Search PubMed⌕ Search

Biomedical subjects

C Assaf

Publications and source records attributed to C Assaf.

At least 19 recordsLinked to original sources
PubMed2006

Minimizing adverse side-effects of oral bexarotene in cutaneous T-cell lymphoma: an expert opinion.

Bexarotene is an oral retinoid therapy that is effective for the treatment of early and advanced-stage cutaneous T-cell lymphoma (CTCL) in patients who have failed on other therapies. However, bexarotene treatment is associated with unavoidable side-effects, in particular hypertriglyceridaemia and hypothyroidism, which are manageable with adequate concomitant medications and are reversible on cessation of treatment. A pragmatic strategy for minimizing bexarotene-associated hypertriglyceridaemia and hypothyroidism is suggested, based on data from the studies with bexarotene in CTCL and on day-to-day experience with this agent in the clinical setting. The strategy anticipates that these common adverse events are likely to occur and recommends the early use of preventive therapy to lower triglycerides and elevate thyroid hormone levels in the blood, followed by subsequent monitoring, dose adjustment during bexarotene treatment, and titration of the daily bexarotene dose from 150 to 300 mg m(-2), which is optimal for most patients. When further information becomes available on how bexarotene interacts with lipid metabolism and thyroid function, the management approach suggested here may need to be changed.

Anticarcinogenic Agents↗
PubMed2006

Three coexisting lymphomas in one patient: genetically related or only a coincidence?

The simultaneous manifestation of different lymphomas in the same patient or even in the same tissue, defined as composite lymphoma, is very rare. The exceptional case of a patient who, presented with simultaneous manifestation of three different lymphomas after 30 years of successful treatment of a nodal T cell lymphoma is reported here. The three lymphomas were: (1) primary cutaneous marginal zone B cell lymphoma (MZBL); (2) nodal Epstein-Barr virus (EBV)-associated classic Hodgkin's lymphoma (cHL) of the B cell type; and (3) peripheral T cell lymphoma coexisting in the skin and cervical lymph node. Immunohistochemical and molecular analyses showed different clonal origins of EBV-negative cutaneous MZBL and EBV-positive B cell cHL and, in addition, the presence of the same clonal T cell population in the skin and lymph node. The simultaneous occurrence of three different, clonally unrelated lymphomas in one patient at the same time has not been reported yet.

Aged↗
PubMed2005

Overexpression of c-myb in leukaemic and non-leukaemic variants of cutaneous T-cell lymphoma.

BACKGROUND: The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL). OBJECTIVE: Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL. METHODS: c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR. RESULTS: Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 +/- 0.5) versus MF (1.2 +/- 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 +/- 31,960.32 AU in SS vs. 1,226.35 +/- 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 x 10(-2) +/- 2.27 x 10(-2) in SS vs. 0.91 x 10(-2) +/- 1.18 x 10(-2) in MF vs. 0.24 x 10(-2) +/- 0.11 x 10(-2) in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 x 10(-2) and 10.78 x 10(-2) +/- 7.24 x 10(-2)). CONCLUSION: Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.

Adult↗
PubMed2004

Cutaneous T cell lymphoma and classic Hodgkin lymphoma of the B cell type within a single lymph node: composite lymphoma.

Composite lymphomas are defined as two unrelated, morphologically and genetically distinct lymphomas occurring at the same point in time within the same tissue or organ. Since their original definition, several composite lymphomas have been reported exclusively based on morphological grounds. However, with the application of immunohistological and molecular biological techniques it has become evident that many so called "composite" lymphomas do not fulfil the necessary criteria, because they merely represent two different morphological phenotypes of the same malignant clone. This report describes the manifestation of a true composite lymphoma within a single cervical lymph node, which is composed of a cutaneous T cell lymphoma and a classic Hodgkin lymphoma of B cell type--a very rare finding indeed.

Aged↗
PubMed2004

Transition of Sézary syndrome into mycosis fungoides after complete clinical and molecular remission under extracorporeal photophoresis.

Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common clinical variants of cutaneous T cell lymphoma. Although thought to be closely related to mature T helper cells, the relation between the neoplastic cells in MF and SS is still not fully clarified. This report describes a patient with complete remission of SS under treatment with extracorporeal photophoresis (ECP), who subsequently developed typical plaques of MF and large cell lymphoma (LCL). Serial polymerase chain reaction analyses confirmed identical T cell receptor beta and gamma gene rearrangements in SS, MF, and LCL, and complete disappearance of the circulating malignant T cell clone from the peripheral blood after ECP. These findings indicate that the neoplastic cells in SS, MF, and LCL are derived from a common precursor T cell, despite the change in clinical phenotype.

Aged↗
PubMed2002

Tight junction proteins: a novel class of integral membrane proteins. Expression in human epidermis and in HaCaT keratinocytes.

