IL-18在体外培养系统中诱导肿瘤快速杀伤效应及肿瘤特异性CTL

目的应用rhlL-18在体外培养系统(Coculture system in vitro，CCs)中诱导快速肿瘤杀伤效应及诱导肿瘤特异性细胞毒性T淋巴细胞(Cytotoxic T Lymphocyte，CTL)。方法 采用StemSep^TM免疫磁性细胞分离法分离人外周血NK细胞、T细胞及树突细胞(DCs)，流式细胞仪分析细胞表型，125I-UdR标记的细胞毒实验检测杀伤活性，ELISA方法检测IFN-7的产生量。结果 在CCs中，rhIL-18诱导出快速肿瘤杀伤效应，这种杀伤效应无抗原特异性、不受MHC限制，DCs和T细胞的存在与否对其无明显影响。在同一培养系统中，肿瘤抗原存在的条件下，96h后，rhIL-18能够诱导并促进CTL介导的肿瘤特异性杀伤效应。结论 rhIL-18能够在体外培养系统中相继诱导肿瘤快速杀伤效应及肿瘤特异性CTL。     

A new pseudo-peptide of Arg-Gly-Asp (RGD) with inhibitory effect on tumor metastasis and enzymatic degradation of extracellular matrix

A series of pseudo-peptide analogs of the Arg-Gly-Asp (RGD) sequence of fibronectin have been synthe-sized, and their anti-metastatic effects in mice and inhibitory effects on tumor cell invasion in vitro have been examined. The partially modified retro pseudo-peptide of RGD, R_rev-COCH₂CO-D (FC-63), was more effective in inhibiting tumor metastasis than the original RGDS peptide. Replacement of the malonyl moiety of FC-63 with a carboxyethylene linkage (R_rev-COCH₂CH₂-D, FC-303 ) achieved more potent inhibition of lung metastasis of melanoma cells than FC-63. Among the analogs, FC-336, a p-xylylendiamine derivative having two FC-303 moieties, showed the most potent inhibitory effect on experimental lung metastasis produced by i.v. co-injection with B16-BL6 melanoma or colon 26 M3.1 cells in a dose-dependent manner. Multiple administrations of FC-336 after tumor inoculation also showed efficient therapeutic potency against spontaneous lung metastasis of B16-BL6 melanoma in mice. Furthermore, FC-336 effectively inhibited the invasion, migration and adhesion of tumor cells in vitro, but its inhibitory effects were not more than those of RGDS peptide. Zymography analysis revealed that FC-336 inhibited the degradation of gelatin substrate by matrix metalloproteinases (MMPs) produced by tumor cells, while the RGDS peptide did not affect the enzymatic degradation. These findings indicate that the pseudo-peptides of the RGD sequence, possessing the inhibitory property of the degradation by MMPs differently from original RGD-containing peptides, may be advantageous and useful in preventing tumor metastasis. © Rapid Science 1998     

Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital

This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an "individual risk" (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.     

Carbon-11 labelled tyrosine to study tumor metabolism by positron emission tomography (PET)

To measure the rate of protein synthesis in human neoplasms by positron emission tomography, we prepared no carrier added DL-(1-¹¹C)-tyrosine by ¹¹C-carboxylation of the appropriate -lithioisocyanide followed by hydrolysis of the isocyanide function and removal of the protecting methoxy group. The purification, resolution and solvent switch to saline was performed by high performance liquid chromatography (HPLC). DL-(1-¹¹C)-Tyrosine in 0.1 N NaH₂PO₄ buffer was prepared with a radiochemical yield of 8%–16% (EOS, 35 min). The enantiomeric separation and solvent switch to saline were achieved in 5 min and 10 min respectively. Consequently L-(1-¹¹C)-tyrosine in physiological saline was obtained in 2%–4% radiochemical yield. Tumor accumulation in rats with the experimental WALKER 256 carcinosarcoma was observed for both the L- and D-isomer. Using positron emission tomography a tumor/muscle ratio of two was observed for the L-isomer 15 min after injection. The corresponding figure for the D-isomer was 2.5. The first clinical results with DL-(1-¹¹C)-tyrosine show accumulation of radioactivity in meningioma, a primary breast carcinoma and in liver metastases of a colonic carcinoma.     

Blast Crisis of Chronic Myelogenous Leukemia with Tumor Formation Characterized by T-cell Features--A Case Report

We report a case of chronic myelogenous leukemia (CML) associatedwith pronounced peripheral lymphadenopathy, with the cells havingthe Philadelphia (Phl) chromosome and T-cell features. A 23-year-oldman who was diagnosed as having CML and treated with busulfanwas admitted to our hospital because of increasing hepatosplenomegalyand pronounced lymphadenopathy. An axillary lymph node biopsydisclosed that the malignant cells formed rosettes with neuraminidase-treatedsheep red blood cells (En) (95.0%) and were positive for Leu1 (91.8%). Of the cytochemical reactions, peroxidase was negativeand periodic acid-Shiff, acid -naphthyl acetate esterase andß-glucuronidase were all positive. The karyotype ofthe bone marrow cells was 46 XY Phl positive (22q–), andthat of the lymph node cells was 51 XY Phl positive +8, +9,+18, +19, +21, 22q–. He was treated with various anti-leukemicagents and irradiation. Despite such treatments, he died ofpneumonia. This is a report of a CML patients with blast crisisand tumor formation characterized by T-cell features.     

