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Biomedical subjects

L E French

Publications and source records attributed to L E French.

At least 19 recordsLinked to original sources
PubMed2006

Regression of extranodal natural killer/T-cell lymphoma, nasal type with denileukin diftitox (Ontak) and bexarotene (Targretin): report of a case.

Denileukin diftitox (Ontak) is a fusion protein comprising a diphtheria toxin and an interleukin (IL)-2 moiety that specifically targets CD25 (IL-2 receptor)-positive tumour cells. We report a patient with rapidly progressive Epstein-Barr virus-positive nasal type extranodal natural killer/T-cell lymphoma (extranodal NKTCL), treated with a combination of denileukin diftitox (Ontak) and oral bexarotene (Targretin). A significant regression of the cutaneous tumours was observed already after the first cycle of denileukin diftitox and was maintained for a period of 5 months with monthly cycles of denileukin diftitox. The treatment was well tolerated. Following this response the patient decided to stop the treatment. He was then followed by his oncologist and lost from dermatological follow-up. Shortly after treatment withdrawal the disease progressed and the patient received one cycle of doxorubicin (Caelyx). He died from septic shock syndrome 2 months later. To our knowledge this is the first case of extranodal NKTCL treated with denileukin diftitox and bexarotene. A striking, albeit transient, response occurred with this therapy. Combination treatment with denileukin diftitox and bexarotene should be further assessed in this aggressive type of cutaneous lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases.

BACKGROUND: Rituximab (MabThera); Roche, Basel, Switzerland; an anti-CD20 chimeric monoclonal antibody) has been shown to have significant activity in nodal B-cell lymphomas, with few associated adverse effects. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. Intravenous and subsequently intralesional administration of rituximab have also been reported to be effective and well tolerated in cutaneous B-cell lymphoma (CBCL). The comparative efficacy of intravenous vs. intralesional rituximab in CBCL is not known. OBJECTIVES: To evaluate the objective response rate, relapse rate, time to progression, and tolerance in patients with CBCL treated with intravenous or intralesional rituximab. METHODS: Eight patients with multiple primary CBCL (four follicle centre lymphoma and four marginal zone lymphoma) were treated with intralesional rituximab (six patients; 10-30 mg per lesion, three times weekly for one or two cycles at a 4-week interval) or intravenous rituximab (two patients; 375 mg m(-2) once weekly for four consecutive weeks). RESULTS: Complete clinical remission was obtained in all cases. The two patients treated intravenously did not relapse during a follow-up period of 18-24 months. Four of six patients treated intralesionally presented a relapse of new lesions at another site within a mean of 6 months after treatment. The injected lesions did not, however, recur. New lesions also responded to another cycle of intralesional rituximab. Tolerance to treatment was very good in both treatment groups. CONCLUSIONS: Rituximab therapy of CBCL appears to have a potential advantage in cases where lesions are localized in sites that are difficult to treat with radiotherapy or surgery and in which secondary scarring or alopecia is likely. Intralesional injections of rituximab allow the use of considerably smaller doses compared with intravenous treatment, with similar response rates and tolerance. However, within a 12-month follow-up period, relapse of CBCL with new lesions at distinct sites was frequently observed after intralesional treatment.

Adult↗
PubMed2005

Extensive annular verrucous late secondary syphilis.

We report an illustrative case of an apparently healthy 38-year-old man with a past history of alopecia universalis who developed extensive, slightly pruritic, infiltrated annular verrucous lesions of the scalp, perioral, lumbar, perianal and genital areas over a 6-month period. The combination of an unusual clinical presentation, positive syphilis serology and rapid response to penicillin therapy was consistent with a diagnosis of extensive annular and verrucous late secondary syphilis. We present this case to illustrate a rare and potentially misleading clinical feature of late secondary syphilis, a disease considered to be of the past but still present in today's practice.

Adult↗
PubMed2004

Dermoscopy of pigmented lesions: a valuable tool in the diagnosis of melanoma.

Although malignant melanoma is not the most frequent cancer, its incidence is increasing faster than any other. Early diagnosis of melanoma is particularly important because if the diagnosis is made at an early stage when the tumour thickness is less than 1 mm the prognosis is excellent. Dermoscopy is an in vivo method for the early diagnosis of melanoma and the differential diagnosis of pigmented lesions of the skin. It has been shown to increase diagnostic accuracy over clinical visual inspection in the hands of experienced physicians. This paper reviews the principles of dermoscopy, diagnostic strategies and recent technological developments.

Diagnosis, Differential↗
PubMed2002

Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis.

