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Cytomegalovirus (CMV) infection and disease are important concerns after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The similarity of hepatitis B virus (HBV) and CMV with regards to their chronic viral persistence and potential reactivation at the time of impaired cellular immunity has raised clinicians' interest in the occurrence and association between them among patients receiving allo-HSCT; however, only limited data have been obtained from a high seroprevalence region of both CMV and HBV. We monitored 117 adult allo-HSCT patients with both CMV polymerase chain reaction and pp65 antigenemia assay weekly until day 100. In 91.8% of our cases, donors and recipients were both CMV seropositive, and 13.7% of the patients were positive for HBV surface antigen. The incidences of CMV infection and disease were 45.3% and 6.8%, respectively. Grade II-IV acute graft-versus-host disease and anti-thymocyte globulin-containing conditioning regimen were associated with an increased risk of CMV infection in a multivariate analysis (hazard ratio 3.02, 95% CI 1.68-5.42, p < 0.001 and hazard ratio 5.29, 95% CI 2.57-10.8, p < 0.001). No survival disadvantage was found in patients who developed CMV infection ( p = 0.699) and CMV disease ( p = 0.093). No clinically significant HBV reactivation was found, and the underlying HBV infection in donors or recipients before allo-HSCT did not increase the risk of CMV infection and CMV disease and did not influence survival after allo-HSCT. [ABSTRACT FROM AUTHOR]

Background: Infectious agents have been shown to contribute to the development of lymphoid malignancies. The different distribution of lymphoid malignancies in Asian and Western populations suggests possibly different etiologies in Asian populations. Herpes zoster infection, commonly seen in immunocompromised persons, has been reported to be associated with lymphoid malignancies in retrospective case–control studies from Western populations, but the results are controversial and large-scale prospective studies from Asian populations are lacking. Methods: A nationwide population-based matched-controlled prospective study on Taiwanese patients was performed using the National Health Insurance Research Database from 1996 to 2007. Herpes zoster and malignancies were defined by compatible ICD-9-CM (International Classification of Disease, 9th Revision, Clinical Modification) codes. Patients who had been diagnosed with any malignancies before herpes zoster, with known viral infections including human immunodeficiency virus, and duration from herpes zoster to diagnosis of malignancies less than 6 months were excluded. Results: Of 42,498 patients with herpes zoster prior to the diagnosis of any malignancies, the cumulative incidence for lymphoid malignancies was 0.11% (n = 48), compared with 0.06% (n = 106) in 169,983 age- and gender-matched controls (univariate hazard ratio (HR): 1.82, 95%CI: 1.29-2.55). The most common lymphoid malignancy was non-Hodgkin’s lymphoma (60.4%, n = 29), followed by multiple myeloma (27.1%, n = 13). Risk for developing lymphoid malignancies is significantly higher in herpes zoster patients (log rank P = 0.005). After adjusting for presence of any comorbidities in Charlson comorbidity index, time-dependent covariate for herpes group, and income category using Cox proportional hazard regressions, herpes zoster patients had an increased risk of developing lymphoid malignancies (adjusted HR: 1.68, 95%CI: 1.35-2.42, P = 0.0026), but did not have an increased risk of developing non-lymphoid malignancies (adjusted HR: 1.00, 95%CI: 0.91-1.05, P = 0.872). Conclusion: Preceding herpes zoster infection is an independent risk marker for subsequent lymphoid malignancies in Taiwanese subjects. Further studies are warranted for pathogenesis exploration and preventive strategies in Asian populations. [ABSTRACT FROM AUTHOR]

Janus kinase 2 mutation ( JAK2V617F) has been identified in myeloproliferative neoplasms. Furthermore, special single nucleoside polymorphisms (SNPs) have been found to be associated with the JAK2V617F mutation. Therefore, the associations among JAK2V617F and special SNPs and the allelic location between them were investigated in patients with essential thrombocythemia (ET). A total of 61 patients with ET and 106 healthy individuals were enrolled. The PCR-RFLP method was applied to investigate the pattern of three SNPs, rs10974944, rs12343867, and rs12340895. Allele-specific PCR was used to examine the allelic location between rs10974944 and JAK2V617F. Among the patients with ET, 34 (55.7%%, 34/61) were JAK2V617F positive (heterozygous) while the other 27 (44.3%%, 27/61) were negative, and there were no MPLW515L/K mutations noted. The pattern of special SNPs in JAK2V617F(++) was significantly different from that in normal individuals ( p <0.05), while there was no difference between JAK2V617F(−−) patients and normal individuals. Allele-specific PCR showed high association of a cis-location between the special G-allele of rs10974944 and JAK2V617F(++). Based on this small numbered study, the results show the association between special SNPs and JAK2V617F mutation and a cis-location between the special G-allelic form of rs10974944 and the JAK2V617F mutation. These data highlight a close relationship between them in patients with ET. [ABSTRACT FROM AUTHOR]

Abstract: The deletion of the long arm of chromosome 20, or del(20q), is a common cytogenetic abnormality in various myeloid disorders and is known to be a favorable prognostic factor in myelodysplastic syndromes (MDS) when it is the sole change. However, del(20q) occurs with one or more cytogenetic changes when it is associated with disease progression. Here, we analyzed 33 patients with MDS and del(20q) to ascertain the risk factors in MDS. We categorized del(20q) into two groups: one with the del(20q) clone (≥50% marrow metaphases), corresponding to genomic integrity, and the other with a late appearance of a minor del(20q) clone (<50% metaphases) with additional cytogenetic changes, representing genomic instability. Of the MDS patients with del(20q) at initial presentation, the negative factors in predicting prognosis on survival are (i) INT-2/High risk according to the International Prognostic Scoring System, (ii) any additional cytogenetic changes, or (iii) minor del(20q) clone. The late appearance of del(20q) at any phase is linked to a significantly unfavorable prognosis, thus indicating the clinical and biological heterogeneity of del(20q) in MDS. [Copyright &y& Elsevier]

Abstract: The deletion of the long arm of chromosome 20, or del(20q), is a common cytogenetic abnormality in various myeloid disorders but is less commonly seen in lymphoid neoplasms. Here we report a case of Waldenström macroglobulinemia with del(20q) as the sole cytogenetic anomaly. No translocation including immunoglobulin genes was identified by spectral karyotyping (SKY) analysis. Reviewing all 11 reported cases of plasma cell dyscrasia possessing sole del(20q), including our case, none of 4 cases with del(20q) as an initial anomaly developed myelodysplastic syndrome–acute myeloid leukemia (MDS/AML), but at least 3 cases with del(20q) appearing after chemotherapy developed MDS/AML at or after the time of del(20q). We propose that the del(20q) may have different clinical significance in plasma cell dyscrasia: one is when del(20q) appears at diagnosis and may involve the initial event of oncogenesis, and the other is when del(20q) appears after treatment and is associated with therapy-related and potential MDS/AML risk. [Copyright &y& Elsevier]

Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world's population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy. [ABSTRACT FROM AUTHOR]

The development and refinement of functional brain circuits crucial to human cognition is a continuous process that spans from childhood to adulthood. Research increasingly focuses on mapping these evolving configurations, with the aim to identify markers for functional impairments and atypical development. Among human cognitive systems, nonsymbolic magnitude representations serve as a foundational building block for future success in mathematical learning and achievement for individuals. Using task‐based frontoparietal (FPN) and salience network (SN) features during nonsymbolic magnitude processing alongside machine learning algorithms, we developed a framework to construct brain age prediction models for participants aged 7–30. Our study revealed differential developmental profiles in the synchronization within and between FPN and SN networks. Specifically, we observed a linear increase in FPN connectivity, concomitant with a decline in SN connectivity across the age span. A nonlinear U‐shaped trajectory in the connectivity between the FPN and SN was discerned, revealing reduced FPN‐SN synchronization among adolescents compared to both pediatric and adult cohorts. Leveraging the Gradient Boosting machine learning algorithm and nested fivefold stratified cross‐validation with independent training datasets, we demonstrated that functional connectivity measures of the FPN and SN nodes predict chronological age, with a correlation coefficient of.727 and a mean absolute error of 2.944 between actual and predicted ages. Notably, connectivity within the FPN emerged as the most contributing feature for age prediction. Critically, a more matured brain age estimate is associated with better arithmetic performance. Our findings shed light on the intricate developmental changes occurring in the neural networks supporting magnitude representations. We emphasize brain age estimation as a potent tool for understanding cognitive development and its relationship to mathematical abilities across the critical developmental period of youth. Practitioner Points: This study investigated the prolonged changes in the brain's architecture across childhood, adolescence, and adulthood, with a focus on task‐state frontoparietal and salience networks.Distinct developmental pathways were identified: frontoparietal synchronization strengthens consistently throughout development, while salience network connectivity diminishes with age. Furthermore, adolescents show a unique dip in connectivity between these networks.Leveraging advanced machine learning methods, we accurately predicted individuals' ages based on these brain circuits, with a more mature estimated brain age correlating with better math skills. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) in diffuse large B-cell lymphoma (DLBCL) is associated with a higher prevalence and distinctive clinical characteristics and outcomes. Methods: A retrospective analysis of adult DLBCL patients from 2011 to 2015 was studied. Results: A total of 206 adult DLBCL were enrolled with 22 (10.7%) HCV-positive patients. Compared to HCV-negative patients, the HCV-positive group had a poor performance status (p = 0.011), lower platelet count (p = 0.029), and higher spleen and liver involvement incidences (liver involvement, p = 0.027, spleen involvement, p = 0.026), and they received fewer cycles of chemotherapy significantly due to morbidity and mortality (p = 0.048). Overall survival was shorter in HCV-positive DLBCL (25.3 months in HCV-positive vs. not reached (NR), p = 0.049). With multivariate analysis, poor performance status (p < 0.001), advanced stage (p < 0.001), less chemotherapy cycles (p < 0.001), and the presence of liver toxicity (p = 0.001) contributed to poor OS in DLBCL. Among HCV-positive DLBCL, the severity of liver fibrosis was the main risk factor related to death. Conclusion: Inferior survival of HCV-positive DLBCL was observed and associated with poor performance status, higher numbers of complications, and intolerance of treatment, leading to fewer therapy. Therefore, anti-HCV therapy, such as direct-acting antiviral agents, might benefit these patients in the future. [ABSTRACT FROM AUTHOR]

Abstract: We searched for the Chlamydia psittaci DNA the touchdown enzyme time release PCR (TETR-PCR) in 23 specimens from 21 patients with ocular adnexal lymphoproliferative disorders, including 12 patients with MALT lymphoma to identify C. psittaci infection. Southern hybridization of the PCR product using the C. psittaci-specific probe failed to detect C. psittaci, although three samples appeared to be positive by ethidium bromide staining. This indicates that technical approach for detecting C. psittaci infection in ocular adnexal lymphoma might be an essential in disclosing this association. [Copyright &y& Elsevier]

Rosa cymosa Tratt is a Chinese herbal remedy that is used in the treatment of diarrhea, burns, rheumatoid arthritis, and hemorrhage. Despite its use in Asian folk medicine, there are limited reports on the biological activity of R. cymosa fruits. This study focused on the investigation of the antitumor effect of the antioxidative ethanolic extract of R. cymosa fruits (RCE) along with its underlying mechanism of action. RCE showed a potent cytotoxic effect against Sup-T1 and Molt-4 lymphoblastic leukemia cells. In the xenograft animal model, the tumor size was significantly reduced to about 59.42% in the RCE-treated group in comparison with the control group. The use of RCE (37.5, 75, or 150 μg/mL) triggered apoptosis by 26.52–83.49%, disrupted mitochondrial membrane potential (MMP) by 10.44–58.60%, and promoted calcium release by 1.29-, 1.44-, and 1.71-fold compared with the control group. The extract induced redox oxygen species (ROS) generation through the elimination of Nrf2/Keap1/P62-mediated oxidative stress response. The loss of phosphatase and tensin homolog (PTEN) activation by RCE impaired PI3K/Akt/Foxo and Jak/Stat activation pathways, which contributed to tumorigenesis. These multiple targets of R. cymosa against hematologic cancer cells suggested its potential application as an antileukemic dietary supplement. [ABSTRACT FROM AUTHOR]

Reported cases of breast cancer have skyrocketed in the last decades with recent advances in examination techniques. Brest cancer has become the second leading cause of mortality among women worldwide, urging the scientific community to develop or find new drugs from natural sources with potent activity and a reasonable safety profile to tackle this ailment. Antrodia cinnamomea (AC) is a treasured medicinal fungus which has attracted attention due to its potent hepatoprotective and cytotoxic activities. We evaluated the antiproliferative activity of the ethanol extract of artificially cultured AC (EEAC) on breast cancer cells (T47D cells) in vivo and in vitro. Ethanol extract of artificially cultured AC inhibited T47D cells' proliferation mediated by cell cycle arrest at G1 phase as well induced autophagy. Immunoblotting assay confirmed that EEAC not only decreased the expression of the cell-cycle-related proteins but also increased the expression of transcription factor FOXO1, autophagic marker LC3 II, and p62. Ethanol extract of artificially cultured AC mediated endoplasmic reticulum stress by promoting the expression of IRE1 (inositol-requiring enzyme 1α), GRP78/Bip (glucose regulating protein 78), and CHOP (C/EBP homologous protein). Apart from previous studies, HDACs (histone deacetylases) activity was inhibited as demonstrated by a cell-free system, immunoblotting, and immunofluorescence assays following EEAC treatment. The in vivo studies demonstrated that EEAC decreased tumor volume and inhibited tumor growth without any significant side effects. High performance liquid chromatography profile demonstrated similar triterpenoids compared to the profile of wild AC ethanol extract. The multiple targets of EEAC on breast cancer cells suggested that this extract may be developed as a potential dietary supplement targeting this debilitating disease. [ABSTRACT FROM AUTHOR]

