Immunotherapy in multiple myeloma: current strategies and future prospects.

Multiple myeloma is still a fatal disease. Despite advances in high-dose chemotherapy supported by autologous transplantations, relapse of the underlying disease remains the primary cause of treatment failure. Strategies for post-transplantation immunomodulation would be desirable for eradication of remaining tumor cells.

Do antimicrobial-impregnated central venous catheters prevent catheter-related bloodstream infection?

Controversy surrounds the role of central venous catheters (CVCs) impregnated with antimicrobial agents in the prevention of catheter-related bloodstream infection (CRBSI). We reviewed the current literature to evaluate the efficacy of antimicrobial-impregnated CVCs for preventing CRBSI. Eleven randomized studies published in article form were identified that included a control group that received nonimpregnated CVCs.

Heparan sulfate regulates targeting of syndecan-1 to a functional domain on the cell surface.

In polarized B lymphoid cells, syndecan-1 is targeted specifically to a discrete membrane domain termed the uropod that is located at the cell's trailing edge. Within this functional domain, syndecan-1 promotes cell-cell adhesion and concentration of heparin binding growth factors. The present study reveals the surprising finding that targeting of syndecan-1 to uropods is mediated by its heparan sulfate chains and that targeting is regulated by cell surface events rather than solely by intracellular mechanisms.

Racial differences in the outcome of patients with colorectal carcinoma.

Background: African-American (AA) patients with colorectal carcinoma have a worse prognosis compared with Caucasians. To analyze the causes of this disparity in survival, a retrospective study of patients with colorectal carcinoma was undertaken. The impact of treatments received and the role of socioeconomic factors such as income, education, and poverty levels were studied.

New insights into role of microenvironment in multiple myeloma.

Multiple Myeloma (MM) is a malignant disease of terminally differentiated B cells. It most likely originates in a B cell which has traversed the germinal center and has been exposed there extensively to antigens based on the high number of somatic mutations in the complementarity determining regions. The cell of origin is either a plasmablast, or more likely, a memory B-cell.

Cleaning patient shower facilities: a novel approach to reducing patient exposure to aerosolized Aspergillus species and other opportunistic molds.

We previously have demonstrated that the hospital water-distribution system could be a reservoir for airborne molds that leads to secondary aerosolization of these molds in patient shower facilities. In this report, we show that cleaning the floors of patient shower facilities in a bone marrow transplantation unit reduced the mean air concentrations of molds, including Aspergillus species (from 12 cfu/m3 to 4 cfu/m3; P=.0047).

Beta(2)-microglobulin as a negative growth regulator of myeloma cells.

High beta(2)-microglobulin (beta(2)m) levels in myeloma correlate with poor prognosis. We hypothesized that beta(2)m may affect myeloma cell growth and survival. In this study, we examined the in vitro effects of beta(2)m on myeloma cells.

Neoglycans, carbodiimide-modified glycosaminoglycans: a new class of anticancer agents that inhibit cancer cell proliferation and induce apoptosis.

The soluble form of the syndecan-1 heparan sulfate proteoglycan acts as a tumor suppressor molecule that inhibits growth and induces apoptosis of some cancer cell lines in vitro. Analogs of syndecan-1 were produced by carbodiimide (EDAC) conjugation of glycosaminoglycan (GAG) chains to a protein scaffold, thereby generating synthetic proteoglycans that were evaluated for anticancer properties. Surprisingly, when analyzing activities of the controls, we discovered that EDAC modified GAG chains inhibit myeloma cell viability even in the absence of protein.

Soluble syndecan-1 promotes growth of myeloma tumors in vivo.

Syndecan-1 (CD138) is a transmembrane heparan sulfate-bearing proteoglycan expressed by most myeloma plasma cells that regulates adhesion, migration, and growth factor activity. In patients with myeloma, shed syndecan-1 accumulates in the bone marrow, and high levels of syndecan-1 in the serum are an indicator of poor prognosis. To test the effect of soluble syndecan-1 on tumor cell growth and dissemination, ARH-77 B-lymphoid cells were engineered to produce a soluble form of syndecan-1.

Use of alternative therapies by patients undergoing surgery for nonmelanoma skin cancer.

Background: The use of alternative therapies is becoming increasingly common and may result in unwanted side effects and drug interactions.

Objective: To determine the frequency of alternative medicine use by patients undergoing Mohs surgery for nonmelanoma skin cancer.

Methods: A written survey concerning use of alternative therapies was given to patients undergoing Mohs surgery for nonmelanoma skin cancer.

Cancer education takes on a spiritual focus for the African American faith community.

Background: The faith community, specifically African American (AA) churches, has been a partner in the delivery of health educational messages for the past two decades.

Methods: This article goes beyond the physical setting of the church to describe how and why spirituality is a particularly effective and essential component of one breast and cervical cancer education program, The Witness Project. Examining the theoretical and methodological foundations of this program demonstrates that the content as well as the messengers are strategically positioned within the AA faith community.

An analysis of telephone interview data collected in 1992 from 820 women who reported problems with their breast implants to the food and drug administration.

How health care providers deal with concerns and feelings of women who have problems with their breast implants affects the women's satisfaction with their breast implants, yet in 1992 little was known about the concerns and feelings of these women. A qualitative analysis of in-depth telephone interviews conducted in 1992 with 820 women from all regions of the United States who reported problems with their breast implants to the Food and Drug Administration and responded to an invitation to be interviewed provided data. Respondents were primarily 40 to 69 years of age at the time of interview, Caucasian, married, and educated beyond high school.

