Tsu Yi Chao

CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer

BACKGROUND/PURPOSEnLung cancer is a heterogeneous disease with varied outcomes. Molecular markers are eagerly investigated to predict a patients treatment response or outcome. Previous studies used frozen biopsy tissues to identify crucial genes as prognostic markers. We explored the prognostic value of peripheral blood (PB) molecular signatures in patients with advanced non-small cell lung cancer (NSCLC).nnnMETHODSnPeripheral blood mononuclear cell (PBMC) fractions from patients with advanced NSCLC were applied for RNA extraction, cDNA synthesis, and real-time polymerase chain reaction (PCR) for the expression profiling of eight genes: DUSP6, MMD, CPEB4, RNF4, STAT2, NF1, IRF4, and ZNF264. Proportional hazard (PH) models were constructed to evaluate the association of the eight expressing genes and multiple clinical factors [e.g., sex, smoking status, and Charlson comorbidity index (CCI)] with overall survival.nnnRESULTSnOne hundred and forty-one patients with advanced NSCLC were enrolled. They included 109 (77.30%) patients with adenocarcinoma, 12 (8.51%) patients with squamous cell carcinoma, and 20 (14.18%) patients with other pathological lung cancer types. A PH model containing two significant survival-associated genes, CPEB4 and IRF4, could help in predicting the overall survival of patients with advanced stage NSCLC [hazard ratio (HR)xa0=xa00.48, pxa0<xa00.0001). Adding multiple clinical factors further improved the prediction power of prognosis (HRxa0=xa00.33; pxa0<xa00.0001).nnnCONCLUSIONnMolecular signatures in PB can stratify the prognosis in patients with advanced NSCLC. Further prospective, interventional clinical trials should be performed to test if gene profiling also predicts resistance to chemotherapy.

Early Treg suppression by a listeriolysin-O-expressing E. coli vaccine in heterologous prime–boost vaccination against cancer

Studies have shown that an enhanced CD8+ T cell response and better tumor protection can be achieved by heterologous prime-boost vaccination in mice. Such heterologous vaccination can be more immunogenic than the homologous setting. We previously demonstrated that a listeriolysin-O (LLO)-expressing E. coli vaccine can enhance CD8-cytotoxic T cell (CTL) responses by reducing regulatory T cell (Treg)-directed suppression. In the present study, we assessed the combination of this approach with plasmid DNA vaccination, in a prime-boost immunization strategy. E. coli-LLO bacteria expressing ovalbumin (OVA) and plasmid pcDNA-encoding OVA were used to vaccinate naive or B16-OVA tumor-bearing C57B6 mice. The anticancer activity was measured in a tumor prevention or therapeutic model. Higher OVA-specific CD8+ T cell responses and greater tumor inhibition were seen in the bacterial-prime/plasmid-boost setting than with the homologous and reversed sequences. This tumor protection effect from heterologous prime-boost remained in the therapeutic model. When examining the Treg effect during the prime-boost immunization, we found that only early Treg-suppression/depletion could lead to better antigen-specific CTL and tumor response. Our studies offer the first evidence that a listeriolysin-O E. coli vaccine can induce an enhanced antitumor effect in conjunction with DNA in a heterologous prime-boost protocol, and suggest that early Treg inhibition is crucial to a successful immunization against cancer.

Clinical efficacy and safety of primary antifungal prophylaxis with posaconazole versus fluconazole in allogeneic blood hematopoietic stem cell transplantation recipients—A retrospective analysis of a single medical center in Taiwan

