The predictive value of CD4, CD8, and C-reactive protein in the prognosis of schistosomal and non-schistosomal colorectal cancer.

BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China and occasional outbreaks occur in Europe in recent years. The relationship between inflammation caused by Schistosoma japonicum and colorectal cancer (CRC) is still obscure, and the inflammation based prognostic systems of schistosomal colorectal (SCRC) has rarely been reported. AIM: To explore the different roles of tumor infiltrating lymphocytes (TILs) and C-reactive protein (CRP) in SCRC and in Non-schistosomal CRC (NSCRC), providing a possible predictive system to evaluate outcomes and to improve the risk stratification for CRC patients, especially for CRC patients with schistosomiasis. METHODS: Three hundred fifty-one CRC tumors were evaluated for density of CD4 + , CD8 + T cells and CRP in intratumoral and stromal compartments by immunohistochemical using tissue microarray. RESULTS: There were no association between TILs and CRP and schistosomiasis. Multivariate analysis identified stromal CD4 (sCD4) (p = 0.038), intratumoral CD8 (iCD8) (p = 0.003), schistosomiasis (p = 0.045) as independent prognostic factors for overall survival (OS) in the whole cohort; and sCD4 (p = 0.006) and iCD8 (p = 0.020) were independent prognostic factors for OS in the NSCRC and SCRC set, respectively. Besides, we found that there were no differences of TILs and CRP, which were distributed in different areas of tumor tissue, between CRC patients with and without schistosomiasis. CONCLUSION: The results remind us that different subtypes of TILs have distinguished biological behavior and prognosis value in the immune microenvironment of NSCRC and SCRC patients. Meanwhile, the findings require us to stratify patients with schistosomiasis and this might facilitate patient counseling and management.

Comparison of the prognostic value of stromal tumor-infiltrating lymphocytes and CD3 + T cells between schistosomal and non-schistosomal colorectal cancer.

AIM: To compare the prognostic value of tumor-infiltrating lymphocytes (TILs) and CD3 + cells and CD20 + cells between schistosomal colorectal cancer (SCRC) and non-schistosomal CRC (NSCRC). BACKGROUND: Although schistosomiasis has been basically eliminated, it has not been completely extinction in China, and occasional outbreaks occur in Europe recently. The role of immune cells in the immune microenvironment of SCRC and NSCRC is remaining obscure, and the inflammation-based prognostic systems of SCRC has rarely been reported. METHODS: HE-stained sections of 349 colorectal cancer (CRC) tumors, which were completely resected, were evaluated for density of TILs. Meanwhile, we evaluated CD3 + T lymphocytes and CD20 + B lymphocytes by immunochemistry. The relationship of these infiltrating immune cells with clinicopathological features, including schistosomiasis, and clinical outcomes was evaluated, and the prognostic roles of TILs in SCRC and NSCRC were explored. RESULTS: Except for age (P < 0.0001), there were no significant differences between NSCRC and SCRC patients in clinicopathological features (P > 0.05). Beside, the positive expression pattern of sTILs, iTILs, CD3, and CD20 between NSCRC and SCRC patients was also similar (P > 0.05). In the whole cohort, sTILs and CD3 were defined as independent prognostic factors (P = 0.031 and P = 0.003, respectively). CD3 was an independent prognostic factor both in the NSCRC and SCRC set (P = 0.026 and P = 0.045, respectively). Higher sTILs, CD3, and CD20 were correlated with less aggressive tumor characteristics in the whole cohort and in subgroups. CONCLUSION: Although CD3 was an independent prognostic factor for both NSCRC and SCRC set, there were no significant differences between SCRC and NSCRC patients in sTILs, CD3, CD20, and in other clinicopathological features.

Angiopoietin2-mediated caveolin1 phosphorylation regulating transcytosis of renal tubular epithelial cell contributes to the occurrence of albuminuria under high glucose exposure.

