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At least 37 records · Page 2Linked to original sources
PubMed1997

Constitutive activation of a slowly migrating isoform of Stat3 in mycosis fungoides: tyrphostin AG490 inhibits Stat3 activation and growth of mycosis fungoides tumor cell lines.

Mycosis fungoides (MF) is a low-grade cutaneous T cell lymphoma of unknown etiology. In this report, the Jak/Stat (Janus kinase/signal transducer and activator of transcription) signaling pathway was investigated in tumor cell lines established from skin biopsy specimens from a patient with MF. Jaks link cytokine receptors to Stats, and abnormal Jak/Stat signaling has been observed in some hemopoietic cancers. In MF tumor cells, a slowly migrating isoform of Stat3, Stat3(sm), was found to be constitutively activated, i.e., (i) Stat3(sm) was constitutively phosphorylated on tyrosine residues, and tyrosine phosphorylation was not enhanced by growth factor stimulation; (ii) band shift assays and immunoprecipitations of DNA/Stat complexes showed constitutive DNA-binding properties of Stat3(sm); and (iii) Stat3(sm) was constitutively associated with Jak3. The abnormal activation of Stat3(sm) was highly specific. Thus, neither the fast migrating isoform of Stat3 (Stat3(fm)) nor other Stats (Stat1, Stat2, and Stat4 through Stat6) were constitutively activated. The Jak kinase inhibitor, tyrphostin AG490, blocked the constitutive activation of Stat3(sm) and inhibited spontaneous as well as interleukin 2-induced growth of MF tumor cells. In conclusion, we have provided evidence for an abnormal Jak/Stat signaling and growth regulation in tumor cells obtained from affected skin of an MF patient.

Cell Division↗
PubMed1993

Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma.

It is well recognized that patients with classical mycosis fungoides (MF) may develop a large-cell lymphoma (LCL), a phenomenon known as "transformation." An unresolved issue regarding the transformation of MF is whether MF and LCL represent two separate lymphomas or whether they are derived from the same T-cell clone. We report the clinicopathologic, immunophenotypic, and immunogenotypic analysis of MF and LCL in a white male. He developed a rash at age 51 that was diagnosed at age 56 as clinical stage IA patch/plaque MF. After topical nitrogen mustard and total skin electron beam therapy for progressive generalized CD3+CD4+ patch/plaque lesions, he developed nodules of Ki-1+ (CD30+) T-LCL at age 72. Southern blot analysis of DNA digested with Bg/II or BamHI and probed with a T-cell receptor (TCR)-beta gene J beta 1/J beta 2 probe showed a single, identical rearranged band in both the MF and LCL skin lesions that had been obtained 4 years apart. V beta gene family--specific gene amplification assays demonstrated dominant V beta 6 PCR products in both types of lesions. These PCR products and lesional cDNA exhibited a monoclonal pattern when amplified with consensus TCR-beta gene VDJ joint primers and electrophoresed under conditions that allowed the resolution of small differences in size. Furthermore, sequence analysis of the V beta 6 PCR products amplified from both the MF and LCL lesions showed an identical nucleotide sequence involving V beta 6.4, D beta 1.1, J beta 1.2, and C beta 1. These findings indicate that both the MF and the LCL in this patient arose from the same T-cell clone and that these diseases developed at a stage in the clone's differentiation subsequent to rearrangement of the TCR-beta gene.

Aged↗
PubMed2006

Molecular staging of lymph nodes from 60 patients with mycosis fungoides and Sézary syndrome: correlation with histopathology and outcome suggests prognostic relevance in mycosis fungoides.

BACKGROUND: Histological evidence of lymph node involvement is associated with a poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To determine whether T-cell receptor (TCR) gene analysis is of prognostic relevance in CTCL. METHODS: TCR gene analysis was performed on lymph node specimens from 60 patients with mycosis fungoides (MF) and Sézary syndrome (SS) using a highly sensitive polymerase chain reaction (PCR)/single-strand conformational polymorphism analysis and results were correlated with skin, overall clinical and histological lymph node stages. RESULTS: The frequency with which a T-cell clone was detected in lymph node samples from patients with MF increased with skin stage, overall clinical stage and with the degree of histological involvement: six of 19 patients with uninvolved lymph nodes or limited histological involvement (LN0-2) and 13 of 14 patients with advanced histological involvement (LN3-4) had a detectable T-cell clone. In SS, 22 of 27 patients had a detectable lymph node T-cell clone. The clonal patients had a poorer prognosis than nonclonal patients (median survival from biopsy of > 72 months vs. 16 months for MF and 41.5 vs. 16.5 months for SS). Regression analysis confirmed that TCR gene analysis identifies a group of MF patients with a worse prognosis (P = 0.013). However, the molecular lymph node stage did not provide independent prognostic information in this cohort of patients in multivariate analysis. CONCLUSIONS: Molecular staging in MF and SS using a PCR-based method for TCR gene analysis provides additional information to histological examination. Specifically, this study identified a group of MF patients with early lymph node involvement with a poorer prognosis. However, a larger prospective study of patients with MF and early histological lymph node involvement is required to confirm whether molecular staging of lymph nodes provides independent prognostic information in a multivariate model.