Chronic graft-versus-host disease (cGVHD) is a multiorgan disorder with skin manifestations resembling scleroderma. Since photopheresis, a treatment that induces an anticlonotypic immune response, has proven to be effective in both cutaneous T cell lymphomas with circulating clonal T cells and in cGVHD, we have searched for circulating clonal T cell populations in patients with cGVHD, and determined whether T cell clonality in the blood is associated with therapeutic response. We screened blood samples from 27 patients after HLA-matched allogeneic bone marrow transplantation (allo-BMT), 10 without cGVHD and 17 with extensive cGVHD, for clonal T cell receptor gamma (TCR gamma) gene rearrangements using fluorescent-based polymerase chain reaction (PCR) and automated high-resolution capillary electrophoresis. Amplified populations of clonal T cells with unique TCR gamma gene rearrangements were found in six of 10 (60%) allo-BMT patients without cGVHD and 13 of 17 (76.5%) allo-BMT patients with cGVHD (P = 0.41), as compared to none of 10 (0%) healthy controls. Twelve patients with cGVHD were treated by photopheresis, and the presence of amplified populations of clonal T cells was found to be associated with a cutaneous response to photopheresis, as eight of eight (100%) clone-positive vs none of four (0%) clone-negative patients experienced a clinically significant cutaneous response to treatment (P = 0.001). Our findings suggest that patients with cGVHD that have detectable expanded clonal T cell populations in their peripheral blood, may be more likely to respond to treatment by photopheresis.

Adult↗
PubMed2002

Optimized lentiviral transduction of erythroid precursors from healthy adults and patients with myelodysplastic syndromes.

Lentivectors, derived from human immunodeficiency virus-1 (HIV-1), represent a novel investigational and therapeutic tool for targeting hematopoietic progenitor cells. We describe a new protocol whereby we achieved a highly efficient lentiviral transduction of erythroid precursor cells originating from the bone marrow of healthy adults and patients with myelodysplastic syndromes (MDS). CD34(+) stem cells from healthy subjects were cultured with erythropoietin, IL-3 and stem cell factor, and thereby expanded approximately 300-fold. When these cultures were transduced with a lentiviral vector expressing GFP as a reporter gene, 70% glycophorin(+) cells were GFP(+). Although proliferation and levels of transduction were reduced in cultures of CD34(+) stem cells from patients with myelodysplastic syndromes, 50% of glycophorin(+) cells became GFP(+), amongst which 30% were sideroblastic erythroid precursors. This study demonstrates that lentiviral vectors are capable of efficiently transducing MDS precursors and offers new perspectives to investigate the influence of specific genes on normal erythroid differentiation. This may eventually help to correct defects in patients suffering from myelodysplastic syndromes.

Adult↗
PubMed2002

Frequent downregulation of Fas (CD95) expression and function in melanoma.

Membrane-bound Fas ligand (FasL, Apo-1L, CD95L) induces rapid apoptosis of Fas (CD95)-sensitive cells on interaction with Fas, and is an important effector molecule of cytolytic T lymphocytes (CTLs). Melanomas are immunogenic and induce the production of specific CTLs, but are usually able to escape immune destruction. We investigated Fas expression and function in 53 cutaneous melanocytic lesions and 13 melanoma cell lines grown in vitro. Immunohistochemical analysis of Fas expression in cutaneous melanocytic lesions showed moderate to high levels of Fas in common benign melanocytic naevi, but low to undetectable levels in atypical naevi, primary (superficial spreading melanoma, nodular melanoma) and cutaneous melanoma metastases. Fluorescence-activated cell sorting (FACS) analysis of Fas expression in melanoma cell lines revealed undetectable or low levels of cell surface Fas expression in five of the 13 melanoma cell lines. Analysis of Fas signalling by quantification of cell death following exposure to recombinant FasL showed that a reduction in Fas expression results in resistance to FasL-mediated cell death. Furthermore, two of the 13 melanoma cell lines were found to be resistant to FasL-mediated cell death despite conserved Fas expression. Thus seven of the 13 melanoma cell lines were found to have impaired Fas signalling. Taken together, our results indicate that downregulation of Fas expression and resistance to Fas-mediated apoptosis are frequent in melanoma.

Apoptosis↗
PubMed2002

Periorbital oedema and erythema as a manifestation of discoid lupus erythematosus.

Periorbital oedema and erythema are a rare cutaneous manifestation of discoid erythematosus (DLE) which is well known to ophthalmologists but less to dermatologists. We report the case of a 74-year-old female patient with periorbital oedema and erythema. Since swelling of the eyelid is common in the dermatological practice, dermatologists should be aware of the differential diagnosis and its occurrence in patients with DLE.

Aged↗
PubMed2001

T cell costimulation by the TNF ligand BAFF.

