Publications by authors named "Wei Zhimin"

24 Publications

  • Page 1 of 1

SH3BGRL3, transcribed by STAT3, facilitates glioblastoma tumorigenesis by activating STAT3 signaling.

Biochem Biophys Res Commun 2021 06 8;556:114-120. Epub 2021 Apr 8.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma (GBM) is the most aggressive tumors of the central nervous system. Here, we report that SH3 binding glutamic acid-rich protein like 3 (SH3BGRL3) was extremely highly expressed in GBM and glioma stem cells. SH3BGRL3 high expression associates with worse survival of GBM patients. Functionally, Targeting SH3BGRL3 obviously impairs GSCs self-renewal in vitro. Most importantly, we first report that SH3BGRL3 is a direct transcriptional target gene of signal transducer and activator of transcription 3 (STAT3) and thereby activating STAT3 signaling in turn. Additionally, forced expression of the constitutively activated STAT3 (STAT3-C) rescued GSCs self-renewal inhibited by SH3BGRL3 silencing. Collectively, we first identified a critical positive feedback loop between SH3BGRL3 and STAT3, which facilitates the tumorigenic potential of GBM.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.165DOI Listing
June 2021

SH3BGRL2 functions as a crucial tumor suppressor in glioblastoma tumorigenesis.

Biochem Biophys Res Commun 2021 04 19;547:148-154. Epub 2021 Feb 19.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma is the most common and severe primary intrinsic tumor of the central nervous system. Glioblastoma harbors glioma stem cells (GSCs) as it not only possesses self-renewal and differentiation properties but also accounts for significant chemotherapy resistance and recurrence. Thus, targeting GSCs may be essential in overcoming the resistance and recurrence thereby improving GBM treatment. However, the underlying mechanism to sustain GSCs remains largely unknown. Here, we report that SH3 domain binding glutamate-rich protein like 2 (SH3BGRL2) is weakly expressed in glioblastoma multiforme (GBM) and isocitrate dehydrogenase1 (IDH1) wildtype GBM and correlated with glioma patients' poor prognosis. Moreover, ectopic expression of SH3BGRL2 significantly inhibited GBM cell growth, migration, and GSCs self-renewal in vitro as well as tumor growth in vivo. Additionally, we found that SH3BGRL2 suppressed SOX2 and CD133 expression, which are key regulators involved in GSCs self-renewal. Collectively, our findings shed additional light on SH3BGRL2 has potential to serve as a biomarker and a potent therapeutic target for patients with glioma.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.035DOI Listing
April 2021

SH3GL3 acts as a novel tumor suppressor in glioblastoma tumorigenesis by inhibiting STAT3 signaling.

Biochem Biophys Res Commun 2021 03 29;544:73-80. Epub 2021 Jan 29.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. Electronic address:

Glioblastoma (GBM) is the most severe malignant tumors of the central nervous system. Glioblastoma stem cells (GSCs) are considered to account for tumor initiation, therapeutic resistance, and tumor relapse. Yet the underlying mechanisms of GSC stemness maintenance remain largely unknown. Abnormal activation of STAT3 signaling is required for GBM tumorigenesis and GSC self-renewal. In this study, we provide evidence that SH3GL3 was weakly expressed in GBM and its high expression correlated with a favorable prognosis for GBM patients. Ectopic of SH3GL3 expression considerably inhibits GBM cell malignant behaviors, including GBM cell proliferation, migration as well as GSCs self-renewal ability. Mechanistically, we first found that SH3GL3 interacts with STAT3, which thereby inhibiting STAT3 nuclear localization. Overexpression of constitutively activated (STAT3-C) restored the growth, migration and self-renewal ability impaired by overexpression of SH3GL3. Together, our work shed insight on a critical regulatory mechanism mediated by SH3GL3 to decrease the stem cell-like property and tumorigenic potential.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.040DOI Listing
March 2021

RGD-modified injectable hydrogel maintains islet beta-cell survival and function.

J Appl Biomater Funct Mater 2020 Jan-Dec;18:2280800020963473

Key laboratory of functional and clinical translational medicine, Fujian province university, Xiamen Medical College, Xiamen city, China.

Objective: A potential solution for islet transplantation and drug discovery vis-à-vis treating diabetes is the production of functional islets in a three-dimensional extracellular matrix. Although several scaffold materials have been reported as viable candidates, a clinically applicable one that is injectable and can maintain long-term functionality and survival of islet pancreatic beta-cells (β-cells) is far from being established.