The present study aimed to elucidate the prognostic mutation signature (PMS) associated with long-term survival in a diffuse large B-cell lymphoma (DLBCL) cohort. All data including derivation and validation cohorts were retrospectively retrieved from The Cancer Genome Atlas (TCGA) database and whole-exome sequencing (WES) data. The Lasso Cox regression analysis was used to construct the PMS based on WES data, and the PMS was determined using the area under the receiver operating curve (AUC). The predictive performance of eligible PMS was analyzed by time-dependent receiver operating curve (ROC) analyses. After the initial evaluation, a PMS composed of 94 PFS-related genes was constructed. Notably, this constructed PMS accurately predicted the 12-, 36-, and 60-month PFS, with AUC values of 0.982, 0.983, and 0.987, respectively. A higher level of PMS was closely linked to a significantly worse PFS, regardless of the molecular subtype. Further evaluation by forest plot revealed incorporation of international prognostic index or tumor mutational burden into PMS increased the prediction capability for PFS. The drug-gene interaction and pathway exploration revealed the PFS-related genes were associated with DNA damage, TP53, apoptosis, and immune cell functions. In conclusion, this study utilizing a high throughput genetic approach demonstrated that the PMS could serve as a prognostic predictor in DLBCL patients. Furthermore, the identification of the key signaling pathways for disease progression also provides information for further investigation to gain more insight into novel drug-resistant mechanisms. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) organoids are frequently used to examine cell proliferation and death as well as cancer development. Invasion/migration assay, xenotransplantation, and reactive oxygen species (ROS) production were used to examine the effects of antioxidant drugs, including perillaldehyde (PEA), cinnamaldehyde (CA), and sulforaphane (SFN), on GC. PEA and CA repressed the proliferation of human GC organoids, whereas SFN enhanced it. Caspase 3 activities were also repressed on treatment with PEA and CA. Furthermore, the tumor formation and invasive activities were repressed on treatment with PEA and CA, whereas they were enhanced on treatment with SFN. These results in three-dimensional (3D)-GC organoids showed the different cancer development of phase II enzyme ligands in 2D-GC cells. ROS production and the expression of TP53, nuclear factor erythroid 2-related factor (NRF2), and Jun dimerization protein 2 were also downregulated on treatment with PEA and CA, but not SFN. NRF2 knockdown reversed the effects of these antioxidant drugs on the invasive activities of the 3D-GC organoids. Moreover, ROS production was also inhibited by treatment with PEA and CA, but not SFN. Thus, NRF2 plays a key role in the differential effects of these antioxidant drugs on cancer progression in 3D-GC organoids. PEA and CA can potentially be new antitumorigenic therapeutics for GC. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on a case of donor cell-derived acute promyelocytic leukemia.

This study aimed to investigate the treatment strategy, prognostic factors, and risk factors of early death in elderly patients (age ≥ 65 years) with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Data from elderly patients diagnosed with DLBCL between 2008 and 2014 were collected for analysis. Patients who were younger and had a better performance status were more likely to receive intensive frontline treatment. The median progression-free survival (PFS) and overall survival were 15 and 21 months, respectively. Anthracycline-containing chemotherapy achieved a higher remission rate and showed a trend towards better overall survival but a higher risk of severe neutropenia. Multivariate analysis revealed that very old age (≥81 years), a high-risk age-adjusted international prognostic index (aaIPI) score, and bone marrow involvement were associated with poorer PFS and overall survival. Progression of lymphoma was the major cause of death in the study population. In addition, approximately 25% of patients died within 120 days of being diagnosed. The risk factors for early mortality included very old age, a high-risk aaIPI score, and bone marrow involvement. The appearance of symptoms or signs of tumour lysis syndrome at diagnosis was associated with a trend towards early death. [ABSTRACT FROM AUTHOR]

The article describes the case of a 49-year old African American woman who was diagnosed with structural abnormality in the transthyretin peptide sequence, T60A and V1221, in endomyocardial and bone marrow biopsies and heterozygous mutations at TTR gene sequencing that are causing onset severe cardiac amyloidosis. It discusses the risk of cardiac amyloidosis in African Americans and the difference in age of onset cardiac amyloidosis. The cardiac manifestations in the patient's case is tackled.

Patients with hematologic malignancies are reported to have a more severe course of coronavirus disease 2019 (COVID-19) and be less responsive to vaccination. In this prospective study, we aimed to evaluate the serological responses to booster COVID-19 vaccines of Taiwanese patients with hematologic malignancies and identify potential predictive markers for effective neutralizing immunity. This study enrolled 68 patients with hematologic malignancies and 68 age- and gender-matched healthy control subjects who received three doses of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 1 January 2022 to 31 October 2022. The SARS-CoV-2 immunoglobulin G (IgG) spike antibody level was measured with the Abbott assay. The effective neutralization capacity was defined as an anti-spike IgG level of ≥4160 AU/mL. Among the 68 patients with hematologic malignancies, 89.7% achieved seroconversion after booster doses. Seven patients with actively treated lymphoma remained seronegative and had the lowest humoral responses among patients with different types of hematologic malignancies. Despite comparable antibody titers between patients and healthy individuals, rates of effective neutralization (66.2% vs. 86.8%, respectively; p = 0.005) were significantly reduced in patients with hematologic malignancies. In a multivariate analysis, the independent predictors for effective neutralization were a lack of B-cell-targeted agents within six months of vaccination (odds ratio, 15.2; 95% confidence interval, 2.7–84.2; p = 0.002) and higher immunoglobulin levels (odds ratio, 4.4; 95% confidence interval, 1.3–14.7; p = 0.017). In conclusion, the majority of patients with hematologic malignancies achieved seroconversion after booster vaccination. Patients with ongoing B-cell depletion and hypogammaglobinemia were identified as having negative predictive markers for effective neutralization. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse large B-cell lymphoma (DLBCL) is a prevalent hematological malignancy which is characterized by rapid cancer cell growth and aggressive progression. The standard treatment is R-CHOP, which offers limited prognosis improvement for only 60% of patients. This study aimed to identify DLBCL tumor markers and to explore cytotoxic medicine. The results demonstrated significant upregulation of G9a/EHMT2 mRNA in DLBCL. Niclosamide effectively suppressed G9a expression, modulated autophagy-related gene expression (p62, BECN1, and LC3), and impeded DLBCL cell proliferation. Analysis of clinical specimens and patients' information revealed a positive correlation between G9a protein levels and DLBCL staging, indicating its potential as a prognostic biomarker. Our study provides valuable insight that highlights the potential of G9a as a therapeutic target and niclosamide as a potential treatment to combat DLBCL. Background: Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers. Methods: TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples. Results: The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells. Conclusion: G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we developed human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes with a high potency of presentation ability. This study aimed to verify the safety, tolerability, and immunoinducibility of HPL-APCs loaded with cancer candidate antigens as a Phase I study. As a result of the interim analysis, safety and tolerability were confirmed in three enrolled patients, and the immune response to cancer antigen candidate peptides predicted in silico was confirmed in two completed cases. This clinical study is the first to verify the feasibility and immunoinducibility of a personalized cancer vaccine using HPL-APCs that would be expected to demonstrate further antitumor activity through optimized combination therapies. Research and development of personalized cancer vaccines as precision medicine are ongoing. We predicted human leukocyte antigen (HLA)-compatible cancer antigen candidate peptides based on patient-specific cancer genomic profiles and performed a Phase I clinical trial for the safety and tolerability of cancer vaccines with human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes. Among the five enrolled patients, two patients completed six doses per course (2–3 × 107 cells per dose), and an interim analysis was performed based on the immune response. An immune response was detected by enzyme-linked immunosorbent spot (ELISpot) assays to HLA-A*33:03-matched KRASWT, HLA-DRB1*09:01-compliant KRASWT or G12D, or HLA-A*31:01-matched SMAD4WT, and HLA-DRB1*04:01-matched SMAD4G365D peptides in two completed cases, respectively. Moreover, SMAD4WT-specific CD8+ effector memory T cells were amplified. However, an attenuation of the acquired immune response was observed 6 months after one course of cancer vaccination as the disease progressed. This study confirmed the safety and tolerability of HPL-APCs in advanced and recurrent cancers refractory to standard therapy and is the first clinical report to demonstrate the immunoinducibility of personalized cancer vaccines using HPL-APCs. Phase II clinical trials to determine immune responses with optimized adjuvant drugs and continued administration are expected to demonstrate efficacy. [ABSTRACT FROM AUTHOR]

