Safe administration of rituximab for follicular lymphoma after obinutuzumab infusion-related reaction.

Obinutuzumab is a novel glycoengineered, type-II anti-CD20 monoclonal antibody that was recently developed to treat follicular lymphoma (FL), the most prevalent subtype of indolent B-cell lymphoma. Several intensely hypermetabolic lesions (SUVmax: 40) were identified in the post-mediastinal and paraaortic lymph nodes by 18F-FDG-PET maximum-intensity projection images of a 58-year-old man who presented with systemic lymphadenopathy. A biopsy at the time of laparotomy definitively diagnosed grade 1 FL. The patient was given the recommended standard premedication, comprising acetaminophen (1000 mg), diphenhydramine (50 mg), and dexamethasone (20 mg), and then started on six cycles of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). However, the patient developed severe hypotension and dyspnea about 15 min after starting obinutuzumab. It was difficult to differentiate between a possible allergic reaction and infusion-related reaction. A pleural effusion was drained to reduce the tumor burden, after which a single course of CHOP was started. Rituximab (R) was added 10 days later without incident, and the patient completed six cycles of the R-CHOP therapy without adverse events. We conclude that R-CHOP was safe for administration to patients who react to infused obinutuzumab. Such patients should be carefully monitored during R infusion, given the risk of cross-reactivity.

Suppression by heat shock protein 20 of hepatocellular carcinoma cell proliferation via inhibition of the mitogen-activated protein kinases and AKT pathways.

Heat shock protein (HSP) 20, one of the low-molecular weight HSPs, is known to have versatile functions, such as vasorelaxation. However, its precise role in cancer proliferation remains to be elucidated. While HSP20 is constitutively expressed in various tissues including the liver, we have previously reported that HSP20 protein levels in human hepatocellular carcinoma (HCC) cells inversely correlate with the progression of HCC. In this study, we investigated the role of HSP20 in HCC proliferation. The activities of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and AKT were negatively correlated with the HSP20 protein levels in human HCC tissues. Since HSP20 proteins were hardly detected in HCC-derived cell lines, the effects of HSP20 expression were evaluated using human HCC-derived HuH7 cells that were stably transfected with wild-type human HSP20 (HSP20 overexpressing cells). In HSP20 overexpressing cells, cell proliferation was retarded, and the activation of the mitogen-activated protein kinases (MAPKs) signaling pathways, including the ERK and JNK, and AKT pathways, as well as cyclin D1 accumulation induced by either transforming growth factor-α (TGFα) or hepatocyte growth factor, were significantly suppressed compared with the empty vector-transfected cells (control cells). Taken together, our findings strongly suggest that HSP20 suppresses the growth of HCC cells via the MAPKs and AKT signaling pathways, thus suggesting that the HSP20 could be a new therapeutic target for HCC.