Lymphatic and haematopoietic cancer mortality in a population attending school adjacent to styrene-butadiene facilities, 1963-1993.
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STUDY OBJECTIVE: To evaluate the risk of mortality from lymphatic and haematopoietic cancers and other causes among students. DESIGN: The study used school records, yearbooks, and Texas Department of Health records for the school years 1963-64 to 1992-93 to construct a cohort of 15,403 students. Three mortality databases were searched to identify deaths, and mortality rates in the cohort were compared with mortality rates from the United States and Texas. Computed standardised mortality ratios and 95% confidence intervals were used. SETTING: Eastern Texas high school adjacent to facilities that have been producing synthetic styrene-butadiene since 1943. MAIN RESULTS: 338 deaths were identified. The all causes standardised mortality ratio was 0.84 (95% confidence intervals 0.74, 0.95) for men and 0.89 (0.73, 1.09) for women. The standardised mortality ratio for all lymphatic and haematopoietic cancers was 1.64 (95% confidence intervals 0.85, 2.87) for men and 0.47 (0.06, 1.70) for women. The slight male excess in lymphatic and haematopoietic cancers was stronger among men who attended school for two years or less. CONCLUSIONS: The overall mortality from lymphatic and haematopoietic cancer among the students was little different from that of the United States as a whole. A moderate excess for men, predominantly among the shorter-term students, was offset by a deficit among women. These variations are compatible with random fluctuations; the overall pattern is not indicative of an effect of environmental exposure sustained while attending the high school. (+info)
Alpha-fetoprotein-specific genetic immunotherapy for hepatocellular carcinoma.
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The majority of human hepatocellular carcinomas overexpress alpha-fetoprotein (AFP). Two genetic immunization strategies were used to determine whether AFP could serve as a target for T-cell immune responses. Dendritic cells engineered to express AFP produced potent T-cell responses in mice, as evidenced by the generation of AFP-specific CTLs, cytokine-producing T cells, and protective immunity. AFP plasmid-based immunization generated less potent responses. These novel observations demonstrate that this oncofetal antigen can serve as an effective tumor rejection antigen. This provides a rational, gene therapy-based strategy for this disease, which is responsible for the largest number of cancer-related deaths worldwide. (+info)
The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression.
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Survivin is the first apoptosis inhibitor described to date to be expressed in G2-M in a cell cycle-dependent manner and to directly associate with mitotic spindle microtubules. To gain additional insights into this novel apoptotic checkpoint, we have now characterized the mouse survivin locus. Hybridization screening of mouse BAC libraries identified a survivin gene containing four exons and three introns, spanning >50 kb on the telomere of chromosome 11E2 and generating a 0.85-kb mRNA versus the 1.9-kb human transcript. A mouse survivin protein of 140 amino acids (Mr approximately 16,200) was 84% identical to its human orthologue and contained a structurally unique single baculovirus iap repeat (BIR) and a -COOH-terminus coiled domain instead of a RING finger. Analysis of the 5'-flanking region of the mouse survivin gene revealed a TATA-less promoter containing a canonical CpG island, numerous Sp1 sites, two cell cycle-dependent elements (CDEs), and one cell cycle gene homology region (CHR), typically found in G2-M-expressed genes. Primer extension and S1 nuclease mapping identified three transcription start sites at position -32, -36, and -40 from the initiating ATG. Transfection of survivin promoter-luciferase constructs identified a minimal promoter region within the most proximal 174 bp upstream of the first ATG. Mutagenesis of the CDE/CHR elements and Sp1 sites in this region, alone or in combination, reduced transcriptional activity by 40-60% in asynchronously growing cells and abolished cell cycle periodicity in G2-M-synchronized cells. These data demonstrate that cell cycle expression of survivin requires integration of typical CDE/CHR G1 repressor elements and basal transcriptional activity by Sp1. Disruption of these transcriptional requirements may provide an alternative strategy to block the overexpression of survivin in cancer. (+info)
Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases.
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A retrospective analysis on chronic lymphocytic leukemia (CLL) patients 55 years of age) were observed. At diagnosis, younger and older patients displayed a similar distribution of clinical features, except for a significantly higher male/female ratio in younger patients (2.85 v 1. 29; P <.0001). Both groups showed an elevated rate of second primary cancers (8.3% v 10.7%), whereas the occurrence of Richter's syndrome was significantly higher in younger patients (5.9% v 1.2%; P <. 00001). Younger and older patients showed a similar overall median survival probability (10 years) but were characterized by a different distribution of causes of deaths: CLL unrelated deaths and second primary malignancies predominated in the older age group, whereas the direct effects of leukemia were prevalent in the younger age group. Although younger and older patients displayed a similar survival, the evaluation of the relative survival rates showed that the disease had a greater adverse effect on the expected survival probability of the younger population. Multivariate analysis showed that for young CLL patients only dynamic parameters, such as lymphocyte doubling time and other signs of active disease, were the independent factors that significantly influenced survival probability (P =.00001). A prolonged clinico-hematologic follow-up allowed us to identify two subsets of young CLL patients with a different prognostic outcome: a group of patients (40%) with long-lasting stable disease without treatment and an actuarial survival probability of 94% at 12 years from diagnosis and another group (60%) with progressive disease and a median survival probability of 5 years after therapy. For the latter patients, the therapeutic effect of innovative therapies with curative intents needs to be investigated in prospective, comparative clinical trials. (+info)
Core needle biopsy is effective in the initial diagnosis of mediastinal lymphoma.
