In primary effusion lymphoma cells, MYB transcriptional repression is associated with v-FLIP expression during latent KSHV infection while both v-FLIP and v-GPCR become involved during the lytic cycle.

International audiencePrimary effusion lymphoma (PEL) is a rare, distinct subtype of non-Hodgkin lymphoma, which is associated with Kaposi sarcoma-associated herpesvirus (KSHV) infection. Although MYB levels are high in most neoplastic B cells, we found that, unexpectedly, both PEL cells and uncultured PEL patients' samples contained very low levels of MYB mRNA when compared to B-cell leukaemia samples obtained from KSHV(-) patients. These results were further confirmed at the protein level. Both latent viral FLICE inhibitory protein (v-FLIP) and early lytic viral G protein coupled receptor (v-GPCR) KSHV proteins were found to activate nuclear factor (NF)-kappaB and transrepress a MYB promoter reporter construct. In contrast, a dominant negative inhibitor of NF-kappaB (IkappaB-alpha) mutant prevented v-FLIP and v-GPCR from inhibiting MYB functions while a v-GPCR mutant that was impaired for NF-kappaB activation could not repress the MYB construct. Transduction of a v-FLIP expressing vector or stable transfection of v-GPCR both resulted in a marked downregulation of the endogenous MYB protein expression. However, MYB expression transactivated the lytic switch Replication and Transcription Activator (RTA) promoter in transient transfection assays. Taken together, our results demonstrate that, contrary to a number of other haematological malignancies, MYB expression is not required for PEL cell proliferation. Repressing MYB expression also helps in maintaining the virus in latency

The conservative management of Paget's disease of the breast with radiotherapy Presented in part at the 38th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Los Angeles, California, October 27-30, 1996.

BACKGROUND The purpose of this study was to evaluate the feasibility of breast-conserving therapy involving limited surgery and definitive radiotherapy as a treatment for Paget's disease, and to determine the disease free and overall survival associated with this approach. METHODS The authors retrospectively reviewed the charts of all patients treated during the period 1980-1994 for Paget's disease of the breast who did not present with a palpable mass or mammographic density. Through a collaborative review, 30 cases were identified. A biopsy confirming the presence of typical Paget's cells was performed on all patients. All patients received external beam radiotherapy to the breast, with a median dose of 50 gray (Gy). Ninety-seven percent received a boost to the remaining nipple or tumor bed, with a median dose to the tumor bed of 61.5 Gy. RESULTS The median follow-up for surviving patients was 62 months. Three patients (10%) developed a recurrence in the breast as the only site of first failure, and 2 additional patients (7%) experienced failure in the breast as a component of first failure. The median time to local failure was 69 months. The 5- and 8-year actuarial estimates of local failure as the only site of first failure were 9% (95% confidence interval [CI], 0-20%) and 16% (95% CI, 0-31%), respectively. Of the 5 patients with local failures, 3 were among 22 patients (14%) who underwent complete resection of the nipple or nipple-areola complex, compared with 2 failures among 6 patients (33%) after partial resection ( P = 0.29). There were no failures among 2 patients who had a biopsy only. Four of 5 local failures were salvaged by mastectomy, and 3 of these patients were free of disease after a median follow-up of 52 months. The 5- and 8-year estimates of disease free survival for the overall series were both 95% (95% CI, 87-100%); cause specific overall survival was 100% at 8 years. CONCLUSIONS Breast-conserving therapy involving complete resection of the nipple-areola complex followed by definitive radiotherapy is a viable alternative to mastectomy in the treatment of Paget's disease. High rates of disease free and cause specific survival, in addition to adequate local control, justify consideration of a conservative approach. Cancer 1997; 80:1065-72. © 1997 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34345/1/8_ftp.pd

Quality of life in 269 patients with poor-risk diffuse large B-cell lymphoma treated with rituximab versus observation after autologous stem cell transplant

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Melioidosis and Hairy Cell Leukemia in 2 Travelers Returning from Thailand

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Vitamin C improves microvascular reactivity and peripheral tissue perfusion in septic shock patients

International audienceBackground: Vitamin C has potential protective effects through antioxidant and anti-inflammatory properties. However, the effect of vitamin C supplementation on microvascular function and peripheral tissue perfusion in human sepsis remains unknown. We aimed to determine vitamin C effect on microvascular endothelial dysfunction and peripheral tissue perfusion in septic shock patients. Methods: Patients with septic shock were prospectively included after initial resuscitation. Bedside peripheral tissue perfusion and skin microvascular reactivity in response to acetylcholine iontophoresis in the forearm area were measured before and 1 h after intravenous vitamin C supplementation (40 mg/kg). Norepinephrine dose was not modified during the studied period. Results: We included 30 patients with septic shock. SOFA score was 11 [8-14], SAPS II was 66 [54-79], and in-hospital mortality was 33%. Half of these patients had vitamin C deficiency at inclusion. Vitamin C supplementation strongly improved microvascular reactivity (AUC 2263 [430-4246] vs 5362 [1744-10585] UI, p = 0.0004). In addition, vitamin C supplementation improved mottling score (p = 0.06), fingertip (p = 0.0003) and knee capillary refill time (3.7 [2.6-5.5] vs 2.9 [1.9-4.7] s, p < 0.0001), as well as and central-to-periphery temperature gradient (6.1 [4.9-7.4] vs 4.6 [3.4-7.0] °C, p < 0.0001). The beneficial effects of vitamin C were observed both in patients with or without vitamin C deficiency. Conclusion: In septic shock patients being resuscitated, vitamin C supplementation improved peripheral tissue perfusion and microvascular reactivity whatever plasma levels of vitamin C

A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial

BACKGROUND: This multicentre, single-arm, open-label phase 2 trial investigated the efficacy and safety of lenalidomide monotherapy in patients with relapsed/refractory peripheral T-cell lymphoma (PTCL). METHODS: Patients received oral lenalidomide 25mg once daily on days 1-21 of each 28-day cycle for a maximum of 24 months, until disease progression or development of unacceptable adverse events (AEs). The primary end-point was efficacy; safety was evaluated as a secondary end-point. This study was registered with ClinicalTrials.gov, number NCT00655668. FINDINGS: A total of 54 patients with PTCL were treated. The overall response rate was 22% (12 of 54), including complete response (CR) or unconfirmed CR (CRu) in 11% of patients; 31% of patients with angioimmunoblastic T-cell lymphoma (AITL) responded (CR/CRu in 15% of patients). The median progression-free survival and median response duration were 2.5 and 3.6 months, respectively, in the intent-to-treat population, and 4.6 and 3.5 months, respectively, in patients with AITL. Thrombocytopenia and neutropenia were the most common grade 3 or 4 haematological AEs, in 11 (20%) and 8 (15%) patients, respectively. Overall, 19 patients (35%) experienced at least 1AE leading to study dose interruption or reduction (commonly neutropenia or thrombocytopenia). Serious AEs were observed in 54% of patients and 12 patients died during the study; lymphoma progression (n=6); and acute respiratory distress syndrome, dyspnea, lung infiltration, neutropenic sepsis, pneumonia and cerebral ischaemia (n=1 each). INTERPRETATION: Lenalidomide exhibited single-agent activity in heavily pretreated patients with PTCL, particularly in patients with AITL. Future development is warranted in specific histologies, such as AITL, and in combination with chemotherapy or other agents considered active in PTCL. FUNDING: Celgene Corporation