Research Progress of HER2 Gene Mutation in Treatment of Breast Cancer / 肿瘤防治研究

HER2 is a tyrosine kinase receptor. It is the main drug target and clinical biomarker for the treatment of breast cancer. About 2% of breast cancer cases has HER2 mutations. Regardless of the expression level or amplification status of HER2, breast cancer with HER2 mutations may respond to targeted HER2 therapy. This article reviews the research progress of HER2 gene mutation in the treatment of breast cancer.

Entinostat, a class I selective histone deacetylase inhibitor, plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Research progress in endocrine clinical treatment of HR +/HER2 - metastatic breast cancer / 国际生物医学工程杂志

Breast cancer, as a heterogeneous disease, has different molecular subtypes. The most common molecular subtype is hormone receptor positive (HR +). Endocrine therapy is the predominant treatment for this subtype. The main treatment modality for HR +/human epidermal growth factor receptor 2-negative (HER2 -) metastatic breast cancer (MBC) is novel targeted agents combined with endocrine therapy. In this review, researches in endocrine clinical treatment of HR +/HER2 - MBC was reviewed to provide a new targeted therapy, including CDK4/6 inhibitors combined with endocrine therapy, the debate between CDK4/6 inhibitors combined with endocrine therapy and chemotherapy, new directions of CDK4/6 inhibitor combination, exploration of multiple treatment strategies after CDK4/6 inhibitor therapy progresses, histone deacetylase inhibitor combined with endocrine therapy, PI3K/Akt/mTOR pathway targeting drugs in combination with endocrine therapy, polyadenosine diphosphate ribose polymerase (PARP) inhibitors for gBRCA1/2 mutated breast cancer, novel targeted drugs, and multi-target/multi-combination therapy model.

Advances in Cardiovascular Toxicity Associated with Targeted Therapy for Breast Cancer / 肿瘤防治研究

Breast cancer is one of the most common malignant tumors in women. Because of the abundance of diagnosis and treatment methods and the wide application of targeted therapy drugs in recent years, the survival time of breast cancer patients is longer than before and the mortality rate shows a downward trend. However, the incidence of cardiovascular toxicity associated with targeted drug therapy in breast cancer patients is also increasing. This article reviews the research progress of cardiovascular toxicity associated with targeted drug therapy in breast cancer.

Clinical analysis of 8 patients with breast mucosa-associated lymphoid tissue lymphoma / 中华普通外科杂志

Objective:To investigate the clinicopathologic features and prognosis of breast mucosa associated lymphoid tissue(MALT) lymphoma.Methods:Clinical data of 8 breast MALT lymphoma patients were retrospectively analyzed at Tianjin Medical University Cancer Institute and Hospital from Jan 1, 2004 to Jan 31, 2017.Results:All were females, median age was 50 years. Tumors were located in the left breast in 3 cases while 5 cases in the right. All tumors were single in the outer-upper 1/4 quadrant of the breast. By Ann Arbor clinical stageⅠ, Ⅱ, Ⅲ and Ⅳ were 3, 2, 1 and 2, respectively. None of patients had B symptoms. 7 cases underwent surgery.All of the 8 cases received chemotherapy, 6 cases had complete response, one partial response, one with stable in efficacy evaluation. The follow-up time was 2-154 months. The 1, 3, 5-year overall survival rate were 100.0%, 50.0%, 50.0%, median survival time was 144.00 months. The 1-year progress free survival rate was 78.0% and median progress free survival time 28.29 months.Conclusion:Breast MALT is extremely rare without specific clinical features. Almost all are single tumors without B symptom. It′s sensitive to chemotherapy and the patients have fair prognosis.