Results: In the current study, we evaluated a ready-to-use and injectable hydrogel's impact on β-cells' function and viability, both in vitro and in vivo. We found that β-cells in high concentration with hydrogels functionalized via Arg-Gly-Asp (RGD) demonstrated better viability and insulin secretory capacity in vitro. Moreover, it is a biocompatible hydrogel that can maintain β-cell proliferation and vascularization without stimulating inflammation after subcutaneous injection. Meanwhile, modifying the hydrogel with RGD can maintain β-cells' secretion of insulin, regulating the blood glucose levels of mice with streptozotocin-induced diabetes.

Conclusions: Thus, these preliminary results indicate that this RGD-modified hydrogel is a potential extracellular matrix for islet transplantation at extrahepatic sites, and they also provide a reference for future tissue engineering study.
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http://dx.doi.org/10.1177/2280800020963473DOI Listing
December 2020

HER2 immunohistochemistry staining positivity is strongly predictive of tumor response to neoadjuvant chemotherapy in HER2 positive breast cancer.

Pathol Res Pract 2020 Nov 10;216(11):153155. Epub 2020 Aug 10.

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United States. Electronic address:

Background: The current recommendation is to reflex test HER2 immunohistochemistry (IHC) equivocal breast cancer cases with fluorescence in situ hybridization (FISH) analysis. Either IHC 3+ or FISH positive cancers are considered HER2 positive (HER2+) and treated with HER2 targeted therapy. This study examined the predictive value of HER IHC or FISH positivity in tumor response to HER2 targeted therapy.

Methods: Biopsies of 76 HER2+ breast cancer cases were evaluated. All patients were treated with neoadjuvant HER2 targeted therapy and chemotherapy. Tumor response was evaluated on the excisional specimens. Cancers with complete pathologic response (pCR) or MD Anderson residual cancer burden-I (RCB-I) were classified as responders and cancers with RCB-II/III as non-responders. Clinicopathologic parameters were correlated with response.

Results: In univariate analysis, small tumor size, low nuclear grade, high Ki67, HER2 IHC 3+, homogenous strong HER2 IHC staining, high HER2/CEP17 ratio, and high HER2 copy number were significantly associated with pCR/RCB-I. In multivariate analysis, homogenous strong HER2 IHC staining pattern was significantly associated with pCR/RCB-I. The receiver operating characteristics (ROC) model showed either high HER2/CEP17 ratio or HER2 copy number individually was predictive of tumor response.

Conclusion: HER2 IHC staining pattern is significantly associated with tumor response to neoadjuvant chemotherapy, reiterating the importance of HER2 IHC evaluation. The ROC model shows either high HER2/CEP17 ratio or high HER2 copy number individually is predictive of tumor response to neoadjuvant HER2 targeted therapy in HER2+ breast cancer.
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http://dx.doi.org/10.1016/j.prp.2020.153155DOI Listing
November 2020

Evaluation of PD-L1, tumor-infiltrating lymphocytes, and CD8+ and FOXP3+ immune cells in HER2-positive breast cancer treated with neoadjuvant therapies.

Breast Cancer Res Treat 2020 Oct 26;183(3):599-606. Epub 2020 Jul 26.

Department of Pathology and Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, USA.

Background: The tumor immune microenvironment plays a critical role in the prognosis and outcome of breast cancers. This study examined the role of tumor-infiltrating lymphocytes (TILs), CD8+, FOXP3+ lymphocytes, PD-L1 expression, and other clinicopathological parameters in HER2+ breast cancer and correlate with tumor response to neoadjuvant therapy.

Methods: We included 173 HER2+ patients treated with neoadjuvant HER2-targeted chemotherapy regimens from 2010 to 2016. 67 cases had biopsy blocks to evaluate TIL, CD8, FOXP3, and PD-L1 immunohistochemistry staining. Tumors were classified as pCR vs non-pCR group. Clinicopathological parameters, TIL, CD8+ and FOXP3+ cell count, and PD-L1 expression were correlated with pCR rate.

Results: Univariate analyses showed that pCR rate was significantly correlated with low PR, low ER, high Ki-67, high FOXP3, HER2 IHC3+ , high HER2 ratio and copy number. By multivariate analysis, Ki-67 was the only variable significantly correlated with pCR. PD-L1 expression was detected in 9.2% cases. TIL hotspot has a non-significant correlation with pCR rate (p = 0.096).