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BACKGROUND AND OBJECTIVE: With the development and refinement of guidance modalities for percutaneous biopsies, many investigators have reported studies supporting the role of guided core needle biopsy in the diagnosis of mediastinal lymphoma. The aims of this report are to evaluate the efficacy of findings at core needle biopsy of mediastinal masses on patient care and define the key determinants of clinical success. DESIGN AND METHODS: Fluoroscopy-guided (in 75 patients) and computed tomography-guided (in 8 patients) core needle biopsies were performed in 83 patients with mediastinal lymphoma: all but one of the patients were at first diagnosis. All the biopsies were performed using a Menghini needle (from 1.2 mm to 1.8 mm). In the vast majority of cases the 1.8 mm gauge was employed. RESULTS: The overall sensitivity for the diagnosis of lymphoma was 81% (67/83 cases). In the remaining 16 patients the lymphoma diagnosis was reached either by mediastinoscopy (11 cases) or anterior mediastinotomy (3 cases) or core needle biopsy of the lung (1 case); one patient was treated directly after the needle biopsy had been unsuccessful because he needed rapid therapy. In 77/82 (93%) patients it was possible to assess the specific histotype. There was no operative mortality; all the biopsies were performed on an outpatient basis. INTERPRETATION AND CONCLUSIONS: Our data indicate that core needle biopsy should be considered as an effective and safe procedure in the diagnosis of patients with mediastinal lymphoma with the possibility of determining the tumor subtype and subsequent specific treatment. (+info)
Diagnostic role of gallium scanning in the management of lymphoma with mediastinal involvement.
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BACKGROUND AND OBJECTIVE: Therapy of both Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) with mediastinal presentation at the time of diagnosis is frequently followed by radiological detection of residual masses. Computed tomography (CT) scanning is generally unable to detect the differences between tumor tissue and fibrosis. Gallium-67-citrate single photon emission ((67)GaSPECT) can potentially differentiate residual active tumor tissue from fibrosis. DESIGN AND METHODS: Seventy-five patients with HD or aggressive NHL presenting mediastinal involvement (64% with a bulky mass) were studied with CT and (67)GaSPECT at the end of combined modality therapy (chemo- and radiation therapy). RESULTS: After treatment, 3/3 (100%) patients with positive (67)GaSPECT and negative CT scan relapsed while only 1/18 (6%) patients with both negative (67)GaSPECT and CT scan did so. At the same time, 54 patients had a positive restaging CT scan (abnormal mass < 10% of size of initial mass). Of these patients, 13 had a positive (67)GaSPECT, 10 of whom (77%) relapsed; 41 had a negative (67)GaSPECT of whom 5 (12%) relapsed. The 4-year actuarial relapse-free survival rate was 90% for those with negative scans compared with 23% for gallium-positive patients (p < 0.000000). INTERPRETATION AND CONCLUSIONS: In lymphoma patients with mediastinal involvement, (67)GaSPECT should be considered, at least in patients who are CT positive, the imaging technique of choice for monitoring and differentiating the nature of any residual masses. (+info)
Quantity and origin of transplanted autologous blood cells are independent factors associated with speed of postransplant hematological reconstitution.
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AIM: Multivariate analysis of the prognostic significance of clinical and laboratory parameters on hematological recovery after autologous hematopoietic stem cell transplantation. METHODS: Sixty-two patients suffering from hematological and non-hematological malignancies entered the study. After conditioning therapy, 28 patients received bone marrow stem cells, 21 received peripheral blood stem cells, and 13 received both. The dynamic of hematological engraftment was calculated as recovery probability of leukocytes and neutrophils. Statistics was done using Kaplan-Meier method and multivariate Cox's proportional regression. RESULTS: Numerous clinical and laboratory parameters correlated with hematological recovery, but only two variables were found to be independently associated. Faster reconstitution correlated with greater number of progenitors and patients who received bone marrow cells recovered significantly later than others. Faster recovery could be expected in patient s receiving >13x10(4) CFU-GM/kg body weight, and significantly slower in those receiving <8.5x10(4) CFU-GM/kg. CONCLUSION: The quantity of progenitor cells and transplant type are variables significantly associated with the speed of postransplant engraftment, but these two parameters are mutually independent. The number of stem cells estimated by CFU-GM assay is a good and reliable routine test for predicting hematopoietic recovery. (+info)
A case of primary bilateral adrenal lymphoma with partial adrenal insufficiency.
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Unilateral or bilateral non-Hodgkin's lymphomas arising primarily in the adrenal glands are extremely rare. These lymphomas are usually present with large, bilateral adrenal masses with or without lymphadenopathy, and may be accompanied by adrenal insufficiency in some cases. A review of the literature indicates that patients with primary lymphoma of the adrenal glands usually do not have disease elsewhere, and if present, it is frequently extranodal. We report here an unusual case of primary bilateral adrenal lymphoma with partial adrenal insufficiency. (+info)