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1.
Pathol Res Pract ; : 152882, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32113795

RESUMO

AIMS: The aim of this study was to explore HER2 status and characteristics in biopsy specimens of gastric cancer (GC) in Chinese population. METHODS AND RESULTS: A total of 27,787 biopsy specimens of GC from 103 hospitals were obtained. Immunohistochemistry (IHC) staining of HER2 was performed. Overall HER2 IHC positive rate was 11.2 %. HER2 positive rate elevated with the increase of age in total patients and both genders. The rates were 7.1 %, 8.1 %, 9.0 %, 10.9 %, 11.8 %, 12.6 %, and 12.1 % when patient age was ≤30, 31-40, 41-50, 51-60, 61-70, 71-80, and >80, respectively (P < 0.001). In male, the rates were 6.5 %, 8.4 %, 9.6 %, 11.5 %, 12.4 %, 13.3 %, and 12.1 % (P < 0.001). In female, the rates were 7.4 %, 7.9 %, 8.0 %, 9.0 %, 9.6 %, 10.6 %, and 11.9 % (P = 0.128). The changes in male were more dramatic than in female (P < 0.001). Furthermore, the proportion of the intestinal type GCs increased with age in total patients and both genders (P < 0.001), and in male the changes were more dramatic (P < 0.001). While the proportion of the diffuse type showed the opposite tendency to that of the intestinal type (P < 0.001). HER2 IHC positive rate showed a positive correlation with the proportion of the intestinal type (r=0.986, P < 0.001), and a negative correlation with the proportion of the diffuse type (r=0.984, P < 0.001). CONCLUSIONS: The HER2 IHC positive rate showed age variation in biopsy specimens of GC. In male the variation was more dramatic than in female. The variation of HER2 positive rate can be attributed to the age variation of the Lauren subtypes.

2.
J Surg Res ; 250: 216-223, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32092599

RESUMO

BACKGROUND: Krüppel-like factor 7 (KLF7), which belongs to the KLF family of zinc finger transcription factors, plays a critical role in regulating gene expression. It was reported that KLF7 overexpression was closely related to the progression of gastric cancer. However, the role of KLF7 in lung adenocarcinoma (LAC) has not been elucidated. The aim of our study is to investigate the expression pattern of KLF7 and explore whether the KLF7 expression is correlated with unfavorable clinical outcome of patients with LAC. MATERIALS AND METHODS: The protein and mRNA levels of KLF7 were examined in LAC tissues by using immunohistochemistry staining and quantitative reverse transcription polymerase chain reaction, respectively. The prognostic role of KLF7 in patients with LAC was assessed using univariate and multivariate analyses. Clinical outcomes were evaluated by Kaplan-Meier analysis and logrank test. The effects of KLF7 on lung cancer cells were investigated through cellular experiments. RESULTS: KLF7 expression was elevated in LAC tissues compared with adjacent normal tissues. High protein level of KLF7 was correlated with larger tumor size, positive lymph node metastasis, and advanced TNM stage. Moreover, patients with LAC with higher expression level of KLF7 had poorer overall survival, and KLF7 was identified as an unfavorable independent prognosis factor. Knockdown of KLF7 can suppress the proliferation and invasion abilities of cancer cells. CONCLUSIONS: Our studies revealed that high KLF7 expression level was significantly associated with the poorer clinical outcomes of patients with LAC, indicating the potential role of KLF7 as a novel prognostic biomarker and therapeutic target.