BACKGROUND: Microlbuminuria is the earliest clinical evidence of diabetic kidney disease (DKD) and contributes to the induction and/or progression of DKD. Previous studies have shown that increased expression of angiopoietin2 (ANGPT2) is correlated with an increase in albuminuria. However, the critical role of ANGPT2 in albuminuria development remains unclear. Some studies have shown the significance of transcytosis in the occurrence of albuminuria, but it is unknown whether it takes place in albumin recycling in renal tubular cells of patients with DKD. Furthermore, the potential mechanism of this association also remains unclear. METHODS: In this study, human renal tubular epithelial cells (HK-2) were cultured with high glucose in a Transwell plate to establish a transcytosis model, while C57BL/6 mice were intraperitoneally injected with streptozotocin to establish a DKD model. The expression of ANGPT2 and caveolin1 (CAV1) phosphorylation was dectected through immunohistochemistry and western blot analysis. RESULTS: Transcytosis of albumin in renal tubular epithelial cells was downregulated after high glucose exposure, and increased expression of ANGPT2 and CAV1 phosphorylation both in vivo and in vitro was observed. Inhibition of ANGPT2 and CAV1 independently promoted transcytosis. Furthermore, ANGPT2 downregulation inhibited CAV1 phosphorylation, whereas CAV1 phosphorylation had no effect on the expression of ANGPT2. CONCLUSIONS: ANGPT2 reduces albumin transcytosis across renal tubular epithelial cells under high glucose conditions by activating CAV1 phosphorylation, thus increasing albuminuria in DKD. These findings suggested that ANGPT2 and CAV1 may be promising therapeutic targets for albuminuria in DKD.

Correlation between schistosomiasis and CD8+ T cell and stromal PD-L1 as well as the different prognostic role of CD8+ T cell and PD-L1 in schistosomal-associated colorectal cancer and non-schistosomal-associated colorectal cancer.

BACKGROUND: The effect of schistosomiasis on CD8+ T cells and then on PD-L1 expression was unknown, and the utility of CD8+ TILs as a biomarker for schistosomal-associated colorectal cancer (SCRC) rarely has been reported. METHODS: Three hundred thirty-eight patients with colorectal cancer (CRC) were enrolled. Immunohistochemical analysis was conducted to evaluate the expression of PD-L1 and the infiltration of CD8+ T cells. RESULTS: In the total cohort, the results showed that CD8+ TIL density was positively correlated with tumoral (p = 0.0001) and stromal PD-L1 expression (p = 0.0102). But there were no correlation between schistosomiasis and CD8+ TILs and PD-L1. Furthermore, CD8+ TIL density (p = 0.010), schistosomiasis (p = 0.042) were independent predictive factors for overall survival (OS). Stromal PD-L1 (sPD-L1) was correlated with OS (p = 0.046), but it was not an independent predictor. In patients without schistosomiasis, CD8 + T cells (p = 0.002) and sPD-L1 (p = 0.005) were associated with better OS. In patients with schistosomiasis, CD8 + T cells were independent prognosis factor (p = 0.045). CONCLUSIONS: The study showed that CD8+ TILs was an independent predictive factor for OS in CRC and SCRC patients. The expression of PD-L1 was positively associated with CD8 + TILs density. There were no correlation between schistosomiasis and CD8 + TILs and PD-L1. Stromal PD-L1 but not tPD-L1 was significantly associated with OS, whereas it was not an independent prognostic factor.

The prognostic role of c-MYC amplification in schistosomiasis-associated colorectal cancer.