Utilidad de la embolización vascular prequirúrgica de tumores renales con trombo tumoral en la vena renal izquierda

Introduction and objectivesPreoperative renal artery embolization (PRAE) for large renal masses may be performed prior to nephrectomy in order to simplify the procedure and reduce intraoperative bleeding. The objective of this work is to determine the role of PRAE on intraoperative bleeding and postoperative complications in left renal tumors with tumor thrombus limited to the left renal vein (level 0).Material and methodsRetrospective analysis to evaluate 46 patients who underwent left radical nephrectomy and thrombectomy for the treatment of renal cell carcinoma with level 0 tumor thrombus during the period 1990-2020. PRAE was limited to those cases in which surgical access to the main renal artery was presumed a priori difficult in the preoperative imaging study (n = 9; 19.6%). Intraoperative bleeding was estimated based on the perioperative transfusion rate, and postoperative complications were categorized according to the Clavien-Dindo classification. The Chi-squared test was used for comparisons. A multivariate analysis was performed to identify predictors of transfusion and complications.ResultsThere were no significant differences in the overall complication rate (11.1% vs. 32.4%, P = .19), major complication rate (0% vs.8.1%, P = .51), or transfusion rate (11.1% vs. 19%, P = .49) between both groups (PRAE vs. non-PRAE). In the multivariate analysis, PRAE did not behave as a predictor of complications (OR:0.11, 95%CI 0.01-2.86; P = .18) nor transfusion (OR:0.46, 95%CI 0.02-7.38;P = .58).ConclusionsIn our study on left renal cell carcinomas with level 0 tumor thrombus and difficult access to the main renal artery, PRAE was not associated with increased bleeding or postoperative complications, and it did not behave as an independent predictor of these variables. Therefore, it could be used as a preoperative maneuver to facilitate vascular management in selected cases.     

Liver transplantation versus liver resection for colorectal liver metastasis: a survival benefit analysis in patients stratified according to tumor burden score

Liver transplantation (LT) for colorectal liver metastasis (CRLM) may provide excellent survival rates in patients with unresectable disease. High tumor load is a risk factor for recurrence and low overall survival (OS) after liver resection (LR). We tested the hypothesis that LT could offer better survival than LR in patients with high tumor load. LR performed at Padua University Hospital for CRLM was compared with LT for unresectable CRLM performed both at Oslo and Padua. High tumor load was defined as tumor burden score (TBS) ≥ 9, and inclusion criteria were as in the SECA-I transplant study. 184 patients were eligible: 128 LRs and 56 LTs. 5-year OS after LR and LT was 40.5% and 54.7% (P = 0.102). In the high TBS cohort, 5-year OS after LR and LT was 22.7% and 52.2% (P = 0.055). In patients with Oslo score ≤ 2 and TBS ≥ 9 (13 LR; 24 LT) the 5-year OS after LR and LT was 14.6% and 69.1% (P = 0.002). The corresponding disease-free survival (DFS) was 0% and 22.9% (P = 0.005). Selected CRLM patients with low Oslo score and high TBS could benefit from LT with survival outcomes that are far better than what is achieved by LR.     

Research on the cutoff tumor size of omitting radiotherapy for BCSS after breast conserving surgery in women aged 65 years or oder with low-risk invasive breast carcinoma: Results based on the SEER database

BackgroundRadiotherapy after breast-conserving surgery (BCS) is not always necessary in older women staged T1N0M0 with low-risk invasive breast cancer, but few studies have concluded the detailed tumor size as a reference for avoiding radiotherapy. The study was conducted to explore and identify the optimal cutoff tumor size.MethodsThe study population was from the Surveillance, Epidemiology, and End Results (SEER) database in 2010–2016. Propensity score matching was used to balance the confounders between groups. Predictors associated with survival were analyzed by Kaplan–Meier, X-tile, Cox proportional hazards model and competing risk model.ResultsA total of 52049 women and 3846 deaths were included in the cohort with a median follow-up of 34 months. Based on the cutoff value determined by X-tile analysis, the study population were divided into small tumor group (≤14 mm in diameter) and large tumor group (>14 mm in diameter). Small tumors and radiotherapy were correlated with better breast cancer-specific survival (BCSS). In subgroup analysis, the absolute benefit of BCSS in 6 years attributed to radiotherapy was only 0.90% (RT vs. non- RT:98.77% vs. 97.87%) for patients with small tumors but up to 3.33% (RT vs. non- RT:97.10% vs. 93.77%) for those with large tumors.ConclusionSmall tumors and adjuvant radiotherapy were associated with improved long-term prognosis, and 14 mm in diameter was the cutoff tumor size of omitting radiotherapy for patients aged 65 or older with T1N0M0 stage, ER+ and HER2-breast carcinoma after BCS.