Search

This study focused on the role of methionine (MET) in the autophagy of gastric cancer stem cells (GCSCs) and aims to elaborate its regulatory mechanism. In the present study, the GCSCs were isolated from human gastric cancer cell lines using an anti-CD44 antibody, and then cultured in MET+ homocysteine (HCY)− or MET−HCY+ medium. In MET+HCY–treated GCSCs, autophagy was suppressed, the methylation and phosphorylation of RAB37 were elevated, and miR-200b expression was down-regulated. Lentiviral vector (LV-) carrying methionine-γ lyase (an enzyme that could specifically lyse MET; Metase) promoted autophagy, reduced the methylation and phosphorylation of RAB37, and up-regulated miR-200b expression in MET+HCY–-treated GCSCs. Then, we found that miR-200b suppressed the expression of protein kinase C α (PKCα), a protein that could inactivate RAB37 through promoting its phosphorylation. LV-Metase down-regulated RAB37 phosphorylation via miR-200b/PKCα, thus promoting the RAB37-mediated autophagy and suppressing cell viability in MET+HCY–treated GCSCs. Finally, the in vivo study proved that LV-Metase treatment inhibited tumor growth through up-regulating RAB37 expression. In conclusion, MET suppressed RAB37 expression via enhancing its methylation and suppressed RAB37 activity via miR-200b/PKCα axis, thus repressing RAB37-mediated autophagy in GCSCs. The supplementation of Metase lysed MET, thus inducing the autophagy of GCSCs and inhibiting tumor growth. [ABSTRACT FROM AUTHOR]

The prognosis and optimal therapy for high-risk early-stage extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) are not well defined. This study was conducted to evaluate the prognostic factors and treatment outcomes in patients with stage II NKTCL of the upper aerodigestive tract (UADT-NKTCL). One hundred and twenty-four patients with stage II UADT-NKTCL were enrolled. Primary tumors were located in the nasal cavity ( n = 53) or extranasal UADT ( n = 71). Eighty-four patients were treated with combined modality therapy (CMT), and 40 patients were treated with radiotherapy alone ( n = 30) or chemotherapy alone ( n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates for all stage II patients were 60.1% and 47.8%, respectively. Primary location and disease extent were the important prognostic factors in univariate and multivariate analyses. CMT significantly improved survival. The 5-year OS and PFS rates were 71.2% and 56.7% for CMT, compared with 35.1% ( p < 0.001) and 26.7% for single modality therapy ( p < 0.001). Survival differences between CMT and single modality therapy were also observed in nasal and extranasal subgroups of UADT-NKTCL. This retrospective study showed significant improvements in OS and PFS in patients who received both chemotherapy and radiotherapy for stage II NKTCL. The findings need further validation in other datasets. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the prognostic importance of rituximab and radiotherapy in patients with primary mediastinal large B-cell lymphoma (PMBCL) receiving doxorubicin-containing chemotherapy. Seventy-nine patients with PMBCL received CHOP chemotherapy with ( n = 39) or without rituximab ( n = 40), and 60 patients received additional radiotherapy. Patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) had significantly superior survival rates. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 83.7% and 76.7% for R-CHOP, compared with 48.3% ( p = 0.011) and 44.2% ( p = 0.012) for CHOP, respectively. Similarly, the 5-year OS and PFS rates for early stage patients were 93.8% and 84.6% with R-CHOP, and 52.0% ( p = 0.002) and 46.6% ( p = 0.003) with CHOP, respectively. Patients treated with chemotherapy and radiotherapy had better survival and local control (LC) rates compared with chemotherapy alone. The 5-year OS, PFS and LC rates for early stage patients were 73.6%, 69.9% and 92.6% for chemotherapy and radiotherapy, and 50.8% ( p = 0.076), 36.9% ( p = 0.008) and 56.4% ( p < 0.001) for chemotherapy alone, respectively. Early stage patients treated with R-CHOP and radiotherapy had 5-year OS, PFS and LC rates of 96.4%, 85.9% and 93.1%. R-CHOP plus consolidation radiotherapy was associated with excellent survival and LC rates. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether the phenotypic characteristics of the two subtypes of CD56++ and CD56−− lymphoma have relevance for their clinical behavior and prognosis. The immunophenotypes of all patients were confirmed using standard criteria for CD20, CD3ℇε, CD56, cytotoxic molecules (T-cell intracellular antigen-1 [[TIA-1]] and granzyme B), and Ki-67, and in situ hybridization for Epstein--Barr virus (EBV)-encoded RNA (EBER). CD56 was expressed in 90 of 118 (76.3%%) patients. The majority (83.3%%) of patients with nasal natural killer/T-cell lymphoma (NKTCL) presented with CD56++ lymphoma, whereas patients with NKTCL of the extranasal upper aerodigestive tract were more likely to have CD56−− lymphoma (53.6%%, p < 0.000). A lower percentage of expression of granzyme B and Ki-67 (>50%%) was found in patients with CD56−− lymphoma compared with those with CD56++ lymphoma ( p < 0.05). The clinical characteristics and prognosis were comparable between patients with CD56++ and CD56−− lymphomas. The corresponding overall survival and progression-free survival rates were 74.1%% and 56.7%%, respectively, for patients with CD56++ lymphoma compared with 81.6%% and 60.5%% for those with CD56−− lymphoma ( p > 0.05). There was no clinical or prognostic significance in determining the two subtypes of CD56++ and CD56−− NKTCL based on their immunophenotypic profiles, which has clinical implications for pathological diagnosis and insight into disease behavior. [ABSTRACT FROM AUTHOR]