OBJECTIVE: The purpose of this study was to explore the prognostic role of c-MYC amplification in colorectal cancer, particularly in schistosomiasis-associated colorectal cancer. METHODS: Three hundred and fifty four cases of colorectal cancer, which were from Qingpu Branch of Zhongshan Hospital affiliated to Fudan University, were retrospectively analyzed in a tissue microarray (TMA) format, with fluorescence in situ hybridization (FISH) assay and immunohistochemistry (IHC). RESULTS: c-MYC gene amplification was found in 14.1% (50 out of 354) of patients with colorectal cancer and was correlated with old age (P = 0.028), positive lymph node metastasis (P = 0.004) and advanced stage tumors (P = 0.002). The overexpression of c-MYC was closely associated with the amplification status (P = 0.023). Kaplan-Meier survival curves for overall survival (OS) showed a statistically significant difference for patients with c-MYC amplification in full cohort of colorectal cancer, stage III-IV set and patients with lymph node metastasis (P = 0.002, 0.034, 0.012, respectively). Further analysis found c-MYC amplification associated with poorer survival in the subgroup of colorectal cancer with schistosomiasis (CRC-S, P < 0.001), but not in colorectal cancer without schistosomiasis (CRC-NS, P = 0.155). By multivariate analysis, c-MYC amplification was an independent poor-prognostic factor in CRC-S set (P = 0.046). CONCLUSIONS: Our study firstly found c-MYC amplification could predict poor prognosis in schistosomiasis-associated colorectal cancer, but not in colorectal cancer without schistosomiasis.

Comparison of non-schistosomal colorectal cancer and schistosomal colorectal cancer.

AIM: The purpose of this study was to compare clinicopathological features of patients with non-schistosomal and schistosomal colorectal cancer to explore the effect of schistosomiasis on colorectal cancer (CRC) patients' clinical outcomes. METHODS: Three hundred fifty-one cases of CRC were retrospectively analyzed in this study. Survival curves were constructed by using the Kaplan-Meier (K-M) method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables. RESULTS: Colorectal cancer patients with schistosomiasis (CRC-S) were significantly older (P < 0.001) than the patients without schistosomiasis (CRC-NS). However, there were no significant differences between CRC-S and CRC-NS patients in other clinicopathological features. Schistosomiasis was associated with adverse overall survival (OS) upon K-M analysis (P = 0.0277). By univariate and multivariate analysis, gender (P = 0.003), TNM stage (P < 0.001), schistosomiasis (P = 0.025), lymphovascular invasion (P = 0.030), and lymph nodes positive for CRC (P < 0.001) were all independent predictors in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was also an independent predictor in patients with stage III-IV tumors and in patients with lymph node metastasis, but not in patients with stage I-II tumors and in patients without lymph node metastasis. CONCLUSION: Schistosomiasis was significantly correlated with OS, and it was an independent prognostic factor for OS in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was still an independently unfavorable prognosis factor for OS in patients with stage III-IV tumors or patients with lymph node metastasis.

High IL2RA mRNA expression is an independent adverse prognostic biomarker in core binding factor and intermediate-risk acute myeloid leukemia.

