Lamin B2 promotes the progression of triple negative breast cancer via mediating cell proliferation and apoptosis

Triple negative breast cancer (TNBC) is a more common type of breast cancer with high distant metastasis and poor prognosis. The potential role of lamins in cancer progression has been widely revealed. However, the function of lamin B2 (LMNB2) in TNBC progression is still unclear. The present study aimed to investigate the role of LMNB2 in TNBC. The cancer genome atlas (TCGA) database analysis and immunohistochemistry (IHC) were performed to examine LMNB2 expression levels. LMNB2 short hairpin RNA plasmid or lentivirus was used to deplete the expression of LMNB2 in human TNBC cell lines including MDA-MB-468 and MDA-MB-231. Alterations in cell proliferation and apoptosis in vitro and the nude mouse tumorigenicity assay in vivo were subsequently analyzed. The human TNBC tissues shown high expression of LMNB2 according to the bioinformation analysis and IHC assays. LMNB2 expression was correlated with the clinical pathological features of TNBC patients, including pTNM stage and lymph node metastasis. Through in vitro and in vivo assays, we confirmed LMNB2 depletion suppressed the proliferation and induced the apoptosis of TNBC cells, and inhibited tumor growth of TNBC cells in mice, with the decrease in Ki67 expression or the increase in caspase-3 expression. In conclusion, LMNB2 may promote TNBC progression and could serve as a potential therapeutic target for TNBC treatment.     

改良乳腺癌根治术后切口感染的病原学特征、影响因素及其凝血纤溶功能研究

摘要 目的：探讨改良乳腺癌根治术后切口感染的病原学特征、影响因素及其对凝血纤溶功能的影响。方法：选取我院于2016年6月~2020年9月期间收治的390例行改良乳腺癌根治术的乳腺癌患者,分析改良乳腺癌根治术后切口感染的病原学特征、影响因素及术后切口感染对凝血纤溶功能的影响。结果：390例行改良乳腺癌根治术的乳腺癌患者,术后发生切口感染28例,术后切口感染率为7.18%（28/390）,将未发生术后切口感染的患者纳为未感染组（n=362）,发生的纳为感染组（n=28）。28例发生感染的患者共分离培养病原菌36株,其中革兰阳性菌14株,占比38.89%（14/36）,以金黄色葡萄球菌、粪肠球菌为主。革兰阴性菌21株,占比58.33%（21/36）,以大肠埃希菌、铜绿假单胞菌为主。改良根治术后乳腺癌患者切口感染的影响因素包括手术时间、术后住院时间、合并基础疾病、引流时间、年龄、白蛋白（P<0.05）。多因素Logistic回归分析发现：合并基础疾病、年龄≥60岁、白蛋白＜35 g/L、手术时间≥120 min均是改良乳腺癌根治术后切口感染的影响因素（P＜0.05）。两组术后30 d凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）升高,且未感染组高于感染组（P<0.05）,纤维蛋白原（FIB）降低,且未感染组低于感染组（P<0.05）。结论：改良乳腺癌根治术后切口感染较为常见,致病菌以革兰阴性菌为主,年龄、合并基础疾病、白蛋白、手术时间均是其影响因素,同时术后切口感染的发生可影响凝血纤溶功能的恢复,临床医生应积极采取措施预防术后切口感染的发生,从而保证手术治疗效果。     

新辅助化疗后腋窝病理完全缓解乳腺癌的预后分析

摘要 目的：研究乳腺癌患者新辅助化疗（NAC）后达到腋窝淋巴结病理完全缓解（pathologic complete response of axillary,apCR）的远期生存以及影响远期生存的相关因素分析。方法：回顾性分析哈尔滨医科大学附属肿瘤医院乳腺外科624例乳腺癌患者的住院资料,采用Kaplan-Meier生存分析以及COX回归分析的统计学分析方法,分析乳腺癌患者新辅助化疗后腋窝状态与无病生存（DFS）和总生存（OS）的关系及影响apCR预后的因素。结果：apCR与非apCR患者比较DFS（P=0.013）和OS（P=0.037）差异具有统计学意义,apCR患者的预后与年龄、肿瘤大小、肿瘤受体状态、HER-2、ki67状态、分子分型等因素无相关性。结论：与非apCR患者相比,乳腺癌患者新辅助化疗后apCR患者预后更好,但apCR患者预后良好的因素仍需进一步临床试验分析。     