Prognosis analysis of primary breast diffuse large B cell lymphoma / 中华肿瘤杂志

Objective@#To investigate the clinical characteristics, therapy modality and prognosis of primary breast diffuse large B-cell lymphoma(PB-DLBCL).@*Methods@#A total of 68 patients with PB-DLBCL treated in Tianjin Medical University Cancer Institute and Hospital were enrolled between January 1, 2004 and January 31, 2017. Clinicopathological data were retrospectively analyzed. 67 patients were female and only one male. The median age was 56 years old. 46 patients had Ann Arbor clinical stageⅠ~Ⅱ disease, and the other 22 were stage Ⅲ~Ⅳ. The patients with and without B symptom were 11 and 57, respectively. Kaplan-Meier method was used for univariate analysis to calculate the 5-year overall survival (OS) rate and 5-year progress-free survival (PFS) rate, compared using the log rank test. Cox regression analysis was used for multivariate analysis.@*Results@#The 1, 3, 5-year OS rate were 84.0%, 78.0% and 73.0%, and 1, 3, 5-year PFS rate were 80.0%, 71.0% and 51.0%, respectively. Univariate analysis indicated that eastern cooperative oncology group (ECOG) score, Ann Arbor clinical stage, international prognostic index (IPI) score, risk stratification, B symptom, β2-microglobulin(β2-MG) level, size of the tumor and cycles of chemotherapy were prognostic factors for OS (all P<0.05), and Ann Arbor clinical stage, IPI score, risk stratification and B symptom were prognostic factors for PFS (all P<0.05). Multivariate analysis indicated that Ann Arbor clinical stage was independent prognostic factor for OS(P=0.029) and B symptom was independent prognostic factor for PFS(P=0.028).@*Conclusions@#Prognosis of PB-DLBCL was relatively good. Ann Arbor clinical stage and B symptom were independent prognostic factors for OS and PFS, respectively.

Specificity of white dermographism in atopic dermatitis and the relationship between its duration and clinical severity of atopic dermatitis / 中华皮肤科杂志

Objective@#To assess the specificity of white dermographism in atopic dermatitis (AD) , and to investigate the relationship between its duration and severity of AD.@*Methods@#From 1st to 30th March 2018, 78 patients with AD (AD group) , 100 patients with non-AD skin diseases (non-AD group) and 100 healthy controls without skin diseases (control group) were enrolled from Department of Dermatology, Wuhan No.1 Hospital. Dermographism test was conducted in each subject, and the subjects′ response and duration of white dermographism were observed. Meanwhile, the severity of skin lesions of the AD patients was evaluated. Statistical analysis was carried out by using Chi-square test, analysis of variance and linear correlation analysis.@*Results@#Of the 78 patients in the AD group, 67 (85.90%) were positive for white dermographism, and the positive rate of white dermographism was significantly higher in the AD group than in the non-AD group (18.00% [18/100], χ2 = 80.97, P<0.017) and control group (5.00% [5/100], χ2 = 119.05, P<0.017) . Additionally, the positive rate of white dermographism was significantly higher in the non-AD group than in the control group (χ2 = 8.30, P<0.017) . The average duration of white dermographism was 1.89 minutes in 30 patients with mild AD, 2.74 minutes in 25 patients with moderate AD, and 4.41 minutes in 12 patients with severe AD. There was a significant difference in the duration of white dermographism among the 3 AD subgroups (F = 64.588, P<0.05) . Moreover, the severity of AD was positively correlated with the duration of white dermographism (r = 0.977, P = 0.136) .@*Conclusion@#White dermographism is a specific clinical manifestation of AD, and its duration is positively correlated with the severity of AD.

Specificity of white dermographism in atopic dermatitis and the relationship between its duration and clinical severity of atopic dermatitis / 中华皮肤科杂志