3.
Transpl Immunol ; 59: 101270, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31953155

RESUMO

BACKGROUND: Accelerated transplant rejection mediated by donor reactive memory T cells is another barrier to the induction of graft tolerance. The aim of this study was to investigate the immunosuppressing effects of vitamin D (1,25(OH)2D3), administered alone or in combination with a costimulatory blockade treatment, on rejection of secondary heart allografts in a mouse model. METHODS: Circular full-thickness skin grafts from BALB/c mice were cut and grafted onto the lumbar regions of C57BL/6 mice as allo-primed recipients. Four weeks after skin grafting, the vascularized hearts from the BALB/c mice were transplanted heterotopically into the allo-primed recipients using a non-suture cuff technique. The recipients were then randomly divided into four groups and given either intraperitoneal injection of isotype, Ab, 1,25(OH)2D3, or a combination of Ab and 1,25(OH)2D3. Allograft incidence was determined by hematoxylin-eosin staining, and cytokine expression was assessed by the quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and cytometric bead arrays. Spleen cells from the recipient were used to assess mixed lymphocyte reactions. Memory T cells and regulatory T cells (Tregs) in spleen cells were measured by flow cytometry. RESULTS: The median allograft survival time was longer with the combined treatment with Ab and 1,25(OH)2D3 than with no treatment or with treatment with Ab or 1,25(OH)2D3 alone. The grafts were protected from infiltration by inflammatory cells and by inhibition of interleukin 2 and interferon gamma expression. Rejection was initially suppressed in the early postoperative period by a reduction in the number of memory T cells and induction of Foxp3+ Tregs, but this effect disappeared by day 15 after transplantation upon withdrawal of the treatment. CONCLUSION: Vitamin D3 administered as an immunosuppressive agent, when combined with monoclonal antibody treatment, may protect heart grafts from memory T cell responses in a secondary heart transplant model.

4.
Biomed Res Int ; 2019: 4860367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31815141

RESUMO

The pathogenesis and prognosis of glioblastoma (GBM) remain poorly understood. Mutual exclusivity analysis can distinguish driver genes and pathways from passenger ones. The purpose of this study was to identify mutually exclusive gene sets (MEGSs) that have prognostic value and to detect novel driver genes in GBM. The genomic alteration profile and clinical information were derived from The Cancer Genome Atlas, and the MEGSA method was used to identify the MEGS. Next, we performed survival analysis and constructed a risk prediction model for prognostic stratification. Leave-one-out cross-validation and permutation test were used to evaluate its performance. Finally, we identified 21 statistically significant MEGSs. We found that the MEGS in the RB pathway was significantly associated with poor prognosis, after adjusting for age and gender (HR = 1.837, 95% CI: 1.192-2.831). Based on the risk prediction model, 208 (80.9%) and 49 (19.1%) patients were assigned to high- and low-risk groups, respectively (log-rank: p < 0.001, adjusted p=0.001). Additionally, we found that SPTA1, a novel gene involved in the MEGS, was mutually exclusive with members of cell cycle, P53, and RB pathways. In conclusion, the MEGS in the RB pathway had considerable clinical value for GBM prognostic stratification. Mutated SPTA1 may be involved in GBM development.

5.
Int J Biol Sci ; 15(13): 2859-2871, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31853223

RESUMO

Triple negative breast cancer (TNBC) is characterized by aggressive malignant tumor, poor prognosis and lack of targeted treatment. Several studies have established that macrophages are closely associated with the progression of TNBC. Through immunohistochemical analysis, we found that the infiltration of macrophage in TNBC tissue was more than that in non-triple negative breast cancer (nTNBC) tissue. Furthermore, the conditioned medium (CM) of MDA-MB-231 and HCC1937, the TNBC cell lines, had significant migration-promoted effect on macrophages. However, the macrophages migration-promoted ability of nTNBC cell line MCF-7 was weaker than that of MDA-MB-231 and HCC1937 cells. Mechanistically, MDA-MB-231 and HCC1937 cells secreted more macrophage colony-stimulating factor (M-CSF) than MCF-7, which is the main inducer of macrophage migration, and the secreted M-CSF promoted the increase in actin and the elongation of pseudopodia. When M-CSF was neutralized by antibody, the elongation of macrophage pseudopodia was disappeared and the migration was inhibited. In vivo, there were more macrophages in tumors induced by MDA-MB-231 than MCF-7 did. Therefore, M-CSF specially secreted by TNBC was the important cause of macrophages aggregation in TNBC, which further promoted the aggressiveness of TNBC.

6.
Nat Commun ; 10(1): 5334, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767869

RESUMO

Protein products of the regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA-DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.

