Myeloma-reactive allospecific cytotoxic T lymphocytes lyse target cells via the granule exocytosis pathway.

Accumulating evidence indicates that a graft-vs.-myeloma effect (GVM) and its associated clinical remission of the disease can be induced by donor lymphocyte infusion in myeloma patients who have relapsed after allogeneic bone marrow transplantation. Although it is believed that GVM is induced by allospecific T cells, T-cell subsets and the mechanisms involved in the killing of myeloma cells by donor T cells have not been studied.

Multicolour spectral karyotyping identifies new translocations and a recurring pathway for chromosome loss in multiple myeloma.

Multicolour spectral karyotyping (SKY) was performed on primary tumour specimens from 100 patients with multiple myeloma (MM) that showed complex clonal chromosome aberrations not fully characterized by G-banding. In this study, SKY was able to identify or revise translocations with breakpoints involving 14q32, 11q13 or 8q24 in 32 patients (32%). Five new recurring translocations were identified, two of which involved chromosome 22.

Cancer therapy and polymorphisms of cytochromes P450.

Cytochrome P450 (CYP) enzymes are important in the metabolism of some endogenous compounds, environmental and dietary xenobiotics and many drugs. Many of these enzymes have genetic polymorphisms that produce significant changes in metabolic activity, however the function of other polymorphisms is unknown. Genetic polymorphisms have important influences on variability in human pharmacokinetics, including intra-individual differences in drug toxicity, drug interactions and response to chemotherapy.

Coping with head and neck cancer during different phases of treatment.

Background: Little is known about how patients cope with head and neck cancer despite its devastating impact on basic functioning. This study examined coping patterns among patients at different phases of illness.

Methods: Participants were 120 patients with advanced disease, who were grouped according to the following phases of illness: (1) pretreatment, (2) on treatment, (3) <6 months after treatment, and (4) >6 months after treatment.

An integrated model of group treatment for cancer patients.

Considerable evidence suggests that group interventions are a valuable resource for cancer patients, but few conceptual frameworks are available to guide decisions about which approaches might be most useful for which patients at what phases of illness. This article presents an integrative treatment model for group services. It describes different group interventions geared toward patients at different phases of illness to accommodate the shifting needs and concerns that evolve over the course of the disease.

Syndecan-1 is targeted to the uropods of polarized myeloma cells where it promotes adhesion and sequesters heparin-binding proteins.

Syndecan-1 (CD138) is a heparan sulfate-bearing proteoglycan present on the surface of myeloma cells where it mediates myeloma cell-cell and cell-extracellular matrix adhesion. In this study, we examined myeloma cell lines for cell membrane localization of syndecan-1. On some cells we note a striking localization of syndecan-1 to a single small membrane protrusion, with the remainder of the cell surface being mostly negative for syndecan-1.

High incidence of chromosome 13 deletion in multiple myeloma detected by multiprobe interphase FISH.

Multiple myeloma (MM) is a hypoproliferative malignancy yielding informative karyotypes in no more than 30% of newly diagnosed cases. Although cytogenetic and molecular deletion of chromosome 13 is associated with poor prognosis, a MM tumor suppressor gene (TSG) has not been identified. To localize a minimal deleted region of chromosome 13, clonotypic plasma cells from 50 consecutive patients with MM were subjected to interphase fluorescence in situ hybridization (FISH) analysis using a panel of 11 probes spanning the entire long arm of chromosome 13.

[Paraneoplastic neurological syndromes: from the diagnosis of exclusion to the use of immunological and molecular markers].

For many years paraneoplastic neurological syndromes have been identified through the exclusion of other neurological complications in patients with cancer. The discovery that many paraneoplastic syndromes are associated with immunological reactions allows a specific and comprehensive definition of these disorders, which often can be promptly recognized by the serological detection of antineuronal antibodies. In a significant number of paraneoplastic syndromes the genes coding for the target onconeuronal antigens have been cloned and their functions are being elucidated.

Evi27 encodes a novel membrane protein with homology to the IL17 receptor.

Evi27 is a common site of retroviral integration in BXH2 murine myeloid leukemias. Here we show that integration at Evi27 occurs in a CpG island approximately 6 kb upstream from a novel gene (designated Evii27) with homology to the IL17 receptor (Il17r) and that proviral integrations result in increased expression of the Evi27 protein on the cell surface. The human EVI27 homolog was also cloned and mapped to chromosome 3p21.

Assessing quality of life in patients with head and neck cancer: cross-validation of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Head and Neck module (QLQ-H&N35).

Objective: To evaluate the reliability and validity of a new, disease-specific quality-of-life measure for patients with head and neck cancer: the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire--QLQ-H&N35.

Design: Cross-sectional study using questionnaire data and medical chart review.

Setting: Academic tertiary care otolaryngology clinic.

Matrix metalloproteinases in multiple myeloma.

Multiple myeloma is a deadly malignancy characterized by plasma cell infiltration of bones. The resulting effect is painful "punched-out" lesions where bone is eroded and filled with myeloma cells that suppress and replace the normal marrow components. Recently it has been shown that myeloma cells produce matrix-metalloproteinase-9 (MMP-9) and MMP-2 and that accumulation of MMP-9 protein is suppressed upon expression of the heparan sulfate proteoglycan, syndecan-1.

