ABSTRACT
This study started from the effect of baicalin (BC), the main active component of the labiaceae plant Scutellaria baicalensis, on collagen-induced arthritis (CIA) in rats, to explore the mechanism of glucose metabolism reprogramming in fibroblast like synoviocytes (FLSs), a key effector cell of synovial inflammation in rheumatoid arthritis (RA). First of all, CIA rats and tumor necrosis factor-α (TNF-α)-induced RASFs in vitro and in vivo models were established, the arthritis index (AI) score and histopathological changes of CIA rats after BC administration were observed, and the levels of inflammatory factors in serum and cell supernatant were quantified by ELISA, immunocytochemistry and Western blot were used to detect the expression of G-protein-coupled receptor 81 (GPR81) and pyruvate dehydrogenase kinase 1 (PDK1) proteins. In addition, the kit was used to measure the levels of key products and enzyme activities in glucose metabolism reprogramming. The results showed that BC (50, 100 and 200 mg·kg-1) could alleviate the symptoms of arthritis in CIA rats in a dose-dependent manner, inhibit synovial hyperplasia, alleviate the infiltration of inflammatory cells, down-regulate the levels of pro-inflammatory factors TNF-α and interleukin (IL)-1β, and up-regulate the levels of anti-inflammatory factor IL-10 in CIA rats. At the same time, the secretion levels of lactate, pyruvate, acetyl-CoA, citrate and the activity of lactate dehydrogenase B (LDH-B) were decreased, and the expressions of GRP81 and PDK1 were down-regulated, suggesting that BC mediated the reprogramming process of glucose metabolism. However, when GPR81 inhibitor 3-OBA inhibited lactate uptake, the activity of LDH-B was significantly increased, suggesting that BC inhibited the expression of PDK1, a key enzyme in the reprogramming metabolism from glycolysis to oxidative phosphorylation. All animal experiments in this study were conducted in accordance with the ethical standards of the Laboratory Animal Care Center of Anhui University of Chinese Medicine (approval number: AHUCM-rats-2021049). These studies revealed that baicalin mediated metabolic reprogramming of RASFs from glycolysis to oxidative phosphorylation by inhibiting PDK1 protein expression, and alleviated joint inflammation in CIA rats.
ABSTRACT
Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.
Subject(s)
Humans , Biomarkers, Tumor/genetics , Gene Amplification , In Situ Hybridization, Fluorescence , Liposarcoma/genetics , Proto-Oncogene Proteins c-mdm2/genetics , RNAABSTRACT
@#With the rise of tumor immunotherapy, small molecule modulators targeting the immune system have become a research hotspot. As well-developed and mature targets, immunity protein kinases have attracted more and more attention. Mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are located at the meeting-point of ERK and p38 MAPK signaling pathways, which can phosphorylate eukaryotic translation initiation factor 4E (eIF4E) at the conserved serine 209 exclusively and modulate the translation of mRNA. Herein we review the structural characteristics, mechanism, signaling transduction pathways and close relationship with tumors of MNKs.Meanwhile, the development process and clinical research progress of the MNKs inhibitors reported by different research institutions are introduced in detail.