BACKGROUND: Elevated protein expressions of CD markers such as IL2RA/CD25, CXCR4/CD184, CD34 and CD56 are associated with adverse prognosis in acute myeloid leukemia (AML). However, the prognostic value of mRNA expressions of these CD markers in AML remains unclear. Through our pilot evaluation, IL2RA mRNA expression appeared to be the best candidate as a prognostic biomarker. Therefore, the aim of this study is to characterize the prognostic value of IL2RA mRNA expression and evaluate its potential to refine prognostification in AML. METHODS: In a cohort of 239 newly diagnosed AML patients, IL2RA mRNA expression were measured by TaqMan realtime quantitative PCR. Morphological, cytogenetics and mutational analyses were also performed. In an intermediate-risk AML cohort with 66 patients, the mRNA expression of prognostic biomarkers (BAALC, CDKN1B, ERG, MECOM/EVI1, FLT3, ID1, IL2RA, MN1 and WT1) were quantified by NanoString technology. A TCGA cohort was analyzed to validate the prognostic value of IL2RA. For statistical analysis, Mann-Whitney U test, Fisher exact test, logistic regression, Kaplan-Meier and Cox regression analyses were used. RESULTS: In AML cohort of 239 patients, high IL2RA mRNA expression independently predicted shorter relapse free survival (RFS, p < 0.001) and overall survival (OS, p < 0.001) irrespective of age, cytogenetics, FLT3-ITD or c-KIT D816V mutational status. In core binding factor (CBF) AML, high IL2RA mRNA expression correlated with FLT3-ITD status (p = 0.023). Multivariable analyses revealed that high IL2RA expression (p = 0.002), along with c-KIT D816V status (p = 0.013) significantly predicted shorter RFS, whereas only high IL2RA mRNA expression (p = 0.014) significantly predicted shorter OS in CBF AML. In intermediate-risk AML in which multiple gene expression markers were tested by NanoString, IL2RA significantly correlated with ID1 (p = 0.006), FLT3 (p = 0.007), CDKN1B (p = 0.033) and ERG (p = 0.030) expressions. IL2RA (p < 0.001) and FLT3 (p = 0.008) expressions remained significant in predicting shorter RFS, whereas ERG (p = 0.008) and IL2RA (p = 0.044) remained significant in predicting shorter OS. Similar analyses in TCGA intermediate-risk AML showed the independent prognostic role of IL2RA in predicting event free survival (p < 0.001) and OS (p < 0.001). CONCLUSIONS: High IL2RA mRNA expression is an independent and adverse prognostic factor in AML and specifically stratifies patients to worse prognosis in both CBF and intermediate-risk AML.

Characterisation of clonal Philadelphia-negative cytogenetic abnormalities in a large cohort of chronic myeloid leukaemia.

BACKGROUND: Clonal Philadelphia (Ph)-negative cytogenetic abnormalities (CPCA) have been reported in chronic myeloid leukaemia (CML) patients treated with either interferon or tyrosine kinase inhibitor (TKI). However, the incidences and types of these cytogenetic abnormalities after treatment vary due to the limited populations enroled. METHODS: We analysed the frequency and types of CPCA in a cohort of 607 CML patients in the chronic phase after TKI treatment. We also followed up these CPCA with a median of 31.8 months (range from 11 to 63 months) from diagnosis and investigated their effects on disease progression. RESULTS: We found 18 out of 607 CML patients had cytogenetic abnormality in the Ph-negative cells with an incidence of 3%. In total, six types of chromosomal abnormalities have been identified in these 18 patients with the majority of them aneuploidy abnormalities, especially the trisomy 8. Four of 18 patients (22.2%) were noted to have several abnormalities in the Ph-negative cells. Furthermore, follow-up studies of these CPCA showed that they could be either persistent or transient (15 vs 3 patients), and may not affect disease progression since none of them developed transformed myelodysplasia or transformed acute myeloid leukaemia. CONCLUSION: Three percent of CML patients in the chronic phase were observed to have CPCA during TKI treatment. Our results suggest that the detection of CPCA in CML may not predict disease progression.

C/EBPα Suppresses Lung Adenocarcinoma Cell Invasion and Migration by Inhibiting ß-Catenin.

BACKGROUND/AIMS: The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor that plays essential roles in tumor progression. Although decreased or absent C/EBPα expression in many cancers suggests a possible role for C/EBPα as a tumor suppressor, the functions of C/EBPα in lung adenocarcinoma remain unclear. METHODS: Here, C/EBPα expression levels in 26 lung adenocarcinoma and para-carcinoma tissue samples were detected by qRT-PCR and immunohistochemistry. Cell transwell assays, wound healing assay and three-dimensional spheroid invasion assay were performed to assess the effects of C/EBPα on migration and invasion in lung adenocarcinoma cells in vitro. Western blotting was applied to analyze the potential mechanisms. RESULTS: C/EBPα was found to be decreased in lung adenocarcinoma tissues compared to para-carcinoma tissues. Overexpression of C/EBPα significantly inhibited the migration and invasion of lung adenocarcinoma cells. In addition, C/EBPα overexpression suppressed the epithelial-mesenchymal transition (EMT) that was characterized by a gain of epithelial and loss of mesenchymal markers. Further study showed that C/EBPα suppressed the transcription of ß-catenin and downregulated the levels of its downstream targets. CONCLUSION: Our data suggest that C/EBPα inhibits lung adenocarcinoma cell invasion and migration by suppressing ß-catenin-mediated EMT in vitro. Thus, C/EBPα may be helpful as a potential target for treatment of lung adenocarcinoma.

