A real-world study on the efficacy and safety analysis of paclitaxel liposome in advanced breast cancer / 中华肿瘤杂志

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.

Supergenes:Generalists in Gene Expression / 中国医学科学院学报

In eukaryote cells,transcription from genome DNA is a key process of gene expression.The transcription products contain not only messenger RNAs that code proteins,but also various types of non-coding RNAs.During transcription,some of the gene loci produce more than one kind of RNA molecule,including coding RNAs and more often non-coding RNAs.These gene loci that generate several kinds of RNA molecules are named supergenes.According to the transcription pattern,supergenes are divided into three types,known as types Ⅰ,Ⅱ and Ⅲ.In this review,we summarize the transcription pattern of each type of supergene,and exposit the role of these genes in cells.

Gastric submucosa is inferior to the liver as transplant site for autologous islet transplantation in pancreatectomized diabetic Beagles / 华中科技大学学报（医学）（英德文版）

Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa (GS) and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS (GS group, n=8) or intrahepatic via portal vein (PV group, n=5). Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation (mean survival time, 7.16±0.69 days). However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group (mean survival time, 120±28.58 days; P<0.01 vs. GS group). The results of intravenous glucose tolerance test (IVGTT) confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.

Operable Breast Cancer of the Inner Hemisphere Is Associated with Poor Survival / 한국유방암학회지

PURPOSE: This study investigated the clinicopathological features of operable breast cancer lesions located in different hemispheres of the breast and determined related survival outcomes. METHODS: Data from 5,330 patients with invasive ductal carcinoma were retrospectively analyzed based on tumor location. RESULTS: The median follow-up time was 68 months (range, 18-176 months). Patients with breast cancer located in the outer hemisphere of the breast had lesions with more advanced nodal stages and more frequently received adjuvant chemotherapy than patients with breast cancer in the inner hemisphere. The 5-year disease-free survival (DFS) rates of patients with tumors located in outer versus inner hemispheres were 81.5% and 77.0%, respectively (p=0.004); the overall survival (OS) rates were 90.7% and 88.8%, respectively (p<0.001). The association between tumor location and the 5-year DFS rate was most apparent in node-positive patients (73.1% vs. 65.8% for outer vs. inner hemisphere lesions, p<0.001) and in patients with primary tumors greater than 2 cm in diameter (78.2% vs. 72.3%, p=0.002). Multivariate analysis showed that tumor location was an independent predictor of DFS (hazard ratio [HR], 1.23; p=0.002) and OS (HR, 1.28; p=0.006). There were no significant differences in 5-year DFS or OS rates between patients with outer versus inner hemisphere tumors when internal mammary node irradiation was performed. CONCLUSION: This study demonstrated that tumor location was an independent prognostic factor for operable breast cancer. Internal mammary node irradiation is recommended for patients with breast cancer of the inner hemisphere and positive axillary lymph nodes or large primary tumors.

Predictive factors for the local recurrence and distant metastasis of phyllodes tumors of the breast: a retrospective analysis of 192 cases at a single center / 癌症

The local recurrence rate of phyllodes tumors of the breast varies widely among different subtypes, and distant metastasis is associated with poor survival. This study aimed to identify factors that are predictive of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in patients with phyllodes tumors of the breast. Clinical data of all patients with a phyllodes tumor of the breast (n = 192) treated at Sun Yat-sen University Cancer Center between March 1997 and December 2012 were reviewed. The Pearson Χ² test was used to investigate the relationship between clinical features of patients and histotypes of tumors. Univariate and multivariate Cox regression analyses were performed to identify factors that are predictive of LRFS, DMFS, and OS. In total, 31 (16.1%) patients developed local recurrence, and 12 (6.3%) developed distant metastasis. For the patients who developed local recurrence, the median age at the diagnosis of primary tumor was 33 years (range, 17-56 years), and the median size of primary tumor was 6.0 cm (range, 0.8-18 cm). For patients who developed distant metastasis, the median age at the diagnosis of primary tumor was 46 years (range, 24-68 years), and the median size of primary tumor was 5.0 cm (range, 0.8-18 cm). In univariate analysis, age, size, hemorrhage, and margin status were found to be predictive factors for LRFS (P = 0.009, 0.024, 0.004, and 0.001, respectively), whereas histotype, epithelial hyperplasia, margin status, and local recurrence were predictors of DMFS (P = 0.001, 0.007, 0.007, and < 0.001, respectively). In multivariate analysis, independent prognostic factors for LRFS included age [hazard ratio (HR) = 3.045, P = 0.005], tumor size (HR = 2.668, P = 0.013), histotype (HR = 1.715, P = 0.017), and margin status (HR = 4.530, P< 0.001). Histotype (DMFS: HR = 4.409, P = 0.002; OS: HR = 4.194, P = 0.003) and margin status (DMFS: HR = 2.581, P = 0.013; OS: HR = 2.507, P = 0.020) were independent predictors of both DMFS and OS. In this cohort, younger age, a larger tumor size, a higher tumor grade, and positive margins were associated with lower rates of LRFS. Histotype and margin status were found to be independent predictors of DMFS and OS.