ABSTRACT
The emergence of regular short repetitive palindromic sequence clusters (CRISPR) and CRISPR- associated proteins 9 (Cas9) gene editing technology has greatly promoted the wide application of genetically modified pigs. Efficient single guide RNA (sgRNA) is the key to the success of gene editing using CRISPR/Cas9 technology. For large animals with a long reproductive cycle, such as pigs, it is necessary to screen out efficient sgRNA
Subject(s)
Animals , CRISPR-Cas Systems/genetics , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Gene Editing , /genetics , SwineABSTRACT
Objective:To evaluate the efficacy and safety of Chinese medicinal formulae in the treatment of antimicrobial-resistant pneumonia. Method:Following article retrieval from eight databases and data extraction by two reviewers， the methodological quality of the included trials was assessed and the outcome indicators were subjected to Meta-analysis using RevMan 5.3. Result:A total of 24 randomized controlled trials （RCTs） were included， involving 1 818 cases. Meta-analysis showed that Chinese medicinal formulae combined with western routine intervention was superior to the western routine intervention in improving the overall response rate （ORR） ［relative risk （RR）=1.27， 95% confidence interval （CI） （1.21， 1.34）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M005.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M005c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］， the bacterial clearance rate ［RR=1.49，95% CI （1.33， 1.66）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M006.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M006c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］， and the clinical pulmonary infection score （CPIS） ［mean difference （MD）=-1.64， 95% CI （-1.87， -1.41）， <inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M007.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M007c.jpg"><?fx-imagestate width="2.28600001" height="2.62466669"?></graphic></alternatives></inline-formula><0.000 01］. There was no significant difference in the incidence of adverse reactions ［RR=0.72， 95% CI （0.48， 1.07），<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mtext> </mml:mtext><mml:mi>P</mml:mi></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M008.jpg"><?fx-imagestate width="3.04799986" height="2.62466669"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/27038DAF-2FF7-4d58-8001-0E6465A33408-M008c.jpg"><?fx-imagestate width="3.04799986" height="2.62466669"?></graphic></alternatives></inline-formula>=0.1］. The comparison with the western routine intervention also revealed that Chinese medicinal formulae better improved the ORR and CPIS. Conclusion:According to the current research results， the Chinese medicinal formulae alone or combined with western routine intervention yielded more favorable clinical outcomes than western routine intervention in the treatment of antimicrobial-resistant pneumonia， without increasing the incidence of adverse events. Due to limited quality and quantity of the included RCTs， more high-quality trials are required to verify the above conclusions.
ABSTRACT
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients' survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.
ABSTRACT
The discovery of penicillin has effectively controlled the infection caused by Gram-positive bacteria. Afterwards, the research and development of antibacterial drugs has entered the golden age, and made a great contribution to human health. However, in recent years, with the increasing use of antibiotics around the world, pathogenic bacteria drive gene mutation to obtain drug resistance to ensure its survival advantage, and promote the transfer of drug-resistant genes, resulting in a sharp increase of drug-resistant bacteria. In addition, the current development speed of new antibiotics is far slower than the growth and spread speed of drug-resistant bacteria, which makes the drug-resistant crisis more serious and becomes one of the biggest threats to the global community. Compared with the same type of bacterial infection, drug-resistant bacterial infection has the characteristics of complexity and refractoriness, which causes worse clinical outcome and higher risk of death in patients, and brings severe challenges to clinical work. If the trend of bacterial drug resistance is not controlled, the crisis of no drug available will come. Therefore, it is urgent to explore effective alternative means to fight against bacterial drug resistance and reduce the harm of drug-resistant bacterial infection. Traditional Chinese medicine（TCM） has unique advantages in the treatment of infectious diseases. Compared with modern antibacterial drugs, it has the characteristics of wide sources, rich active ingredients, and is not easy to produce drug resistance. It may be an important source for screening and developing new anti-infective drugs. Therefore, it is promising to develop and utilize TCM to solve the problem of drug-resistant bacteria infection. This paper will review relevant studies in recent years in terms of interfering with the biochemical metabolism of drug-resistant bacteria to directly inhibit or kill drug-resistant bacteria, improving bacterial drug resistance to indirectly inhibit bacteria and kill bacteria, and maintaining the balance of the body and regulating the treatment of drug-resistant bacteria infection as a whole, so as to provide references for guiding clinical medication and research and development of new traditional Chinese medicines.