Adolescent↗
PubMed1989

Retinoids plus PUVA (RePUVA) and PUVA in mycosis fungoides, plaque stage. A report from the Scandinavian Mycosis Fungoides Group.

Sixty-nine patients with mycosis fungoides, plaque stage, were treated in an open study with photochemotherapy (PUVA) or the combination of oral retinoids and PUVA (RePUVA). The response rate of Re-PUVA was equal to that of PUVA, with complete remission in 73% and 72%, respectively. Remissions were obtained with fewer PUVA sessions, and with a lower UVA dosage, if PUVA was combined with retinoids. A lower UVA dosage was needed if treatment was given four times weekly in stead of twice weekly. The duration of the remissions tended to be prolonged if retinoids were given as maintenance therapy.

Adult↗
PubMed1981

Photochemotherapy (PUVA) in the pretumour stage of mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Study Group.

Fifty-one patients with mycosis fungoides of pretumour stage were treated with oral 8-MOP and UVA photochemotherapy (PUVA). Complete remission was induced within 2--3 months in 58% of the cases. Twenty-seven patients are still in remission on maintenance therapy 9--53 months after starting treatment. In 9 cases PUVA treatment was stopped due to therapeutic failure and in another 15 cases due to various side effects. Maintenance therapy was given weekly, monthly, or at even longer intervals. Maintenance at long intervals seems preferable.

Adolescent↗
PubMed1981

Photochemotherapy (PUVA) in the tumour stage of mycosis fungoides: a report from the Scandinavian Mycosis Fungoides Study Group.

Twenty-five patients with mycosis fungoides in the tumour stage were treated with oral 8-Methoxypsoralen followed by UVA (PUVA), sometimes in combination with topical or systemic chemotherapy. In 17 patients the disease was confined to the skin, in 7 lymph nodes also were involved, and one had visceral involvement. Complete and partial remission was achieved in 14/17 patients with the disease limited to the skin (82%), and partial remission of the skin lesions in 5/8 patients with extracutaneous location.

Adult↗
PubMed1983

Mycosis fungoides of the mastoid, middle ear, and CNS. Literature review of mycosis fungoides of the CNS.

Facial nerve paralysis developed in a man with tumor-stage mycosis fungoides (MF). Mastoidectomy disclosed that MF had involved the mastoid and middle ear. Meningeal lymphoma, confirmed by the finding of Sézary cells in the CSF, was subsequently established. Autopsy disclosed MF lymphoma in the leptomeninges, medulla, spinal cord, and cranial nerves. A unique feature was the formation of a communicating hydrocephalus. Case reports of 23 patients with MF of the CNS, including 21 autopsies, are reviewed. Practically all had tumor-stage or erythrodermic MF. Atypical mononuclear cells were found ante mortem in the CSF in eight patients. In contrast to other CNS lymphomas, bone marrow involvement was uncommon. Cranial, especially facial, nerve paralyses were often premonitory signs of meningeal lymphomas. Patients with MF having such symptoms should have cytologic examination of the CSF.

Adult↗
PubMed1979

Epipodophyllotoxin (VP-16-213) in mycosis fungoides: A report from the Scandinavian mycosis fungoides study group.

Epipodophyllotoxin (VP-16-213) was administered to 9 patients with mycosis fungoides in various stages, most of them in the advanced tumour stage. In 4 of the patients VP-16 was combined with cyclophosphamide. VP-16 alone or in combination with cyclophosphamide was capable of inducing remission initially in all cases, complete in 2, partial in 3 and improvement to a lesser degree in the remaining 5 patients, but it was unable to maintain the remission. The induced remission has to be upheld by other agents, possibly added to VP-16.

Adult↗