We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of H. pylori-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled H. pylori was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of H. pylori did not affect the proliferation of each H. pylori-infected cancer organoid. To clarify the role of HDGF and TNFα secreted from H. pylori-infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of H. pylori, but TNFα decreased the cell viability in H. pylori-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of H. pylori-infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by H. pylori. Recombinant HDGF and TNFα inhibited the development and invasion of H. pylori-infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of H. pylori-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells. [ABSTRACT FROM AUTHOR]

The article discusses the use of the manual polybrene method of detecting red blood cell (RBC) antibodies in patients with daratumumab therapy. Topics include reason that interference of daratumumab with compatibility test for pretransfusion examination is a concerning issue, proposed solutions to overcome this issue, and the main shortcoming of the MP test.

Since 1993, following the National Thalassemia Major Prevention Program and an increase in immigration and interracial marriages, especially in southern Taiwan, the distribution of hemoglobinopathies may have changed. This study investigates the epidemiologic transition of hemoglobinopathies. We analyzed 1870 specimens collected between 2003 and 2012 in southern Taiwan, used gap-polymerase chain reaction and PCR-restriction fragment length polymorphism-based methods, and confirmed genotypes of hemoglobinopathies by DNA sequencing. We found a 91% reduction in the incidence of thalassemia major compared with samples from between 1986 and 1995. The most common genotypes of α-thalassemia and α Hb variants were the SEA type (69.4%) and Hb Quong Sze (1.54%). The most common genotypes of β-thalassemia and β Hb variants were IVS-II-654 (46.2%) and Hb E (2.2%), respectively. Compared with studies performed in different areas of and time intervals in Taiwan, a higher prevalence of -α3.7, Hb Quong Sze, and Hb E and a lower prevalence of the SEA type were found in this study. However, the SEA type remained the most common genotype observed. In addition, an increasing number of cases with an -α3.7 type carrier, Hb Quong Sze carrier, and Gγ(Aγδβ)° were identified following a peak of interracial marriages between 2003 and 2005, reflecting a regional difference and the impact of interracial marriage. In conclusion, global migration and international marriage have changed the distribution of hemoglobinopathies in Taiwan. A more comprehensive prenatal screening for new immigrants with a longer follow-up is warranted. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the association between previous exposure to statins and the risk of non-Hodgkin lymphoma (NHL). Methods: This nationwide population-based case–control study was conducted using the National Health Insurance Research Database of Taiwan. The NHL group consisted of the patients with a first-time diagnosis of NHL between 2005 and 2008. The cases of the control group were pair-matched to the NHL group according to sex, year of birth and date of NHL diagnosis (index date). The statin administration data from both groups were retrospectively collected from the index date to January 1, 1996. The cumulative defined daily dose (cDDD) was estimated to evaluate the statin exposure. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression. Results: The study population was composed of 1715 NHL patients and 16942 control subjects. The analysis revealed that previous statin administration was associated with a reduced risk of subsequent NHL with an adjusted OR of 0.52 (95% CI, 0.43–0.62). Additionally, there was a dose-response relationship between statin administration and the risk of NHL. The adjusted ORs were 0.63 (95% CI, 0.46–0.86), 0.58 (95% CI, 0.42–0.79), 0.51 (95% CI, 0.38–0.67), and 0.36 (95% CI, 0.24–0.53) for the subjects with statin administrations of fewer than 28, 28 to 90, 91 to 365, and more than 365 cDDDs, respectively, relative to the subjects without any statin administration. Conclusions: The results of this study suggest that previous statin administration is associated with a lower risk of subsequent NHL. As statins are widely used medications, the magnitude of the risk reduction may have a substantial influence on public health. Further studies to confirm our findings are warranted. [ABSTRACT FROM AUTHOR]

Stomach cancer has a high mortality, which is partially caused by an absence of suitable biomarkers to allow detection of the initiation stages of cancer progression. Thus, identification of critical biomarkers associated with gastric cancer (GC) is required to advance its clinical diagnoses and treatment. Recent studies using tracing models for lineage analysis of GC stem cells indicate that the cell fate decision of the gastric stem cells might be an important issue for stem cell plasticity. They include leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5+), Cholecystokinin receptor 2 (Cckr2+), and axis inhibition protein 2 (Axin2+) as the stem cell markers in the antrum, Trefoil Factor 2 (TFF2+), Mist1+ stem cells, and Troy+ chief cells in the corpus. By contrast, Estrogen receptor 1 (eR1), Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1), SRY (sex determining region Y)-box 2 (Sox2), and B lymphoma Mo-MLV insertion region 1 homolog (Bmi1) are rich in both the antrum and corpus regions. These markers might help to identify the cell-lineage identity and analyze the plasticity of each stem cell population. Thus, identification of marker genes for the development of GC and its environment is critical for the clinical application of cancer stem cells in the prevention of stomach cancers. [ABSTRACT FROM AUTHOR]