Objective To assess the specificity of white dermographism in atopic dermatitis (AD), and to investigate the relationship between its duration and severity of AD. Methods From 1st to 30th March 2018, 78 patients with AD (AD group), 100 patients with non-AD skin diseases (non-AD group)and 100 healthy controls without skin diseases(control group)were enrolled from Department of Dermatology, Wuhan No.1 Hospital. Dermographism test was conducted in each subject, and the subjects' response and duration of white dermographism were observed. Meanwhile, the severity of skin lesions of the AD patients was evaluated. Statistical analysis was carried out by using Chi-square test, analysis of variance and linear correlation analysis. Results Of the 78 patients in the AD group, 67(85.90％)were positive for white dermographism, and the positive rate of white dermographism was significantly higher in the AD group than in the non-AD group(18.00％[18/100],χ2=80.97, P<0.017)and control group(5.00％[5/100],χ2=119.05, P<0.017). Additionally, the positive rate of white dermographism was significantly higher in the non-AD group than in the control group (χ2 = 8.30, P<0.017). The average duration of white dermographism was 1.89 minutes in 30 patients with mild AD, 2.74 minutes in 25 patients with moderate AD, and 4.41 minutes in 12 patients with severe AD. There was a significant difference in the duration of white dermographism among the 3 AD subgroups(F=64.588, P<0.05). Moreover, the severity of AD was positively correlated with the duration of white dermographism(r=0.977, P=0.136). Conclusion White dermographism is a specific clinical manifestation of AD, and its duration is positively correlated with the severity of AD.

Advances in targeted therapy for triple-negative breast cancer / 中国肿瘤临床

Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is characterized by the lack of estro-gen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), thereby making it difficult to treat. Owing to the aggressive clinical behavior of TNBC and the lack of recognized molecular targets for therapy, patients with TNBC have shown poorer outcomes than those with other subtypes of breast cancer. Chemotherapy is the primary established systemic treatment for TNBC. However, various novel therapeutic targets have come into focus with the advances in molecular characterization of TNBC. In recent years, several targeted drugs have undergone clinical trials and have shown certain curative effects with relatively mild adverse reactions. The Food and Drug Administration has approved some of these drugs. In the current review, we have summa-rized the advances in the targeted therapy of TNBC.

Clinicopathological features and prognostic factors of patients with bone-only metas-tases / 中国肿瘤临床

Objective: To investigate the clinicopathological characteristics and prognostic factors in breast carcinoma patients with bone-only metastasis (BOM). Methods: A total of 967 patients with metastatic breast cancer treated in Tianjin Medical University Insti-tute and Hospital between January 2009 and December 2016 were screened, and the case data were retrospectively analyzed. These data involve 180 cases in the BOM group and 787 cases in the non-BOM group. We performed univariate analysis and Cox regression model multivariate analysis of prognostic factors in patients with BOM. Subgroup analysis was performed according to the hormone re-ceptor (HR) status, number of bone metastases, and treatment approaches. Results: Patients in the BOM group had a median progres-sion-free survival (PFS) of 19.4 months, and non-BOM patients had a median PFS of 10.0 months. Patients in the BOM group had a me-dian overall survival (OS) of 45.6 months. The proportions of patients with HR positivity were 81.7% (147/180) in the BOM group and 64.7% (509/787) in the non-BOM group (P<0.001). Cox regression model multivariate analyses found that HR status, location of bone metastases, number of bone metastases, and treatment approach were independent factors influencing the prognosis of patients with BOM. Among patients with HR-positive BOM, the prognosis of patients receiving endocrine therapy (P=0.004) or combinatory therapy (P<0.001) was significantly better than that of patients receiving chemotherapy alone. The number of bone metastases and endocrine therapy were independent prognostic factors in patients with HR-positive BOM. Patients with single bone metastases who received en-docrine therapy (P=0.004) or combinatory therapy (P=0.002) had better prognosis than patients who received chemotherapy alone. Patients with multiple bone metastases who received combinatory therapy had better prognosis than patients who received endo-crine therapy (P=0.04) or chemotherapy alone (P<0.001). Conclusions: For HR-positive BOM patients, especially those with single me-tastases, endocrine therapy can obtain satisfactory outcomes. For patients with multiple metastases, combinatory therapy can be con-sidered.