The research of combining high resolution melting with multiplex ligation-dependent probe amplification technology in the mutation scanning for PAH gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the value of combining high resolution melting (HRM) with multiplex ligation-dependent probe amplification (MLPA) for detecting mutations underlying phenylketonuria.</p><p><b>METHODS</b>HRM was used for detecting small mutations in phenylalanine hydroxylase gene (PAH) of 26 phenylketonuria patients. The results were verified with DNA sequencing. MLPA was used for detecting potential deletions/duplications in the PAH gene. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed for additional potential mutations.</p><p><b>RESULTS</b>A total of 21 mutations were found in 44/52 alleles (84.62%), which included a dupEx4. Among the 21 types of mutation, 19 were reported previously, and the remaining two were novel mutations: c.584_585insA and IVS10+1G>T. In addition, the mutation of R243Q (25%) was the most common type in China.</p><p><b>CONCLUSION</b>The study showed that the combination of HRM and MLPA could increase the detection rate for mutation in PKU. The study has added new information to the human mutation database of PAH and provided a basis for clinical diagnosis and prenatal counseling.</p>

Clinical features and survival analysis of different subtypes of patients with breast cancer brain metastases / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The brain is one of the most common metastatic sites of breast cancer. Brain metastases develop in 10%-15% of patients with breast cancer and are associated with poor prognosis. The purpose of this retrospective study was to analyze the clinical characteristics and survival of patients with brain metastases due to breast cancer of different subtypes and to identify the prognostic factors that affect clinical outcome.</p><p><b>METHODS</b>A total of 89 patients with breast cancer brain metastases diagnosed between October 1997 and July 2008 at Sun Yat-sen University Cancer Center were included in this study. Among the 89 patients, the number of luminal A, luminal B, human epidermal growth factor receptor 2 (HER-2), and triple-negative (TN) subtypes were 30, 20, 16, and 14, respectively; 9 patients had an unknown subtype. The clinical characteristics, pathologic features, and prognostic factors were analyzed both at the initial diagnosis and at the diagnosis of brain metastases. Endocrine therapy for patients with luminal subtypes was further studied.</p><p><b>RESULTS</b>The median age of patients was 46 years (range 28-74 years). The median survival time was 8.0 months (range, 0-80 months), the 1-year survival rate was 32% and the 5-year survival rate was 4%. The time to brain metastasis differed according to clinical stage at the initial diagnosis, and the time for patients with the luminal A subtype was the longest (P < 0.001). Multivariate analysis demonstrated that performance status score > 1, multiple brain metastases and without whole brain radiotherapy (WBRT) in combination with chemotherapy were associated with poor prognosis. Compared with the luminal A subtype, features of the HER-2 and TN subtypes included early metastases, rapid progression after first-line treatment (8.0 months vs. 11.0 months), and poor overall survival (25.0 months vs. 63.0 months). The luminal A subtype showed a tendency for good prognosis and slow growth. Tamoxifen could improve the survival of luminal A/B subtypes (median survival 24.0 months vs. 7.0 months, respectively, P = 0.002).</p><p><b>CONCLUSIONS</b>The prognosis of brain metastases from breast cancer was poor, especially in patients with HER-2 and TN subtypes. Generally, WBRT in combination with chemotherapy was the standard treatment modality. Patients with the luminal subtypes could benefit from tamoxifen.</p>