Tight junction proteins comprise a novel group of integral membrane proteins necessary for cell-to-cell contacts and responsible for the barrier function in epithelial and endothelial cells in various tissues. The tight junction membrane domain contains at least three distinct proteins, named occludin, claudin and junctional adhesion molecule. Claudins are products of a gene family consisting of more than 20 members. We investigated mRNA expression of occludin and 13 different claudins in neonatal foreskin, adult skin and cultivated HaCaT keratinocytes by the Northern blot technique, and performed immunohistochemical staining of adult skin for occludin, claudin 1 and claudin 2. Occludin, claudin 1 and claudin 3 mRNAs were expressed in human neonatal and adult keratinocytes as well as in HaCaT keratinocytes. All other tested claudins were negative. Immunohistochemical staining of adult skin was positive for occludin in the intercellular space of the granular layer, and for claudin 1 in the inter-cellular space of the spinosum layer and basal layer, but negative for claudin 2 in all skin layers. Claudin 1 was also positive in the outer root sheath of hair follicles. Our results indicate that occludin, claudin 1 and claudin 3 are involved in cell-to-cell contacts between keratinocytes in human epidermis, although their functional importance remains unknown.

Adult↗
PubMed2000

High detection rate of T-cell receptor beta chain rearrangements in T-cell lymphoproliferations by family specific polymerase chain reaction in combination with the GeneScan technique and DNA sequencing.

The distinction between benign polyclonal and malignant monoclonal lymphoid disorders by morphology or immunophenotyping is frequently difficult. Therefore, the demonstration of clonal B-cell or T-cell populations by detecting identically rearranged immunoglobulin (Ig) or T-cell receptor (TCR) genes is often used to solve this diagnostic problem. Whereas the detection of rearranged Ig genes is well established, TCR gamma (gamma) and beta (beta) gene rearrangements often escape detection with the currently available polymerase chain reaction (PCR) assays. To establish a sensitive, specific, and rapid method for the detection of rearranged TCR-beta genes, we developed a new PCR approach with family-specific Jbeta primers and analyzed the resulting PCR products by high-resolution GeneScan technique. The superior efficiency of this new method was demonstrated by investigating 132 DNA samples extracted from lymph node and skin biopsy specimens (mostly formalin fixed) and blood samples of 62 patients who had a variety of T-cell lymphomas and leukemias. In all but 1 of the tumor samples (98.4%) a clonal amplificate was detectable after TCR-beta PCR and the same clonal T-cell population was also found in 15 of 18 (83%) of the regional lymph nodes and in 7 of 11 (64%) of the peripheral blood samples. Direct comparison of these results with those obtained currently by the most widely applied TCR-gamma PCR revealed an approximate 20% lower detection rate in the same set of samples than with the TCR-beta PCR method. These results indicate that the new TCR-beta PCR is most suitable for a rapid and reliable detection of clonal T-cell populations. (Blood. 2000;96:640-646)

Clone Cells↗
PubMed2000

Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease.

Recent molecular single-cell studies have shown that in approximately 95% of cases, Reed-Sternberg cells of classic Hodgkin disease (HD) are derived from B cells of germinal center origin. Attempts to determine the cellular nature of the remaining cases have so far failed. To clarify whether they are derived from T cells, this study examined 791 single CD30(+) Hodgkin and Reed-Sternberg (HRS) cells from 13 T-cell marker-positive cases and from 6 cases with null-cell phenotype for rearranged T-cell receptor-gamma (TCR-gamma) genes by single copy polymerase chain reaction. Monoclonally rearranged TCR-gamma genes were detectable in 2 of the 13 classic HD cases with T-cell marker-positive HRS cells, with none detectable in the null-cell cases. Eight of the T-cell marker-positive cases and all 6 null-cell cases were also studied for rearrangements of immunoglobulin genes. Six of the 8 T-cell marker-positive cases harbored clonal immunoglobulin gene rearrangements. The 2 cases without rearranged immunoglobulin genes were those that contained clonal TCR-gamma rearrangements and lacked expression of the B-cell-specific activator protein. From these findings we conclude that cases of classic HD with T-cell-derived HRS cells definitely exist, although their overall incidence at 1% to 2% is very low. Even within the T-cell marker-positive cases only a minority (15%) were derived from T cells. The majority (85%) originated from B cells, indicating that the T-cell antigens expressed by HRS cells are, in contrast to those expressed in non-Hodgkin lymphoma, not lineage specific.

Adolescent↗
PubMed1999

Clonal T-cell receptor gamma-chain gene rearrangement by PCR-based GeneScan analysis in advanced cutaneous T-cell lymphoma: a critical evaluation.