Aeroplysinin-1 is a brominated isoxazoline alkaloid that has exhibited a potent antitumor cell effect in previous reports. We evaluated the cytotoxicity of aeroplysinin-1 against leukemia and prostate cancer cells in vitro. This marine alkaloid inhibited the cell proliferation of leukemia Molt-4, K562 cells, and prostate cancer cells Du145 and PC-3 with IC50 values of 0.12 ± 0.002, 0.54 ± 0.085, 0.58 ± 0.109 and 0.33 ± 0.042 µM, respectively, as shown by the MTT assay. Furthermore, in the non-malignant cells, CCD966SK and NR8383, its IC50 values were 1.54 ± 0.138 and 6.77 ± 0.190 μM, respectively. In a cell-free system, the thermal shift assay and Western blot assay verified the binding affinity of aeroplysinin-1 to Hsp90 and Topo IIα, which inhibited their activity. Flow cytometry analysis showed that the cytotoxic effect of aeroplysinin-1 is mediated through mitochondria-dependent apoptosis induced by reactive oxygen species (ROS). ROS interrupted the cellular oxidative balance by activating NOX and inhibiting HIF-1α and HO-1 expression. Pretreatment with N-acetylcysteine (NAC) reduced Apl-1-induced mitochondria-dependent apoptosis and preserved the expression of NOX, HO-1, and HIF-1a. Our findings indicated that aeroplysinin-1 targeted leukemia and prostate cancer cells through multiple pathways, suggesting its potential application as an anti-leukemia and prostate cancer drug lead. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a B-cell lymphoma featuring an aggressive course and a progressive relapsing pattern. International guidelines recommend early consolidative autologous stem cell transplant (auto-SCT) for eligible patients while reserving allogeneic SCT (allo-SCT) as therapy for refractory cases. Since data describing the implementation of transplants in the Asian population with MCL are limited, we aimed to analyze post-SCT outcomes of 99 MCL patients from the Taiwan Bone Marrow Transplant Registry database. The median age was 56 years, and 11% of the patients had blastoid variant MCL. Ninety-four patients received auto-SCT, while 13 patients received allo-SCT, eight of which received allo-SCT after failing auto-SCT. Before auto-SCT, 52% of the patients were in their first complete remission (CR1). Overall, 37 patients (39%) relapsed after auto-SCT. The median post-auto-SCT progression-free survival and overall survival (OS) were 43.6 months and not reached, respectively. Blastoid variant MCL, transplant not received in CR1, and disease progression within 12 months post-auto-SCT independently predicted inferior OS in multivariable analysis. The median post-allo-SCT OS was 74 months. Two patients (15%) died of MCL recurrence post-allo-SCT. Three patients with refractory diseases were salvaged with ibrutinib or venetoclax to allo-SCT. Treatment strategies incorporating novel agents warrant further optimization. [ABSTRACT FROM AUTHOR]

Infection is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) especially cytomegalovirus (CMV) infection and invasive fungal infection (IFI). Taiwan is a high CMV seroprevalence area. Our study aimed to evaluate the incidence, risk factors, the impact on survival of CMV infection (including reactivation and disease) and the association of CMV infection and IFI in recipients after allo-HSCT during the first 100 days after transplantation. This was a retrospective study including 180 recipients of allo-HSCT. A total of 99 patients had CMV reactivation, and nine patients had CMV diseases. There were more mismatched donors, more ATG usage and more transplantation from CMV IgG-negative donor in patients with CMV reactivation. There was no survival difference in patients with or without CMV reactivation. A total of 34 patients had IFIs, and IFI after allo-HSCT was associated with significantly inferior survival. Patients with CMV reactivation did not increase the incidence of overall IFI, but they did result in more late-onset (>40 days) IFI (p = 0.056). In this study, we demonstrated real-world data of CMV infection and IFI from a high CMV seroprevalence area. [ABSTRACT FROM AUTHOR]

Objectives: The Janus kinase 2 mutation, JAK2 (V617F), and megakaryocytic mutations, MPL (W515L/K), have been identified and correlated with a subtype of essential thrombocythemia (ET) patients. We investigated the frequency of mutations in ET patients and analyzed the relationship with their clinical features. Methods: Fifty-three ET patients were enrolled in the study. The amplification refractory mutation system was applied for the mutation survey of the JAK2V617F , while the polymerase chain reaction with sequencing was used for the mutation survey of MPLW515L/K . Results: Thirty-five (66%) patients harboring the JAK2 V617F mutation, including 3 homozygous and 32 heterozygous changes, but no MPLW515L/K mutation, were found. During follow-up, 17 (32.1%) patients suffered from documented thrombotic events, with 15 having JAK2V617F mutations. Statistical analysis showed that patients with the JAK2 mutation had significantly higher leukocytes, hemoglobin level, and thrombotic event (p = 0.043, p = 0.001, and p = 0.029, respectively). Thrombotic events were also significantly correlated with leukocytosis and older age. Conclusions: The JAK2V617F mutation was noted in a certain population of ET patients and correlated with leukocytosis, high hemoglobin level, and thrombosis. Therefore, detection of the JAK2V617F mutation can affect not only the diagnosis, but also the management of ET patients. [Copyright &y& Elsevier]

Primary central nervous system lymphoma (PCNSL) is a rare lymphoma, and the disease course is often aggressive with poor prognosis outcomes. PCNSL undergoes germinal center reactions and impairs B-cell maturation. However, angiogenesis is also involved in the tumorigenesis and progression of PCNSL. This study investigated the effects of the tumor microenvironment and angiogenesis-associated genomic alterations on the outcomes of PCNSL. The analysis also evaluated the influence of treatment modality and timing on PCNSL survival using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and disease outcomes with a small sample of measurements and structural models. A total of 19 immunocompetent PCNSL samples were analyzed by exome sequencing. Our results suggest that the timing of radiotherapy and mutations of ROBO1 and KAT2B are potential indicators of PCNSL outcomes and may be affected by baseline characteristics such as age and sex. Our results also showed that patients with no mutations of ROBO1 and KAT2B, SubRT subgroup showed favorable survival outcomes compared with no SubRT subgroup in short-term follow-up. All SubRT patients have received high-dose methotrexate induction chemotherapy in the initial treatment. Therefore, initial induction chemotherapy combined with subsequent radiotherapy might improve survival outcomes in PCNSL patients who have no ROBO1 and KAT2B somatic mutations in short-term follow-up. The overall findings suggest that the tumor microenvironment and angiogenesis-associated genomic alterations and treatment modalities are potential indicators of overall survival and may be affected by the baseline characteristics of PCNSL patients. [ABSTRACT FROM AUTHOR]