7.
J BUON ; 24(4): 1679-1685, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646825

RESUMO

PURPOSE: To explore the prognostic value of SOX11 in patients with mantle cell lymphoma (MCL). METHODS: The clinical data and paraffin-embedded tissue of 75 primary MCL in Shanxi Tumor Hospital were collected, and the MCL international prognostic index (MIPI) was rechecked in all cases according to simplified (sMIPI) formula. The expression of SOX11 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and the relationship of survival with SOX11 mRNA and MIPI in MCL patients was evaluated. RESULTS: Median survival was 44 months in cases with low-risk, 31 months in cases with intermediate-risk and 30 months in cases with high-risk. There was statistically significant difference between low-risk and high-risk group (p=0.0033), while there was no statistical difference between low-risk group and intermediate-risk group (p=0.1067) and the intermediate-risk group and high-risk group (p=0.6149). Furthermore, cases were divided into group SOX11mRNA

8.
Oncol Rep ; 42(5): 1935-1945, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545454

RESUMO

Distant metastasis is a major cause of cancer­associated mortality in patients with colon cancer. Insulin­like growth factor binding protein 7 (IGFBP7) has been identified as a crucial inhibitor of human cancer. However, the role of IGFBP7 in the pathogenesis of metastatic colon cancer has not been investigated. In the present study, the expression of IGFBP7 in 81 pairs of colon cancer tissues and adjacent normal tissues were investigated using immunohistochemistry. Furthermore, 24 pairs of primary colon cancer and matched liver metastasis tissues were analyzed. LοVο cells with IGFBP7­knockdown and HT­29 cells with IGFBP7­overexpression were employed. The expression levels of E­cadherin, N­cadherin and Vimentin were quantified and compared. Significant alterations in the expression of IGFBP7 between late stage (III + IV) colon cancer and adjacent normal colonic mucosa were observed. (P=0.031). The association between IGFBP7 and epithelial­mesenchymal transition (EMT) markers were validated in primary colon cancer and matched liver metastasis tissues. The invasive front of liver metastatic colon tissues revealed reduced IGFBP7 expression. Additionally, knockdown of IGFBP7 in LοVο cells resulted in decreased E­cadherin, and increased N­cadherin and Vimentin expression compared with the control group. Overexpression of IGFBP7 in HT­29 cells induced an upregulation of E­cadherin; however, the N­cadherin and Vimentin levels were decreased. In conclusion, the results of the present study suggested that IGFBP7 may prevent colon cancer metastasis by inhibiting EMT, and serves as a potential diagnostic marker and therapeutic target for patients with colon cancer.


Assuntos
Neoplasias do Colo/patologia , Regulação para Baixo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Células CACO-2 , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HT29 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Estadiamento de Neoplasias
9.
Cancer Med ; 8(5): 2157-2166, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30945461

RESUMO

OBJECTIVE: This study aims to screen the MSI detection loci suitable for the East Asian colorectal cancer patients. and explore its intratumoral heterogeneity. METHODS: A total of 271 pathological tissues specimens of colorectal cancer were collected. The MSI status was detected using different PCR reagent kits with different detection loci. Then, the results were compared with the immunohistochemical (IHC) staining results. Microdissection of pathological tissues specimens detected to be MSI-H was performed to examine whether there was intratumoral heterogeneity of MSI status. RESULTS: Thirty-nine out of 271 cases were dMMR. dMMR occurred mostly in patients with right-hemi colon cancer (P < 0.0001). Compared with dMMR patients, the clinical stages of pMMR patients were more inclined to be in the late stage with lymph node metastasis (P < 0.0001). MSI-H tumors were significantly associated with KRAS mutation (P = 0.036) and PD-L1 expression (P = 0.038). Compared with Promega panel and 24-locus detection, the consistency between NCI MSI panel and IHC staining results were the highest with the Kappa value of 0.850. The sensitivity of detection decreased from 87.18% to 56.41% with the increase in detection loci. Single locus analysis showed that the first two loci with the highest sensitivity were both mononucleotide loci, namely, BAT-26 (95.45%) and BAT-25 (86.36%). The dinucleotide locus with highest sensitivity was D2S123 (50%). The main detection loci of MSI-H showed no intratumoral heterogeneity. CONCLUSION: The combination of 2 mononucleotide loci (BAT25, BAT26) and 3 dinucleotide loci (D2S123, D5S346, D17S250) might be the most suitable loci for MSI detection in East Asian population. There is no intratumoral heterogeneity in the main MSI loci.