Development of near-infrared imaging agents for detection of junction adhesion molecule-A protein

IntroductionProstate and breast cancer are the most prevalent primary malignant human tumors globally. Prostatectomy and breast conservative surgery remain the most common definitive treatment option for the >500,000 men and women newly diagnosed with localized prostate and breast cancer each year only in the US. Morphological examination is the mainstay of diagnosis but margin under-sampling of the excised cancer tissue may lead to local recurrence. In despite of the progress of non-invasive optical imaging, there is still a clinical need for targeted optical imaging probes that could rapidly and globally visualize cancerous tissues.MethodsElevated expression of junctional adhesion molecule-A (JAM-A) on tumor cells and its multiple pro-tumorigenic activity make the JAM-A a candidate for molecular imaging. Near-infrared imaging probe, which employed anti-JAM-A monoclonal antibody (mAb) phthalocyanine dye IR700 conjugates (JAM-A mAb/IR700), was synthesized and used to identify and visualize heterotopic human prostate and breast tumor mouse xenografts in vivo.ResultsThe intravenously injected JAM-A mAb/IR700 conjugates enabled the non-invasive detection of prostate and breast cancerous tissue by fluorescence imaging. A single dose of JAM-A mAb/IR700 reduced number of mitotic cancer cells in vivo, indicating theranostic ability of this imaging agent. The JAM-A mAb/IR700 conjugates allowed us to image a specific receptor expression in prostate and breast tumors without post-image processing.ConclusionThis agent demonstrates promise as a method to image the extent of prostate and breast cancer in vivo and could assist with real-time visualization of extracapsular extension of cancerous tissue.     

Understanding the function of the tumor microenvironment,and compounds from marine organisms for breast cancer therapy

The pathology and physiology of breast cancer(BC),including metastasis,and drug resistance,is driven by multiple signaling pathways in the tumor microenvironment(TME),which hamper antitumor immunity.Recently,long non-coding RNAs have been reported to mediate pathophysiological developments such as metastasis as well as immune suppression within the TME.Given the complex biology of BC,novel personalized therapeutic strategies that address its diverse pathophysiologies are needed to improve clinical outcomes.In this review,we describe the advances in the biology of breast neoplasia,including cellular and molecular biology,heterogeneity,and TME.We review the role of novel molecules such as long non-coding RNAs in the pathophysiology of BC.Finally,we provide an up-to-date overview of anticancer compounds extracted from marine microorganisms,crustaceans,and fishes and their synergistic effects in combination with other anticancer drugs.Marine compounds are a new discipline of research in BC and offer a wide range of anti-cancer effects that could be harnessed to target the various pathways involved in BC development,thus assisting current therapeutic regimens.     

Detection of Breast Cancer Based on Fuzzy Frequent Itemsets Mining

Background: Breast cancer, a type of malignant tumor, affects women more than men. About one third of women with breast cancer die of this disease. Hence, it is imperative to find a tool for the proper identification and early treatment of breast cancer. Unlike the conventional data mining algorithms, fuzzy logic based approaches help in the mining of association rules from quantitative transactions.Methods: In this study a novel fuzzy methodology IFFP (Improved Fuzzy Frequent Pattern Mining), based on a fuzzy association rule mining for biological knowledge extraction, is introduced to analyze the dataset in order to find the core factors that cause breast cancer. This method consists of two phases. During the first phase, fuzzy frequent itemsets are mined using the proposed algorithm IFFP. Fuzzy association rules are formed during the second phase, indicating whether a person belongs to benign or malignant. This algorithm is applied on WBCD (Wisconsin Breast Cancer Database) to detect the presence of breast cancer.Results: It is determined that the factor, Mitoses has low range of values on both malignant and benign and hence it does not contribute to the detection of breast cancer. On the other hand, the high range of Bare Nuclei shows more chances for the presence of breast cancer.Conclusion: Experimental evaluations on real datasets show that our proposed method outperforms recently proposed state-of-the-art algorithms in terms of runtime and memory usage.     

