A new approach to tumor immunobiological therapy：tumor vesicles / 中国肿瘤生物治疗杂志

@#[摘 要] 正常细胞及肿瘤细胞在发生凋亡或受到某些信号刺激时均可释放出直径为0.1~1 μm的膜状囊泡。肿瘤细胞受到信号刺激后骨架改变，导致细胞质膜包裹细胞内容物并向膜外侧起泡形成囊状小体，称为肿瘤囊泡，其不仅影响肿瘤细胞的生物学特性，对肿瘤免疫微环境也产生深刻的影响。除生物学效应外肿瘤囊泡还可作为一种天然的药物载体将治疗药物递送到肿瘤细胞，发挥抗肿瘤作用。研究证实，载药的肿瘤囊泡在天然免疫和获得性免疫反应中均体现良好的抗肿瘤激活效应，目前载药肿瘤囊泡已经进入临床应用阶段，在胆管癌、恶性胸腔积液的治疗中展现了良好的应用前景。

Effect of prophylactic transcatheter arterial chemoembolization on hepatocellular carcinoma with microvascular invasion after R0 resection. A case-control study

ABSTRACT BACKGROUND: Transcatheter arterial chemoembolization (TACE) is thought to prevent recurrence of hepatocellular carcinoma (HCC), but its efficacy is a matter of controversy. OBJECTIVES: We investigated the effect of preventive TACE on the tumor, nodes, metastasis (TNM) classification in cases of stage II HCC (T2N0M0) after R0 resection. DESIGN AND SETTING: Case-control study conducted in a tertiary-level public hospital. METHODS: We analyzed recurrence rates and mortality rates over time for 250 consecutive cases of HCC in TNM classification cases of stage II HCC (T2N0M0) after R0 resection. These cases were divided into patients who underwent TACE (TACE+) and presented microvascular invasion (MVI+; n = 80); TACE+ but did not present MVI (MIV−; n = 100); MVI+ but did not undergo TACE (TACE−, n = 30); and TACE−/MVI− (n = 40). RESULTS: MVI+ patients in the TACE+ group had significantly lower recurrence rates and mortality rates at one, two and three years than those in the TACE- group (all P < 0.05). Among MVI- patients, the TACE+ group did not have significantly lower recurrence rates and mortality rates at one, two and three years than the TACE- group (all P > 0.05). Regardless of whether TACE was performed or not, MVI− patients had significantly lower recurrence rates and mortality rates at two and three years after their procedures than did MVI+ patients (all P < 0.05). CONCLUSION: Recurrence rates and mortality rates for MVI+ patients were significantly higher than for MVI− patients, beyond the first year after TACE. Postoperative adjuvant TACE may be beneficial for HCC patients with MVI.

Anticancer effects of FL34 through the inhibition of GLI1 in glioblastoma

Background: The hedgehog (HH) signaling pathway is abnormally activated in glioblastoma (GBM); thus, its downstream effector GLI1 may be a suitable target for the treatment of GBM. The aim of the present study was to evaluate the antitumor activities of a novel compound, FL34, in GBM through the inhibition of GLI1. Methods: The effect of FL34 on suppressing the proliferation, angiogenesis, and invasion of GBM cells was investigated in vitro using proliferation, invasion, tube formation, flow cytometry, GLI1 dual luciferase, reverse transcription-quantitative polymerase chain reaction, and western blot assays. A subcutaneously transplanted and orthotopic U-87 MG GBM cell xenograft model was used to study the effect of FL34 on tumor growth in vivo. Results: The results of the present study demonstrated that FL34 markedly inhibited the proliferation, invasion, and angiogenesis of GBM, in addition to decreasing the transcriptional activity and expression of GLI1, resulting in the downregulation of GLI1 target genes, including B-cell lymphoma-2, vascular endothelial growth factor, and matrix metalloproteinases. Furthermore, FL34 inhibited the activation of GLI1 without influencing upstream canonical HH/Smoothened signaling or through crosstalk with other oncogenic pathways, including Ras/ERK and AKT signaling. At a dose of 30.0 mg/kg, FL34 suppressed tumor growth by 78.74% in tumor weight in subcutaneously transplanted U-87 MG xenograft models and by 64.24% in volume in orthotopic U-87 MG GBM xenograft models. Conclusions: These data suggested that FL34 exerted antitumor activity mediated by the inhibition of GLI1 and that FL34 may be a potential antitumor candidate compound that could be used to develop new antitumor drugs for the treatment of GBM

Pulmonary cryptococcosis in non-AIDS patients

OBJECTIVE: To investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients. METHOD: 24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied. RESULTS: 15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2 ± 11.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. CONCLUSION: Non-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.