Cases reported "Recurrence"

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1/10. Boon's disease: hemorrhagic cystitis in conjunction with massive exfoliation of degenerated urothelial cells (apoptosis?) during intercontinental flights in an otherwise healthy person.

    Hemorrhagic cystitis is a well-defined clinical emergency, usually occurring in the course of treatment with toxic agents such as cyclophosphamide. We present a case of hemorrhagic cystitis in an otherwise completely healthy female. The three documented attacks were severe and started during intercontinental flights. This type of hemorrhagic cystitis as a disease proved to be a boon, treatable by drinking large amounts of water, and was diagnosed by and in Dr. Boon; thus was the appellation Boon's disease coined. Cellular changes in the urine specimen taken after onset of the disease indicated massive exfoliation of degenerated urothelial cells with morphological features suggestive of apoptosis. It seems likely that this process can be initiated by any event which is associated with compromise of vitality of the urinary bladder lining, such as may occur in hypovolemia. This type of hemorrhagic cystitis is most probably not uncommon in susceptible individuals during intercontinental flights.
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keywords = apoptosis
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2/10. tamoxifen-based treatment induces clinically meaningful responses in multiple myeloma patients with relapsing disease after autotransplantation.

    tamoxifen has been shown to induce apoptosis in multiple myeloma cell lines and primary myeloma cells. Daily tamoxifen was given to 12 consecutive multiple myeloma patients who either relapsed following autologous stem cell transplantation (11) or had progressive disease on conventional chemotherapy (1). methotrexate was also given biweekly to enhance the antiangiogenetic effect. Two patients achieved complete remission lasting 8 and 18 months. Two additional patients had stable disease (SD) for 7 and 11 months. All responders were men and the earliest signs of response were seen after approximately 6-8 weeks of treatment. The regimen was very well tolerated. Speculations about a possible mechanism of action of tamoxifen in multiple myeloma are discussed.
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keywords = apoptosis
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3/10. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications.

    The proteasome inhibitor PS-341 inhibits nuclear factor-kappaB (NF-kappaB) activation, induces apoptosis in cancer cells, including multiple myeloma (MM) cells, and has marked clinical activity as a monotherapy for MM. In this study, we found that subtoxic concentrations of PS-341 potently sensitized MM cell lines and patient cells to dna-damaging chemotherapeutic agents such as doxorubicin and melphalan, including cells resistant to these drugs and those isolated from a patient who had relapsed after PS-341 monotherapy. Moreover, PS-341 abolished cell adhesion-mediated drug resistance. Using gene expression profiling and proteomic analysis, we demonstrate that PS-341, among its other proapoptotic effects, down-regulates the expression of several effectors involved in the cellular response to genotoxic stress. These data suggest that, in addition to down-regulating the expression of apoptosis inhibitors, PS-341 inhibits genotoxic stress response pathways and thereby restores sensitivity to dna-damaging chemotherapeutic agents. These studies, therefore, provide the framework for clinical use of this agent in combination with conventional chemotherapy.
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keywords = apoptosis
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4/10. Late recurrence of inflammatory first-stage lesions in incontinentia pigmenti: an unusual phenomenon and a fascinating pathologic mechanism.

    BACKGROUND: incontinentia pigmenti (IP) is an X-linked genodermatosis that is manifested by neonatal inflammatory vesicles localized along the lines of Blaschko. These lesions usually clear spontaneously within a few months, leaving hyperpigmentation. Ophthalmologic and neurologic symptoms can be associated with IP. Late recurrences of the first-stage inflammatory lesions after the initial rash are uncommon and have been reported infrequently. The mechanism involved in this phenomenon is unclear. However, the recent identification of NEMO/IKKgamma as the gene responsible for IP sheds new light on its pathophysiologic origins. OBSERVATIONS: We report 5 cases of children who experienced episodes of late reactivation of IP. In all cases, the recurrences occurred on the previously hyperpigmented streaks several months or years after resolution of the initial eruptions. In most cases, the recurrences were preceded by an infectious episode. CONCLUSIONS: These IP recurrences suggest that mutated cells can persist a long time in the epidermis. We theorize that infections trigger the reactivations. The NEMO/IKKgamma gene encodes a protein essential in nuclear factor kappaB activation, which is required for resistance to tumor necrosis factor alpha-induced apoptosis. We discuss the role of a proinflammatory cytokine such as tumor necrosis factor alpha as a triggering factor for the reactivation.
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keywords = apoptosis
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5/10. Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma.

    multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)-6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL-2 family proteins (BCL-2, BCL-XL, BAX and MCL-1) were also investigated. In addition, the RPMI 8226 cell line (IL-6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time- and dose-dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 micromol/l). BCL-2, BCL-XL and MCL-1 showed decreased expression in depsipeptide-treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM.
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keywords = apoptosis
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6/10. Anti-CD20 therapy of treatment-resistant Wegener's granulomatosis: favourable but temporary response.

