1.The latest developments in targeted therapy for triple-negative breast cancer
China Oncology 2017;27(1):36-40
Triple-negative breast cancer (TNBC) is a special type of breast cancer, accounting for 15%-20% of all diagnosed breast cancer cases. Its estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) expression is negative, with unique biological characteristics, clinicopathological features and tumor heterogeneity. Its clinical features include high incidence of relapse, early metastasis and poor prognosis. Currently, it lacks effective treatment. This review described the clinicopathological features of TNBC, its molecular subtypes, several important pathways and targets, as well as presented the progress in clinical studies of targeted drugs in the hope of generating new ideas for the treatment of TNBC in the future.
2.Progress in research on mechanisms of bone metastasis in breast cancer
China Oncology 2009;19(12):963-968
Breast cancer ranks among the most prevalent malignancies in women. Specific aspects of both breast cancer cells and the bone microenvironment contribute to the development of bone metastases. Breast cancers express chemokine receptors, integrins, cadherins, and bone-resorbing and bone-forming factors that contribute to the successful and preferential spread of tumor from breast to bone. Bone is rich in growth factors and cell types that make it a favorable environment for breast cancer cell growth. Once breast cancer cells enter the bone, breast cancer cells can secrete factors that act on bone cells and other cells within the bone, causing them to secrete factors that act on adjacent cancer cells. The steps in the metastatic cascade and the vicious cycle within bone offer unique targets for adjuvant treatments to treat and cure bone metastasis.
3.Advance in the study of microRNA in tumor metastasis
China Oncology 2009;19(10):793-796
Within the past few years, studies on MicroRNA (miRNA) and tumor metastasis have become the focus of attention. Multiple lines of evidence demonstrated the involvement of specific miRNAs in tumor metastasis, which can negatively regulate the expression of target mRNA and post-transcriptionally control gene expression. Metastasis is the key indicator of tumor malignancy and is the main reason of death of the tumor patients, so how to prevent and control it is important to increase the survival of the tumor patients. This review summarized the recent progress on the research field of miRNA and its association with tumor metastasis.
4.Advances in the research on the STK11 gene
Zan SHEN ; Zhimin SHAO ; Zhenzhou SHEN ;
China Oncology 1998;0(04):-
STK11 gene is a recently found tumor suppressor gene. It maps 19p13.3. This gene can express a kind of serine threonine kinases. STK11 gene plays an important role in the regulation of cell cycle progression, and it may relate to cell apoptosis. However, until now the mechanisms of STK11 gene is not very clear and progress in the research of this new tumor suppressor gene is sitll needed.
5.Study of the expression of Id1 gene to invasion of the pituitary adenoma
Bo MA ; Zhiqiang LI ; Zan SHEN
Chinese Journal of Primary Medicine and Pharmacy 2015;22(1):1-4,后插1
Objective To explore the pathogenesis of invasive pituitary adenomas,and to improve the effect of clinical treatment.Methods 15 pairs of invasive pituitary adenoma tissues and noninvasive pituitary adenoma tissues were selected from 114 specimens collected and the Id1 gene expression and Id1 protein expression in invasive pituitary adenoma tissues and noninvasive pituitary adenoma tissues were tested by quantitative RT-PCR,Western blot and immunohistochemical methods;Then small interfering RNA (siRNA) was used to interfer Id1 gene expression in NQ-04 cells.Results The Id1 gene expression in invasive pituitary adenoma tissues was significantly higher than that in noninvasive pituitary adenoma tissues(n =15,t =2.725,P =0.013) ;The migration of pituitary adenoma cells interfered was significantly reduced.Conclusion The invasive pituitary adenoma tissues has high level of Id1 gene expression,which may be correlated with its invasion.And Id1 is expected to become a biological marker of diagnosis and determination in the prognosis of pituitary adenoma.