Most acute myeloid leukemia (AML) cells are argininosuccinate synthetase‐deficient. Pegylated arginine deiminase (ADI‐PEG20) monotherapy depletes circulating arginine, thereby selectively inducing tumor cell death. ADI‐PEG20 was shown to induce complete responses in ~10% of relapsed/refractory or poor‐risk AML patients. We conducted a phase I, dose‐escalation study combining ADI‐PEG20 and low‐dose cytarabine (LDC) in AML patients. Patients received 20 mg LDC subcutaneously twice daily for 10 days every 28 days and ADI‐PEG20 at 18 or 36 mg/m2 (dose levels 1 and 2) intramuscularly weekly. An expansion cohort for the maximal tolerated dose of ADI‐PEG20 was planned to further estimate the toxicity and preliminary response of this regimen. The primary endpoints were safety and tolerability. The secondary endpoints were time on treatment, overall survival (OS), overall response rate (ORR), and biomarkers (pharmacodynamics and immunogenicity detection). Twenty‐three patients were included in the study, and seventeen patients were in the expansion cohort (dose level 2). No patients developed dose‐limiting toxicities. The most common grade III/IV toxicities were thrombocytopenia (61%), anemia (52%), and neutropenia (30%). One had an allergic reaction to ADI‐PEG20. The ORR in 18 evaluable patients was 44.4%, with a median OS of 8.0 (4.5‐not reached) months. In seven treatment‐naïve patients, the ORR was 71.4% and the complete remission rate was 57.1%. The ADI‐PEG20 and LDC combination was well‐tolerated and resulted in an encouraging ORR. Further combination studies are warranted. (This trial was registered in ClinicalTrials.gov as a Ph1 Study of ADI‐PEG20 Plus Low‐Dose Cytarabine in Older Patients With AML, NCT02875093). [ABSTRACT FROM AUTHOR]

The reactions of azidopyrazole with some of primary amines and active methylene compounds were studied. Structures of the prepared compounds were identified using spectroscopic techniques. The reactions mechanisms were also proposed. The cytotoxic and antimicrobial activities were also examined for the newly synthesized compounds. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 51-year-old woman who was admitted to the hospital due to history of ecchymosis and general malaise. She was diagnosed with postallogeneic hematopoietic stem cell transplantation relapse of acute myeloid leukemia (AML) with salivary gland myelosarcoma. The results of her examinations are also provided, including molecular analysis, bone marrow biopsy, and computed tomography.

Abstract: We report a patient with myelodysplastic syndrome (refractory anemia) showing the karyotype 46,XY,+1,der(1;10)(q10;p10), resulting in trisomy 1q and monosomy 10q abnormality. This finding suggests that either trisomy of 1q or centromeric connection between chromosomes 1 and 10, rather than the absence of 10q, might be essential toward neoplastic transformation. [Copyright &y& Elsevier]

Hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). We conducted this study to investigate the incidence and risk factors of hepatic VOD for patients receiving HSCT in Taiwan. We retrospectively analyzed the data from a nationwide registry for patients receiving HSCT, which was collected by the Taiwan Society of Blood and Marrow Transplantation. The data collection period was from 2009 to 2014. A total 2345 patients were reviewed and 39 patients among them were diagnosed as having hepatic VOD. The cumulative incidence of hepatic VOD in the whole cohort of 2345 patients was 1.66%. In multivariate analysis, disease diagnosis of myelodysplastic syndrome, chronic HCV infection, condition regimens of bulsulfan intravenously administered, and antithymocyte immunoglobulin were independent factors to predict higher risk of hepatic VOD. The overall mortality rate for patients with hepatic VOD was 79%. Patients with hepatic VOD had significant worse survival outcomes when compared with those without hepatic VOD (P = 0.00063). In conclusion, although the incidence is low, hepatic VOD remains a serious complication after HSCT in Taiwan. The findings of this study could be the basis for developing prophylactic or early treatment strategies for hepatic VOD. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most dismal malignancies worldwide. Despite multidisciplinary involvement in interventions involving surgery, radiotherapy, and chemotherapy, most pancreatic cancer patients eventually develop distant metastasis. S-phase kinase–associated protein 2 (Skp2) plays an important role in cell-cycle regulation in pancreatic cancer. However, the role of Skp2 in individualized PDAC treatment is largely unknown. Immunoblotting, quantitative reverse transcription polymerase chain reaction, cell viability test, chromatin immunoprecipitation assay, and xenograft in vivo assay were performed in parental and Skp2-depleted cells. The immunohistochemistry of Skp2 was analyzed on the tissue microarrays of 45 PDAC cases and mice tissues. In this study, we observed that Skp2 is a marker for poor prognosis in PDAC patients. Upregulation of the inhibitor of κB (IκB)-inducing kinase–nuclear factor kappa B (NF-κB) signal cascade mediated Skp2 expression thereby promoting epithelial–mesenchymal transition (EMT). Depletion of NF-κB-associated signaling effectively prevented Skp2-mediated pancreatic cancer cell migration. As a functional consequence, Skp2 orchestrated with Myc to induce zinc finger E -box binding homeobox 1 (Zeb1) transcription by recruiting p300 to the Zeb1 promoter independent of Skp2 E3–ligase activity. Therefore, blockade of Skp2 could significantly reduce the expression of Zeb1 and inhibit cancer cell migration. In conclusion, Skp2 regulated Zeb1 activity to control the migration and invasion abilities of pancreatic cancer cells. Skp2 expression in PDAC may affect cell vulnerability to standard chemotherapy regimens. Therefore, in patients with PDAC, modulation of Skp2 expression could be a novel strategy for preventing cancer cell metastasis. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) constitutes one of the most dismal malignancies worldwide. Despite multidisciplinary involvement in interventions involving surgery, radiotherapy, and chemotherapy, most pancreatic cancer patients eventually develop distant metastasis. S-phase kinase–associated protein 2 (Skp2) plays an important role in cell-cycle regulation in pancreatic cancer. However, the role of Skp2 in individualized PDAC treatment is largely unknown. Immunoblotting, quantitative reverse transcription polymerase chain reaction, cell viability test, chromatin immunoprecipitation assay, and xenograft in vivo assay were performed in parental and Skp2-depleted cells. The immunohistochemistry of Skp2 was analyzed on the tissue microarrays of 45 PDAC cases and mice tissues. In this study, we observed that Skp2 is a marker for poor prognosis in PDAC patients. Upregulation of the inhibitor of κB (IκB)-inducing kinase–nuclear factor kappa B (NF-κB) signal cascade mediated Skp2 expression thereby promoting epithelial–mesenchymal transition (EMT). Depletion of NF-κB-associated signaling effectively prevented Skp2-mediated pancreatic cancer cell migration. As a functional consequence, Skp2 orchestrated with Myc to induce zinc finger E -box binding homeobox 1 (Zeb1) transcription by recruiting p300 to the Zeb1 promoter independent of Skp2 E3–ligase activity. Therefore, blockade of Skp2 could significantly reduce the expression of Zeb1 and inhibit cancer cell migration. In conclusion, Skp2 regulated Zeb1 activity to control the migration and invasion abilities of pancreatic cancer cells. Skp2 expression in PDAC may affect cell vulnerability to standard chemotherapy regimens. Therefore, in patients with PDAC, modulation of Skp2 expression could be a novel strategy for preventing cancer cell metastasis. [ABSTRACT FROM AUTHOR]