Interpretation of guideline for breast cancer screening in Chinese women / 中国肿瘤临床

Breast cancer is the most common cancer for Chinese women. Early screening is the best way to improve the rates of early diagnosis and early treatment of breast cancer. The peak ages of breast cancer in Chinese women are obviously different from those in the European and American countries. It is imperative to develop a guideline for breast cancer screening that is suitable for Chinese women. Based on the analysis and summary of breast cancer screening data in China, and the latest guidelines and consensus on breast cancer screening in Europe, the United States and East Asia, China Anti-Cancer Association and National Clinical Research Center for Cancer (Tianjin Medical University Cancer Institute and Hospital) has developed a population-based guideline for breast cancer screening in Chinese women. This guideline has provided detailed recommendations on the screening starting age, screening modalities, and screening interval in Chinese women with average risk and high risk of breast cancer, respectively. This article aims to interpret the above guideline, providing references for professionals in breast cancer screening.

Establishment of real-time observational models of apoptosis induced by the aroma-tase inhibitor letrozole in breast cancer cells / 中国肿瘤临床

Objective: To construct an aromatase-overexpressing breast cancer cell model and observe the real-time apoptosis of breast cancer cells induced by the aromatase inhibitor, letrozole. Methods: The lentivirus-mediated gene transfection method was used to construct the MCF-7-VC3AI and ZR7530-VC3AI cell lines,which stably expressed the apoptotic fluorescent indicator protein VC3AI.Simultaneously,letrozole-induced apoptosis models of the MCF-7-VC3AI and ZR7530-VC3AI breast cancer cell lines were also constructed.Real-time quantitative PCR(qPCR)and Western blot methods were used to detect the mRNA and protein levels of aroma-tase in the cells.Cell proliferation ability was measured using MTT.The proliferation of cells in vitro under testosterone,estradiol,or letrozole combined with testosterone treatments were also observed.Results:qPCR results showed that the expression of the aroma-tase mRNA was significantly higher in both the MCF-7 and ZR7530 cell models when compared to the MCF-7-VC3AI and ZR7530-VC3AI cell models.Western blot results showed that the expression of the aromatase protein was significantly increased in both cell models. MTT assay results showed that the proliferation of a cell model could be promoted by testosterone and estrogen stimulation.Under 100 nmol/L testosterone,the proliferation rate of over-expressed aromatase MCF-7-VC3AI cells was about 1.2 times than that of the control group(P<0.01)and the proliferation rate of ZR7530-VC3AI cells was about 1.5 times than that of the control group(P<0.01). However,letrozole inhibited the proliferation induced by testosterone in a dose-dependent manner.Under the effect of letrozole at 10 μmol/L,the proliferation rate of over-expressed aromatase MCF7-VC3AI cells was 80% of the control group(P<0.05),while the prolifer-ation rate of over-expressed aromatase ZR7530-VC3AI cells was 68% of the control group(P<0.05).Conclusions:The successful estab-lishment of cell models that can detect letrozole-induced apoptosis provides an important foundation for further investigating the mechanism of letrozole.

Establishment of an athymic BALB/c mouse model with chronic infection due to Phialophora verrucosa / 中华皮肤科杂志

