Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer / 中华胃肠外科杂志

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

Comparison of Volatile Components in Citri Sarcodactylis Fructus from Guangdong Province Before and After Being Steamed by GC-MS / 中国实验方剂学杂志

Objective:To compare volatile components in raw products and steamed products of Citri Sarcodactylis Fructus. Method:Volatile oil in different batch of raw products and steamed products of Citri Sarcodactylis Fructus was extracted by steam distillation, and volatile components were identified by GC-MS.The determination was performed with injector temperature of 280℃, high pure helium(≥ 99.999%) as carrier gas, split ratio of 10:1, and sample size of 3 μL with temperature programming.Mass spectrum conditions included electron bombardment ion source, electron bombardment energy of 70 eV, ion source temperature of 230℃, acceleration voltage of 34.6 V, resolution of 2 500, scanning range of m/z 40-350.Peak matching, cutting and noise filtering were used in analyzing data based on GC-MS combined with orthogonal partial least square-discriminant analysis(OPLS-DA). Result:A total of 58 components were separated and identified from the different batches of raw Citri Sarcodactylis Fructus and their processed products, and 27 differential chemical components were identified by multivariate statistical analysis, among them, 15 common differential components presented different changing laws.The relative contents of α-pinene, β-pinene, p-cymene, β-linalool, L-4-terpinenol, α-terpineol, nerol, β-cyclocitral, geraniol and α-citral in raw products were higher than that of their corresponding processed products.The relative contents of β-caryophyllene, cis-α-bergamotene, γ-muurolene, γ-elemene and β-bisabolene in processed products were higher than that of their corresponding raw products. Conclusion:The content and composition of volatile components in Citri Sarcodactylis Fructus from Guangdong province have changed after being steamed.The results can provide experimental basis for expounding the processing principle and quality evaluation of Citri Sarcodactylis Fructus, and have positive significance for promoting the research and development of this Lingnan characteristic decoction pieces.

Role of dysregulation of Bim in resistance of melanoma cells to endoplasmic reticulum stress-induced apoptosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a model of ER stress-induced apoptosis with tunicamycin and to examine whether Bim is dysregulated and its potential role in resistance of melanoma cells to apoptosis under endoplasmic reticulum (ER) stress.</p><p><b>METHODS</b>A model of ER stress-induced apoptosis was established with tunicamycin. Apoptotic cells were quantitated using the annexin V/propidium iodide method by flow cytometry. Hoechst staining was also used to confirm the apoptotic cell death. Western blotting was used to measure the activation of caspase-3 and -9, and the expression of Bim, GRP78, CHOP, and Foxo1 at the protein level. The expression of Bim, CHOP and Foxo1 at the mRNA level was quantitated by qPCR. The siRNA technique was used to inhibit the expression of Bim.</p><p><b>RESULTS</b>Treatment of the melanoma cells with tunicamycin did not induce significant apoptosis and activation of caspase cascade, whereas it caused marked activation of caspase-3 and -9, and apoptosis in HEK293 cells which were used as a control. With exposure to tunicamycin (3 µmol/L) for 12, 24, 36 hours the Bim protein levels were not increased in Mel-RM and MM200 cells. Its mRNA levels were 0.37 ± 0.05, 0.13 ± 0.02 and 0.02 ± 0.01 in Mel-RM cells, while 0.41 ± 0.06, 0.16 ± 0.04 and 0.21 ± 0.03 in MM200 cells, respectively. The expression of Bim mRNA was significantly reduced compared with that in the control groups of the two cell lines (P < 0.01). siRNA knockdown of Bim protected HEK293 cells against activation of caspase-3. The cell apoptosis of Bim siRNA group was (5.69 ± 0.38)%, significantly lower than that of the siRNA control group (40.32 ± 1.64)% and blank control group (35.46 ± 2.01)% (P < 0.01). In the melanoma cells after exposure to tunicamycin (3 µmol/L) for 6, 12, 24, and 36 hours the transcription factor CHOP at mRNA level were significantly increased and the expressions at protein level were also up-regulated. The expressions of another transcription factor Foxo1 at mRNA level significantly decreased and the expressions at protein level were down-regulated, too.</p><p><b>CONCLUSIONS</b>The lack of Bim up-regulation contributes to the resistance of melanoma cells to ER stress-induced apoptosis and may be a mechanism by which melanoma cells adapt to ER stress conditions. Transcription factors CHOP and Foxo1 may be responsible for the dysregulation of Bim in melanoma cells upon ER stress.</p>

Three cases of orthotopic heart transplantation surviving more than 10 years / 中华器官移植杂志

Objective To summarize the experience of long-term survival of the patients under- going orthotopic heart transplantation.Methods Heart transplantation was performed on 2 cases of dilated cardiomyopathy and one case of Keshan disease.Before operation,pulmonary artery pressure was 42-53 mm Hg(5.60-7.07 kPa)and pulmonary vascular resistance 5.6-7.0 wood.The body weight difference between donors and receptors was 10%-15%.There were three same antigens in HLA zygosity experiment for all of three patients.Two cases were subjected to standard heart trans- plantation and one case to whole heart transplantation.All the atriums and big vessels were sutured by evting suture method.Cyclosporin A,azathioprine and corticosteroid were used to prevent patients from rejection.Results Survival time of 3 patients was 13 years and 10 months,12 years and 10 years and 3 months.Heart functions of three patients were NYHAⅠand all of 3 patients are living and working commonly.Six,3 and 1 rejection(s)occurred in 3 patients respectively and cured by appro- priate treatment.Electrocardiogram revealed that case 1 and case 2 had two P waves and case 3 sinus rhythm.Ultrasonic cardiogram showed that in case 1 and case 2,the left and right atriums were enlarged and tricuspid valve had slight backstreaming,and in case 3,all of the cardiac chambers were normal and had no backstreaming of tricuspid valve and mitral valve.No abnormal findings were found in 3 cases by 4-9 times of coronary arteriongraphy.Conclusion The important factors for the patients' long-term survival after heart transplantation include the choice of appropriate donors and acceptors, protection of donors' hearts,selection of appropriate operations and suture methods,rational use of im- munosuppressants and prevention of cardiac allograft vasculopathy.