Interleukin-3 receptor α chain (CD123) is preferentially expressed in immature T-ALL and may not associate with outcomes of chemotherapy.

Interleukin-3 (IL-3) receptor α chain (CD123) plays an essential role in regulating the proliferation of hematopoietic stem cells. In the hematopoietic malignancies, CD123 expression has been found in acute myeloid leukemia (AML), B-precursor acute lymphoblastic leukemia (B-ALL), as well as dendritic cell malignancies. However, whether CD123 is also expressed in T-acute lymphoblastic leukemia (T-ALL) remains unknown. Using multi-parameter flow cytometry, we analyzed CD123 expression in 160 consecutive diagnostic T-ALL patients, including 88 pediatric T-ALL cases and 72 adult T-ALL cases. The minimal residual disease (MRD) was detected after one course of induction therapy to evaluate the treatment effects. CD123 expression was detected in 24 out of 88 (27 %) pediatric T-ALLs and 30 out of 72 (42 %) adult T-ALLs. Further analysis revealed that CD123 expression is associated with the maturation stage of T-ALLs. The frequencies of CD123-positive cases decreased from 83 to 40 % and 21 % in early T-precursor ALLs, T-precursor ALLs, and mature T-ALLs, respectively. Interestingly, we detected the CD4+CD8+ double-positive leukemic cells in 22 immature and 34 mature T-ALL patients. Of note, only 4 % of these patients expressed CD123. In addition, we found that 79 % of CD33+ and 64 % of CD117+ immature T-ALL patients also expressed CD123. However, CD123 expression did not predict the outcomes of the first course of induction therapy in T-ALL patients. In conclusion, we found that CD123 is preferentially expressed in immature T-ALL. Moreover, CD123 expression is strongly associated with cross-lineage expression of myeloid markers in early T-precursor ALL.

Analysis of hematogones in bone marrow from acute myeloid leukaemia cases posttherapy.

BACKGROUND: Increased bone marrow (BM) hematogones (HGs) are often observed in patients with marrow regenerating status. Many studies have focused on the role of HGs in acute lymphoblastic leukaemia (ALL), but very little has been done to understand their effects on acute myeloid leukaemia (AML). MATERIALS AND METHODS: Through immunophenotyping, HGs were quantified in 471 BM samples from 292 postchemotherapy AML cases. These samples were analysed to determine whether there is any relationship between HGs percentages and French-American-British (FAB) subtypes or risk stratification of AML. RESULTS: HGs were identified in 57.75% of 471 patient samples (271) with a mean percentage of 3.87 ± 0.25%. No significant differences were found amongst different FAB subtypes of AML (P > 0.05). However, significant differences (P < 0.05) in HG numbers were noted between AML patients experiencing haematological complete remission (HCR) and those who have relapsed. HGs were identified in 59.9% of samples under HCR with a mean per cent of 3.98 ± 0.31%, and 36.7% of individuals who have relapsed have detectable HGs with a mean per cent of 1.75 ± 0.47. In addition, HGs in patients groups with low risk or intermediate risk were elevated when compared with high-risk groups (P < 0.05), whilst no significant difference was found between low-risk patients and intermediate-risk patients (P > 0.05). Patients with >0.1% of HGs had a significantly better median leukaemia-free survival (LFS) and overall survival (OS) than those with <0.1% of HGs (P < 0.01). CONCLUSIONS: Therefore, our data indicate that HGs in bone marrow may be used as a favourable prognostic factor that predict for a better outcome of AML patients.

