Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma.

Background: Liposarcoma (LS) is the second-most common type of soft-tissue sarcoma. Despite advances in knowledge and treatment of this disease, there remains a need for more effective LS therapy. Steroid hormone receptors regulate metabolism in adipocytes.

Analysis of prognostic factors impacting oncologic outcomes after neoadjuvant tyrosine kinase inhibitor therapy for gastrointestinal stromal tumors.

Background: Management of gastrointestinal stromal tumors (GISTs) has been transformed with tyrosine kinase inhibitors (TKIs). While data on optimal duration of adjuvant imatinib remains elusive, guidelines for administration of neoadjuvant TKIs remain unknown.

Methods: Under an institutional review board-approved protocol, patients at our institution with a diagnosis of GIST treated with neoadjuvant TKIs and surgical resection were identified.

Staging soft tissue sarcoma: evolution and change.

Soft tissue sarcoma (STS) is an extremely heterogeneous group of rare tumors that share a putative mesenchymal cell origin. STS can occur in any soft tissue in the body, yet all share a common feature of primarily disseminating hematogenously, particularly to the lungs. Staging for STS is particularly useful in prognosis, design of effective multimodality treatment programs, and comparing treatment outcomes from different centers and different eras.

Platelet-activating factor mediates MMP-2 expression and activation via phosphorylation of cAMP-response element-binding protein and contributes to melanoma metastasis.

Overexpression of cAMP-response element (CRE)-binding protein (CREB) and activating transcription factor (ATF) 1 contributes to melanoma progression and metastasis at least in part by promoting tumor cell survival and stimulating matrix metalloproteinase (MMP) 2 expression. However, little is known about the regulation of CREB and ATF-1 activities and their phosphorylation within the tumor microenvironment. We analyzed the effect of platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, for its ability to activate CREB and ATF-1 in eight cultured human melanoma cell lines, and we found that PAF receptor (PAFR) was expressed in all eight lines.

Using a xenograft model of human breast cancer metastasis to find genes associated with clinically aggressive disease.

Metastasis is the primary cause of death from breast cancer. A xenograft model was used to identify genes potentially involved with metastasis, comparing expression in the poorly metastatic GI101A human breast cancer cell line and a highly metastatic variant, GILM2. cDNA microarray analyses of these isogenic variants were done using 16K Operon 70-mer oligonucleotide microarray slides.

Inhibition of platelet-derived growth factor receptor signaling restricts the growth of human breast cancer in the bone of nude mice.

Purpose: Bone is a common site for breast cancer metastasis. Platelet-derived growth factor (PDGF) and PDGF receptors (PDGFR) are involved in the regulation of bone resorption. This study examined the effects of STI571 (imatinib mesylate), which inhibits PDGFR tyrosine kinase signaling, on the growth of human breast cancer cells in the bone of nude mice with consequent osteolysis.

Different signalling pathways regulate VEGF and IL-8 expression in breast cancer: implications for therapy.

Elevated expression of pro-angiogenic cytokines is associated with aggressive tumour growth and decreased survival of patients with breast cancer. In general, the breast cancer cell lines with high vascular endothelial growth factor (VEGF) expression also express high levels of interleukin-8 (IL-8). The consequence of inhibiting mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K), both implicated in regulation of these cytokines, was examined in four cell lines.

alphaB-crystallin as a marker of lymph node involvement in breast carcinoma.

Background: It was found previously that alphaB-crystallin, a small heat-shock protein, was overexpressed in a metastatic variant of the GI101A human breast carcinoma cell line. The objective of the current study was to determine whether the expression of alphaB-crystallin in primary breast carcinomas was associated with lymph node metastasis and survival.

Methods: Expression of alphaB-crystallin was measured in human breast carcinoma cell lines by immunoblotting.

Vascular endothelial growth factor expression promotes the growth of breast cancer brain metastases in nude mice.

Patients with breast cancer brain metastases cannot be cured and have a poor prognosis, with a median survival time of six months after diagnosis, despite developments in diagnostic and therapeutic modalities. In large part the progress in understanding the biology of breast cancer brain metastasis has been limited by the lack of suitable cell lines and experimental models. The objective of this study was to develop a reliable experimental model to study the pathogenesis of breast cancer brain metastases, using intra-internal carotid artery injection of breast cancer cells into nude mice.

Exposure of melanoma cells to dacarbazine results in enhanced tumor growth and metastasis in vivo.

Purpose: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF).

A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo.

Purpose: The melanoma cellular adhesion molecule, also known as MUC18, is highly expressed on several tumors, including bone sarcomas. The level of MUC18 expression has been found to correlate directly with tumor progression and metastatic potential. These observations have established MUC18 as a candidate mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might be a potential target for immunotherapy against several MUC18-expressing tumors, including human bone sarcomas.

Selection of more aggressive variants of the gI101A human breast cancer cell line: a model for analyzing the metastatic phenotype of breast cancer.

In vivo models utilizing orthotopic injection of tumor cells into nude mice have proven valuable for the study of metastasis. However, breast cancers are among the more difficult of human tumors to grow in immunodeficient mice, with a relatively low tumor take. Fewer still develop spontaneous metastases.

Dacarbazine causes transcriptional up-regulation of interleukin 8 and vascular endothelial growth factor in melanoma cells: a possible escape mechanism from chemotherapy.

The incidence of cutaneous malignant melanoma in the United States has increased more than any other cancer in recent years. Chemotherapy for metastatic melanoma is disappointing, there being anecdotal cases of complete remission. Dacarbazine (DTIC) is considered the gold standard for treatment, having a response rate of 15-20%, but most responses are not sustained.

Cellular adhesion pathways and metastatic potential of human melanoma.

Cellular adhesion molecules of the cadherin, integrin, and immunoglobulin superfamilies are important to both growth and metastasis of many cancers, including malignant melanoma. Malignant melanoma is an excellent model for studying these molecules, due in part to a sequential series of five defineable stages. As the malignant phenotype of melanoma cells changes from the noninvasive radial growth phase to the vertical growth phase, which has high metastatic potential, so does the repertoire of the cellular adhesion molecules expressed on the cells surface.

Therapeutic intervention with breast cancer metastasis.

Metastatic disease, mainly to the lungs, liver, bone, and brain, is the most common cause of death from breast cancer, despite advances in surgical and clinical management. Two basic principles govern the process of metastasis. First, that tumors are heterogeneous populations of cells, and second, that the process is a sequence of events that depends on tumor cell properties and interactions with the microenvironment at the site of metastasis.

Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571.

Purpose: Osteosarcoma is an aggressive primary bone cancer characterized by expression of platelet-derived growth factor (PDGF) and its cognate receptor. Coexpression of the growth factor and receptor suggests their role in autocrine or paracrine growth mechanisms. It has been reported previously that STI571 has specific activity in inhibiting select tyrosine kinase receptors, including PDGF and c-Kit.