Conclusions: High Ki-67 is a strong predictor for pCR in HER2+ breast cancer. TIL and FOXP3 T cells may play a role in tumor response in HER2+ cancer. PD-L1 is expressed in a subset of HER2+ breast cancer, supporting a role of immunotherapy in treating a subset of HER2+ breast cancers. The role of PD-L1, TIL, and other markers of immunogenicity as predictors of response to neoadjuvant chemotherapy in HER2+ breast cancer should be further evaluated.
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http://dx.doi.org/10.1007/s10549-020-05819-8DOI Listing
October 2020

Inflammatory Demyelinating Pseudotumor With Liver Dysfunction: IgG4 Related Disease With Primary Biliary Cholangitis.

Am J Med Sci 2020 10 28;360(4):410-413. Epub 2020 May 28.

Department of Rheumatology, The Affiliation Hospital of Qingdao University, Qingdao City, Shandong Province, China. Electronic address:

Immunoglobulin G4 related disease (IgG4-RD) is a recently recognized immune-mediated disease which is far from understanding. A case of inflammatory demyelinating pseudotumor had been confirmed as IgG4-RD according to pathology features and clinical context. Combined with liver dysfunction, IgG4 related sclerotic cholangitis was suspected. However, primary biliary cholangitis was finally diagnosed by immune marks and histopathological findings. This is the first report in which mass lesions in the brain parenchyma were caused by IgG4-RD while liver dysfunction was due to primary biliary cholangitis. The clinical features of IgG4-RD are miscellaneous, and the accumulation of case reports might enrich clinicians experience and broaden their horizons about this condition.
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http://dx.doi.org/10.1016/j.amjms.2020.05.031DOI Listing
October 2020

Pyrrolo [3,4-]-quinolin-9-amine compound FZU-0038-056 suppresses triple-negative breast cancer partially through inhibiting the expression of Bcl-2.

Aging (Albany NY) 2020 05 23;12(10):9621-9632. Epub 2020 May 23.

Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China.

Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes of breast cancer; however, it lacks effective targeted therapies clinically. In this study, we found FZU-0038-056, a novel compound derived from last-stage functionalization of tetrahydro-β-carboline scaffold, showed the most potent anti-cancer activity against TNBC cells among the 42 synthesized derivatives. We found FZU-0038-056 significantly induces apoptosis in HCC1806 and HCC1937 TNBC cells. FZU-0038-056 reduces the expression levels of several anti-apoptosis proteins, including Bcl-2, Mcl-1 and XIAP. Furthermore, we found FZU-0038-056 induces apoptosis partially through inhibiting the expression of Bcl-2. Finally, we found FZU-0038-056 significantly suppresses HCC1806 xenograft tumor growth in nude mice without affecting their body weight. Therefore, FZU-0038-056 has the potential to be a new anticancer agent for treating human TNBC.
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http://dx.doi.org/10.18632/aging.103232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288966PMC
May 2020

Suppression of KIF3A inhibits triple negative breast cancer growth and metastasis by repressing Rb-E2F signaling and epithelial-mesenchymal transition.

Cancer Sci 2020 Apr 28;111(4):1422-1434. Epub 2020 Feb 28.

Department of Pathology, School of Basic Medicine, Qingdao University, Qingdao, China.

Triple negative breast cancer (TNBC) displays higher heterogeneity, stronger invasiveness, higher risk of metastasis and poorer prognosis compared with major breast cancer subtypes. KIF3A, a member of the kinesin family of motor proteins, serves as a microtubule-directed motor subunit and has been found to regulate early development, ciliogenesis and tumorigenesis. To explore the expression, regulation and mechanism of KIF3A in TNBC, 3 TNBC cell lines, 98 cases of primary TNBC and paired adjacent tissues were examined. Immunohistochemistry, real-time PCR, western blot, flow cytometry, short hairpin RNA (shRNA) interference, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation techniques, transwell assays, scratch tests, and xenograft mice models were used. We found that KIF3A was overexpressed in TNBC and such high KIF3A expression was also associated with tumor recurrence and lymph node metastasis. Silencing of KIF3A suppressed TNBC cell proliferation by repressing the Rb-E2F signaling pathway and inhibited migration and invasion by repressing epithelial-mesenchymal transition. The tumor size was smaller and the number of lung metastatic nodules was lower in KIF3A depletion MDA-MB-231 cell xenograft mice than in the negative control group. In addition, KIF3A overexpression correlated with chemoresistance. These results suggested that high expression of KIF3A in TNBC was associated with the tumor progression and metastasis.
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http://dx.doi.org/10.1111/cas.14324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156822PMC
April 2020

PTEN Inhibits Inflammatory Bone Loss in Ligature-Induced Periodontitis via IL1 and TNF-.

Biomed Res Int 2019 30;2019:6712591. Epub 2019 Nov 30.

Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

Phosphatase and tensin homolog (PTEN) is a critical regulator of tumorigenesis and bone remodeling, which is also found expressed in the periodontal tissues. Periodontitis is one of the most common oral diseases and associated with alveolar bone resorption and tooth loosening in adults. However, the functional relevance of PTEN in periodontitis remains unclear. Here, we report that PTEN plays an essential role in periodontitis. The in vivo results of our study showed a significant decrease of PTEN in the ligature-induced mouse periodontitis model. The function of PTEN in the macrophages was shown to be associated with inflammatory factors interleukin 1 (IL1) and tumor necrosis factor (TNF-) by using overexpression and silence methods. Further mechanistic studies indicated lack of PTEN-activated IL1 and TNF-, which increased the number of osteoclasts and led to alveolar bone erosion and loss. Moreover, PTEN nanoparticles could directly inhibit the inflammatory process and bone erosion, suggesting a controlling role of PTEN during bone remodeling. All these data identified the novel function of PTEN as a key factor in periodontitis and bone remodeling.
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http://dx.doi.org/10.1155/2019/6712591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914910PMC
May 2020

Clinicopathologic Factors Associated With Response to Neoadjuvant Anti-HER2-Directed Chemotherapy in HER2-Positive Breast Cancer.

Clin Breast Cancer 2020 02 18;20(1):19-24. Epub 2019 Sep 18.

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA. Electronic address:

Background: HER2-targeted neoadjuvant therapy has high efficacy in treating HER2-positive breast cancer. Response to neoadjuvant therapy helps clinicians make treatment decisions and make estimates about prognosis. This study examined clinicopathologic features to determine which may be most predictive of response to neoadjuvant therapy in HER2 breast cancer.

Patients And Methods: Patients with HER2 breast cancer (n = 173) who had an initial biopsy performed between 2010 and 2016 were identified at our institution. Tumor response was evaluated on excisional specimens using the MD Anderson residual cancer burden (RCB) classification. Tumors with pathologic complete response (defined as no residual invasive carcinoma in the breast and lymph nodes) and RCB-I were classified as having response and tumors with RCB-II and -III as having no response. Patient age, tumor size, nuclear grade (1/2 vs. 3), mitosis, Nottingham grade, HER2 immunohistochemistry (1/2+ vs. 3+), HER2/CEP17 (chromosome enumeration probe 17) ratio, HER2 copy number, estrogen receptor, progesterone receptor, Ki-67, and tumor-infiltrating lymphocytes (TIL) were evaluated and correlated with response. TILs were evaluated for an average and also for the hot spot/total tumor stromal ratio.

Results: Small tumor size, low estrogen receptor and progesterone receptor expression, HER2 immunohistochemistry 3+, high Ki-67, high HER2/CEP17 ratio, and high HER2 copy number were significantly associated with response (all P < .05). TIL hot spot was associated with RCB in univariate (P < .05) but not multivariate analyses.

Conclusion: Clinicopathologic features may help predict HER2 breast cancer response to neoadjuvant therapy. Larger studies would be useful to confirm these associations, which may have relevance to clinical practice.
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http://dx.doi.org/10.1016/j.clbc.2019.09.003DOI Listing
February 2020

Regulation of endogenous phytohormones alters the fluoranthene content in Arabidopsis thaliana.

Sci Total Environ 2019 Oct 24;688:935-943. Epub 2019 Jun 24.

College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095, People's Republic of China; Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, Nanjing 210014, People's Republic of China. Electronic address:

Phytohormones are crucial endogenous modulators that regulate and integrate plant growth and responses to various environmental pollutants, including the uptake of pollutants into the plant. However, possible links between endogenous phytohormone pathways and pollutant accumulation are unclear. Here we describe the fluoranthene uptake, plant growth, and superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione S-transferase (GST) activities in relation to different endogenous phytohormones and different levels in Arabidopsis thaliana. Three phytohormone inhibitors-N-1-naphthyl-phthalamic acid (NPA), daminozide (DZ), and silver nitrate (SN)-were used to regulate endogenous auxin, gibberellin, and ethylene levels, respectively. Fluoranthene inhibited plant growth and root proliferation while increasing GST and SOD activity. The three inhibitors reduced fluoranthene levels in Arabidopsis by either affecting plant growth or modulating antioxidant enzyme activity. NPA reduced plant growth and increased CAT activity. SN promoted plant growth and increased POD and CAT activity, whereas DZ increased POD activity.
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http://dx.doi.org/10.1016/j.scitotenv.2019.06.384DOI Listing
October 2019

The revised complete mitogenome sequence of the tree frog (Anura, Rhacophoridae) by next-generation sequencing and phylogenetic analysis.