ABSTRACT
OBJECTIVE: To investigate the inhibitiom effect of PTEN(gene of phosphate and tension homology deleted on chromsome ten) combined with adriamycin on proliferation, migration and invasion of non-Hodgkin lymphoma cell line Raji in vitro. METHODS: Cell proliferation was determined by MTT in Raji cells response to adriamycin with different concentrations. Transwell assay was performed to evaluate the effects of adriamycin and PTEN on migration and invasion of Raji cells. RT-qPCR was conducted to measure the expression of PTEN in Raji cells after adriamycin treatment. RESULTS: Adriamycin significantly inhibited the proliferation of Raji cells in a concentration dependent manner (r=-0.925, P<0.001). Adriamycin inhibited invasion and migration in Raji cells. Moreover, adriamycin promoted the expression of PTEN. Overexpression of PTEN markedly suppressed invasion and migration in Raji cells. The combination of adriamycin and PTEN strikingly decreased the proliferation, invasion and migration of Raji cells. CONCLUSION: Adriamycin and PTEN would inhibite the proliferation, invasion and migration of Raji cells. PTEN drastically enhances the inhibition of adriamycin on the proliferation, migration and invasion of Raji cells.
ABSTRACT
Diabetes mellitus complicated with cerebral infarction is the commonest and most serious vascular complication of diabetes mellitus. With a high disability and mortality rate, it seriously threatens human health. Because the pathogenesis is still unclear, more and more scholars have focused on the research of diabetic cerebral infarction at home and abroad. Traditional Chinese medicine(TCM) compounds have a remarkable curative effect in the treatment of diabetic cerebral infarction. Its mechanisms of action mainly include anti-hypertension, reduction of blood sugar and lipid, promotion of vascular regeneration and vascular endothelial function, anticoagulation, anti-thrombosis, improvement of nerve function defect, reduction of infarct volume, improvement of hemorheological, inhibition of inflammation and platelet aggregation, and promotion of collateral circulation. Through literature search, this paper summarizes the research progress of the mechanisms of TCM compounds in treating diabetic cerebral infarction in recent five years at home and abroad, in order to provide reference for clinical treatment.
ABSTRACT
Sphingosine 1-phosphate(SIP) is an important signal molecule produced by the metabolism of cell membrane sphingomyelin. SIP can be transported to the extracellular domain, and plays a role in activating a series of downstream signals, such as Ras/RafyERK, PI3K/AKT, by acting on SIP receptors. It can also act as a second messenger directly on intracellular targets such as HDAC, TRAF2. Its mediated signaling pathway plays a role in many physiological and pathological processes such as cell proliferation and migration, inflammatory cytokine infiltra tion, angiogenesis and autoimmunity. This article explores the role of SIP and its signaling pathways in inflammation-related diseases from the extracellular and intracellular roles of SIP, and reviews the research progress of SI P signaling pathway related drugs.
ABSTRACT
Objective@#To compare the performance of Miseq and Ion Torrent PGM platforms and library construction method for next-generation sequencing (NGS) technology for formalin-fixed and paraffin-embedded (FFPE) samples.@*Methods@#A total of 204 FFPE cancer samples including 100 non-small cell lung cancers at the First Affiliated Hospital of Zhejiang University, and 104 colorectal cancers at West China Hospital of Sichuan University were retrospectively selected from January 2013 to December 2016. By using the same samples, DNA was extracted, and the same amount of DNA was used for library construction with the same kit, and sequenced on Miseq and Ion Torrent PGM respectively, after passing the quality control. Any discordant mutations between two platforms were validated by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR) method and Sanger sequencing.@*Results@#A total of 204 FFPE samples were included and 197 samples were successfully analyzed by both platforms. The number of reads generated by the samples on Miseq platform sequencing was higher than PGM platform (median 391 634 vs. 298 030, P<0.01). Alignment with human reference genome showed that the mapping rate of Miseq platform was higher than PGM platform (median 100.0% vs. 99.7%, P<0.01). The median sequence depth of samples on Miseq was higher than PGM platform (median 853× vs. 698×, P<0.01). A total of 236 mutations were detected by two platforms, of which 221 were detected on both platforms, with a 93.6% concordance. Miseq platform detected 11 mutations not detected on PGM platform, while PGM platform detected 4 more mutations not detected on Miseq platform. With validation by ARMS-PCR and Sanger sequencing, Miseq platform was more reliable for low-frequency mutations. The main reasons for the discordant mutations between two platforms were that mutation frequency on undetected platform was lower than mutation reporting range (5%) and FFPE samples were stored for a long time.@*Conclusions@#Compared with PGM, Miseq platform shows higher sequencing quality in terms of the number of reads, alignment results and coverage depth, and the test results are more reliable. In clinical practice, the appropriate platform should be chosen based on sample size and actual throughput requirements to aid in the molecular characterization of tumors.