Several molecular markers, such as NPM1, FLT3 and CEBPA, have been incorporated into both the World Health Organization and European LeukemiaNet classifications as routine assessments for the diagnosis and evaluation of prognostic significance in acute myeloid leukemia (AML). Lipocalin 2 ( LCN2) is related to cancer development and is believed to be associated with the outcome of cytogenetically normal (CN)-AML. In the present study, we analyzed the prognostic effects and interactions of LCN2 expression (by molecular analysis, quantitative real-time polymerase chain reaction [qRT-PCR]) with neucleophosmin 1, fms-related tyrosine kinase 3 ( FLT3) and CCAAT/enhancer-binding protein alpha mutations in 85 patients with CN-AML receiving intensive induction chemotherapy. Our results indicate that patients with higher LCN2 mRNA expression in the bone marrow ( LCN2high), especially in combination with wild type FLT3-ITD, had better prognoses. FLT3-ITD compensated LCN2-overexpression-enhanced oxidative stress-induced apoptosis in cell line studies. In conclusion, LCN2high was associated with better prognosis, and FLT3 status had an adjuvant effect on overall survival. [ABSTRACT FROM AUTHOR]

The study was designed to investigate the effects of exogenous hydrogen sulfide (H2S) on expression of heme oxygenase-1 (HO-1) in rat hepatocytes induced by LPS. The cultured rat hepatocyte line BRL cells were treated with different dose of LPS and H2S donor NaHS respectively. In separate expriment, hepatocytes were pre-treated with NaHS for 24h or post-treated with different dose of NaHS for 1h then incubated with LPS for another 12h. The expression of HO-1 protein was detected with Western blotting.Compared with vehicle, LPS induced profound upregulation of HO-1 protein expression in a dose- and time-dependent manner. Both of pre-conditioning and post-conditioning with NaHS led to upregulation of HO-1 protein expression in a dose-dependent manner,further HO-1 protein expression were more in pre-conditioning than in post-conditioning with NaHS. However,compared with LPS, pre-conditioning or post-conditioning with NaHS at 50, 100 and 200 micromol/L together with LPS induced the marked upregulation of HO-1 protein expression,up-regulating to 31.54%, 44.05%, 66.07% and 17.19%, 22.52%, 60.53%, respectively. It is well known that HO-1 is an antioxidant protein, and its product carbon monooxide also has an antioxidant capacity. Thses results showed pre-conditioning and post-conditioning with exogenous H2S promoted LPS-induced upregulation of HO-1 protein in hepatocytes synergily, indicating that HO-1 or carbon monooxide mediated the biological effects in part of exogenous H2S. [ABSTRACT FROM AUTHOR]

The study was carried out to investigate the role of endoplasmic reticulum stress (ERS) in regulation of endogenous hydrogen sulfide (H2S) for hepatocyte apoptosis induced by lipopolysaccharide (LPS). The cultured rat hepatocyte line BRL cells were treated with LPS and ERS inducer thapsigargin (TG), ERS inhibitor 4-phenylbutyric acid (4-PBA) respectively or in a different combination manner. RNA interference technique was used to silence the expression of CBS and CSE. H2S level, cell viability and apoptosis rate were measured. The expressions of CBS and CSE mRNA and protein, GRP78,CHOP, caspase-12 and caspase-3 were detected with RT-PCR and Western blotting. Compared with vehicle, LPS caused a decrease in cell viability, an increase in apoptosis rate and significantly increased expression of GRP78 protein in a dose- and time-dependent manner. Almost similar increases were observed in expression of CHOP,caspase-12 and caspase-3 proteins. TG led to a marked decrease in cell viability and an increase in apoptosis rate. Furthermore, TG exacerbated while 4-PBA alleviated LPS-induced hepatocyte injuries. LPS induced a up-regulation of CBS-H2S and CSE-H2S systems. Both of CBS siRNA and CSE siRNA reversed the increased endogenous H2S formation and up-regulation of CBS and CSE expressions, inhibited the decreased cell viability and increased apoptosis rate and obviously decreased expressions of GRP78, CHOP, caspase-12, caspase-3 induced by LPS. Results showed that endogenous H2S can aggravate LPS-induced hepatocyte apoptosis through enhancement of ERS. [ABSTRACT FROM AUTHOR]

A series of efficient zinc catalysts supported by sterically bulky benzotriazole phenoxide ( BTP) ligands are synthesized and structurally characterized. The reactions of diethyl zinc (ZnEt2) with CMe2PhBTP-H, t-BuBTP-H, and TMClBTP-H yield monoadduct [(μ- BTP)ZnEt]2 ( 1- 3), respectively. Bisadduct complex [( t-BuBTP)2Zn] ( 4) results from treatment of ZnEt2 with t-BuBTP-H (2 equiv.) in toluene, but treatment of TMClBTP-H with ZnEt2 in the same stoichiometric proportion in Et2O produces five-coordinated monomeric complex [( TMClBTP)2Zn(Et2O)] ( 5). The molecular structures of compounds 1, 4, and 5 are characterized by X-ray crystal structure determinations. All complexes 1- 5 are efficient catalysts for the ring-opening polymerization of ε-caprolactone (ε-CL) in the presence of 9-anthracenemethanol. Experimental results indicate that complex 3 exhibits the greatest activity with well-controlled character among these complexes. The polymerizations of ε-CL and β-butyrolactone catalyzed by 3 are demonstrated in a 'living' character with narrow polydispersity indices (monomer-to-initiator ratio in the range of 25-200, PDIs ≤ 1.10). The 'immortal' character of 3 provides a way to synthesize as much as 16-fold polymer chains of poly(ε-CL) (PCL) with narrow PDI in the presence of a catalyst in a small proportion. The controlled fashion of complex 3 also enabled preparation of the PCL- b-poly(3-hydroxybutyrate) copolymer. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011 [ABSTRACT FROM AUTHOR]

