ABSTRACT
Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target.
Subject(s)
Gene Expression Regulation, Neoplastic , Lymphoma, Large B-Cell, Diffuse/diagnosis , Receptors, Lysosphingolipid/analysis , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Female , Germinal Center , Humans , Immunohistochemistry , Lymphoma, Large B-Cell, Diffuse/chemistry , Lysophospholipids , Male , Middle Aged , Phosphorylation , Prognosis , RNA, Messenger/analysis , Receptors, Lysosphingolipid/genetics , STAT3 Transcription Factor/metabolism , Sphingosine/analogs & derivatives , Testicular NeoplasmsABSTRACT
We describe the case of a 52-year-old Japanese woman with advanced adenocarcinoma of the lung, in whom once-daily treatment with 250 mg ZD1839 ('Iressa') demonstrated a marked antitumour effect. She had initially achieved a partial response with cisplatin-based combination chemotherapy, but had subsequently progressed and had failed to respond to salvage chemotherapy. She had also received whole-brain irradiation for brain metastases. On admission, the patient was confined to bed due to dyspnoea and had rapidly progressing hypoxia secondary to lymphangitis carcinomatosa and a massive right pleural effusion. She was treated with oxygen supplementation and oral ZD1839, which, within a week, led to marked tumour regression and gradually improving dyspnoea. The main adverse event observed was a grade 2 rash. A month after starting ZD1839 treatment, the patient was discharged without the need for oxygen supplementation and had since returned to full-time work. This is a demonstration of ZD1839 producing a dramatic clinical response when administered to a patient with poor performance status who had received extensive prior treatment with cytotoxic agents.'Iressa' is a trademark of the AstraZeneca group of companies.
Subject(s)
Adenocarcinoma/drug therapy , Camptothecin/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/drug therapy , Enzyme Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Paclitaxel/analogs & derivatives , Quinazolines/therapeutic use , Taxoids , Adenocarcinoma/secondary , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/administration & dosage , Cisplatin/administration & dosage , Docetaxel , Epidermal Growth Factor/antagonists & inhibitors , Female , Gefitinib , Humans , Irinotecan , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Protein-Tyrosine Kinases/antagonists & inhibitors , Salvage Therapy , Treatment OutcomeABSTRACT
A case of pituitary adenoma associated is neurofibromatosis type 1 is reported. On June 6, 2000, a 49-year-old man was admitted to the Department of Neurological Surgery, Okayama University Hospital, for bitemporal hemianopsia. Twenty-nine years previously, he had been operated on for a left inguinal tumor that proved to be a neurofibroma. Based on the presence of other manifestations, such as café-au-lait spots and subcutaneous nodules, he had been diagnosed with neurofibromatosis type 1, the same as his father, sister, and daughter. Computed tomography and magnetic resonance imaging demonstrated an intrasellar mass lesion with a cystic portion in the suprasellar region. Endocrinologically, almost all of his basic hormone levels were normal. A right front-temporal craniotomy was performed for a preoperative diagnosis of craniopharyngioma, and total intracapsular tumor extirpation was achieved. The histological diagnosis was clinically silent corticotroph pituitary adenoma. Neurofibromatosis is sometimes associated with neoplasms of the central nervous system, usually optic gliomas. Associations between pituitary adenomas and NF 1 are very rare and have been reported in only four cases, including the present case.