Objective To establish an athymic (nu/nu)BALB/c mouse model with chronic subcutaneous infection due to Phialophora verrucosa (P.verrucosa),and to explore the role of T lymphocytes in defensing against invasive infection due to P.verrucosa.Methods Six immunocompetent BALB/c mice and 6 nu/nu BALB/c mice were subcutaneously inoculated with 100 μl of P.verrucosa hyphae suspensions at a concentration of 5.0 × 108 colony-forming unit (CFU)/ml into one footpad,while another 6 immunocompetent BALB/c mice and 6 nu/nu BALB/c mice were subcutaneously inoculated with 100 μl of 5.0 × 108 CFU/ml P.verrucosa conidium suspensions into one footpad.The degree of footpad swelling was measured with a vernier caliper every 3 days.Histopathological characteristics of infected footpads were further analyzed.Biopsy tissues were also subjected to fungal culture to analyze the growth of P.verrucosa in infection foci in mice.Results After the treatment with hyphae or conidium suspensions,the BALB/c mice experienced transient footpad swelling within 12 days,and basically recovered after 50 days.However,the nu/nu BALB/c mice experienced persistent footpad swelling with recurrent ulceration and crusting.As pathological examination revealed,all the inoculation loci in BALB/c mice experienced local infection,and the morphology of P.verrucosa in the infected foci was not changed over time.However,invasive infections due to P.verrucosa hyphae alone or a mixture of P.verrucosa hyphae and sclerotic cells were observed in all the inoculation loci in nu/nu BALB/c mice.The fungal culture showed that P.verrucosa could not grow in the footpads of BALB/c mice after 21 days,while P.verrucosa could persistently grow in the footpads of nu/nu BALB/c mice.Conclusion An experimental model with subcutaneous phaeohyphomycosis due to P.verrucosa has been successfully established by using nu/nu BALB/c mice,and the nu/nu BALB/c mice are more susceptible to P.verrucosa infection compared with the immunocompetent BALB/c mice.

Establishment of an athymic BALB/c mouse model with chronic infection due to Phialophora verrucosa / 中华皮肤科杂志

Objective To establish an athymic (nu/nu)BALB/c mouse model with chronic subcutaneous infection due to Phialophora verrucosa (P.verrucosa),and to explore the role of T lymphocytes in defensing against invasive infection due to P.verrucosa.Methods Six immunocompetent BALB/c mice and 6 nu/nu BALB/c mice were subcutaneously inoculated with 100 μl of P.verrucosa hyphae suspensions at a concentration of 5.0 × 108 colony-forming unit (CFU)/ml into one footpad,while another 6 immunocompetent BALB/c mice and 6 nu/nu BALB/c mice were subcutaneously inoculated with 100 μl of 5.0 × 108 CFU/ml P.verrucosa conidium suspensions into one footpad.The degree of footpad swelling was measured with a vernier caliper every 3 days.Histopathological characteristics of infected footpads were further analyzed.Biopsy tissues were also subjected to fungal culture to analyze the growth of P.verrucosa in infection foci in mice.Results After the treatment with hyphae or conidium suspensions,the BALB/c mice experienced transient footpad swelling within 12 days,and basically recovered after 50 days.However,the nu/nu BALB/c mice experienced persistent footpad swelling with recurrent ulceration and crusting.As pathological examination revealed,all the inoculation loci in BALB/c mice experienced local infection,and the morphology of P.verrucosa in the infected foci was not changed over time.However,invasive infections due to P.verrucosa hyphae alone or a mixture of P.verrucosa hyphae and sclerotic cells were observed in all the inoculation loci in nu/nu BALB/c mice.The fungal culture showed that P.verrucosa could not grow in the footpads of BALB/c mice after 21 days,while P.verrucosa could persistently grow in the footpads of nu/nu BALB/c mice.Conclusion An experimental model with subcutaneous phaeohyphomycosis due to P.verrucosa has been successfully established by using nu/nu BALB/c mice,and the nu/nu BALB/c mice are more susceptible to P.verrucosa infection compared with the immunocompetent BALB/c mice.

Clinical research progress on treatments for HER-2-positive breast cancer / 中国肿瘤临床

For HER-2 positive breast cancer, HER-2-targeted agents combined with agents that target downstream signaling or alternative pathways, and endocrine therapy has been investigated in clinical settings. This paper focuses on studies involving phaseⅡand phaseⅢclinical trials for new targets with enhanced clinical applications, including novel small molecular targeting agents, monoclonal antibody-targeted drugs, monoclonal antibody conjugates, dual target drug combination therapy, drug targeting combined with endocrine and targeted chemotherapies, trastuzumab subcutaneous injection, and HER-2 tumor vaccine.