10.
Am J Pathol ; 189(5): 1105-1120, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30862482

RESUMO

Mitochondrial ribosome proteins (MRPs), which are encoded by the nuclear genomic DNA, are important for mitochondrial-encoded protein synthesis and mitochondrial function. Emerging evidence suggests that several MRPs also exhibit important extra-mitochondrial functions, such as involvement in apoptosis, protein biosynthesis, and signal transduction. In this study, we demonstrate a significant role of MRP L35 (MRPL35) in colorectal cancer (CRC). The expression of MRPL35 was higher in CRC tissues than in matched cancer-adjacent tissues and higher in CRC cells than in normal mucosal epithelial cells. Higher MRPL35 expression in CRC tissue correlated with shorter overall survival for CRC patients. In vitro, down-regulation of MRPL35 led to increased production of reactive oxygen species (ROS) together with DNA damage, loss of cell proliferation, G2/M arrest, a decrease in mitochondrial membrane potential, apoptosis, and autophagy induction. MRPL35 knockdown inhibited tumor proliferation in a CRC xenograft nude mouse model. Furthermore, overexpression of MRPL35 or treatment of cells with the ROS scavenger, N-acetyl cysteine, abrogated ROS production, cell cycle arrest, and apoptosis in vitro. These findings suggest that MRPL35 plays an essential role in the development of CRC and may be a potential therapeutic target for CRC.


Assuntos
Apoptose , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Neoplasias Colorretais/patologia , Animais , Biomarcadores Tumorais/genética , Ciclo Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Nus , Prognóstico , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Oncol Lett ; 17(1): 1062-1070, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655866

RESUMO

The tumor microenvironment contributes to the survival and development of tumor cells and is therefore a key target for cancer therapy. The tumor microenvironment has unique physical and chemical properties and is associated with inflammation and immunity. To examine the correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer, and to compare the differences between two treatments [neoadjuvant chemotherapy (NAC) vs. neoadjuvant chemoradiotherapy (NACR)], an immunohistochemical method was used to measure the expression levels of CD4+ tumor-infiltrating lymphocytes (TILs), cluster of differentiation (CD)8+TILs, forkhead box P3 (FOXP3)+TILs, cytotoxic T lymphocyte-associated antigen-4+TILs and programmed death ligand-1 (PD-L1)+TILs in 109 patients with rectal cancer, pre- and post-neoadjuvant therapy. The significance of these protein expression patterns was also analyzed using tissue microarrays, and the prognostic significance of these findings evaluated. The results indicated that high levels of CD4+TILs, CD8+TILs and PD-L1+TILs may be associated with favorable responses to neoadjuvant therapy, whereas high levels of FOXP3+TILs were associated with poor therapeutic responses. Expression levels of CD8+TILs and FOXP3+TILs following neoadjuvant therapy were independent prognostic factors and affected the total survival of patients subjected to neoadjuvant therapy for the treatment of rectal cancer. Moreover, the effects of NAC and NACR on the tumor microenvironment may be different.

12.
Int J Surg Pathol ; 27(1): 28-42, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29961402

RESUMO

Primary pancreatic hepatoid carcinoma (PHC) is very rare. Here, we reported 3 such cases with review of additional 31 cases in the literature. Our 3 patients were male (83, 72, and 54 years old, respectively). Serum α-fetoprotein (AFP) was elevated in 1 patient (case 3, 8338 ng/mL) and not measured in the other two. The PHC in patient 1 (pathological stage pT2N0M0) and patient 2 (pT3N0M0) showed pure hepatocellular carcinoma (HCC)-like morphology, whereas in case 3 it was a PHC with true glandular differentiation (pT4N0M0). The diagnosis of PHC was confirmed with positive immunohistochemical staining in the tumor cells for AFP (2/3), Hep Par 1 (3/3), glypican-3 (2/3), arginase-1 (2/3), and Sal-like protein 4 (1/3). CD10 and polyclonal carcinoembryonic antigen stains show focal canalicular pattern in 2/3 tumors. Patient 1 did not receive further treatment after resection and was alive with no evidence of disease at 107 months. Patient 2 died of postoperative complications, whereas patient 3 received postsurgical chemoradiation and died of disease at 29 months. Our findings and literature review indicate that PHCs can be divided into 4 histological subtypes: with pure HCC-like morphology (n = 22), with neuroendocrine differentiation (n = 8), with true glandular differentiation (n = 3), and with acinar cell differentiation (n = 1). On univariate analysis, pure HCC-like morphology was associated with better disease-specific survival (DSS; P = .04), whereas lymph node and distant metastases were associated with worse DSS ( P = .002 for both). Age, gender, presenting symptoms, serum AFP level, and T stage were not associated with DSS. On multivariate analysis, none of these parameters was significantly associated with DSS.