PeerJ 2019 1;7:e7415. Epub 2019 Aug 1.

College of Animal Sciences and Technology, Sichuan Agricultural University, Chengdu, Sichuan Province, China.

The mitochondrial genome (mitogenome) sequence of the tree frog (16,473 bp) was previously reported as having the unusual characteristic of lacking the ND5 gene. In this study, a new mitogenome of (19,952 bp) was resequenced using the next-generation sequencing (NGS) and standard Sanger sequencing technologies. It was discovered that the ND5 gene was not lost but translocated to the control region (CR) from its canonical location between the ND4 and ND6 genes. In addition, a duplicated control region was found in the new mitogenome of this species. Conservative region identification of the ND5 gene and phylogenetic analysis confirmed that the ND5 gene was located between two control regions. The phylogenetic relationship among 20 related species of anura revealed a rearrangement of the ND5 gene during the evolutionary process. These results also highlighted the advantages of next-generation sequencing. It will not only decrease the time and cost of sequencing, but also will eliminate the errors in published mitogenome databases.
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http://dx.doi.org/10.7717/peerj.7415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679912PMC
August 2019

The complete mitogenome of the granular torrent frog, (Anura: Ranidae).

Mitochondrial DNA B Resour 2019 Jul 19;4(2):2643-2644. Epub 2019 Jul 19.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.

We obtained the complete mitochondrial genome of , which was 17,785 bp in length and it contained the 37 typical mitochondrial genes: 2 ribosomal RNAs, 22 transfer RNAs (tRNAs), 13 protein-coding genes (PCGs), and 1 control region (CR). The hotspot of gene arrangement was ranged as 'W-gap-O-gap-A-N-gap-C-Y' which consisted with most published mitogenomes. Our phylogenetic results suggested the gene arrangement of 'WANCY' region can facilitate to distinguish the species as an efficient genetic marker.
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http://dx.doi.org/10.1080/23802359.2019.1643800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706465PMC
July 2019

The complete mitogenome of the splendid japalure (Squamata, Agamidae).

Mitochondrial DNA B Resour 2019 Jul 19;4(2):2641-2642. Epub 2019 Jul 19.

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China.

The complete mitogenome of (16,673 bp in length) is determined and analyzed in this study. It contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and one non-coding regions. All the genes in are distributed on the H-strand, except for the gene and seven tRNA genes which are encoded on the L-strand. The phylogenetic tree suggests that and formed a sister group and reveals the order ((((, ), ((, ), ))), ) with substantial support for the monophyly.
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http://dx.doi.org/10.1080/23802359.2019.1643797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706609PMC
July 2019

The Complete Mitochondrial Genome of and Molecular Phylogenetic Analysis.

Genes (Basel) 2019 06 27;10(7). Epub 2019 Jun 27.

College of Animal Sciences and Technology, Sichuan Agricultural University, Chengdu 611130, Sichuan, China.

is the only living representative species of Platysternidae and only three subspecies remain: , , and . However, previous reports implied that . . has distinct morphological and molecular features. The characterization of the mitogenome has been accepted as an efficient means of phylogenetic and evolutionary analysis. Hence, this study first determined the complete mitogenome of with the aim to identify the structure and variability of the mitogenome through comparative analysis. Furthermore, the phylogenetic relationship of the three subspecies was tested. Based on different tRNA gene loss and degeneration of these three subspecies, their rearrangement pathways have been inferred. Phylogenetic analysis showed that is a sister group to ( and ). Furthermore, the divergence time estimation of these three subspecies coincided with the uplift of the Tibetan Plateau. This study shows that the genetic distances between . . and the other two subspecies are comparable to interspecific genetic distances, for example within . In general, this study provides new and meaningful insights into the evolution of the three Platysternidae subspecies.
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http://dx.doi.org/10.3390/genes10070487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678547PMC
June 2019

Impact of Lymphocyte Subsets on Chemotherapy Efficacy and Long-term Survival of Patients with Advanced Non-small-cell Lung Cancer.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2017 Jun;39(3):371-376