The TNF ligand family member BAFF (B cell activating factor belonging to the TNF family, also called Blys, TALL-1, zTNF-4, or THANK) is an important survival factor for B cells [corrected]. In this study, we show that BAFF is able to regulate T cell activation. rBAFF induced responses (thymidine incorporation and cytokine secretion) of T cells, suboptimally stimulated through their TCR. BAFF activity was observed on naive, as well as on effector/memory T cells (both CD4+ and CD8+ subsets), indicating that BAFF has a wide function on T cell responses. Analysis of the signal transduced by BAFF into T cells shows that BAFF has no obvious effect on T cell survival upon activation, but is able to deliver a complete costimulation signal into T cells. Indeed, BAFF is sufficient to induce IL-2 secretion and T cell division, when added to an anti-TCR stimulation. This highlights some differences in the BAFF signaling pathway in T and B cells. In conclusion, our results indicate that BAFF may play a role in the development of T cell responses, in addition to its role in B cell homeostasis.

B-Cell Activating Factor↗
PubMed2001

Identification of clonal T cells in the blood of patients with systemic sclerosis: positive correlation with response to photopheresis.

OBJECTIVES: To search for circulating clonal T-cell populations in patients with systemic sclerosis (SSc), and to determine whether T-cell clonality in the blood predicts therapeutic response to photopheresis. DESIGN: Analysis of clonal T-cell receptor gamma gene rearrangements before photopheresis treatment and blinded clinical evaluation of cutaneous response to photopheresis in a case series. SETTING: University hospital setting. PATIENTS: Thirteen consecutive patients with SSc. INTERVENTIONS: Photopheresis in 11 patients. MAIN OUTCOME MEASURES: Clonality of T cells in the blood before photopheresis and clinical response to photopheresis. RESULTS: Screening of blood samples from 13 SSc patients for clonal T-cell receptor gamma gene rearrangements revealed a monoclonal T cell population in 6 (46%) of 13 SSc patients. Clinical response to photopheresis in 11 patients was evaluated in a blinded manner using skin severity scores. Clonality of T cells appeared to be associated with a higher chance of response to photopheresis therapy, as 4 (67%) of 6 patients in the clone-positive group vs 1 (20%) of 5 in the clone-negative group experienced a clinically significant response to treatment. CONCLUSIONS: A high proportion of patients with SSc have detectable expanded clonal T-cell populations in the peripheral blood, and such patients appear more likely to respond to photopheresis.

Adult↗
PubMed2001

Selective expression of FLIP in malignant melanocytic skin lesions.

FLIP (FLICE Inhibitory Protein) is a recently identified intracellular inhibitor of caspase-8 activation that potently inhibits cell death mediated by all death receptors including Fas and TRAIL. FLIP has recently been shown to favor tumor growth and immune escape in mouse tumor models. We analyzed FLIP expression by immunohistochemistry in a panel of 61 benign and malignant human melanocytic skin lesions. FLIP expression was undetectable in all but one benign melanocytic lesion (31/32, 97%). In contrast, FLIP was strongly expressed in most melanomas (24/29 = 83%). Overexpression of FLIP by transfection in a Fas- and TRAIL-sensitive human melanoma cell line rendered this cell line more resistant to death mediated by both TRAIL and FasL. Selective expression of FLIP by human melanomas may confer in vivo resistance to FasL and TRAIL, thus representing an additional mechanism by which melanoma cells escape immune destruction.

Antibody Specificity↗
PubMed2001

Regression of multifocal, skin-restricted, CD30-positive large T-cell lymphoma with interferon alfa and bexarotene therapy.

We report the case of a 43-year-old male patient with persistent multifocal, skin-restricted, CD30-positive, large T-cell lymphoma. Combination therapy of systemic interferon alfa and oral bexarotene was initiated on an experimental basis in the hope of circumventing therapies such as methotrexate, radiotherapy, or multiple-agent chemotherapy that may be required in such cases. This treatment was associated with rapid and marked regression of the patient's cutaneous lesions.

Administration, Oral↗
PubMed2001

Therapeutic advances in biological response modifiers in the treatment of cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is most often a skin-infiltrating malignancy of clonal CD4+ T-cells. Therapy is based on staging and the likelihood of progression. Biological response modifiers and chemotherapeutic agents are used to preserve the integrity of the host antitumour response while selectively targeting the malignant cells. The biological response-modifying treatment options currently used to treat CTCL are bexarotene, denileukin diftitox, interferon-alpha, interferon-gamma and interleukin-12, as well as extracorporeal photopheresis and phototherapy. A combination therapy approach maximises response in patients with advanced CTCL. Biological response modifiers in combination with photopheresis are used for patients with the leukaemic phase of the disease. Among the majority of patients with advanced stage disease so treated, immune response augmentation appears to prolong survival. Future areas of research should assess not only survival and optimal treatment combinations, but also quality of life during the treatment period.

