Research Progress on Immunization and Targeted Therapy for Triple-negative Breast Cancer / 肿瘤防治研究

Triple-negative breast cancer (TNBC) accounts for approximately 15%–20% of all breast cancers. Patients with TNBC have a rapidly progressive clinical course, an earlier age of onset, faster distant recurrence, and more common visceral metastases as compared with other subtypes. However, treatment of TNBC is often limited to chemotherapy and has a poor prognosis. Therefore, developing the best treatment strategy for patients is essential to reduce the burden of disease caused by TNBC. Various potential available drug targets have been discovered, as well as precision treatment and classified treatment are changing the clinical practice of TNBC, thereby indicating a new therapeutic area for TNBC in addition to traditional chemotherapy. This article reviews the systemic treatment options for TNBC in recent years, including immunotherapy and targeted therapy.

Predictive Factors and Prognostic Value of Pathologic Complete Response of Internal Mammary Lymph Nodes in Breast Cancer After Neoadjuvant Chemotherapy / 肿瘤防治研究

Objective To explore the prognostic factors of the pathological complete response of internal mammary lymph node (ipCR) after neoadjuvant chemotherapy and its effect on breast cancer prognosis. Methods We retrospectively analyzed the clinical data of 70 patients with primary breast cancer with internal mammary lymph node metastasis who received neoadjuvant chemotherapy. Patients were divided into the ipCR group and non-ipCR group based on their postoperative pathology. χ2 test, Fisher, and Logistic regression were used for univariate and multivariate analysis. Meanwhile, the Kaplan-Meier curve and Cox regression were used for prognostic analysis. Results Of 70 patients, 31 obtained ipCR (44.3%). Univariate analysis showed that the expression levels of apCR, HR, and HER2 status were related to ipCR (P < 0.05). Multivariate analysis showed that age, apCR, and HER2 status were independent predictors of ipCR (P < 0.05). The average DFS of ipCR group was better than non-ipCR group (96.0 vs. 67.1 months, P < 0.05). The risk of recurrence and metastasis was 87% lower in the ipCR group than in the non-ipCR group (HR=0.13, 95%CI: 0.04-0.44, P < 0.01). ipCR, Ki67 expression level, and breast pCR (bpCR) were independent factors affecting patients' prognosis. Conclusion There is a correlation between clinico pathological factors and ipCR after neoadjuvant chemotherapy. ipCR can be used to predict the prognosis of patients with internal mammary lymph node metastasis.

IFN-γ Inhibits Proliferation and Migration of Esophageal Squamous Cell Carcinoma by Downregulating CXCL8 Expression / 肿瘤防治研究

Objective To investigate the effect of IFN-γ on the proliferation and migration of esophageal squamous cell carcinoma cell line Eca9706 and related mechanism. Methods Cells were cultured in vitro and treated with interferon-γ. Cell morphology changes were observed under microscope, cell proliferation ability was detected by CCK-8 experiment, and cell migration ability was detected by cell scratch experiment and Transwell experiment. Real-time PCR method was used to detect the expression efficiency of chemokine CXCL8 (interleukin 8), and the ELISA experiment was used to detect the change of CXCL8 secretion. Results Compared with the blank control group, Eca9706 cells treated with different concentrations of interferon-γ did not change significantly in cell morphology. CCK8 experiment confirmed that the proliferation ability of Eca9706 cells after IFN-γ treatment was significantly reduced (P < 0.01). Cell scratch experiment found that IFN-γ significantly decreased the migration ability of Eca9706 cells (P < 0.01). Transwell experiment showed that after IFN-γ treatment, the migration ability of Eca9706 cells was significantly inhibited (P < 0.01). CXCL8 gene expression level in Eca9706 cells treated with interferon-γ was significantly down-regulated (P < 0.01), and the amount of CXCL8 secretion significantly reduced (P < 0.05). Conclusion Interferon-γ can inhibit the proliferation and migration of esophageal cancer cell line Eca9706, which may be related to its inhibition of the expression and secretion of CXCL8.