Objective To analyze the impact of lymphocyte subsets on chemotherapy efficacy and long-term survival of patients with advanced non-small cell lung cancer(NSCLC).Methods Totally 125 NSCLC patients who had received first-line chemotherapy including paclitaxel and pemetrexed with/without platinum were enrolled in this study.Lymphocytes from peripheral blood were collected before and after two cycles of first-line chemotherapy.Flow cytometry was performed to determine the expressions of 21 fluorescence-labeled lymphocyte subsets.Based on the imaging findings,chemotherapy efficacy was evaluated,and impact of the lymphocyte subsets on progression-free survival(PFS)and overall survival(OS)were analyzed.Results The baseline peripheral lymphocyte subsets showed no significant difference among groups receiving different treatment protocols(all P>0.05).After 2 cycles of chemotherapy,the percentage of CD4CD29lymphocytes was(16.87±5.28)% in progressive disease group,which was significantly lower than those in complete remission+partial remission group [(22.42±7.88)%,P=0.013] and stable disease group [(21.88±6.81)%,P=0.009].The median PFS was 7.07 months and median OS was 23.00 months.Cox multivariable regression analysis showed that the percentages of HLA-DR(HR:1.03,95%CI:1.01-1.05,P<0.001) and CDHLA-DRlymphocytes (HR:1.05,95%CI:1.01-1.08,P<0.001)were positively correlated with OS.Conclusions The rise of CD4CD29T lymphocytes in patients after chemotherapy indicates good chemotherapy efficacy.Higher percentage of HLA-DRand CD3HLA-DRlymphocytes in peripheral blood before chemotherapy predicts favorable prognosis.
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http://dx.doi.org/10.3881/j.issn.1000-503X.2017.03.012DOI Listing
June 2017

Non-calcified ductal carcinoma in situ of the breast: comparison of diagnostic accuracy of digital breast tomosynthesis, digital mammography, and ultrasonography.

Breast Cancer 2017 Jul 11;24(4):562-570. Epub 2016 Nov 11.

The Department of Breast Imaging, The Affiliated Hospital of Qingdao University, No.16, Jiangsu Road, Qingdao, 266003, Shandong province, China.

Background: To retrospectively compare the diagnostic accuracy of digital breast tomosynthesis (DBT), digital mammography (DM), and ultrasonography (US) in non-calcified ductal carcinoma in situ (DCIS, include DCIS with micro-invasion).

Patients And Methods: Ninety-eight patients with non-calcified DCIS (include DCIS with micro-invasion) were enrolled in our study. Breast carcinoma in situ was confirmed by surgical pathologic evaluation. Our Institutional Review Board granted approval and the participating women provided written informed consent. The imaging findings were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS) of the American College of Radiology (ACR) by comparing the differences in the detection rate and diagnostic accuracy among the three techniques in all cases, in dense breasts, and in non-dense breasts.

Results: The detection rates of DBT, DM, and US for non-calcified DCIS in all cases were 83.7, 68.4, and 94.9%, respectively, and in patients with dense breasts were 81.2, 63.8, and 95.0%. The detection rate of US was higher than DBT, which, in turn, was higher than DM both in all cases and in dense breasts. Pairwise comparisons among the three techniques showed that the differences were statistically significant (P = 0.000 and P = 0.000, respectively). The experts identified a case as abnormal for all criteria (BI-RADS score of 4B-5) in 68.4% of ratings using DBT, 43.9% of ratings using DM, and 66.3% of ratings using US; for dense breasts, the positive identification rates were 62.5% of ratings using DBT, 41.2% of ratings using DM, and 61.2% of ratings using US. The diagnostic accuracy of DBT and US was significantly higher than that of DM in all cases (P = 0.001 and P = 0.006, respectively) and in dense breasts (P = 0.007 and P = 0.011, respectively). The diagnostic accuracy of DBT was slightly higher than US in all cases and in dense breasts, but the difference was not statistically significant (P = 0.761 and P = 0.871, respectively). By DBT, most non-calcified cases of DCIS presented as a mass lesion (54.9%) with an irregular shape (46.7%), indistinct margin (53.3%), and isodense composition (71.1%). Using US, 72 of 93 patients (77.4%) were shown to have a mass. Most mass lesions had an irregular shape (83.3%), indistinct margin (55.5%), and parallel the skin (82.8%).

Conclusion: DBT and US gave better detection rates and diagnostic accuracy for non-calcified DCIS compared with DM in all cases and in dense breasts. The detection rate of DBT was lower than that of US in all cases and in dense breasts. The diagnostic accuracy of DBT was slightly higher than that of US in all cases and in dense breasts, but the difference was not statistically significant. Imaging findings for non-calcified DCIS were relatively non-specific.
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http://dx.doi.org/10.1007/s12282-016-0739-7DOI Listing
July 2017

Suppression of motor protein KIF3C expression inhibits tumor growth and metastasis in breast cancer by inhibiting TGF-β signaling.

Cancer Lett 2015 Nov 10;368(1):105-114. Epub 2015 Aug 10.