Regulation of gut microbiota: a novel pretreatment for complications in patients who have undergone kidney transplantation.

Kidney transplantation is an effective method to improve the condition of patients with end-stage renal disease. The gut microbiota significantly affects the immune system and can be used as an influencing factor to change the prognoses of patients who have undergone kidney transplantation. Recipients after kidney transplantation showed a lower abundance of Firmicutes and Faecalibacterium prausnitzii and a higher proportion of Bacteroidetes and Proteobacteria. After using prebiotics, synbiotics, and fecal microbiota transplantation to regulate the microbial community, the prognoses of patients who underwent kidney transplantation evidently improved. We aimed to determine the relationship between gut microbiota and various postoperative complications inpatients who have undergone kidney transplantation in recent years and to explore how gut microecology affects post-transplant complications. An in-depth understanding of the specific functions of gut microbiota and identification of the actual pathogenic flora during complications in patients undergoing kidney transplantation can help physicians develop strategies to restore the normal intestinal microbiome of transplant patients to maximize their survival and improve their quality of life.

Novel Prognostic Nomogram to Predict Progression-Free Survival of Patients with Hepatocellular Carcinoma After Transarterial Chemoembolization.

Purpose: A retrospective analysis of hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE) to identify risk factors was conducted, and a novel predictive nomogram model was constructed. Patients and Methods: A total of 346 HCC patients who underwent TACE as initial treatment were retrospectively included, of which 208 were randomly allocated to the derivation cohort and 138 were allocated to the validation cohort. Progression-free survival (PFS) was used as the follow-up endpoint according to mRECIST. Kaplan‒Meier analysis and the Cox regression model screened out some indicators associated with short-term prognosis, and R language was further used to construct a nomogram model. The nomogram was compared with the classical BCLC staging system. Results: The independent predictors affecting PFS in HCC patients undergoing TACE included the following: 1. Baseline indicators: age (P=0.013), albumin-bilirubin (ALBI) grade (grade 2 vs grade 1, P=0.029; grade 3 vs grade 1, P<0.001), and portal vein tumour thrombus (PVTT, P<0.001); 2. Indicators at the 1-month follow-up: Neutrophil To Lymphocyte Ratio (NLR, P=0.032) and changes in alpha-fetoprotein (AFP, P<0.05) and des-γ-carboxy prothrombin (DCP, P<0.001); and 3. Cumulative treatment numbers of TACE in 6 months (P=0.007). In the derivation cohort, the calibration curve of the nomogram showed a high consistency between the predicted and actual PFS probability, and the nomogram outperformed the BCLC staging system (P=0.004). This result was also confirmed in the validation cohort (P=0.012). Conclusion: The constructed nomogram was suggested to have good predictive efficacy and could be used as a complementary assessment to predict the survival and prognosis of HCC patients treated with TACE.

Exosomal circCARM1 from spheroids reprograms cell metabolism by regulating PFKFB2 in breast cancer.

Cancer stem cells (CSC) are the major obstacle for cancer therapy in clinic. Exosomes are one type of vesicles that containing circular RNA (circRNAs) involved in cell-cell communication. However, the roles of breast CSC (BCSC) exosomes are still unclear, and the purpose of the study was to investigate breast cancer cell metabolism reprogramming by circRNAs from BCSC exosomes. The circRNA array was performed in the exosomes secreted from spheroids of MDA-231 cells. circCARM1 was higher in BCSC exosomes than it in the parent breast cancer cells. Further investigation demonstrated that BCSC exosomes circCARM1 played an important role in breast cancer cell glycolysis by miR-1252-5p/PFKFB2. In a conclusion, BCSC exosome-derived circCARM1 played an important role in breast cancer cell glycolysis by sponging miR-1252-5p which regulated PFKFB2 expression.