Histone deacetylase inhibitor down-regulated the expression of HER-2 in breast cancer through the changes in miRNA / 中国肿瘤临床

Objective:To investigate the mechanism of histone deacetylase (HDAC) inhibitor in down-regulating the expression of HER-2 in breast cancer cells and to provide an innovative therapeutic option to overcome the disadvantages of anti-HER-2 therapy. Meth-ods:HER-2-positive breast cell lines were treated with HDAC inhibitors. The changes in the gene and protein levels of HER-2 were de-tected by qPCR and Western blot. MiRNA microarray was used to identify the HDAC inhibitors, whereas qPCR was used to verify the miRNA expression. Results:In vitro cell experiments confirmed that the HDAC inhibitors TSA and SAHA can down-regulate the expres-sion of HER-2 in breast cancer cell lines. TSA can down-regulate the expression of HER-2 gene in BT474 and decrease the concentra-tions of 100 nmol by 10.7%and 200 nmol by 38.9%(P<0.05). TSA had no effect on the primary cells. The expression of HER-2 gene of BT474 was down-regulated by 93.9%(P<0.05) in the 5μmol/L group but not in the 1μmol/L group. SAHA significantly affected the pri-mary cells at a concentration of 1μmol/L and reduced the cells at 87.1%at a concentration of 5μmol/L. Seven miRNAs were identified from the miRNA microarray. MiR-762 was used as a basis to identify the changes in miRNA. The miRNA sputum identified by miRNA microarray and qPCR may be associated with the down-regulation of HER-2 by HDAC inhibitors. Conclusion: HDAC inhibitors may down-regulate the expression of HER-2 in breast cancer cells by changing some miRNAs.

Effects and mechanism of overexpression of Mfn-2 gene on photodynamic therapy sensitivity of T47D cells in human breast cancer / 国际肿瘤学杂志

Objective To investigate the effects and possible mechanisms of Mfn-2 gene overexpression on photodynamic therapy (PDT) sensitivity of T47D cells in human breast cancer.Methods pEGFP and pEGFP-Mfn-2 were transfected into human breast cancer T47D cells,and then the mRNA and protein expression of Mfn-2 gene in T47D cells were detected by real-time PCR (RT-PCR) and Western blotting in pEGFP group and EGFP-Mfn-2 group,respectively.After pEGFP and pEGFP-Mfn-2 were transfected into human breast cancer T47D cells for 48 hours,methyl thiazolil tetracolium (MTT) assay was used to measure the PDT sensitivity of T47D cells in human breast cancer in pEGFP group and pEGFP-Mfn-2 group.pEGFP + PDT group and pEGFP-Mfn-2 + PDT group were obtained by PDT irradiating pEGFP and pEGFP-Mfn-2 which were transfected into human breast cancer T47D cells.Cell apoptosis and mitochondrial membrane potential of T47D cells were assayed by flow cytometry in pEGFP + PDT group and pEGFP-Mfn-2 + PDT group.Laser scanning confocal fluorescence microscope was applied to observe the morphological ultrastructure of mitochondria in pEGFP group,pEGFP-Mfn-2 group,pEGFP + PDT group,and pEGFP-Mfn-2 + PDT group.Results RT-PCR showed that after transfecting T47D cells with pEGFP,the expression of Mfn-2 mRNA was 1.01 ±0.12.After transfecting T47D cells with pEGFP-Mfn-2,the expression of Mfn-2 mRNA was 1 067.00 ±41.72.There was statistical significance (t =67.541,P ＜ 0.001).Western blotting revealed that compared with the pEGFP group,the pEGFP-Mfn-2 transfection group had higher expression of Mfn-2 gene in T47D cells.MTT assay showed that pEGFP-Mfn-2 transfection significantly enhanced the PDT sensitivity of T47D cells in hunan breast cancer compared with the pEGFP + PDT group.When the concentration of methylene blue was 5.00 μmol/ml,the survival rate of the pEGFP +PDT group and pEGFP-Mfn-2 + PDT group were (59.96％ ± 1.21％) vs.(46.50％ ± 1.72％),with significant difference (t =34.403,P ＜ 0.001).Flow cytometry assay showed that the cell apoptosis rates in pEGFP-Mfn-2 + PDT group was markedly higher compared with the pEGFP + PDT group [(81.21 ± 2.13)％ vs.(68.82 ±2.64)％,P=0.024],with statistical significance.Also,the mitochondrial membrane potential was obviously lower in pEGFP-Mfn-2 +PDT group compared with the pEGFP +PDT group [(1.37 ±0.12)％ vs.(23.33 ± 1.86)％,P＜0.001],with statistical significance.Laser scanning confocal fluorescence microscope showed that cells in pEGFP group showed network structure,both pEGFP-Mfn-2 group and pEGFP + PDT group could cause mitochondrial fusion,and the pEGFP-Mfn-2 + PDT group could induce mitochondrial disintegration and lose its normal morphology completely.Conclusion Mfn-2 may enhance the PDT sensitivity of T47D cells in human breast cancer,which is possibly related with the normal morphology alteration of mitochondria and the inducement of mitochondrial apoptosis.