Real-world Research of Trastuzumab and Pertuzumab Combined with Chemotherapy in Neoadjuvant Treatment of HER2-positive Breast Cancer / 肿瘤防治研究

Objective To analyze the efficacy and safety of trastuzumab (H) and pertuzumab (P) combined with different chemotherapy regiments in neoadjuvant therapy for HER2-positive breast cancer. Methods We retrospectively analyzed the clinical data of the patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy and completed surgery. The primary endpoint was total pathologic complete response (tpCR) (ypT0/isypN0), the secondary endpoints were breast pathologic complete response(bpCR) (ypT0/is) and axillary pathologic complete response (apCR) (ypN0), and the factors influencing pCR were analyzed. Results A total of 63 patients were included, of whom 23 were treated with TCbHP, 27 were treated with THP regimen, and 13 were treated with AC-THP. The overall tpCR rate was 65.1%, of which TCbHP was 73.9%, THP was 55.6%, and AC-THP was 69.2%. The tpCR rate of HR-negative patients was 79.2%, higher than that of HR-positive 56.4%. The overall bpCR rate was 69.8%, and apCR rate was 81.0%. Univariate analysis showed that HER2 status was a related factor affecting tpCR (P=0.023). The total effective rate by MRI was 87.3%. The level 3 and 4 toxicity of the TCbHP regimen was slightly higher than those of the THP and the AC-THP regimens. Conclusion HP combined with chemotherapy have achieved relatively high pCR. HER2 status is a related factor that affects tpCR. The adverse reactions are controllable.

Risk of Primary Lung Cancer in Breast Cancer Patients: A Systematic Review and Meta-analysis / 肿瘤防治研究

Objective To systematically evaluate the risk of primary lung cancer in breast cancer patients. Methods A computer-based search was conducted for the English literatures about the risk of primary lung cancer in breast cancer patients in Medline, Scopus and Embase databases. Two researchers independently screened the literatures, extracted the data and assessed the risk of bias. The statistical analysis was performed using the Stata 15.5 software. Results A total of 7 references were included, and the overall risk of primary lung cancer in female breast cancer patients was slightly higher than that in the general population (SIR: 1.18, 95%CI: 1.09-1.27). Subgroup analysis showed that the risk of lung cancer was significantly increased in women aged < 50 years after diagnosis of breast cancer (SIR: 1.99, 95%CI: 1.48-2.69). Conclusion Compared with the general population, the risk of primary lung cancer is increased in female breast cancer patients, especially in young women with breast cancer.

Research progress on the relationship between TET1 and tumor invasion and metastasis / 国际外科学杂志

TET1 has been discovered capable of promoting DNA demethylation by mediating 5-methylcytosine to inhibit the genesis and development of cancer.Epithelial-Mesenchymal transition is a complex cellular program in cancer progression and metastasis,whose hallmark is loss of cell polarity and cell adhesion and acquirement of migration and invasion abilities,leading tumor cells into blood vessel and lymphatic vessels to form new metastatic lesions.Epigenetics plays a vital role in epithelial-mesenchymal transition.This review focuses on the relationship of TET1,epigenetics and epithelial-mesenchymall transition,and the research progression of TET1's role in cancer invasion and metastasis.

Anti-miR-145 promotes human airway smooth muscle cell proliferation and osteopontin synthesis in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of anti-miR-145 on human airway smooth muscle cell (HASMC) proliferation and osteopontin systhesis in vitro and explore the mechanisms.</p><p><b>METHODS</b>HASMCs were treated with 10-100 nmol/L anti-miR-145, and the cell proliferation and apoptosis were investigated using a CCK-8 assay and flow cytometry, respectively. The changes in osteopontin synthesis after the treatment was quantified with Western blotting.</p><p><b>RESULTS</b>Treatment with 10 and 50 nmol/L anti-miR-145 significantly promoted the proliferation and osteopontin synthesis in HASMCs (P<0.05 or <0.01), and 50 nmol/L anti-miR-145 obviously inhibited the cell apoptosis (P<0.01).</p><p><b>CONCLUSION</b>Anti-miR-145 promotes HASMC proliferation and osteopontin synthesis and inhibits HASMC apoptosis in vitro, indicating the important role of anti-miR-145 in the pathogenesis of airway remodeling.</p>