A Six-Gene Risk Model Based on the Immune Score Reveals Prognosis in Intermediate-Risk Acute Myeloid Leukemia.

Tumor microenvironment (TME) has been revealed as an important determinant of diagnosis and treatment response in AML patients. The scores of immune and stromal cell scores of AML in the intermediate-risk group from The Cancer Genome Atlas (TCGA) database were calculated using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data algorithm. Differentially expressed genes were identified between high and low scores. Gene set enrichment and pathway analyses were performed. A risk score model based on TME for six immune-related genes was established and validated. Patients with a lower immune score had a longer overall survival than those with a higher score (P = 0.044). A total of 805 intersected genes as differentially expressed genes were identified and selected according to the comparison of both immune and stromal scores. The functional enrichment analysis shows that these genes are mainly associated with the immune/inflammatory response. The risk score model based on TME for six immune-related genes (including MEF2C, ENPP2, FAM107A, CD37, TNFAIP8L2, and CASS4) was established and validated in the TCGA database and well validated in the TARGET database (P = 0.005). A key microenvironment-related gene signature was identified that affects the outcomes of AML patients in the intermediate-risk group and might serve as therapeutic targets.

PACT promotes the metastasis of basal-like breast cancer through Rac1 SUMOylation and activation.

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which is associated with high malignancy, high rate of recurrence and distant metastasis, and poor prognosis among all types of breast cancer. However, there are currently no effective therapies for BLBC. Furthermore, chemoresistance limits the therapeutic options for BLBC treatment. In this study, we screen out protein activator of the interferon-induced protein kinase (PACT) as an essential gene in BLBC metastasis. We find that high PACT expression level was associated with poor prognosis among BLBC patients. In vivo and in vitro investigations indicated that PACT could regulate BLBC metastasis by interacting with SUMO-conjugating enzyme Ubc9 to stimulate the SUMOylation and thus consequently the activation of Rac1. BLBC patients receiving chemotherapy presents poorer prognosis with PACT high expression, and PACT disruption sensitizes experimental mammary tumor metastases to chemotherapy, thus providing insights to consider PACT as a potential therapeutic target to overcome acquired chemoresistance in BLBC.

Recycling of mullite from high-alumina coal fly ash by a mechanochemical activation method: Effect of particle size and mechanism research.

High-alumina coal fly ash (HAFA) is a special solid waste since its alumina content can reach 40-50 wt%, which is seen as a potential resource for mullite material production. However, obtaining an ideal mullite material from HAFA is difficult because of its low Al2O3/SiO2 mass ratio. In this work, the microstructure characteristics of HAFA were systematically analyzed by combining multiple characterization techniques. It was found that HAFA had a core-shell structure with a mullite/corundum crystal core and a silica-rich amorphous phase shell. The novel mechanochemical activation-desilication process was used to remove amorphous phase from HAFA and elevate the Al2O3/SiO2 mass ratio. In particular, the effect of particle size after mechanical treatment and mechanism of the desilication process were extensively investigated. On decreasing the particle size, a high leaching rate of alumina was achieved during mechanochemical activation, thus generating a hydroxysodalite coating layer as desilication was suppressed, and the amorphous phase was effectively removed. The mineralogical phase of the desilicated HAFA is mainly mullite and corundum, and the Al2O3/SiO2 mass ratio was elevated from 1.29 to 3.02. Mullite refractory obtained from the desilicated HAFA exhibited excellent physical properties. This study provides insights into further high-valued utilization of HAFA.