Using cultural beliefs and patterns to improve mammography utilization among African-American women: the Witness Project.

Breast cancer and early detection of the disease is a significant issue for all women. Moreover, the sociocultural implications in the differential mortality rates increased interest in possible barriers to screening practices. Recently, a number of studies have investigated African Americans' cultural beliefs associated with breast cancer.

Assessing margin status.

As little time ago as 1991 the NIH Consensus conference could not agree on the need for negative margins. Today, negative margin status has become a prerequisite for BCT recognizing that positive margins impact negatively on local recurrence rates. The science of margin evaluation is fast becoming recognized to play a key role in providing patients with the opportunity for breast conservation therapy as well as the best possible cosmetic result.

The proliferative potential of myeloma plasma cells manifest in the SCID-hu host.

The low proliferative activity of myeloma plasma cells prompted the notion that the clonotypic B cells that exist in the blood and bone marrow of all myeloma patients contain the proliferative myeloma cells (stem cell). We have exploited our severe combined immunodeficiency (SCID)-hu host system for primary myeloma to investigate whether myeloma plasma cells are capable of sustained proliferation. Purified CD38(++)CD45(-) plasma cells consistently grew and produced myeloma and its manifestations in SCID-hu hosts (8 of 9 experiments).

In vivo human metabolism of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

To better understand the interactions of the pathways of activation and detoxification on the metabolism of the putative carcinogen, PhIP, we administered a dose of 70-84 microg [2-14C] PhIP (17.5 [microCi 14C) 48-72 h before scheduled colon surgery. Blood and urine collected for the next 48-72 h was evaluated by linear accelerator mass spectroscopy (AMS) and scintillation counting LC-MS to identify specific PhIP metabolites.

Patients with multiple myeloma may safely undergo autologous transplantation despite ongoing RSV infection and no ribavirin therapy.

Respiratory syncytial virus (RSV) has been reported as a cause of death among autologous peripheral blood stem cell (ASCT) and marrow recipients and recommendations for therapy with aerosolized ribavirin plus intravenous immunoglobulin (IVIG) made. This therapy is expensive, may be toxic, and causes a significant disruption of patient care. The purpose of this study was to evaluate the morbidity and mortality of RSV infections in patients with multiple myeloma undergoing ASCT without ribavirin therapy.

Evaluation of seprase activity.

Seprase is a serine protease that is integral to the plasma membrane and is overexpressed by invasive tumor cells (Piñeiro-Sánchez et al., J Biol Chem 1997; 272: 7595-601; Monsky et al., Cancer Res 1994; 54: 5702-10).

Subareolar versus peritumoral injection for location of the sentinel lymph node.

Background: Sentinel lymph node (SLN) biopsy is fast becoming the standard for testing lymph node involvement in many institutions. However, questions remain as to the best method of injection. The authors hypothesized that a subareolar injection of material would drain to the same lymph node as a peritumoral injection, regardless of the location of the tumor.

Increasing mammography practice by African American women.

Purpose: This study examines the effectiveness of the Witness Project, a culturally competent cancer education program that trains cancer survivors to promote early detection and increased breast self-examination and mammography in a population of rural, underserved, African American women.

Description Of Study: The primary setting for the Witness Project-an intensive, community-based, culturally sensitive educational program that incorporates spirituality and faith-was the African American church. Baseline and 6-month follow-up surveys were obtained from 206 African American women in two intervention counties and from 204 African American women in two control counties in the rural Mississippi River Delta region of Arkansas.

Role of NF-kappaB in the rescue of multiple myeloma cells from glucocorticoid-induced apoptosis by bcl-2.

The molecular mechanisms by which multiple myeloma (MM) cells evade glucocorticoid-induced apoptosis have not been delineated. Using a human IgAkappa MM cell line (ARP-1), we found that dexamethasone (Dex)-induced apoptosis is associated with decreased NF-kappaB DNA binding and kappaB-dependent transcription. Both nuclear p50:p50 and p50:p65 NF-kappaB complexes are detected in ARP-1 cells by supershift electrophoretic mobility shift assay (EMSA).

Advances in therapy of multiple myeloma: lessons from acute leukemia.

This paper traces the lack of progress, until recently, in the treatment of multiple myeloma (MM) to having ignored the principles that led to cure in acute leukemia more than 2 decades ago. Only in the mid-1980s did investigation begin to consider complete remission (CR) a research objective, representing a necessary first step toward cure. The experience with autologous and allogeneic stem cell-supported high-dose therapy is reviewed, demonstrating, in both historically controlled and randomized studies, the validity of the dose-response concept in MM in terms of increased CR rates as well as extended event-free (EFS) and overall survival (OS).

Syndecan-1 expression suppresses the level of myeloma matrix metalloproteinase-9.

ARH-77 human myeloma cells invade into type I collagen gels but become non-invasive when engineered to express syndecan-1, a heparan sulphate proteoglycan that promotes cell adhesion to collagen. To determine if syndecan-1 expression influences the activity of proteases that may facilitate invasion, we analysed media harvested from syndecan-1 expressing and non-expressing cells. High levels of a 92 kD gelatinase accumulated in serum-free growth medium of both parental and control-transfected ARH-77, but much less 92 kD gelatinase accumulated in the medium of ARH-77 transfectants expressing syndecan-1.