Clinical characteristics and prognosis of different subtypes of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and prognosis of patients with different subtypes of breast cancer: basaloid, HER-2 and luminal types, and try to find the evidence of individualized treatment for the patients.</p><p><b>METHODS</b>1280 histologically and immunohistochemically proven patients with resectable breast cancer were treated, and the clinical data including characteristics, relapse and survival of the patients with different subtypes of breast cancer were analyzed retrospectively.</p><p><b>RESULTS</b>Of the 1280 breast cancer patients, basaloid, HER-2 and luminal types accounted for 20.9%, 23.2% and 55.9%, respectively. Basaloid type was more likely to be found in younger patients frequently with a family history of breast cancer. HER-2 type usually had a tumor of larger size with more advanced stage disease and more metastatic lymph nodes. Luminal type was likely to occur in aged patients with an earlier stage disease. The recurrence rates in basaloid, HER-2 and luminal types were 25.0%, 27.9% and 11.7%, respectively. Patients with basaloid or HER-2 type were found to have a significantly higher recurrence rate than the patients with luminal type breast cancer (P < 0.001), but no significant difference was observed between the basaloid and HER-2 types. However, patients with basaloid type breast cancer were more likely to develop lung metastasis than HER-2 type (13.4% vs. 7.1%, P = 0.017). Up to December 2006, the 5-year disease-free survival (DFS) rates for patients with basaloid, HER-2 and luminal types were 72.2%, 68.2% and 86.2% (P < 0.001), respectively. The overall 5-yr survival (OS) rates of the three groups were 88.6%, 83.8% and 95.8% (P < 0.001) , respectively. Of the patients with luminal type breast cancer, HER2-negative patients had a higher DFS (86.2% vs 57.0%, P < 0.001) and OS (95.8% vs 87.7%, P = 0.0001) compared with those with HER2-positive. The results of Multivariate Cox Regression showed that tumor size and lymph node state were the most important factors influencing the prognosis.</p><p><b>CONCLUSION</b>Each subtype of breast cancer has somewhat its own specific clinical features in terms of recurrence pattern and prognosis, therefore, individualized treatment regimen may be required.</p>

Significance of EGFR and p-ERK expression in nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect the expression of EGFR and p-ERK in nasopharyngeal carcinoma (NPC) and investigate their clinical significance.</p><p><b>METHODS</b>Immunohistochemistry LSAB method was adopted to detect the expression of EGFR and p-ERK. Statistical analysis was performed using SPSS statistical software package (10.0) to correlate their expression with clinical characteristics and prognosis.</p><p><b>RESULTS</b>Positive staining for EGFR was observed in 39 of 55 cases (70.9%). The EGFR expression was correlated with clinical stage and gender. EGFR expression was correlated with poorer overall survival (OS) and shorter time to progression (TTP). Positive staining for p-ERK was observed in 29 of 55 cases (52.7%). There was a statistically significant association between positive p-ERK expression and advanced clinical stage. Positive p-ERK expression was correlated with poorer OS, disease-free survival (DFS) and TTP. EGFR expression was correlated with the expression of p-ERK. On multivariate analysis, age over 50 years was an independent poor prognostic factor for NPC. Both EGFR and p-ERK were not independent prognostic factors for NPC.</p><p><b>CONCLUSION</b>Expressions of EGFR and p-ERK are detected in NPC. Their abnormally high expression signifies poor prognosis in NPC patients.</p>

Morphology research of the rat sciatic nerve bridged by collage-heparin sulfate scaffold / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the treating effect of collage-heparin sulfate after the 10 mm rat sciatic nerve defect was bridged by it.</p><p><b>METHODS</b>A new kind of nervous tissue engineering scaffold was produced by freeze-drying technique from collagen-heparin sulfate. Thirty-two SD rats were randomly divided into A, B, C and D groups. Sciatic nerve defect in group A was bridged by collagen-heparin sulfate. In group B, sciatic nerve was bridged by auto-nerve transplantation. Group C was the blank control group. Animals in group D were normal. And 10 mm sciatic nerve defect was bridged in the experiment. Thirty-six weeks after the operation, the experimental animals were detected by HRP labeled retrograde trace, HE staining, toluidine staining, silvering staining, S100, GAP-43 and NF immunohistological staining, MBP immunofluorescence staining and transmission electron microscope to observe the nerve regeneration inducing effect of this new scaffold.</p><p><b>RESULTS</b>Nine months after operation, the collage-heparin sulfate scaffold was replaced by newly regenerated nerve. The number of HRP labeled spinal cord anterior horn cells and the area of sensation nerve fiber at the posterior horn were similar with that was repaired by auto-nerve. GAP-43, NF and S100 labeled regenerated nerve fiber had passed the total scaffold and entered the distal terminal. The regenerated nerve fibers were paralleled, lineage arranged, coincide with the prearranged regenerating "channel" in the collagen-heparin sulfate scaffold. MBP immunofluorescence staining also proved that the newly regenerated nerve fiber could be ensheathed. In the experimental group, the area of myelinated nerve fiber and the thickness of the myelin sheath had no obvious difference with that of the group repaired by auto-nerve, except that the density of the regenerated myelinated sheath fiber was lower than that of the control group.</p><p><b>CONCLUSION</b>Nervous tissue engineering scaffold produced by collagen-heparin sulfate can guide the regeneration of nerve fibers. The nerve function recovers fine. This kind of material has great application potential.</p>