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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]

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]

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]

Myeloproliferative neoplasms (MPNs) represent a heterogeneous group of clonal hematopoietic disorders, cause myeloproliferation, splenomegaly, and constitutional symptoms, and are associated with I JAK2 i , I MPL i , and I CALR i mutations.[1] As for multiple myeloma (MM), a malignant neoplasm of plasma cells produces monoclonal immunoglobulin, is often associated with several complicated pathophysiologic pathway. Bone marrow (BM) examination revealed hypercellularity (cellularity 90%) with increased megakaryocytes, increased myeloid/erythroid (M/E) ratio (Figure 1A,B), prominent granulocytic proliferation, but silver stain reveals no reticulin fiber. But I JAK2V617F i plays a role in the developing of secondary malignancy.[[1], [4]] Our case was negative for I JAK2V617F i mutation, which was also reported in another study. [Extracted from the article]

JunB is a component of the activator protein 1 transcription factors and has been identified to be important in hematopoiesis. Transgenic mice lacking JunB expression develop myeloproliferative disease resembling human chronic myeloid leukemia (CML). JunB expression was significantly decreased in CML patients. We used real-time quantitative reverse transcription-polymerase chain reaction analysis to monitor both JunB and BCR-ABL expression during imatinib therapy. Nineteen patients were evaluated every 2 to 4 weeks, and their levels of JunB expression before therapy were significantly decreased compared with those of healthy individuals. After imatinib therapy, an increase in JunB expression was found in 5 patients, all of whom achieved a complete cytogenetic response (CCR) and molecular response (MR), with a decrease in BCR-ABL expression. JunB expression decreased to a very low level in 2 patients, both of whom showed progression to blast crisis. Variable JunB expression was found in the other 12 patients, and their outcomes were mostly driven by BCR-ABL levels. The patients with an increase in JunB expression were statistically more likely to achieve a major cytogenetic response (P = .045), CCR (P = .033), and MR (P = .033) than the group with no increase in JunB expression, and a durable response was observed. This study revealed that an increase in JunB expression is a good prognostic marker for predicting clinical response in CML patients treated with imatinib when such data are combined with an evaluation of BCR-ABL expression. [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]

Background/purpose. 5-Fluorouracil (5-FU) remains the most frequently used chemotherapy agent in various human cancers. Over 80% of the 5-FU administered is metabolized by dihydropyrimidine dehydrogenase (DPD) in the liver. However, mutations in the DPD gene have been found to be associated with low DPD activity causing severe complications. The aim of this study was to determine the frequency of 11 known mutations in Taiwanese subjects and the relationship between mutation and DPD level. Methods. Samples from a total of 300 subjects were investigated in this study. The PCR-RFLP method was used to identify 11 mutations of the DPYD gene, including 62G>A, 74A>G, 85T>C (DPYD*9A), 812delT, 1003G>T, 1156G>T, 1627A>G (DPYD*5), 1714C>G, 1897delC (DPYD*3), 2194G>A (DPYD*6), and IVS14+1G>A (DPYD*2A). DPD protein levels were determined using a DPD ELISA kit. Results. Four mutations, including 74A>G, 85T>C (DPYD*9A), 1627A>G (DPYD*5), and 2194G>A (DPYD*6), were found in our 300 samples. The following mutations were not detected: 62G>A, 812delT, 1003G>T, 1156G>T, 1714C>G, 1897delC (DPYD*3), and IVS14+1G>A (DPYD*2A). The phenotype analysis by DPD protein level indicated that the 1627A>G (DPYD*5) mutation was not associated with the DPD protein level and might be a polymorphism in the DPD gene. The DPD level was also not correlated with gender. Conclusion. No significant correlations between these 11 mutations and DPD protein level were found indicating that examination of these mutations is insufficient to provide a high-value prediction of the 5-FU pharmacogenetic syndrome in Taiwanese. Genotype and phenotype analysis indicated the 1627A>G (DPYD*5) mutation to be a polymorphism. [ABSTRACT FROM AUTHOR]

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]

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]