    Rituximab is a genetically engineered chimeric monoclonal immunoglobulin (Ig)G1 antibody. It binds the CD20 trans-membrane surface antigen expressed by mature B cells but not by antibody secreting plasma cells, and removes the cells by activating complement, inducing cell-mediated lysis, and by apoptosis. Mainly used for the treatment of non-Hodgkin's lymphomas, rituximab has recently been tried with favourable responses in rheumatoid arthritis, systemic lupus erythematosus, and other chronic immunological diseases. Wegener's granulomatosis (WG) is a granulomatous vasculitis with high morbidity and mortality. It is thought that anti-neutrophil cytoplasmatic antibodies (ANCA) with specificity for proteinase 3 (PR3) are possibly involved in the pathogenesis of the disease. Conventional therapy with cyclophosphamide and corticosteroids generally succeeds in inducing remission, but relapses frequently follow. Among the biological agents, tumour necrosis factor-alpha (TNF-alpha) inhibitors have been tried with some success. Based on a case report we recently treated three refractory WG patients with rituximab and achieved almost complete but temporary remission. CD20 cells disappeared rapidly in peripheral blood, only to rise prior to subsequent disease flares occurring at 34, 63, and 54 weeks, respectively (Figure 1). A new flare occurred in one patient at 86 weeks. At the end of the observation periods (54, 102, and 120 weeks), only one patient had proteinuria. Chest radiographs became normal in two patients, while infiltrates remained unchanged in the third. Granulomatous retro-orbital or sinus masses in two patients seemed unresponsive to therapy.
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keywords = apoptosis
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7/10. Transcriptional profiling of granulosa cells from a patient with recurrent empty follicle syndrome.

    Empty follicle syndrome (EFS) is characterized by the absence of oocytes after apparently normal follicular development and the pathogenesis of this syndrome is not well characterized. The aim of this study was to analyse whole gene expression of granulosa cells (GC) from a patient with recurrent EFS by using Affymetrix GeneChip. A total of 160 genes were identified as being differentially expressed (by at least two-fold) between EFS GC and the control GC. Most of the differentially expressed genes were involved in cell growth and death. Among these were MAPK3, which plays an important role in the inhibition of apoptosis, was down-regulated 2.3-fold in EFS GC. Moreover, secretory phospholipase A2 and transforming growth factor receptor II, key regulators of cell death pathway, were down-regulated 3.54- and 2.82-fold respectively in EFS. Gene expression of granulosa cells from the EFS patient was significantly altered. The absence of the oocytes might be due to the increased apoptotic gene expression and the reduction of transcripts whose products are responsible for healthy follicular growth. Gene expression analyses might be a useful technique in identifying markers to follow a healthy follicular maturation and understanding the events that lead to EFS.
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keywords = apoptosis
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8/10. Unilateral central corneal epithelial dysplasia.

    A unilateral, apparently nonfamilial disease process affecting the interpalpebral portion of the corneal epithelium is reported. The patient, a 62-year-old man, was in good general health; he had no disease of the skin or mucous membranes and no history of trauma. Severe intermittent discomfort of the left eye had been present for several months. Corneal epithelial scrapings were performed on two occasions with a one-year interval, the condition having recurred during the intervening months. Material from both biopsy specimens showed dysplasia of the epithelium with foci of acantholysis and dyskeratosis and features of apoptosis. Transmission electron microscopic findings included intracytoplasmic desmosomes, conspicuous thickened tonofibrils, irregular convoluted cytoplasmic membranes, and dyskeratotic bodies.
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keywords = apoptosis
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9/10. Peculiar facial erythematosquamous lesions in two siblings with cyclical summer improvement and winter relapse: a variant of keratosis lichenoides chronica?

    A 7-year-old girl had erythematous hyperkeratotic papules and plaques that improved in summer and recurred in winter since the age of 4 months. She had had irregular, ridge-like erythematosquamous lesions on the arms with the same seasonal variation. The lesions on the arms improved with age. light and electron microscopic examination showed marked degeneration of keratinocytes and prominent apoptosis. Her older brother had a similar but milder dermatosis. We believe these cases may represent a variant of keratosis lichenoides chronica.
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ranking = 0.2
keywords = apoptosis
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10/10. CD95 (APO-1/Fas) mutations in childhood T-lineage acute lymphoblastic leukemia.

    CD95 (APO-1/Fas)-mediated apoptosis is pivotal in normal lymphocyte homeostasis and mutations of CD95 cause a benign autoimmune lymphoproliferation syndrome (ALPS) in humans and mice. However, tumors only rarely develop in these patients, and no CD95 mutations have yet been directly implicated in tumorigenesis. We therefore examined 81 de novo childhood T-lineage acute lymphoblastic leukemias (T-ALL) including 54 steroid-poor responders, 10 relapsed T-ALL, and 10 leukemic T-cell lines, for the presence of CD95 mutations using single-strand confirmation polymorphism and sequence analysis. In leukemic blasts and normal T cells of one patient, a heterozygous mutation in exon 3 of CD95 causing a 68Pro --> 68Leu change associated with decreased CD95-mediated apoptosis was found. In leukemic blasts and normal T cells of a second patient, a homozygous mutation in the promoter of CD95 causing disruption of a consensus sequence for AP-2 binding without decreasing constitutive CD95 expression was detected. No large intragenic alterations of CD95 were found, no homozygous loss was detected in the cell lines, and no CD95 mutations were detected in the relapses. The data presented here show that CD95 mutations occur in some T-ALL and may be of biological importance.
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ranking = 0.4
keywords = apoptosis
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