BACKGROUND/PURPOSEnThe efficacy and safety of posaconazole compared to fluconazole as antifungal prophylaxis in patients receiving allogeneic blood hematopoietic stem cell transplantation (allo-HSCT) during the early neutropenic phase without graft-versus-host disease (GVHD) was uncertain.nnnMETHODSnThe medical records of allo-HSCT recipients from a single institution, who received oral fluconazole (from January 2005 to June 2011) or oral posaconazole (from June 2011 to December 2013) during the early neutropenic phase (until engraftment), were retrospectively reviewed.nnnRESULTSnThere were 52 allo-HSCT recipients, two of whom were younger than 18 years of age. Twelve cases received posaconazole and 40 cases received fluconazole as primary antifungal prophylaxis. The two groups had similar transplant characteristics, conditioning, and GVHD prophylaxis regimens. The fluconazole group had a higher risk for development of invasive fungal infections within 90 days after allo-HSCT (43% vs. 8.3%, pxa0=xa00.039). Kaplan-Meier analysis indicated that the cumulative incidence of invasive fungal infection for 90 days after allo-HSCT was higher in the fluconazole group (log rank test, pxa0=xa00.047). Early discontinuation of antifungal prophylaxis for intolerance was significantly lower in the posaconazole group (8.3% vs. 50%, pxa0=xa00.017). Both groups had similar rates of impaired liver function.nnnCONCLUSIONnAnalysis of primary fungal prophylaxis during the early neutropenic phase following allo-HSCT indicated that posaconazole was more effective and was better tolerated than fluconazole. Both drugs had similar safety profiles.

Distinct MR Imaging Features of Triple‐Negative Breast Cancer with Brain Metastasis

Patients with triple‐negative breast cancer (TNBC) are at increased risk of brain metastases (BMs). In this retrospective single‐institutional study, we assessed the radiographic features from a cohort of breast cancer (BC) patients with confirmed BM.

The treatment outcome of multiple myeloma patients ineligible for hematopoietic transplantation—a single institutional experience in Taiwan

Multiple myeloma (MM) is characterized by the neoplastic proliferation of monoclonal plasma cells in the bone marrow and results in complications. In Taiwan, melphalan and several novel agents are used to treat myeloma patients who are not candidate for hematopoietic stem cell transplant (HSCT). This retrospective study aimed to evaluate the characteristics, treatment outcome, and prognostic factors of MM patients who were ineligible for HSCT at our institution from October 2000 until November 2012. A total of 101 MM patients were reviewed. The median age was 71.0xa0years, and median overall survival (OS) was 22.0xa0months. Most of patients were diagnosed as IgG-type myeloma (55.4xa0%). The initial presentations included anemia (89.1xa0%), skeletal events (49.5xa0%), severe renal insufficiency (30.7xa0%), and hypercalcemia (28.7xa0%). With regard to the frontline therapy, thalidomide/steroid was the most common. Infection was the leading cause of death and adverse effects. Treatment with bortezomib, almost in the second- or third-line setting, was associated with longer median OS (35.5xa0months) and the median time to progression (TTP) (6.0xa0months). Bortezomib treatment, chemotherapy, International Staging System (ISS) stage I, and better performance status significantly correlated with survival benefit. In the bortezomib-treated subgroup, better treatment response caused excellent median OS (67.7xa0months) and also significantly delayed TTP. Therefore, this current analysis concluded a median OS of 22xa0months in myeloma patients ineligible for HSCT at our institution during the past 10xa0years. The use of bortezomib with better treatment response also achieved significantly better median OS and TTP.

Effects of bariatric weight loss surgery on glucose metabolism, inflammatory cytokines, and serum tartrate-resistant acid phosphatase 5a in obese Chinese adults.

BACKGROUNDnWe determined effects of bariatric weight loss surgery on serum tartrate-resistant acid phosphatase 5a (TRACP 5a), inflammatory cytokines and glucose homeostasis in severely obese Chinese adults.nnnMETHODSnSeverely obese adults undergoing bariatric surgery were recruited. Anthropometry, insulin resistance (IR), inflammatory markers and serum TRACP 5a were measured at baseline and 3, 6 and 12months postoperatively.nnnRESULTSnData of 93 patients, including 69 non-diabetic (non-DM group) and 24 diabetic (DM group), were analyzed. Anthropometry decreased significantly at 3months postoperatively in both groups; low-density lipoprotein cholesterol decreased obviously at 3, 6 and 12months in non-DM group, while improving significantly at 6 and 12months in DM group. Homeostasis model assessment for IR (HOMA-IR) improved significantly at 3, 6 and 12months in non-DM group and 12months in DM group. In DM group, C-reactive protein (CRP) decreased significantly at 3months postoperatively and inflammatory markers interleukin-6 (IL-6) and TRACP 5a improved at 6months postoperatively; in non-DM group, serum TRACP 5a decreased obviously at 12months postoperatively without significant changes in CRP and IL-6.nnnCONCLUSIONnWeight reduction by bariatric surgery decreases anthropometry, IR, lipids and inflammatory markers in severely obese Chinese adults.

