Do oncologists believe new cancer drugs offer good value?

Background: Substantial debate centers on the high cost and relative value of new cancer therapies. Oncologists play a pivotal role in treatment decisions, yet it is unclear whether they perceive high-cost new treatments to offer good value or how therapeutic costs factor into their treatment recommendations.

Methods: We surveyed 139 academic medical oncologists at two academic hospitals in Boston.

Prostate-specific antigen nadir and cancer-specific mortality following hormonal therapy for prostate-specific antigen failure.

Purpose: For men receiving androgen-suppression therapy (AST) for a rising postoperative or postradiation prostate-specific antigen (PSA), we evaluated whether a PSA nadir of more than 0.2 ng/mL was significantly associated with prostate cancer-specific mortality (PCSM).

Patients And Methods: The study cohort comprised 747 men with rising PSA and negative bone scan after surgery (n = 486) or radiation therapy (n = 261) who were treated with AST.

Identifying patients at risk for significant versus clinically insignificant postoperative prostate-specific antigen failure.

Purpose: We evaluated whether men at risk for significant versus clinically insignificant prostate-specific antigen (PSA) failure after radical prostatectomy could be identified using information available at diagnosis.

Patients And Methods: A prospective prostate cancer screening study that enrolled, diagnosed, and treated 1,011 men with radical prostatectomy at Barnes-Jewish Hospital (St Louis, MO) from January 1, 1989, to June 1, 2002, for localized prostate cancer formed the study cohort. Preoperative predictors of a postoperative PSA doubling time (DT) of less than 3 months and more than 12 months or no PSA failure were identified using logistic regression.

Response to docetaxel/carboplatin in patients with hormone-refractory prostate cancer not responding to taxane-based chemotherapy.

Few treatment options are available for patients with metastatic hormone-refractory prostate cancer (HRPC) that is not responsive to or continues to progress after taxane-based chemotherapy. Although single-agent carboplatin has modest activity in HRPC, carboplatin chemotherapy could induce a synergistic effect when combined with taxanes in patients with disease resistant to taxane-based chemotherapy. We report a case series of 4 consecutive patients treated with docetaxel (60-70 mg/m2) plus carboplatin (area under the curve of 4/5) following progression after taxane-based chemotherapy.

Early detection of disease and scheduling of screening examinations.

Special examinations exist for many chronic diseases, which can diagnose the disease while it is asymptomatic, with no signs or symptoms. The earlier detection of disease may lead to more cures or longer survival. This possibility has led to public health programs which recommend populations to have periodic screening examinations for detecting specific chronic diseases, for example, cancer, diabetes, cardiovascular disease and so on.

Activin a in the regulation of corneal neovascularization and vascular endothelial growth factor expression.

Activin A, a dimeric glycoprotein that belongs to the transforming growth factor-beta superfamily, governs cellular differentiation in a wide variety of models and has been implicated in the regulation of angiogenesis. We examined the role of activin A and its downstream signaling pathway in a murine model of inflammatory corneal neovascularization induced by mechanical injury (debridement), and in vitro in corneal epithelial cells. Activin A expression increased steadily from day 2 until day 8 after mechanical debridement in vivo, paralleling vascular endothelial growth factor (VEGF) expression.

Stem cell transplantation-harnessing of graft-versus-malignancy.

Purpose Of Review: Allogeneic transplantation can cure a number of hematologic malignancies; however, the cost in morbidity and mortality is high. Much of the toxicity is a direct consequence of the intensity of the conditioning regimen. It has gradually been recognized that the conditioning regimen is important but not critical for the success of transplantation, particularly in the less aggressive hematologic malignancies.

BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis.

Glycolysis and apoptosis are considered major but independent pathways that are critical for cell survival. The activity of BAD, a pro-apoptotic BCL-2 family member, is regulated by phosphorylation in response to growth/survival factors. Here we undertook a proteomic analysis to assess whether BAD might also participate in mitochondrial physiology.

Molecular regulation of vertebrate early endoderm development.

Detailed study of the ectoderm and mesoderm has led to increasingly refined understanding of molecular mechanisms that operate early in development to generate cellular diversity. More recently, a number of powerful studies have begun to characterize the molecular determinants of the endoderm, a germ layer previously neglected in developmental biology. Work in diverse model systems has converged on an integrated transcriptional and signaling pathway that serves to establish the vertebrate endoderm.

BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway.