Case Report: Asymmetric Bone Marrow Involvement in Patients With Acute Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

After allogeneic hematopoietic stem cell transplantation (allo-HSCT), acute leukemia relapse is common, and asymmetric bone marrow recurrence hasn't been reported. Because the anatomical distribution of acute leukemia clones in the bone marrow after allo-HSCT is presumed to be diffuse, bone marrow aspirations are performed in single site. The first case was a 20-year-old man who was diagnosed with acute myelomonocytic leukemia and received haploidentical allo-HSCT. Routine bone marrow biopsy of his left posterior iliac bone marrow showed 52% leukemia blasts, while the right side had 0% blasts 10 days later. The second case was a 23-year-old woman who was diagnosed with acute B lymphoblastic leukemia and received HLA-identical sibling allo-HSCT. Although 62% of blasts were found in her left iliac marrow on day +122, 0% of blasts were found on a sample obtained from the right iliac crest on day +128. Bilateral iliac bone marrow pathology and whole-body 18F-FDG PET/CT scans confirmed that the leukemic infiltration in her bone marrow was asymmetric. To our knowledge, these are the first case reports of asymmetric bone marrow infiltration of blasts in acute leukemia patients after allo-HSCT. Bilateral posterior iliac crest aspirations or 18F-FDG-PET/CT scans may help distinguish such involvement.

Multimer technologies for detection and adoptive transfer of antigen-specific T cells.

Identification and purification of antigen-specific T cells without altering their functional status are of high scientific and clinical interest. Staining with major histocompatibility complex (MHC)-peptide multimers constitutes a very powerful method to study antigen-specific T-cell subpopulations, allowing their direct visualization and quantification. MHC-peptide multimers, such as dimers, tetramers, pentamers, streptamers, dextramers and octamers have been used to evaluate the frequency of CD8(+) T cells, specific for tumor/leukemia-associated antigens as well as for viral antigens, e.g., CMVpp65 and EBV-EBNA. Moreover, MHC-peptide multimers have been used for rapid and efficient ex vivo isolation and expansion of T cells. A recent development in the field of MHC-peptide multimers led to the purification of CD8(+) T cells specific for leukemia antigens. This might help to select leukemia-specific donor lymphocyte infusions (DLIs), thus allowing dissection of the noxious graft-versus-host disease (GvHD) from beneficial anti-viral and even anti-leukemic effects. This review covers different types of MHC-peptide multimers and their applications, as well as the impact that multimers might have on further development of DLIs.

PALB2 as a potential prognostic biomarker for colorectal cancer.

Partner and localizer of BRCA2 (PALB2) is regarded as a colorectal cancer (CRC) risk gene, but the prognostic implication of PALB2 in CRC remains unclear. In this study, we evaluate the prognostic value of the gene copy number alteration (CNA) and mRNA expression of PALB2 in The Cancer Genome Atlas (TCGA) database, and then validated with our database. We downloaded the copy number and mRNA data of PALB2 from TCGA database and examined the relationship among the genetic alterations, expression levels and survival outcomes. Gene ontology (GO) analysis was performed to study the function of PALB2. cBioPortal database was used to explore the potential co-expression genes of PALB2. There were 6.3% (37 of 582) CRC patients diagnosed as PALB2 gene deletion. The PALB2 deletion group expressed significantly lower of PALB2 mRNA than the non-deletion group (P < 0.001). Survival analysis showed that PALB2 deletion was significantly associated with shorter disease-free survival (DFS) (P = 0.026) and overall survival (OS) (P = 0.028). Low mRNA expression of PALB2 correlated with shorter OS (P < 0.001). Multivariate analysis also confirmed that PALB2 deletion and low mRNA expression of PALB2 were independent prognostic factors of poor OS in CRC (P = 0.019, 0.034, respectively). In validation cohort, negative expression of PALB2 was associated with shorter OS (P = 0.006) in stage I patients. Multivariate analysis confirmed that negative expression of PALB2 was a poor-prognostic factor (P = 0.002). GO analysis and co-expression analysis investigated that PALB2 is primarily involved in the DNA repair process. These results suggest that PALB2 gene copy number deletion and low mRNA expression could be novel prognostic biomarkers for CRC.