Department of Pathology, Medical College of Qingdao University, Qingdao, China; Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Breast cancer is the most common cause of death among women. KIF3C, a member of kinesin superfamily, functions as a motor protein involved in axonal transport in neuronal cells. To explore the expression, regulation and mechanism of KIF3C in breast cancer, 4 breast cancer cell lines and 93 cases of primary breast cancer and paired adjacent tissues were examined. Immunohistochemistry, Real Time Polymerase Chain Reaction (RT-PCR), Western blot, flow cytometry, short hairpin RNA (shRNA) interference, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation techniques and xenograft mice model were used. We found that KIF3C was over-expressed in breast cancer tissues and such high KIF3C expression was also associated with tumor recurrence and lymph node metastasis. Silencing of KIF3C by shRNA inhibited epithelial-mesenchymal transition and metastasis by inhibiting TGF-β signaling and suppressed breast cancer cell proliferation through inducing G2/M phase arrest. The tumor size was smaller and the number of lung metastatic nodules was less in KIF3C depletion MDA-MB-231 cell xenograft mice than in negative control group. These results suggested that high expression of KIF3C in breast cancer may be associated with the tumor progression and metastasis.
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http://dx.doi.org/10.1016/j.canlet.2015.07.037DOI Listing
November 2015

A phase II open-label clinical study of comparing nab-paclitaxel with pemetrexed as second-line chemotherapy for patients with stage IIIB/IV non-small-cell lung cancer.

Med Oncol 2015 Aug 14;32(8):216. Epub 2015 Jul 14.

Department of Oncology, General Hospital of Chinese PLA, 28 Fuxing Road, Beijing, 100853, China.

Current choices of second-line chemotherapy regimens for patients with advanced non-small-cell lung cancer (NSCLC) are extremely limited. We applied a new strategy of using nab-paclitaxel as single chemotherapy regimen in second-line setting for patients with unsuccessful first-line chemotherapy. The efficacy and safety were compared with patients who received standard second-line regimen pemetrexed. Patients with stage IIIB/IV NSCLC and unsuccessful first-line platinum-based chemotherapy were randomly divided into two arms. Arm I received pemetrexed 500 mg/m(2) intravenously (i.v.) on day 1 of 3-week cycle. Arm II received nab-paclitaxel 150 mg/m(2) i.v. on days 1 and 8 of 3-week cycle. The primary endpoint was overall survival (OS). One hundred and eleven patients were randomly assigned to receive pemetrexed (n = 56) and nab-paclitaxel (n = 55). Median OSs were 9.4 months (95% CI 7.1-12.5 months) for pemetrexed and 9.9 months (95% CI 8.2-11.9 months) for nab-paclitaxel. Median PFS was 4.6 months (95% CI 2.7-6.1 months) for pemetrexed and 5.1 months (95% CI 3.9-7.4 months) for nab-paclitaxel. While no CR was reported for either treatment, PRs + SDs were seen in 32/56 (57.1%) patients in pemetrexed arm and 36/55 (65.5%) patients in nab-paclitaxel arm. Grade 3 and grade 4 adverse events were comparable between two treatment arms. New second-line chemotherapy single-regimen nab-paclitaxel showed equivalent efficacy and toxicity profiles as pemetrexed in treating patients with NSCLC.
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http://dx.doi.org/10.1007/s12032-015-0660-5DOI Listing
August 2015

Effect of Panax notoginseng in patients with multiple fractured ribs and pulmonary contusions caused by the 2008 Wenchuan earthquake.

Forsch Komplementmed 2014 9;21(6):360-4. Epub 2014 Dec 9.

Orthopedics Department, Chengdu University of Traditional Chinese Medicine Hospital, Chengdu, Sichuan, China.

Background: The aim of this study was to investigate whether the combination of conventional treatment and Panax notoginseng (PN group) is superior to conventional treatment alone (CG group) in reducing the clinical symptoms of patients with multiple fractured ribs and pulmonary contusions.

Patients And Methods: We retrospectively analyzed the medical records of patients treated for multiple fractured ribs and pulmonary contusions with either conventional treatment (n = 17) or P. notoginseng (n = 18). Visual analog scale (VAS) pain scores and arterial oxygen saturation were measured at baseline and at 1 and 2 weeks following treatment. The duration of mechanical ventilation, systemic analgesics, and hospital stay were also recorded.

Results: VAS scores in the PN group were lower than in the CG group at 1 week (p < 0.01) and at 2 weeks (p < 0.05). Arterial oxygen saturation in both groups was higher after treatment than at baseline (p < 0.05), but there was no statistically significant difference between the 2 groups (p > 0.05). The duration of mechanical ventilation, systemic analgesics administration, and hospital stay in the PN group was remarkably decreased as compared to the CG group (p < 0.05).