ABSTRACT
Objective@#To investigate whether small endoscopic biopsies of colorectal cancer were sufficient for quality and accurate mutational analysis by amplicon-based next-generation sequencing (NGS).@*Methods@#By using an amplicon-based targeted NGS panel for mutational detection on Illumina Miseq platform, a total of 109 formalin-fixed and paraffin-embedded (FFPE) endoscopic biopsies of colorectal cancer were retrospectively selected, based on specific histopathologic criteria, from January 2012 to June 2016 at West China Hospital of Sichuan University and Peking University Third Hospital. Twelve of these biopsies had corresponding FFPE surgical resection specimens. Quality control parameters of NGS testing were analyzed and NGS results were confirmed by other methods. Mutation calls of the 12 paired endoscopic biopsies and surgical resections were compared.@*Results@#Of the endoscopic biopsy specimens, 97.2% (106/109) had sufficient DNA and qualified sequencing library. NGS generated excellent sequencing data, with a median of 848× for median read depth and 95.7% for uniformity. The success rate of NGS was 95.4% (104/109). Conventional methods confirmed the results of NGS for KRAS and BRAF, and the concordance rate was 100.0%. The clinically actionable mutations detected in the 12 paired endoscopic biopsies and surgical resections were concordant.@*Conclusion@#FFPE endoscopic biopsies of colorectal cancer is suitable for targeted NGS, providing quality sequencing data and accurate mutational information to guide targeted therapy.
ABSTRACT
BACKGROUND@#Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice.@*METHODS@#The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China.@*RESULTS@#Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation.@*CONCLUSIONS@#A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , China , Epidemiology , Early Detection of Cancer , Lung Neoplasms , Diagnostic Imaging , Epidemiology , Mass Screening , Patient Selection , Practice Guidelines as Topic , Radiation Dosage , Risk , Rural Population , Tomography, Spiral ComputedABSTRACT
Objective@#To investigate the response to neoadjuvant chemotherapy (NAC) among different molecular subtypes of breast cancers using molecular classification with Ki-67 (ER+ PR+ HER2+ Ki-67) or without Ki-67 (ER+ PR+ HER2).@*Methods@#One hundred and twenty-seven cases of invasive breast cancer confirmed by core needle biopsy before NAC were collected from January 2007 to December 2009 and diagnosed at West China Hospital, Sichuan University. The cases were classified into different molecular subtypes using molecular classifications with or without Ki-67. Their clinical and pathological response to NAC was evaluated and compared.@*Results@#The different subtypes using both molecular classifications showed significant difference in clinical response(with Ki-67: χ2=22.40, P<0.01; without Ki-67: χ2=9.202, P=0.027)but not pathological(P>0.05) response to NAC. By multivariate analysis, Ki-67 was predictive for a clinical complete response (P=0.041) and clinical overall response (P<0.01); also Ki-67 was the only clinicopathological factor predictive of pathological response(P=0.041).@*Conclusion@#The molecular classification with Ki-67 is better to predict breast cancers responsiveness to NAC than the molecular classification without Ki-67.