Impaired G2/M cell cycle arrest induces apoptosis in pyruvate carboxylase knockdown MDA-MB-231 cells

BackgroundPrevious studies showed that suppression of pyruvate carboxylase (PC) expression in highly invasive breast cancer cell line, MDA-MB-231 inhibits cell growth as a consequence of the impaired cellular biosynthesis. However, the precise cellular mechanism underlying this growth restriction is unknown.MethodsWe generated the PC knockdown (PCKD) MDA-MB-231 cells and assessed their phenotypic changes by fluorescence microscopy, proliferation, apoptotic, cell cycle assays and proteomics.ResultsPC knockdown MDA-MB-231 cells had a low percentage of cell viability in association with accumulation of abnormal cells with large or multi-nuclei. Flow cytometric analysis of annexin V-7-AAD positive cells showed that depletion of PC expression triggers apoptosis with the highest rate at day 4. The increased rate of apoptosis is consistent with increased cleavage of procaspase 3 and poly (ADP-Ribose) polymerase. Cell cycle analysis showed that the apoptotic cell death was associated with G2/M arrest, in parallel with marked reduction of cyclin B levels. Proteomic analysis of PCKD cells identified 9 proteins whose expression changes were correlated with the degree of apoptosis and G2/M cell cycle arrest in the PCKD cells. STITCH analysis indicated 3 of 9 candidate proteins, CCT3, CABIN1 and HECTD3, that form interactions with apoptotic and cell cycle signaling networks linking to PC via MgATP.ConclusionsSuppression of PC in MDA-MB-231 cells induces G2/M arrest, leading to apoptosis. Proteomic analysis supports the potential involvement of PC expression in the aberrant cell cycle and apoptosis, and identifies candidate proteins responsible for the PC-mediated cell cycle arrest and apoptosis in breast cancer cells.General significanceOur results highlight the possibility of the use of PC as an anti-cancer drug target.     

Expressions of E2 and E7-HPV16 proteins in pre-malignant and malignant lesions of the uterine cervix

Continuous production of the E7 protein from different types of high risk human papilloma virus (HPV) is required for progression of malignancy. We developed antibodies against HPV type 16 E7 and E2 proteins to evaluate their utility as markers for diagnosis during early stages of cervical cancer. Forty biopsies from uterine cervices were diagnosed as low grade intraepithelial lesion (LSIL), high grade intraepithelial lesion (HSIL), squamous carcinoma (SC), in situ adenocarcinoma (ISA) and invasive adenocarcinoma (AC), all of which were infected with HPV 16. Immunohistochemistry was used to investigate the expressions of E7 and E2 (both from HPV 16) and p16. P16 was expressed in eight of 12 LSILs, in all HSILs, in 16 of 18 SC and in all ACs. E2 was expressed in six of 12 LSILs. E7 was positive in eight of 12 LSILs and in all HSIL and carcinomas. The expressions of E2 and E7 of HPV16 related to p16 expression confirmed the value of the viral oncogenic proteins as complementary to histology and support the carcinogenic model of the uterine cervix, because HPVDNA integration into cellular DNA implies the destruction of the gene encoding E2, which suppresses the expression of the E6 and E7 oncoproteins. E2 from HPV16 could be marker for LSILs, while E7 could be a marker for progression of LSILs to HSILs in patients infected by HPV16, because viral typing has little positive predictive value.     

2- and 3-[(Aryl)(azolyl)methyl]indoles as Potential Non-steroidal Aromatase Inhibitors

The present study was designed to follow our pharmacomodulation work in the field of non-steroidal aromatase inhibitors. All target compounds 12a–h and 28a–h were tested in vitro for human placental aromatase inhibition, using testosterone or androstenedione as the substrate for the aromatase enzyme and the IC₅₀ and relative potency to aminoglutethimide data are included. A SAR study indicated that 3-[(4-fluorophenyl)(1H-imidazol-1-yl)methyl]-1-ethyl-2-methyl-1H-indole (28?g) was a highly potent and selective aromatase inhibitor with IC₅₀ value of 0.025?μM. 28?g was also a weak inhibitor of androstenedione synthesis.