Conclusion: Combining conventional treatment and P. notoginseng seems to be an efficient method that can improve the clinical symptoms of multiple fractured ribs and pulmonary contusions.
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http://dx.doi.org/10.1159/000370011DOI Listing
March 2016

Luminal breast cancer classification according to proliferative indices: clinicopathological characteristics and short-term survival analysis.

Med Oncol 2014 Jul 17;31(7):55. Epub 2014 Jun 17.

Breast Center, Qingdao University Affiliated Hospital, No. 59 of Haier Road, Qingdao, 266000, China.

The classification of luminal breast cancer has been a popular topic regarding its heterogeneity with distinct biological features and clinical outcomes. This study aimed to assess the power of proliferative indices (Ki67 and histological grade) to determine various clinicopathological characteristics and survival in luminal disease. A total of 541 patients with stage I-III luminal breast cancer were enrolled. Subtypes were determined using proliferative indices and were compared with clinicopathological variables and short-term survival. The significance of various treatments was evaluated in a subgroup of pN0 (lymph node negative) patients. Histological grade, independent of other variables, was a better predictor in the ER/PR+, human epidermal growth factor receptor 2 (Her-2) subgroup (p = 0.011) and the pN0 subgroup (p = 0.044) compared with Ki67, which only showed significance in the ER/PR+, Her-2 subgroup (p = 0.008). Neither grade nor Ki67 was associated with outcomes in the luminal Her-2 class. In pN0 patients, various treatments did not show significance in short-term survival. Histological grade outperformed Ki67 as a determinant for the stratification of luminal class regarding short-term survival. Chemotherapy most likely did not provide additional benefit to pN0 patients with luminal breast cancer compared with endocrine therapy.
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http://dx.doi.org/10.1007/s12032-014-0055-zDOI Listing
July 2014

Hepcidin plays a negative role in liver regeneration.

Acta Biochim Biophys Sin (Shanghai) 2013 Dec 11;45(12):1049-54. Epub 2013 Oct 11.

Department of Pathology, Yan'an Hospital, Kunming 650051, China.

Hepcidin is a key regulator of iron metabolism. The expression of hepcidin is significantly induced by iron overload, inflammation, and infection of pathogens. Recent studies have indicated that the expression of hepcidin in the liver is also regulated during liver regeneration. However, the mechanism of the regulation of hepcidin expression and its role in liver regeneration remain unclear. In this study, we found that the hepatocyte growth factor inhibited hepcidin expression in the liver during the late stage of liver regeneration. Meanwhile, we investigated the effect of hepcidin on liver regeneration. Mice overexpressing hepcidin-1 exhibited impaired hepatic regeneration after partial hepatectomy, as determined by immunohistochemical staining of the proliferation cell nuclear antigen. Our results demonstrated a negative role of hepcidin in modulating liver regeneration, and suggested that a sustained high iron level by the down-regulation of hepcidin at the late stage of liver regeneration is required for hepatocyte proliferation.
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http://dx.doi.org/10.1093/abbs/gmt107DOI Listing
December 2013

Clinical value of mean platelet volume for impaired cardiopulmonary function in very old male patients with chronic obstructive pulmonary disease.

Arch Gerontol Geriatr 2012 Mar-Apr;54(2):e109-12. Epub 2011 Oct 20.

Second Geriatric Cardiology Division, Chinese PLA General Hospital, Beijing, China.

High mean platelet volume (MPV) is a marker of platelet activation. The present study was designed to test if high MPV is associated with impaired cardiopulmonary function in patients with COPD. One hundred and sixteen male outpatients (mean age, 86.03±4.29 years) with COPD were recruited. Blood samples were collected for measurements of MPV and other laboratory data. Lung function and cardiac function were also assessed. Multiple linear regression analyses revealed that MPV was negatively correlated with left ventricular ejection fraction (β=-0.252, p=0.008) and the predicted value of forced expiratory volume in one second (FEV(1)% predicted) (β=-0.384, p=0.0001), whereas MPV was positively correlated with right pulmonary arterial diameter (β=0.311, p=0.005). The present study showed an association between high MPV, a marker of platelet activation, and impaired cardiopulmonary function in elderly COPD male patients. High MPV may be regarded as an early predictive marker of impaired cardiopulmonary function in COPD.
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http://dx.doi.org/10.1016/j.archger.2011.09.013DOI Listing
June 2012
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