Chinfloxacin hydrochloride inhibits HERG potassium channel at open state / 药学学报

This study is designed to investigate the effects of chinfloxacin hydrochloride (CFX) on the kinetics of HERG K+ channel. Whole cell patch clamp technique was used to record HERG K+ currents from HEK293 cells transiently transfected with cgi-HERG-GFP plasmids and channel kinetics were assessed in the absence and presence of CFX and moxifloxacin hydrochloride (MOX). Results demonstrated that the open state of HERG K+ channel was inhibited by CFX in a concentration- and time-dependent manner, with an IC50 of 162.1 +/- 14.2 micromol x L(-1), two folds higher than its positive control MOX. But there were no significant effects on channel kinetics. In addition, the inhibitory effect of CFX on HERG was enhanced when cells were subjected to altered extracellular K+ concentration.

Incidences of nutrition risks, malnutrition ( undernutrition), overweight, and obesity, and nutrition support in tertiary hospitals in Xinjiang Uigur Autonomous Region / 中华临床营养杂志

Objective To investigate the incidences of nutrition risks, malnutrition ( undernutrition),overweight, and obesity, and nutrition support in tertiary hospitals in Xinjiang Uigur Autonomous Region. Methods Using fixed-point consecutive sampling, we collected the clinical data of inpatients in 6 departments of five tertiary hospitals in Xinjiang. According to the Nutrition Risk Screening 2002 (NRS 2002 ) published by European Society for Parenteral and Enteral Nutrition, patients were graded as at nutritional risk when their NRS 2002 scores ≥3 and as malnutrition when the body mass index (BMI) was ＜ 18.5 kg/m2 (or albumin ＜ 30 g/L). NRS 2002 screening was performed on the next morning after a patient was admitted. The nutrition supports within 2 weeks after admission were also investigated. The relationship between nutrition risks and nutrition support was analyzed.Results A total of 4036 inpatients were investigated, among them 3913 patients received NRS 2002 screening.The malnutrition (undernutrition) rate and the proportion of patients at nutritional risk were 8.4% and 34. 2%, respectively. The percentage of nutrition support was 10. 2%, which included parenteral nutrition (8. 5% ) and ena simple, fast and convenient tool for the investigation of nutrition risks and can provide a basis for reasonable nutrition support Therefore, it should be widely applied in clinical practice.

Preparation of tumor-specific CTLs and their therapeutic effects on bone marrow micrometastasis of breast cancer / 中国肿瘤生物治疗杂志

Objective: To prepare auto-tumor-specific cytotoxicity T lymphocytes (CTLs) of breast cancer patients and to observe their therapeutic effects on bone marrow micrometastasis (BMM) of breast cancer. Methods: BMM in 82 patients with primary breast cancer (stage Ⅰ to Ⅲ) , who were treated in the Fourth Affiliated Hospital of Hebei Medical University from March to December in 2007 (all the patients signed paper of informed consent), was exmined by flow cytometryusing CK18 and CK19 as marker. Twenty-three patients with BMM were randomly divided into two groups: 17 patients were treated with tumor-specific CTLs (therapy group), and 6 patients were treated with IL-2 (control group). Tumor-specific CTLs were induced in vitro from axillary lymph nodes and peripheral blood of breast cancer patients in ther-apy group, and were reinfused into the same patient 10-14 days after operation. The therapeutic effects of tumor-specific CTLs on BMM of breast cancer patients were observed. Results: Twenty-three cases (28.05%) in 82 breast cancer patients were BMM positive as detected by FCM. BMM positive rates increased with the increase of clinical TNM stages and histological grades of breast cancer, and decreased with the increase of ER and PR protein expression in cancer tis-sues. Dendritic cells (DCs) were successfully isolated and induced from the peripheral blood of breast cancer patients. Tumor-specific CTLs were induced by co-culturing lymphocytes from axillarey lymph nodes with auto-tumor antigen-im-pulsed DCs. Fourteen cases in the therapy group became negative of BMM after treatment with tumor-specific CTLs (14/ 19, 82.35%). Only one case in the control group became negative of BMM after treatment with IL-2 (1/6, 16.67%, P=0.00028). Conclusion: Tumor-specific CTLs have been successfully prepared and they show a satisfactory therapeu-tic effect on bone marrow micrometastasis of breast cancer.