6.Applications of Bone Marrow Stromal Cells in Gene Therapy of Central Nervous System Diseases
Kun ZAN ; Yonghai LIU ; Chenghua XIAO ; Zunsheng ZANG ; Xia SHEN
International Journal of Cerebrovascular Diseases 2008;16(2):131-136
Gene therapy refers to the introduction of normal genes into human target cells for correcting gene defects or exerting therapeutic action,and thus achieves the goal of treatment of disease.Bone marrow stromal cells (BMSCs) are stem cells that possess self-renewal and multi-directional differentiation potential and easy to amplify in vitro,and they also express many therapeutic exogenous genes in vitro or in vivo.So BMSCs have been regarded as an ideal target cell of cell and gene therapy.This article reviews the biological characteristic of BMSCs,some commonly used gene therapy vectors and their applications in gene therapy of central nervous system diseases.
7.Clinical signiifcance of ICAM-1 expression and its correlation with prognosis of triple-negative breast cance r
Zimei LIU ; Wenxi YU ; Chu SUN ; Yuan YUAN ; Zan SHEN
China Oncology 2017;27(2):121-127
Background and purpose:Triple negative breast cancer (TNBC) is with high invasion, poor prognosis and lack of usefull treatment. This study investigated expression status of ICAM-1 protein in TNBC in order to explore its relationship with clinicopathological features and outcome in patients.Methods:Fifty-nine tissue samples of TNBC were collected while 50 cases of para-carcinoma tissue samples were used as negative controls. Immunohistochemical staining was conducted to detect expression level of ICAM-1 protein. The relationship of ICAM-1 protein expression with clinicopathological features (age, tumor size, subtype, grade, status of lymph node metastasis, TNM stage, vascular tumor thrombus, nerve inifltration, Ki-67, p53 and E-cadherin expression) and outcome in patients were analyzed.Results:The ICAM-1 protein expression of TNBC was signiifcantly higher than that in adjacent tissues (P=0.000). ICAM-1 expression was related to status of lymph node metastasis, grade and TNM stage (with aP-value of 0.036, 0.027 and 0.048, respectively), while demonstrated an undeifned relationship with tumor size, subtype, vascular tumor thrombus and expression of Ki-67, p53 and E-cadherin. The disease-free survival (DFS) of ICAM-1 high expression set was shorter than that of the lower one but has nothing to do with overall survival (OS). In addition, Cox proportional hazards model showed that ICAM-1 expression and lymph node metastasis were independent risk factors of DFS in patients (HR=3.2, 95%CI: 1.6 to 6.4, HR=2.7, 95%CI: 1.28 to 5.9,P<0.05).Conclusion:ICAM-1 could serve as a predictive factor for differentiation status of TNBC. The high expression of ICAM-1 in TNBC may indicate poorer prognosis.
8.Effects of glivec combined with everolimus on mouse pituitary AtT-20 cells
Hao LI ; Kaimin WANG ; Zhiqiang LI ; Zan SHEN
Journal of Medical Postgraduates 2016;29(7):698-702
Objective Medication for pituitary adenomas is mainly targeted on the prolactin-secreting and growth-hormone types and shows poor therapeutic effects on other adenomas .Therefore, new drugs urgently need to be developed for this purpose .This study was to investigate the effects of glivec and everolimus on mouse pituitary AtT-20 cells and their molecular mechanisms in vitro. Methods Mouse pituitary AtT-20 cells were incubated with glivec or everolimus or combination of both and their inhibitory effect on the proliferation of the cells was measured by CCK-8 assay.The mRNA levels of AKT and ERK were determined by q-PCR and the ex-pressions of the phosphorylated AKT (p-AKT) and ERK (p-ERK) were detected by Western blot. Results Used alone, both glivec and everolimus inhibited the proliferation of the AtT-20 cells in a time-and dose-dependent manner , but their combination produced a mutually antagonistic effect, with combination index values of 1.13 ±0.06, 1.12 ±0.03, and 1.07 ±0.03 respectively.The two a-gents , either used alone or in combination , induced no significantly inhibitory effects on the mRNA and protein expressions of AKT and ERK ( P >0.05 ).Both glivec and everolimus up-regulated the expressions of p-AKT and p-ERK, and their combination manifested an even stronger effect (P>0.05). Conclusion Both glivec and everolimus inhibit the proliferation of AtT-20 cells when administered alone, but their combination produces an antagonistic effect .Their action mechanism might be that when targeting some signaling path-ways to inhibit cell proliferation , glivec, as well as everolimus , in-duces a feedback activation of AKT and ERK .