Syndecan-1 in B lymphoid malignancies.

Syndecans are heparan sulfate-bearing proteoglycans that are found on the surface of most cells. Syndecan-1 is expressed predominantly on epithelia, but is also present on pre-B cells and plasma cells. The syndecans act to bind various effector molecules via their heparan sulfate chains, including both soluble and insoluble molecules within the extracellular milieu.

Pathogenic Aspergillus species recovered from a hospital water system: a 3-year prospective study.

Nosocomial aspergillosis, a life-threatening infection in immunocompromised patients, is thought to be caused primarily by Aspergillus organisms in the air. A 3-year prospective study of the air, environmental surfaces, and water distribution system of a hospital in which there were known cases of aspergillosis was conducted to determine other possible sources of infection. Aspergillus species were found in the hospital water system.

The clinical spectrum and pathogenesis of paraneoplastic disorders of the central nervous system.

Paraneoplastic neurologic disorders (PND) refer to neurologic disorders of unknown cause that occur at higher frequency in patients with cancer than in the general population. There is increasing evidence that many of these disorders are immune mediated and associated with cytotoxic antitumor immunity. The identification of the immune responses in these patients facilitates the diagnosis of the PND and has led to the cloning and characterization of the target antigens in the nervous system and tumor.

The photoreceptor cell-specific nuclear receptor is an autoantigen of paraneoplastic retinopathy.

Objectives: To report a novel antibody associated with paraneoplastic retinopathy and to characterize the retinal autoantigen.

Methods: Immunohistochemistry of rat and human tissues was used to identify antiretinal antibodies. Serologic screening of a bovine retinal cDNA expression library was performed to clone the target antigen.

Sperm protein 17 is expressed on normal and malignant lymphocytes and promotes heparan sulfate-mediated cell-cell adhesion.

Sperm protein 17 (Sp17) is a highly conserved mammalian protein present on acrosome-reacted sperm that is thought to promote fertilization by binding sulfated carbohydrates of the oocyte zona pellucida. Although Sp17 was originally described as a testis-specific antigen, emerging evidence indicates that it may be more ubiquitously expressed than was previously thought. With the use of a specific antiserum, Sp17 was found to be present on the surface of malignant lymphoid cells, including B- and T-lymphoid cell lines, and on the surface of primary cells isolated from 2 patients having B-lymphoid tumors.

Cyclin D3 at 6p21 is dysregulated by recurrent chromosomal translocations to immunoglobulin loci in multiple myeloma.

Reciprocal chromosomal translocations, which are mediated by errors in immunoglobulin heavy chain (IgH) switch recombination or somatic hypermutation as plasma cells are generated in germinal centers, are present in most multiple myeloma (MM) tumors. These translocations dysregulate an oncogene that is repositioned in proximity to a strong IgH enhancer. There is a promiscuous array of nonrandom chromosomal partners (and oncogenes), with the 3 most frequent partners (11q13 [cyclin D1]; 4p16 [FGFR3 and MMSET]; 16q23 [c-maf]) involved in nearly half of MM tumors.

Structural and functional characterization of the human gene for sorting nexin 1 (SNX1).

The aim of the present study was to identify the gene for sorting nexin 1 (SNX1) to evaluate the potential for tissue-specific alternative splicing and to analyze the activity of the SNX1 promoter. The coding DNA for SNX1 was divided between 15 exons in 43 kb of genomic DNA located on human chromosome 15q22. Although SNX1 mRNA expression was widespread in human tissues, alternative splicing is thought to generate skipped exons in SNX1 cDNAs.

The rhombic bilobed flap for nasal reconstruction.

Background: The bilobed flap is a useful tool for reconstruction of the nose but is occasionally complicated by pincushioning or trapdoor deformity.

Objective: To describe the use of a rhombic bilobed flap for use in reconstructing defects on the lower third of the nose.

Methods: Reconstruction of skin cancer defects following Mohs surgery was performed using a bilobed rhombic flap design in 10 patients.

High-dose therapy and innovative approaches to treatment of multiple myeloma.

High-dose therapy in multiple myeloma (MM) appears to be superior in terms of event-free survival and overall survival compared with conventional therapy. Melphalan-based high-dose therapy increases complete remission rates from 5% to 50% and extends event-free survival beyond 3 years and overall survival beyond 6 years. Critical disease features associated with durable complete remission, event-free survival, and overall survival include the absence of chromosome 13 deletion, low beta(2)-microglobulin, and low C-reactive protein levels.

Heparan sulfate proteoglycans in invasion and metastasis.

Because heparan sulfate proteoglycans mediate cell adhesion and control the activities of numerous growth and motility factors, they play a critical role in regulating the metastatic behavior of tumor cells. Due to their utilitarian nature, heparan sulfate proteoglycans may at times act as inhibitors of cell invasion and at other times as promoters of cell invasion, with their function being determined by their location (cell surface or extracellular matrix), the heparin-binding molecules they associate with, the presence of modifying enzymes (proteases, heparanases) and the precise structural characteristics of the proteoglycan. Also, the tissue type and pathophysiological state of the tumor influence proteogylcan function.