"A case of lymphocutaneous sporotrichosis caused by Sporothrix schenckii sensu stricto finally diagnosed by molecular identification based on ""ITS"" and ""CAL"" coding regions in combination with phenotypic analysis" / 中华皮肤科杂志

A 54-year-old female farmer presented with a pea-sized red nodule on the left upper limb near the wrist for 15 days,which occurred after trauma,gradually became swollen and ruptured,and developed into multiple nodules arranged in a chain in 30 days.Skin examination revealed multiple hard purple-red nodules arranged in a line on her left upper limb,some of which were ruptured with a small amount of purulent exndate.Histopathological examination further revealed that the focus of infection manifested as pyogenic granuloma-like inflammation mainly infiltrated with mixed inflammatory cells.Periodic acid Schiff (PAS) staining showed no fungal structures,including fungal spores,hyphae and asteroid body.The biopsy tissue culture yielded the fungus.According to the morphological analysis of the cultures and results of molecular identification based on internal transcribed spacer (ITS) and calmodulin (CAL) coding regions,this case was finally diagnosed as lymphocutaneous sporotrichosis caused by Sporothrix schenckii sensu stricto.The patient was treated with oral potassium iodide 10％ solution in a dose of 10 ml thrice a day.After 2-month treatment,the patient felt that the lesions were obviously improved,but afterwards she was lost to follow-up.This research report suggests that phenotypic analysis combined with ITS/CAL-based molecular identification can accurately identify Sporothrix schenckii complex at the species level.

Clinical efficacy of apatinib in treating refractory triple-negative advanced breast cancer / 中国肿瘤临床

Objective:To evaluate the effectiveness and safety of using apatinib in the treatment of refractory triple-negative advanced breast cancer. Methods:Eight cases of advanced triple-negative breast cancer patients confirmed via histopathology, who were previously treated with anthracycline, taxane, gemcitabine, capecitabine, and 500 mg/d apatinib in our hospital from July 2015 to November 2016, were retrospectively analyzed. The time of disease progress, effective rate, clinical benefits, and side effects were observed. Results:Eight patients were administrated with an average of 4 treatment cycles, and the effects were evaluated after 2 weeks. Four patients exhibited partial remission, 3 had a stable disease, and 1 had a progressive disease. The disease control rate was 87.5%, and the median progression free survival was 4.2 months. The main side effects were hand-foot syndrome (3/8), bone marrow arrest (4/8), hypertension (2/8), proteinuria (3/8), hemoptysis (1/8), nausea (2/8), and fatigue (2/8). Most of these side effects were tolerable. Conclusion:Apatinib can effectively and tolerably prolong survival time and improve the quality of life of patients with advanced triple-negative breast cancer.

A multicenter, randomized, controlled, phase Ⅲ clinical study of PEG-rhG-CSF for preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.</p><p><b>METHODS</b>According to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.</p><p><b>RESULTS</b>The duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).</p><p><b>CONCLUSIONS</b>In patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.</p>