Biomedical subjects

H T Cunningham

Publications and source records attributed to H T Cunningham.

4 recordsLinked to original sources

PubMed1999

Development of a sensitive, specific reverse transcriptase polymerase chain reaction-based assay for epithelial tumour cells in effusions.

We developed a sensitive and specific method for the detection of epithelial cancer cells in effusions with a two-stage molecular-based assay which combined enrichment for cancer cells by immunomagnetic bead selection and reverse transcriptase polymerase chain reaction (RT-PCR) detection of epithelial glycoprotein 2 (EGP-2) RNA. Preliminary experiments indicated that immunobead selection was essential to avoid occasional false-positive RT-PCR results, and this method detected ten breast cancer cells electively added to 10(7) cytologically negative effusion cells. We studied 110 cases of pleural (n = 68) and peritoneal (n = 42) effusions (30 from patients with known carcinoma and 80 from those without known carcinoma), and the results were compared with cytological findings. Of 18 effusions that were cytologically positive or suspicious for malignant cells, 17 (94%) were positive for EGP-2 RNA (the one negative sample was from a patient who recently received combination chemotherapy). Of 92 cytologically negative samples, 11 (12%) were positive for EGP-2, including six patients with a history of previous or current carcinoma. Our method appears to be highly specific and increases the sensitivity of detection of malignant cells; it may be a useful adjunct to routine cytopathological examination.

Ascitic Fluid↗

PubMed1998

Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer.

The goal of our study was to develop a panel of tumor cell lines along with paired non-malignant cell lines or strains collected from breast cancers, predominantly primary tumors. From a total of 189 breast tumor samples consisting of 177 primary tumors and 12 metastatic tissues, we established 21 human breast tumor cell lines that included 18 cell lines derived from primary tumors and 3 derived from metastatic lesions. Cell lines included those from patients with germline BRCA1 and FHIT gene mutations and others with possible genetic predisposition. For 19 tumor cell lines, we also established one or more corresponding non-malignant cell strains or B lymphoblastoid (BL) lines, which included 16 BL lines and 7 breast epithelial (2) or stromal (5) cell strains. The present report describes clinical, pathological and molecular information regarding the normal and tumor tissue sources along with relevant personal information and familial medical history. Analysis of the breast tumor cell lines indicated that most of the cell lines had the following features: they were derived from large tumors with or without axillary node metastases; were aneuploid and exhibited a moderate to poorly differentiated phenotype; were estrogen receptor (ER)- and progesterone receptor (PR)-negative; and overexpressed p53 and HER2/neu proteins. Of 13 patients with primary breast cancers receiving curative intent mastectomies, 7 were dead after a mean period of 10 months. Our panel of paired tumor and non-malignant cell lines should provide important new reagents for breast cancer research.

Adult↗

PubMed1996

Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells.

Inadequate presentation of tumor antigens by host professional antigen-presenting cells (APCs), including dendritic cells (DCs), is one potential mechanism for the escape of tumors from the host immune system. Here, we show that human cancer cell lines release a soluble factor or factors that dramatically affect DC maturation from precursors without affecting the function of relatively mature DCs. One factor responsible for these effects was identified as vascular endothelial growth factor (VEGF). Thus, VEGF may play a broader role in the pathogenesis of cancer than was previously thought, and therapeutic blockade of VEGF action may improve prospects for immunotherapy as well as inhibit tumor neovasculature.

Antigen Presentation↗

PubMed1996

IL-12 and mutant P53 peptide-pulsed dendritic cells for the specific immunotherapy of cancer.

Mice bearing palpable tumors expressing a mutant p53 gene were treated with intravenous injection of mutant p53-specific peptide-pulsed dendritic cells (DCs). Control groups were treated with control peptide-pulsed DCs. All mice received three injections of 10(5) DCs on days 0, 5, and 10 after the start of the therapy. Half of the animals in each group were also treated with intraperitoneal injections of interleukin (IL)-12 (300 ng per mouse every other day, from day 0 to day 20). Mice treated with control peptide-pulsed DCs showed fast tumor progression. This growth was not substantially affected by treatment with IL-12 alone. Tumor growth in mice treated with mutant p53 peptide-pulsed DCs was significantly slowed during therapy, but resumed after cessation of therapy. In contrast, tumor growth in mice receiving both specific peptide-pulsed DCs and IL-12 remained very slow even 4 weeks after termination of the immunotherapy. To investigate the immunological basis for these effects, mutant p53 specific cytotoxic T lymphocyte (CTL) response was tested in mice 2 weeks after the last injection of DCs. Significant levels of CTLs were registered only in mice treated with IL-12 in addition to specific immunization. Thus, IL-12 dramatically improved the effect of the mutant p53-specific immunotherapy of palpable, preexisting tumors, supporting the use of IL-12 as an immunoadjuvant in clinical trials of tumor-specific peptide-pulsed DC.

Amino Acid Sequence↗