Nutritional assessments, including the Geriatric Nutritional Risk Index (GNRI), have emerged as prediction tools for long-term survival in various cancers. This study aimed to investigate the therapeutic strategy and explore the prognostic factors in the elderly patients (≥65 years) with diffuse large B cell lymphoma (DLBCL). The cutoff value of the GNRI score (92.5) was obtained using the receiver operating characteristic curve. Among these patients (n = 205), 129 (62.9%) did not receive standard R–CHOP chemotherapy. Old age (≥80 years), poor performance status, low serum albumin level, and comorbidities were the major factors associated with less intensive anti-lymphoma treatment. Further analysis demonstrated that a lower GNRI score (<92.5) was linked to more unfavorable clinical features. In the patients who received non-anthracycline-containing regimens (non-R–CHOP), multivariate analysis showed that a low GNRI can serve as an independent predictive factor for worse progression-free (HR, 2.85; 95% CI, 1.05–7.72; p = 0.039) and overall survival (HR, 2.98; 95% CI, 1.02–8.90; p = 0.045). In summary, nutritional evaluation plays a role in DLBCL treatment and the GNRI score can serve as a feasible predictive tool for clinical outcomes in frail elderly DLBCL patients treated with non-anthracycline-containing regimens. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether the progression risk score (PRS) developed from cytoplasmic immunohistochemistry (IHC) biomarkers is available and applicable for assessing risk and prognosis in oral cancer patients. Participants in this retrospective case-control study were diagnosed between 2012 and 2014 and subsequently underwent surgical intervention. The specimens from surgery were stained by IHC for 16 cytoplasmic target markers. We evaluated the results of IHC staining, clinical and pathological features, progression-free survival (PFS), and overall survival (OS) of 102 oral cancer patients using a novel estimation approach with unsupervised hierarchical clustering analysis. Patients were stratified into high-risk (52) and low-risk (50) groups, according to their PRS; a metric consisting of cytoplasmic PLK1, PhosphoMet, SGK2, and SHC1 expression. Moreover, PRS could be extended for use in the Cox proportional hazard regression model to estimate survival outcomes with associated clinical parameters. Our study findings revealed that the high-risk patients had a significantly increased risk in cancer progression compared with low-risk patients (hazard ratio (HR) = 2.20, 95% confidence interval (CI) = 1.10–2.42, p = 0.026). After considering the influences of demographics, risk behaviors, and tumor characteristics, risk estimation with PRS provided distinct PFS groups for patients with oral cancer (p = 0.017, p = 0.019, and p = 0.020). Our findings support that PRS could serve as an ideal biomarker for clinical use in risk stratification and progression assessment in oral cancer. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article that was published in the October 30, 2013 issue of the periodical which discusses the posaconazole prophylaxis treatment given to the patient with acute myeloid leukemia suffering with Fusarium solani infection.

Simple Summary: In head and neck squamous cell carcinoma (HNSCC), more than 60% of patients presenting with locally advanced disease carries a high risk of recurrence and distant metastasis, with a poor prognosis (five-year overall survival (OS), <50%). Therefore, further prevention of recurrence and distant metastasis is crucial for survival improvement in advanced HNSCC patients. In this retrospective study, we investigated the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced HNSCC (LA HNSCC). Our data showed that adding tegafur–uracil after curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved OS, DFS, and DMFS in patients with LA HNSCC. As a metronomic maintenance regimen, tegafur–uracil was well tolerated with minimal adverse effects. We suggested tegafur–uracil as a maintenance therapy of choice for patients with LA HNSCC. Metronomic chemotherapy inhibits tumor growth by continuous administration of lower-dose chemotherapy. Our study aimed to demonstrate the outcomes of metronomic chemotherapy with tegafur–uracil in locally advanced head and neck squamous cell carcinoma (LA HNSCC). This was a retrospective study including 240 patients with LA HNSCC. After standard treatment, 96 patients were further treated with metronomic tegafur-uracil, and 144 patients were not. No statistical differences were found between both groups with regard to sex, clinical stage, or primary treatment choice. There were more hypopharyngeal cancers and more patients with poor clinicopathological features, including lymphovascular invasion, extranodal extension, and positive margins in the tegafur–uracil group. The median follow-up duration was 31.16 months. Overall survival (OS) was not reached in the tegafur–uracil group and was 54.1 months in the control group (p = 0.008). The median disease-free survival (DFS) was 54.5 months in the tegafur–uracil group and 34.4 months in the control group (p = 0.03). Neither group reached distant metastasis-free survival (DMFS, p = 0.02). In patients with LA HNSCC, adding tegafur–uracil as metronomic chemotherapy after either curative surgery with adjuvant chemoradiotherapy or definitive concurrent chemoradiotherapy significantly improved the OS, DFS, and DMFS with tolerable adverse events. [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.

13-Acetoxysarcocrassolide (13-AC), a marine cytotoxic product isolated from the alcyonacean coral Lobophytum crassum, exhibited potent antitumor and immunostimulant effects as reported in previous studies. However, the 13-AC antitumor mechanism of action against oral cancer cells remains unclear. The activity of 13-AC against Ca9-22 cancer cells was determined using MTT assay, flow cytometric analysis, immunofluorescence, immunoprecipitation, Western blotting, and siRNA. 13-AC induced apoptosis in oral cancer cells Ca9-22 through the disruption of mitochondrial membrane potential (MMP) and the stimulation of reactive oxygen species (ROS) generation. It increased the expression of apoptosis- and DNA damage-related proteins in a concentration- and time-dependent manner. It exerted potent antitumor effect against oral cancer cells, as demonstrated by the in vivo xenograft animal model. It significantly reduced the tumor volume (55.29%) and tumor weight (90.33%). The pretreatment of Ca9-22 cells with N-acetylcysteine (NAC) inhibited ROS production resulting in the attenuation of the cytotoxic activity of 13-AC. The induction of the Keap1-Nrf2 pathway and the promotion of p62/SQSTM1 were observed in Ca9-22 cells treated with 13-AC. The knockdown of p62 expression by siRNA transfection significantly attenuated the effect of 13-AC on the inhibition of cell viability. Our results indicate that 13-AC exerted its cytotoxic activity through the promotion of ROS generation and the suppression of the antioxidant enzyme activity. The apoptotic effect of 13-AC was found to be mediated through the interruption of the Keap1/Nrf2/p62/SQSTM1 pathway, suggesting its potential future application as an anticancer agent. [ABSTRACT FROM AUTHOR]