9.The inlfuence of diagnostic interval and other clinicopathological factors on the prognosis of triple-negative breast cancer
Chu SUN ; Hongtao LI ; Zimei LIU ; Yuan YUAN ; Zan SHEN
China Oncology 2016;26(6):538-545
Background and purpose:The time from ifrst onset of symptoms or signs to a deifnitive diagnosis is deifned as diagnostic interval (DI). The relation of DI to other clinicopathological parameters andthe impact of DI on prognosis of patients with triple-negative breast cancer (TNBC) remain unclear.This article plans to make an intensive study of these questions.Methods:The clinical records of a series of 83 consecutively presenting unselected patients referred to the Shanghai Sixth People’s Hospital with diagnosed TNBC between September 2009 and September 2015 were retrospectively reviewed. Clinical and pathological factors included were investigated by univariate analysis using the Kaplan-Meier method, the factors associated with prognosis were further evaluated by multivariable analysis with Cox progression model.t-test and Kruskal-Wallis test were used to study the correlation between DI and other characters.Results:DI: stage T3>T1 (P=0.01), stageⅢ>Ⅱ (P=0.03) andⅠ (P=0.01). Compared with patients of DI≥3 months, the <3 months group had earlier age (P=0.028) and TNM stage (P=0.035). T stage, N stage, neoadjuvant chemotherapy, TNM stage and DI are inlfuencing factors of overall survival (OS). Age, T stage, N stage, TNM stage, menstrual status and neoadjuvant chemotherapy are inlfuencing factors of progression-free survival (PFS). TNM staging is an independent inlfuencing factor for OS and PFS.Conclusion:Patients with later disease stage were more likely to have a longer DI; The shorter DI, the earlier age and stage of disease; DI is the inlfuence factor of OS; TNM stage is an independent inlfuencing factor for OS and PFS.
10.Expression and clinical signiifcance of PAK5 protein expression in osteosarcoma
Cong TIAN ; Lina TANG ; Feng LIN ; Zan SHEN ; Jie CHEN ; Yang YAO ; Daliu MIN
China Oncology 2014;(1):1-7
Background and purpose: p21-activated kinase 5 (PAK5) is a recently identified member of PAKs that regulate many intracellular processes such as cytoskeleton remodeling, cell proliferation, cell differentiation, gene transcription and cell apoptosis. Recently, studies found that PAK5 was overexpressed in some cancer such as gastric and colon cancer. However, the expression status and biological function of PAK5 in osteosarcoma are not clearly known. The objective of this study was to investigate the expression of PAK5 in osteosarcoma tissue and their relationships with the prognosis of osteosarcoma. Methods: The expression of PAK5 was detected by using immunohistochemical method in 92 specimens of human osteosarcoma tissues and 33 cases of osteoclastoma tissue, respectively. Results: The positive rate of PAK5 was 71.7% (66/92) in all the 92 cases of osteosarcoma. PAK5 expressions were not related to clinical variables such as gender, age, tumor location, tumor size, histological type and local recurrence, but signiifcantly related to Enneking grade, tumor cell necrosis rate and lung metastasis, and the high expression of PAK5 may reduce the efifciency of chemotherapy. Survival analysis indicated that high expression of PAK5 correlated with poor prognosis of patients with osteosarcoma. Univariate survival analysis showed that the signiifcant prognostic factors were tumor size, Enneking grade, local recurrence, lung metastasis and expression levels of PAK5. COX multivariate regression identified that the PAK5 expression levels (P=0.001) and lung metastasis (P=0.015) were independent prognostic factors of patients with osteosarcoma. Conclusion:The positive expressions of PAK5 closely correlate with Enneking grade, tumor cell necrosis rate and lung metastasis. Detection of PAK5 may be used as a molecular marker for prognosis of osteosarcoma. The high expression of PAK5 may reduce the efifciency of chemotherapy.