Detection of clonal T-cell receptor gamma (TCRgamma)-chain gene rearrangement is a promising approach to distinguish between cutaneous T-cell lymphomas (CTCLs) and reactive T-cell infiltrates. Despite the improved sensitivity by using the polymerase chain reaction (PCR) rather than Southern blot analysis, monoclonality could be demonstrated in only 53-90 per cent of CTCL biopsies in recent studies. In the present study, formalin-fixed, paraffin-embedded specimens of 21 selected patients with clear-cut advanced-stage CTCL were analysed using a semi-nested TCRgamma PCR with newly developed consensus primer pairs. Detection of PCR products was done by GeneScan analysis (GSA); this technique is advantageous due to its sensitivity and accuracy in the detection and size determination of PCR products and it is easier to interpret than direct read-outs from TGGE or DGGE gels. In serial dilution experiments, TCRgamma-PCR-GSA allowed the detection of clonal, rearranged T-cells with a high in vitro sensitivity against a polyclonal background (1-6 per cent). Despite the selection of clear-cut, advanced-stage CTCL cases, however, dominant clonal TCRgamma-chain gene rearrangement was found in only 16 of the 21 patients analysed, indicating an overall clinical sensitivity of 76 per cent. Specificity was evaluated using biopsy specimens from 21 control patients suffering from long-standing psoriasis (n=13) and eczema (n=8). Surprisingly, GeneScan profiles showing apparently single dominant peaks were detected in 14 per cent of these skin lesions, but these profiles turned out to be pseudo-monoclonal by repeated determinations. In conclusion, TCRgamma-PCR-GSA does not suffice reliably to exclude malignancy, due to its limited clinical sensitivity, but with precautions taken to detect pseudo-monoclonality and to secure specificity, TCRgamma-PCR-GSA is a valuable instrument in the diagnosis of CTCL.

Diagnosis, Differential↗
PubMed1999

T-cell and T/natural killer-cell lymphomas involving ocular and ocular adnexal tissues: a clinicopathologic, immunohistochemical, and molecular study of seven cases.

OBJECTIVE: Lymphomas of the eye and its adnexa are frequently of B lineage. This study aims to characterize the clinical and histopathologic features of the rare non-B-cell non-Hodgkin lymphomas (NHL) of these locations. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Seven cases of T- and T/NK-cell lymphomas involving the ocular and ocular adnexal tissues. METHODS: A morphologic, immunohistochemical, and molecular analysis (polymerase chain reaction) of each of the tumors was undertaken. The lesions were classified according to the Revised European-American Lymphoma (REAL) classification. The clinical and follow-up data were collected. RESULTS: The patients included four women and three men ranging in age from 32 to 88 years (mean, 63 years). The presenting ophthalmic symptoms varied from a small nodule on the upper eyelid and conjunctival swellings to dramatic loss of vision associated with gross protrusion of the globe. Five of the cases presented were secondary manifestations of a systemic lymphoma in ocular tissues; two cases represented primary disease. Three cases were "peripheral T-cell lymphomas (PTCL), unspecified" with positivity for CD3, CD8, and betaF1 and negativity for CD56. Two cases were CD3+, CD30+, and CD56- and were classified as "anaplastic large-cell lymphomas of T-cell type" (T-ALCL). The remaining two cases showed an immunophenotype of CD3+, CD56+, and betaF1- and proved to contain Epstein-Barr virus (EBV) by in situ hybridization, consistent with "T/natural killer (NK)-cell lymphoma of nasal type." Clonal T-cell populations were shown in all three of the PTCLs by Southern blot (n = 1) and polymerase chain reaction (n = 2) for the T-cell receptor gamma and beta genes in one case of ALCL but not in the T/NK-cell lymphomas. Five patients died within 2 years; only two patients (one primary PTCL and one cutaneous T-ALCL) were disease free at 4 and 5 years' follow-up, respectively. CONCLUSION: This study shows that a heterogeneous group of T-cell lymphomas can involve the eye and its adnexal tissue. Most T-cell neoplasms are secondary manifestations of systemic disease and carry a poor prognosis. These findings, in conjunction with published data on ocular B-NHL, also indicate that immunophenotypic differentiation between T- and B-NHL in these locations is of clinical importance.

Adult↗
PubMed1999

Follicular mycosis fungoides.

We describe a patient with follicular mycosis fungoides (MF), a rare folliculotropic variant of cutaneous T-cell lymphoma (CTCL). Follicular involvement in CTCL usually presents clinically as alopecia mucinosa associated histologically with follicular mucinosis. Follicular MF differs from alopecia mucinosa/follicular mucinosis associated with MF with regard to its clinical presentation, histology and, presumably, prognosis. Our patient presented with the characteristic findings of follicular MF, i.e. infiltrated plaques showing numerous enlarged, comedo-like follicular infundibula; histology was dominated by exclusive folliculotropism of atypical lymphocytes sometimes forming follicular Pautrier's microabscesses, and by lack of epidermotropism and follicular mucinosis. Despite photochemotherapy and treatment with oral retinoids and interferon alpha, the patient's follicular MF rapidly developed into a progressive CTCL with large tumorous lesions, but responded to electron beam therapy. The course of our patient's disease confirms the notion that follicular MF may be associated with a worse prognosis than classical MF. However, electron beam irradiation induced remission of follicular MF that was maintained by a combination therapy consisting of extracorporeal photopheresis and interferon alfa.

Aged↗