The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are associated with early-onset breast and/or ovarian cancer and encode products that each interact with the product of the eukaryotic RecA homologue, hRad51. We have recently found that BRCA1 and BRCA2 coexist in a common biochemical complex. The two proteins also colocalize in subnuclear foci in somatic cells as well as on the axial elements of developing synaptonemal complexes in meiotic cells.

Interaction of Hic-5, A senescence-related protein, with focal adhesion kinase.

Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like phenotype. Structurally, Hic-5 and paxillin, a 68-kDa cytoskeletal protein, share homology such as the LD motifs in the N-terminal half and the LIM domains in the C-terminal half. Here we show that Hic-5 binds to focal adhesion kinase (FAK) by its N-terminal domain, and is localized to focal adhesions by its C-terminal LIM domains.

An activity specified by the osteosarcoma line U2OS can substitute functionally for ICP0, a major regulatory protein of herpes simplex virus type 1.

Among the five immediate-early regulatory proteins of herpes simplex virus (HSV) type 1, only ICP0 is capable of activating all kinetic classes of viral genes. Consistent with its broad transactivating activity, ICP0 plays a major role in enhancing the reactivation of HSV from latency both in vivo and in vitro. Although not essential for viral replication, ICP0 confers a significant growth advantage on the virus, especially at low multiplicities of infection.

Antifolates can potentiate topoisomerase II inhibitors in vitro and in vivo.

Antifolates have been shown to increase the DNA strand breaks produced by the topoisomerase inhibitor etoposide. PT523 is a potent new antifolate that cannot be polyglutamated. Human SCC-25 squamous carcinoma cells were exposed to methotrexate, trimetrexate or PT523 at a concentration of 5 microM for 24 h along with various concentrations of etoposide or novobiocin during the final 2 h.

Presentation of exogenous antigens by macrophages: analysis of major histocompatibility complex class I and II presentation and regulation by cytokines.

There is an antigen presenting cell (APC) in the lymphoid organs capable of presenting exogenous antigen (Ag) with major histocompatibility complex (MHC) class I molecules. This study was initiated to isolate clones of these APC to definitively establish their phenotype and to further study their properties. Murine bone marrow macrophages (BM M psi) were immortalized by overexpression myc and raf oncogenes.

Signal transduction of steel factor and granulocyte-macrophage colony-stimulating factor: differential regulation of transcription factor and G1 cyclin gene expression, and of proliferation in the human factor-dependent cell line MO7.

Steel factor (SF) synergizes with a variety of hemopoietins to support the growth and differentiation of human progenitor cells. The human factor-dependent cell line MO7 has been used as a model to study the interaction of SF with other growth factors such as GM-CSF, because both factors support the proliferation of this cell line and are synergistic in combination. Previous studies have shown that this effect is not readily explained by the synergistic activation of early, cytosolic signal transduction intermediates such as tyrosine kinases, Raf-1, MAP2 kinase, or phospholipase C gamma.

Polymorphic Hh genes in the HLA-B(C) region control natural killer cell frequency and activity.

We demonstrated earlier that individuals homozygous for conserved major histocompatibility complex (MHC)-extended haplotypes have low natural killer (NK) activity as measured by cytolysis of the K562 tumor cell lines. In the present study, we investigated the segregation and MHC linkage of NK activity in families in which MHC haplotypes of human histocompatibility leukocyte antigens (HLA)-A, -C, and -B, complotype, and DR specificities are known. In two informative families, low activity was inherited as a recessive trait linked to the MHC.

Regulation of the 28 kDa heat shock protein by retinoic acid during differentiation of human leukemic HL-60 cells.

Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately, relatively little is known about how cell differentiation is regulated. Considering that heat shock proteins (hsp) and specifically the small hsps have been increasingly linked to growth regulation, we sought to determine whether the mammalian small hsp (hsp28) is a growth-regulatory candidate during hematopoietic cell differentiation.

Generation of a large library of point mutations in polyoma middle T antigen.

Polyoma middle T antigen (MTAg) transforms cells by associating with and activating a variety of intracellular proteins, including src family members and a phosphatidylinositol-3 kinase. In order to assist in the study of the relative importance of the various associated biochemical activities for transformation by polyomavirus MTAg, a library of MTAg mutants was constructed. Chemically mutagenized MTAg DNA was purified from wild-type DNA by separation on denaturing gradient gels and placed into a recombinant retrovirus vector.