ABSTRACT
PURPOSE: Metastasis and local recurrence are the primary causes of treatment failure and patient death in breast cancer. The aim of this study was to validate a metastasis- and local recurrenceassociated biomarker for prognostic evaluation and planning treatment strategies. METHODS: Formalin-fixed, paraffin-embedded tissues from a cohort of 312 patients (all stage II and III) were used. The prevalence of CD49f⁺ cells in the patients' tumors was analyzed and correlated with clinical characteristics to determine its prognostic and clinical implications. RESULTS: CD49f⁺ tumor cells were found in a minority of tumors, with 62.8% of the samples showing not a single cell of this subtype. In the clinical characteristics analysis, which were performed with t-tests, CD49f⁺ tumors were not associated with age, tumor size, World Health Organization grade, nodal status, human epidermal growth factor receptor 2 status, progesterone receptor status, or estrogen receptor status, although they were significantly associated with disease recurrence (distant metastasis or/and local recurrence). Univariate survival analysis using the Kaplan-Meier method showed that CD49f⁺ tumors were associated with markedly decreased disease-free survival (DFS); the same result was found using multivariate Cox analysis, even when only chemotherapy-treated patients were analyzed. CONCLUSION: Our results indicated that breast tumors with CD49f⁺ cancer cells are associated with an increased risk for disease recurrence after initial surgery with poor clinical outcomes (decreased DFS). Therefore, as it requires testing for only one additional protein, adding CD49f testing to conventional surgical pathology is a strategy that has great potential for prognostic and treatment-guidance purposes.
Subject(s)
Humans , Breast Neoplasms , Breast , Cohort Studies , Disease-Free Survival , Estrogens , Integrin alpha6 , Methods , Neoplasm Metastasis , Neoplastic Stem Cells , Pathology, Surgical , Prevalence , Prognosis , ErbB Receptors , Receptors, Progesterone , Recurrence , Treatment Failure , World Health OrganizationABSTRACT
In order to enhance the anticoagulant properties of decellularized biological materials as scaffolds for tissue engineering research via heparinized process, the decellularized porcine liver scaffolds were respectively immobilized with heparin through layer-by-layer self-assembly technique (LBL), multi-point attachment (MPA) or end-point attachment (EPA). The effects of heparinization and anticoagulant ability were tested. The results showed that the three different scaffolds had different contents of heparin. All the three kinds of heparinized scaffolds gained better performance of anticoagulant than that of the control scaffold. The thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) of EPA scaffold group were longest in all the groups, and all the three times exceeded the measurement limit of the instrument. In addition, EPA scaffolds group showed the shortest prepared time, the slowest speed for heparin release and the longest recalcification time among all the groups. The decellularized biological materials for tissue engineering acquire the best effect of anticoagulant ability in vitro via EPA heparinized technique.
Subject(s)
Animals , Anticoagulants , Chemistry , Biocompatible Materials , Chemistry , Heparin , Chemistry , Liver , Swine , Tissue Engineering , Tissue ScaffoldsABSTRACT
Pathology rotation is an important part in resident standardization training. Impor-tance should be attached to the residents' learning during the standardization training in Pathology De-partment, such as standardizing training and strict departmental rotation examination, developing the residents' thinking ability of the relationship between clinical and pathology with the main line of spe-cialty pathology learning , and improving clinical research capacity through pathology technical methods and principles, and training pathology literacy from pathology requisition filled to interpreta-tion of the pathology report, which will also help to improve the medical service quality of the hospital.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the standards of HER2 immunohistochemistry (IHC) interpretation in invasive micropapillary carcinoma of the breast (IMPC).</p><p><b>METHODS</b>HER2 expression in 60 cases of IMPC was evaluated by IHC and fluorescence in situ hybridization (FISH) using TMA-based techniques. The characteristics between cases with HER2 IHC and HER2 gene amplification results were compared.