Assuntos
Adenocarcinoma/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia
13.
Cancer Biol Ther ; 20(4): 435-443, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30359168

RESUMO

Ras-specific guanine nucleotide-releasing factor 2 (RasGRF2) is a member of the guanine nucleotide exchange factors family which is expressed in a variety of tissues and cancer. However, the role of RasGRF2 in cancer is less reported, especially in colorectal cancer(CRC). Hence, the present study aimed to investigated the function of RasGRF2 and ways in which it affects tumor progression in CRC samples and cell lines. We first measured RasGRF2 mRNA level in 26 paired tumor and nontumor colon tissues after colon cancer surgical resection, and determined RasGRF2 protein level in 97 paired paraffin-embedded colon cancer tissues, and found that levels of RasGRF2 mRNA and protein were increased in colorectal tumor tissues, compared with adjacent non-tumor tissues. We then examined the effects of RasGRF2 knockdown on proliferation, migration and invasion were analyzed in CRC cells (SW480, HCT116 and LS174T). HCT116 cells with RasGRF2 knockdown were injected into the tail vein in nude mice to yield metastatic model, and tumor metastasis was measured as well. We found that knockdown of RasGRF2 in CRC cells reduced their migration and invasion in vitro and metastasis in mice. Furthermore, we explored the underlying molecular mechanism for RasGRF2-mediated CRC migration and invasion. The results showed that knockdown of RasGRF2 in CRC cells impairing the expression of MMP9 and inhibiting the activation of Src/Akt and NF-κB signaling. We conclude that RasGRF2 plays a role in controlling migration and invasion of CRC and modulates the expression of MMP9 through Src/PI 3-kinase and the NF-κB pathways.

14.
Thorac Cancer ; 10(1): 47-53, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468296

RESUMO

BACKGROUND: The study was conducted to investigate the clinicopathological features and prevalence of ROS1 gene fusion in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: The presence of ROS1 fusion was assessed by quantitative real-time PCR. Associations between ROS1 fusion and clinical characteristics were analyzed. RESULTS: In total, 6066 patients with pathologically confirmed NSCLC and ROS1 fusion test results were enrolled. The average age was 60.89 ± 10.60 years and fusion was detected in 157 (2.59%) patients. Fusion frequency was significantly correlated with age, gender, smoking status (all P < 0.001), pathology type (P = 0.017), and lymph node metastasis stage (P = 0.027). ROS1 fusion-positive patients were significantly younger (55.68 ± 11.34 vs. negative 61.02 ± 10.44 years; P < 0.01). Fusion frequency was higher in women (3.71% vs. men 1.81%), never-smokers (3.33% vs. smokers 1.21%), and patients with adenocarcinoma (2.77% vs. squamous lung cancer 0.93%) and at advanced node stages (1.31%, 1.40%, 2.07%, and 3.23% for N0, N1, N2, and N3, respectively). No significant correlation between ROS1 fusion status and pathological stage was found in subgroups classified by pathological, tumor, or metastasis stage (P > 0.05). Age, smoking status, and lymph node stage were statistically significantly correlated with ROS1 fusion frequency (all P < 0.05); gender and pathology type were not significantly correlated with ROS1 fusion status after adjusting for smoking status. CONCLUSION: An overall ROS1 fusion frequency of 2.59% was confirmed in this study. ROS1 fusion was more prevalent among younger patients, never-smokers, and those at advanced node stages.