Bexarotene↗
PubMed2000

Fas-mediated cell death in toxic epidermal necrolysis and graft-versus-host disease: potential for therapeutic inhibition.

Death receptors are a growing family of transmembrane proteins which can detect the presence of specific extracellular death signals and rapidly trigger cellular destruction by apoptosis. The best studied to date is Fas (CD95). Expression and signalling by Fas and its ligand (FasL, CD95L) is a tightly regulated process essential for key physiological functions in a variety of organs, including the maintenance of immune homoeostasis. Recently, strong evidence has shown that dysregulation of Fas expression and/or signalling contributes to the pathogenesis of toxic epidermal necrolysis and acute graft-versus-host disease. With these new developments, strategies for modulating the function of Fas signalling have emerged and opened up novel therapeutic possibilities. Specific blockade of Fas, for example with intravenous immunoglobulin preparations containing specific anti-Fas antibodies, has shown great promise in the treatment of toxic epidermal necrolysis and may also be useful in the treatment of acute graft-versus-host disease. Further developments in this field may have important clinical implications for the treatment of such diseases.

Acute Disease↗
PubMed2000

Cutaneous pseudolymphoma, lymphomatoid contact dermatitis type, as an unusual cause of symmetrical upper eyelid nodules.

We describe a 74-year-old woman who rapidly developed bilateral voluminous nodules on the upper eyelids, following 4 months' treatment for chalazion. Histological and immunohistochemical findings were suggestive of cutaneous pseudolymphoma (CPL), and extensive screening for malignant lymphoma (ML) remained negative. Cutaneous pseudolymphomas are inflammatory diseases that can simulate ML either clinically, histopathologically, or both. They are a rare cause of nodules of the upper eyelids, usually characterized by a benign evolution, that can be secondary to ultraviolet sensitivity, adverse reactions to systemic medications and contact sensitization, among others. In our case, epicutaneous patch tests were strongly positive for a series of allergens contained in the ophthalmological preparations used; therefore, they were suggestive that the patient had CPL, lymphomatoid contact dermatitis type. In addition, the patient had been treated previously with several drugs, known to cause CPL and immune dysregulation. Complete regression of the lesions required treatment with systemic steroids and chlorambucil. No relapse occurred within a 5-year follow-up period.

Aged↗
PubMed2000

Death receptors in cutaneous biology and disease.

Death receptors are a growing family of transmembrane proteins that can detect the presence of specific extracellular death signals and rapidly trigger cellular destruction by apoptosis. Expression and signaling by death receptors and their respective ligands is a tightly regulated process essential for key physiologic functions in a variety of organs, including the skin. Several death receptors and ligands, Fas and Fas ligand being the most important to date, are expressed in the skin and have proven to be essential in contributing to its functional integrity. Recent evidence has shown that Fas-induced keratinocyte apoptosis in response to ultraviolet light, prevents the accumulation of pro-carcinogenic p53 mutations by deleting ultraviolet-mutated keratinocytes. Further- more, there is strong evidence that dysregulation of Fas expression and/or signaling contributes to the pathogenesis of toxic epidermal necrolysis, acute cutaneous graft versus host disease, contact hypersensitivity and melanoma metastasis. With these new developments, strategies for modulating the function of death receptor signaling pathways have emerged and provided novel therapeutic possibilities. Specific blockade of Fas, for example with intravenous immunoglobulin preparations that contain specific anti-Fas antibodies, has shown great promise in the treatment of toxic epidermal necrolysis and may also be useful in the treatment acute graft versus host disease. Likewise, induction of death signaling by ultraviolet light can lead to hapten-specific tolerance, and gene transfer of Fas ligand to dendritic cells can be used to induce antigen specific tolerance by deleting antigen-specific T cells. Further developments in this field may have important clinical implications in cutaneous disease.

Animals↗
PubMed2000

Successful reversal of recalcitrant hepatic allograft rejection by photopheresis.

Extracorporeal photopheresis (ECP) is an immunologic modality that has shown efficacy in the treatment of clonal T-cell diseases, including Sézary syndrome and allograft rejection. In this case report, we expand on this observation to include recalcitrant hepatic allograft rejection. A 14-year-old boy with hepatic allograft rejection refractory to high-dose corticosteroid and lymphocytolytic therapy was treated with 4 sessions of ECP over a 6-week period. After 2 sessions, a liver biopsy showed complete reversal of acute cell-mediated rejection. No opportunistic infections or other adverse events were noted. Photopheresis appears to be a safe and effective modality for the treatment of refractory hepatic allograft rejection.

Adolescent↗