</p><p><b>RESULTS</b>Using 2007 American Society of Clinical Oncology/College of American Pathologist (ASCO/CAP) criteria, among the 52 cases that were successfully stained by IHC, 40 were HER2 IHC negative and 12 were equivocal (2+). Fifteen cases of HER2 IHC 0 were negative for amplification by FISH. Twenty-five cases with IHC 1+ were tested by FISH; and of these, one showed HER2 amplification, 2 were equivocal, and the others were not amplified. All cases of IHC 2+ showed HER2 amplification by FISH. IHC staining of HER2 was located at cell-cell membrane or basolateral membrane of micropapillary structure, but not in the cytoplasmic membrane facing the stroma in all 13 cases which were HER2 amplified, including 12 showing very strong staining and one showing moderate staining. Among the 37 non amplified HER2 cases, 22 showed IHC staining at cell-cell membrane or basolateral membrane (including 15 weak staining and 7 moderate staining).</p><p><b>CONCLUSIONS</b>HER2 IHC detection in IMPC is characterized by staining at cell-cell membrane or basolateral membrane of the micropapillary structure, and absence of staining in the cytoplasmic membrane. It is suggested that interpretation of HER2 IHC staining should be based on membrane staining intensity, but not the completeness of the membrane staining in IMPC. It is suggested to determine the HER2 gene amplification status by using FISH when IHC staining shows moderate or strong intensity.</p>
Subject(s)
Female , Humans , Adenocarcinoma, Papillary , Chemistry , Pathology , Breast Neoplasms , Chemistry , Pathology , Immunohistochemistry , In Situ Hybridization, Fluorescence , Receptor, ErbB-2ABSTRACT
PURPOSE: It is well established that breast cancer stem cells (BCSCs) play an essential role in tumor invasion for both local and distant metastasis. The aim of this study was to establish whether BCSCs could act as a prognostic and clinical marker. METHODS: We analyzed tumor tissues from 161 breast cancer patients. Dual immunohistochemistry and immunofluorescence were performed on all the slides, and we analyzed the relationship between EpCAM-/CD49f+ tumor cells and key clinical and prognostic factors. RESULTS: Univariate survival analysis using the Kaplan-Meier method showed that the presence of EpCAM-/CD49f+ tumor cells in breast cancer was significantly associated with shorter disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that the presence of EpCAM-/CD49f+ cells was associated with shorter DFS (p=0.010; hazard ratio [HR], 2.070) and OS (p=0.002; HR, 3.235). Tumors containing EpCAM-/CD49f+ cells were also more likely to metastasize after initial surgery (p=0.048). CONCLUSION: Our study suggests that breast tumors containing EpCAM-/CD49f+ cells are more likely to undergo distant metastasis after initial surgery and are associated with a shorter DFS and OS.
Subject(s)
Humans , Biomarkers , Breast Neoplasms , Breast , Disease-Free Survival , Fluorescent Antibody Technique , Immunohistochemistry , Multivariate Analysis , Neoplasm Metastasis , Neoplastic Stem Cells , Prognosis , Stem CellsABSTRACT
<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunophenotype and prognosis of matrix-producing metaplastic carcinoma (MPC).</p><p><b>METHODS</b>Sixteen cases of MPC diagnosed between 2002 and 2012 in West China Hospital were identified. The clinicopathologic features were analyzed. Immunohistochemistry for E-cadherin, S-100 protein, CK5/6, HCK, PCK, CK7, CK8, p63, SMA, EMA, CD99, MSA, CK14, EGFR, ER, PR, HER2 and Ki-67 was performed with EnVision method. The clinical outcome was evaluated and compared to matched controls of invasive ductal carcinoma.</p><p><b>RESULTS</b>All patients were women and ranged in age from 29 to 69 years (median age 48 years). The median size of primary tumor was 4 cm. Most of the tumors were well-circumscribed with expansile and multinodular appearance. Histology showed invasive carcinoma with a direct transition from carcinoma to cartilaginous/chondromyxoid matrix without an intervening spindle cell component. Tumor distribution was either nodular or diffuse. The matrix component accounted for 10%-80% of the tumor volume. All the tumors were strongly positive for S-100 protein and basal-like cytokeratin with triple negative phenotype (ER, PR and HER2 negative). Alcian blue stain was positive for the cartilaginous/chondromyxoid matrix. Compared with invasive ductal carcinoma, patients with MPC had increased locoregional recurrence (P = 0.010), increased distant recurrence (P = 0.011) and shorter disease-free survival (P = 0.017).</p><p><b>CONCLUSIONS</b>MPC is a rare variant of mammary metaplastic carcinoma with unique characteristics of morphology and immunohistochemical staining pattern. This subtype seems to have aggressive biologic behavior.</p>