Clinical characteristics of adult Wilms' tumor / 中华泌尿外科杂志

Objective To investigate the clinical characteristics of adult Wilms'tumor in Chinese adults and to improve the recognition of adult Wilms'tumor.Methods The clinical data of 6 Wilms'tumor patients treated in our hospital were reviewed. Of them, there were 4 male patients and 2 female patients with mean age of 31 years old. Four patients with abdominal and flank pain and 2 patients with abdominal masses were the main clinical manifestations. One case accompanied with hematuria and another one had fever.Tumor masses were palpable by physical examination in 4 patients. Five patients had percussion tenderness over kidney region and 1 case had abdominal tenderness. Six cases underwent urinalysis and red blood cell was positive in 2 cases. There were no abnormal results in other laboratory tests. Chest X-ray was routinely performed before operation. Six patients underwent ultrasonography and all showed hypoechoic masses (5.0cm×5.0 cm-22.0 cm×25.0 cm) with clear margin. Four cases examined by CT and all had solid masses with inhomogeneous density and clear margin. On enhanced CT scan, 1 of 4 cases demonstrated irregular enhancement of the mass with local hemorrhagic necrosis area. The CT value ranged from 11-40 HU, with an average value of 22.5 HU, and increased to 35-78 HU, with an average value of 63.5 HU after administration of contrast. Two cases of MRI revealed solid mass defects.Three cases underwent IVU examination and showed the enlargement of renal umbra as well as thinning of renal calices caused by the compression of tumor and 1 case showed hydronephrosis.Thus, 5 cases were diagnosed with renal tumor and 1 case was diagnosed with cavitas pelvis tumor before operation. Five patients successfully underwent nephrectomies and 1 patient accepted oophorotomy with no subsequent complication.Retroperitoneal lymph node dissection(RPLND) was performed at the time of radical nephrectomy or oophorotomy in all patients. The tumor was found to be about 5-25 cm in size during operation. One of the tumors had invaded pancreas tail, one had invaded to the lateral abdominal wall and one had invaded into the inferior caval vein. Renal hilar lymph node was found to be exceeded 1.5 cm×1.5 cm in 2 patients. The post-operative incisal surface of the tumor presented with gray-yellow color. Capsule was intact in 4 patients. Three cases had hemorrhagic necrosis in tumor center. All the specimens sent for the pathological examination. None received adjuvant therapy before operation. Four patients received chemotherapy plus radiotherapy after surgery and other 2 patients received chemotherapy only. All patients were followed up with routine lab tests, ultrasonography and chest X-ray.Results Six patients were staged according to the National Wilms'Tumor Study staging system as follows: 1 case in stage Ⅰ, 2 cases in stageⅡ, 2 cases in stage Ⅲ and 1 case in stage Ⅳ. Nephrectomies or oophorotomy were performed in all patients successfully. Tumor diameters were from 4.5-25.0 cm, in average 11.8 cm.All cases had pathological diagnosis of Wilm's tumor. Five cases were classified into favorable histologic type and 1 case was in unfavorable histologic type. Two patients with lymph node metastasis and 3 patients with local invasion were observed. One patient with pulmonary metastasis was recorded. Six patients were followed up for 1-7 years. Five patients survived with no evidence of cancer recurrence. One patient died of pulmonary metastasis 2 years after surgery.Conclusions The majority of adult Wilms'tumors are found with local invasion and metastasis. The incidence of hematogenous metastasis in adult Wilms'tumor is higher than other types of renal tumor as well. The early diagnosis and radical surgical treatment and adjuvant chemoradiotherapy could improve the survival rate.

The clinical effect of enteral nutrition on the patients with acute respiratory failure phase COPD / 肠外与肠内营养

Objective: To observe the clinical effect of enteral nutrition on the patients with acute respiratory failure phase COPD.Methods: 60 cases of COPD patients in the acute respiratory failure phase were randomly divided into two groups: treatment group and control group,30 cases respectively.The two groups had the same formal diet,anti-infection,oxygen therapy,spasmolysis therapy,eliminate sputum therapy,adjustment acid-base imbalance and electrolyte disturbances.Additionally,the treatment group had been given oral lishikang(a kind of nutrient solution)for two weeks.Results:Compared with the control group,treatment group had the improvement on the body measurement,pulmonary function and serum albumin.The difference between the two groups were remarkable(P