Abstract: Zinc complexes supported by NN-bidentate AA Bn ligand (AA Bn -H=(E)-N-[2-(benzyliminomethyl)phenyl]-2,6-diisopropylaniline) are synthesized and fully characterized. The reaction of diethyl zinc (ZnEt2) with AA Bn -H (1.1mol equiv) yields three-coordinated mono-adduct zinc complex [(AA Bn )ZnEt] (1). However, treatment of AA Bn -H with ZnEt2 in the same stoichiometric proportion in the presence of 4-dimethylaminopyridine (DMAP, one equiv) affords [(AA Bn )Zn(DMAP)Et] (2) as the tetra-coordinated monomeric zinc complex. Bis-adduct complex [(AA Bn )2Zn] (3) results from treatment of ZnEt2 with AA Bn -H (two equiv) in refluxing toluene in high yield. Complexes 1 and 3 are efficient catalysts for the ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) in the presence of alcohol. The “controlled” character of Zn complex 1 also enabled preparation of the PEG-b-PCL copolymer. [Copyright &y& Elsevier]

Simple Summary: Haploidentical hematopoietic stem cell transplantation haplo-HSCT is now increasingly recognized as a valid treatment for patients with hematologic malignancies. The two most noteworthy strategies are posttransplantation cyclophosphamide (PTCy) with or without anti-thymoglobulin and granulocyte colony stimulating factor-primed bone marrow plus peripheral blood stem cells (GIAC). Direct comparisons of these approaches are rare, which makes physicians hard to choose the optimal treatment strategy for patients. We used a nationwide blood and marrow transplantation registry to compare these approaches. We found that patients in the modified GIAC (mGIAC) group had the most favorable platelet and neutrophil engraftment kinetics but had a higher extensive chronic graft-versus-host disease rate. The patients receiving mGIAC had the lowest nonrelapse mortality and highest overall survival rates. Physicians can choose the optimal treatment for patients based on the distinct clinical features and outcomes of these strategies. This study may pave the way for further prospective trials. Background: The two most noteworthy strategies for haploidentical stem cell transplantation (haplo-HSCT) are posttransplantation cyclophosphamide (PTCy) with or without thymoglobulin (ATG) and granulocyte colony stimulating factor-primed bone marrow plus peripheral blood stem cells (GIAC). We aimed to compare these approaches in patients with hematological malignancies. Methods: We enrolled 178 patients undergoing haplo-HSCT, including modified GIAC (mGIAC), PTCy without ATG, and PTCy with ATG. Results: The patients in the mGIAC group had the most favorable platelet and neutrophil engraftment kinetics. Although the grade III–IV acute graft-versus-host-disease (GvHD) rates were similar, those receiving mGIAC had a significantly higher extensive chronic GvHD rate. The patients receiving mGIAC had a similar cumulative incidence of relapse (CIR) to that in the patients receiving PTCy with ATG, but this was lower than that in the patients receiving PTCy without ATG. The patients receiving mGIAC had the lowest nonrelapse mortality (NRM) and the highest overall survival (OS) rates. The differences in CIR, NRM, and OS remained significant when focusing on patients with low/intermediate-risk diseases before haplo-HSCT. Intriguingly, among patients with high/very-high-risk diseases before haplo-HSCT, no differences were observed in the CIR, NRM, OS, or GvHD/relapse-free survival. Conclusion: the mGIAC approach may yield a better outcome in Taiwanese patients with hematologic malignancies, especially for those with low/intermediate-risk diseases. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the cost-effectiveness of treating transplant-ineligible myeloma patients with either a bortezomib plus thalidomide plus dexamethasone (VTD) or a bortezomib plus melphalan plus prednisolone (VMP) treatment in Taiwan. Methods: Newly diagnosed, transplant-ineligible myeloma patients with VTD or VMP therapy were enrolled from two medical centers in southern Taiwan. Quality-adjusted life years (QALYs) were used as the measurement unit of the effectiveness evaluation, and the incremental cost-effectiveness ratio (ICER) was used for comparison between the two groups. A net monetary benefit approach and cost-effectiveness acceptability curve were also used for the cost-effectiveness assessment. A one-way sensitivity analysis was used to check the impact of different parameters. In total, 77 patients were enrolled in the study with 43 patients in the VTD group and 34 patients in the VMP group. Clinical presentations were similar without significant difference, except the VTD group had a higher survival rate (p = 0.029). Comparisons of the two groups over an eight-month time horizon revealed a significant lower mean of direct medical costs in the VTD group than in the VMP group (p < 0.001), and a significantly higher average QALY was gained (p < 0.001). Conclusions: The study demonstrated the greater clinical benefit and cost-effectiveness of VTD compared to VMP therapy in transplant-ineligible, newly diagnosed myeloma patients. [ABSTRACT FROM AUTHOR]

There is considerable cellular diversity in the human stomach, which has helped to clarify cell plasticity in normal development and tumorigenesis. Thus, the stomach is an interesting model for understanding cellular plasticity and for developing prospective anticancer therapeutic agents. However, many questions remain regarding the development of cancers in vivo and in vitro in two- or three-dimensional (2D/3D) cultures, as well as the role of Helicobacter pylori (H. p.) infection. Here, we focus on the characteristics of cancer stem cells and their derived 3D organoids in culture, including the formation of stem cell niches. We define the conditions required for such organoid culture in vitro and examine the ability of such models for testing the use of anticancer agents. We also summarize the signaling cascades and the specific markers of stomach-cancer-derived organoids induced by H. p. infection, and their stem cell niches. [ABSTRACT FROM AUTHOR]

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as a chronic bladder disorder with suprapubic pain (pelvic pain) and pressure and/or discomfort related to bladder filling accompanied by lower urinary tract symptoms, such as urinary frequency and urgency without urinary tract infection (UTI) lasting for at least 6 weeks. IC/BPS presents significant bladder pain and frequency urgency symptoms with unknown etiology, and it is without a widely accepted standard in diagnosis. Patients' pathological features through cystoscopy and histologic features of bladder biopsy determine the presence or absence of Hunner lesions. IC/PBS is categorized into Hunner (ulcerative) type IC/BPS (HIC/BPS) or non-Hunner (nonulcerative) type IC/BPS (NHIC/BPS). The pathophysiology of IC/BPS is composed of multiple possible factors, such as chronic inflammation, autoimmune disorders, neurogenic hyperactivity, urothelial defects, abnormal angiogenesis, oxidative stress, and exogenous urine substances, which play a crucial role in the pathophysiology of IC/BPS. Abnormal expressions of several urine and serum specimens, including growth factor, methylhistamine, glycoprotein, chemokine and cytokines, might be useful as biomarkers for IC/BPS diagnosis. Further studies to identify the key molecules in IC/BPS will help to improve the efficacy of treatment and identify biomarkers of the disease. In this review, we discuss the potential medical therapy and assessment of therapeutic outcome with urinary biomarkers for IC/BPS. [ABSTRACT FROM AUTHOR]

Hemophagocytic syndrome is a rare complication of acute Q fever. We reported the case of 26-year-old man with fever, chills, severe headache, non-productive cough and progressive thrombocytopenia. Bone marrow aspirate revealed hemophagocytosis. We discussed the differences among the three previous reported cases and the possible mechanisms of hemophagocytic syndrome. [ABSTRACT FROM AUTHOR]