Assuntos
Adenocarcinoma/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , China/epidemiologia , Feminino , Rearranjo Gênico/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Caracteres Sexuais , Fumar/efeitos adversos , Fumar/genética
15.
Pathol Res Pract ; 215(2): 265-271, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30466764

RESUMO

Although dose intensification strategies achieve a favorable prognosis for pediatric patients of T-lmphoblastic lymphoma/leukemia (T-LBL/ALL), numerous side effects have been followed. Molecular targeted therapies will be needed to optimize the current treatment strategy for T-LBL/ALL. The aim of this study was to analyse expression and significance of CD47, PD1 and PDL1 in. T-LBL/ALL. We performed immunohistochemistry staining and real time fluorescence quantitative PCR (qRT-PCR) on FFPE tissues. Immunohistochemistry results showed that the high expression rate of CD47 protein was 46.4% (26/56) and the positive expression rate of PDL1 protein was 37.5% (21/56). PD1 expression was observed in tumor infiltrating lymphocytes in approximately 20% of T-LBL/ALL patients, but not expressed on tumor cells of T-LBL/ALL. And the results of qRT-PCR showed that the relative expression levels of CD47, PDL1 and PD1 mRNA in 56 cases of T LBL/ALL were significantly higher than those in control group (6.915 vs 4.050, 12.255 vs 2.575, 37.990 vs 3.615), and the differences were all statistically significant (p all <0.05). Univariate analysis showed that age, CD47 protein, CD47 mRNA,PDL1 protein and PDL1 mRNA expression were closely correlated with prognosis (P all <0.05). We found that the overall one-year survival rates of patients with a high expression (≥M) of CD47 and PDL1 mRNA were higher than in patients with low expression (25 years old. Multivariate Cox regression analysis showed that the high expression of CD47 and PDL1 protein were independent prognostic factors (both p < 0.05). In a word, PD1/PDL1 and CD47 may be involved in the disease progression and prognosis of T-LBL/ALL, and detection and targeting of CD47 and PD1/PDL1 may provide a rational basis to for treatment of T-LBL/ALL.


Assuntos
Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/análise , Antígeno CD47/biossíntese , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Receptor de Morte Celular Programada 1/biossíntese , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Transcriptoma , Adulto Jovem
16.
J Investig Med ; 67(3): 699-705, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30368484

RESUMO

This study aims to understand the clinical features, treatment, and prognosis of patients with male breast cancer (MBC) in Shanxi province of China from 2007 to 2016. Data for 77 patients with MBC were collected for analysis. Immunohistochemistry, pathological results, and other data such as demographic characteristics (age, marital status, smoking history, drinking history, and family history of cancer) as well as clinical data were investigated by retrieving information from the patients' medical records. A total of 12,404 patients were diagnosed with breast cancer between 2007 and 2016, and 77 were patients with MBC among them. The median diagnosis age of patients with MBC was 62 years (range, 24-84 years). The most common complaint was a painless lump in the breast, accounting for 68.8% of the patients, and the main pathological type in MBC was infiltrating ductal carcinoma (66.2%). In terms of hormone receptors, 80.5% (62/77) of patients with MBC were estrogen receptor positive, 75.3% (58/77) of patients were progesterone receptor positive, and only 6.5% (5/77) of patients were HER2 overexpressing. The multivariant Cox proportional hazards regression analysis showed that M stage is an independent prognostic factor (p=0.018, HR=18.791, 95% CI 1.663 to 212.6). The epidemiological and clinical features of Chinese MBC are similar to that of other countries. As the Chinese public have limited knowledge of MBC, it is necessary to increase awareness among them about it. Further research with a large sample size is required for better understanding of the risks associated with MBC.

