred to the Charite Cervix Center, Charite University, Berlin, Germany, were included. Patients with abnormal Pap smear results, vulvar lesions, or a biopsy report of neoplasia of the lower genital tract were included into the study.

A flow cytometry-based assay to assess minute frequencies of CD8+ T cells by their cytolytic function.

Limited sample size and low sensitivity of currently used functional assays challenge direct analysis of cytotoxic CD8+ T lymphocyte activity to quantify antigen-specific immunity after infection or vaccination. Our flow cytometry-based assay reproducibly detects at least three epitope-specific CD8+ T lymphocytes by their cytolytic function. As exemplified for viral epitopes restricted to the human leukocyte antigen (HLA)-A2, the HLA-A2+ human somatic cell hybrid T2 provided an about 10-fold more sensitive readout as compared to autologous B-lymphoblastoid cells or the human erythroleukemia cell line K562 transfected to express HLA-A2 when used as target cells.

Non-physiological overexpression of the low density lipoprotein receptor (LDLr) gene in the liver induces pathological intracellular lipid and cholesterol storage.

Background: Gene therapy of familial hypercholesterolemia (FH) requires successful transfer and lifelong expression of a functional low density lipoprotein receptor (LDLr) gene in the liver. Most of the vector systems currently employed for gene therapy use promoter elements which do not modulate transgene expression in a physiological manner.

Methods: To study the in vivo effects of constitutive LDLr gene expression in the absence of interfering immunological reactions we established a new mouse model which combines homozygous LDLr deficiency and severe combined immune deficiency (SCID).

Hepatocarcinoma cells constitutively expressing adenoviral E1-genes provide a tumor model for intratumoral replication of E1-deficient adenoviruses.

The elimination of malignant tumors by intratumoral virus replication is a challenging therapeutic approach but is critically dependent on the speed and efficacy of intratumoral virus spread. The expression of oncolytic transgenes in the context of a replicating virus may help to enhance the therapeutic potency of this strategy. We have established a human hepatocarcinoma-derived cell line (Huh7-E1) which stably expresses adenoviral E1-genes.