17.
Pathol Res Pract ; 214(12): 2011-2017, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30301635

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinomas (ICCs) are primary liver malignancies and are the second most common type of malignancy after hepatocellular carcinoma. ICCs are heterogeneous in clinical features, genotype, and biological behavior, suggesting that ICCs can initiate in different cell lineages. AIM: We investigated intrahepatic cholangiocarcinoma RBE cell lines for the markers neural cell adhesion molecule (NCAM) and c-Kit, which possess hepatic progenitor cells properties. METHODS: NCAM + c-Kit + cells were tested for hepatic progenitor cell properties including proliferation ability, colony formation, spheroid formation, and invasiveness in NOD/SCID mice. The Agilent Whole Human Genome Microarray Kit was used to evaluate differences in gene expression related to stem cell signaling pathways between NCAM + c-Kit + and NCAM-c-Kit- subset cells. Microarray results were further confirmed by real-time RT-PCR. RESULTS: NCAM + c-Kit + cells showed hepatic progenitor cell-like traits including the abilities to self-renew and differentiate and tumorigenicity in NOD/SCID mice. Differences were observed in the expression of 421 genes related to stem cell signaling pathways (fc ≥ 2 or fc ≤ 0.5), among which 231 genes were upregulated and 190 genes were downregulated. CONCLUSION: NCAM + c-Kit + subset cells in RBE may have properties of hepatic progenitor cells. NCAM combined with c-Kit may be a valuable marker for isolating and purifying ICC stem/progenitor cells.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Biomarcadores Tumorais/metabolismo , Colangiocarcinoma/diagnóstico , Fígado/metabolismo , Moléculas de Adesão de Célula Nervosa/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Células-Tronco/metabolismo , Animais , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Linhagem Celular Tumoral , Proliferação de Células , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Humanos , Fígado/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco/patologia
18.
J Immunol Res ; 2018: 9485285, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854854

RESUMO

Krukenberg tumor (KT) is an uncommon ovarian metastatic signet-ring cell adenocarcinoma that mostly metastasizes from gastrointestinal carcinoma. Optimal treatment options for KTs are limited. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have shown remarkable activity in clinical trials for metastatic tumors. Here, we evaluated PD-L1 expression and T cell infiltration in KTs and their corresponding primary tumors. Positive tumor PD-L1 expression was detected in 9 (25.7%) KTs from gastric carcinomas (GCs) and in 20 (66.7%) KTs from colorectal carcinomas (CRCs). Patient survival was assessed according to the PD-L1 status and CD8+ T cell density. Positive tumor PD-L1 expression in KTs from GCs was associated with poor prognosis. In contrast, positive tumor PD-L1 expression in KTs from CRCs was associated with an improved prognosis. We analyzed copy number variations of the PD-L1 gene in KTs. PD-L1 expression was higher in cases with copy number gains. The T cell densities within KTs and their corresponding primary tumors were compared. The densities of CD8+ T cells correlated significantly between the primary tumors and KTs from the same case. Taken together, the research further highlighted targets for immune-based therapy in KTs from GCs and CRCs.


Assuntos
Adenocarcinoma/diagnóstico , Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Neoplasias do Colo/diagnóstico , Imunoterapia/métodos , Tumor de Krukenberg/diagnóstico , Neoplasias Ovarianas/diagnóstico , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Estudos de Coortes , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Feminino , Dosagem de Genes , Humanos , Imuno-Histoquímica , Tumor de Krukenberg/mortalidade , Tumor de Krukenberg/secundário , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/secundário , Polimorfismo Genético , Valor Preditivo dos Testes , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Adulto Jovem
19.
Sci Rep ; 8(1): 6267, 2018 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-29674626

RESUMO

Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still demonstrate discrepancies among different studies. We aimed to do a systematic review and meta-analysis on the relationships between overexpression MYC and/or BCL2 and DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study followed the guidelines of PRISMA and Cochrane handbook. The hazard ratios (HRs) for overall survival (OS) were pooled to estimate the main effect size. Twenty studies recruited a total of 5576 patients were available for this meta-analysis. The results showed that MYC (HR = 1.96, 95%CI (confidence interval) = 1.69-2.27)without heterogeneity(I2 = 17.2%, P = 0.280), BCL2 (HR = 1.65, 95%CI = 1.43-1.89, I2 = 20.7%, P = 0.234) protein overexpression, and co-overexpression (HR = 2.58, 95%CI = 2.19-3.04, I2 = 17.2%, P = 0.275) had a poor prognosis in R-CHOP treated DLBCL patients, respectively. The current analysis indicated that MYC and/or BCL2 protein overexpression, and particularly co-overexpression was related to short overall survival in R-CHOP treated DLBCL patients, showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/terapia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Prednisona/uso terapêutico , Prognóstico , Rituximab , Análise de Sobrevida , Vincristina/uso terapêutico
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