The Clinical Efficacy and Cardiotoxicity of Fixed-Dose Monthly Trastuzumab in HER2-Positive Breast Cancer: A Single Institutional Analysis

Objective Trastuzumab-containing treatment regimens have been shown to improve survival outcomes in HER2-positive breast cancer (BC). It is much easier to infuse a fixed one-vial dose to every patient on a regular schedule in the general clinical setting. The aims of this study were evaluating the efficacy of a 440 mg fixed-dose of trastuzumab administered on a monthly infusion schedule, and the risk factors for cardiac events. Patients and methods We retrospectively reviewed data from 300 HER2-positive BC patients in our institute: 208 were early-stage BC patients undergoing adjuvant trastuzumab treatment, and 92 were metastatic BC patients treated with trastuzumab infusions until disease progression. There were 181 patients receiving regular trastuzumab infusions every 3 weeks (Q3W; 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks), and the other 119 patients were treated monthly with a fixed 440 mg dose (QM; fixed 440 mg every 4 weeks). Results The medians of progression-free survival (PFS) and overall survival (OS) in the adjuvant setting were not reached in both treatment groups. In the metastatic setting, there was no significant difference between groups in PFS or OS. The median time to significant cardiovascular (CV) dysfunction was 4.54 months. The incidence of congestive heart failure requiring medication in our cohort was 3.4%. Conclusion In our study, we found that fixed-dose monthly trastuzumab was feasible and effective. In addition, the CV risk was not higher with the fixed-dose protocol. This treatment modality could lower the cost and was easier to implement in clinical practice. Larger prospective randomized studies with longer-term follow up are needed to confirm our results.

The Relationship Between Inflammatory Biomarkers and Symptom Distress in Lung Cancer Patients Undergoing Chemotherapy

Background: Symptom distress often occurs in lung cancer patients undergoing chemotherapy. However, a biomarker has not been identified to reflect the severity of their symptom distress. Objective: The aim of this study was to investigate the relationship between symptom distress and serum inflammatory biomarkers in lung cancer patients undergoing chemotherapy. Methods: A longitudinal, repeated-measures design was used to assess subjective symptoms (fatigue, sleep disturbance, pain, depression, and confusion), serum biomarkers (tartrate-resistant acid phosphatase 5a [TRACP5a], interleukin 6 [IL-6], IL-8, and C-reactive protein), and white blood cells in 62 lung cancer patients recruited from a single medical center at 3 time points: T1 was the baseline, T2 was the eighth day after the first chemotherapy cycle, and T3 was prior to the second cycle. Symptom distress was measured individually by 5 questionnaires (General Fatigue Scale, Pittsburgh Sleep Quality Index, Brief Pain Inventory, Profile of Mood States–Depressive, and Confusion). Results: The trend of TRACP5a was positively correlated to the trend of the patients’ symptom distress. However, the trends of IL-6 and IL-8 did not correlate. Conclusions: Serum TRACP5a was associated with symptom distress in lung cancer patients. Therefore, TRACP5a might be a potential biomarker to assess symptom distress of lung cancer patients undergoing chemotherapy. Implications for Practice: Oncology nurses may be able to apply TRACP5a expression to predict or monitor multiple distress symptoms in lung cancer patients undergoing chemotherapy. Furthermore, nurses can use these study findings to better understand the patients who need more attention to improve their quality of life.

Association of Tartrate-Resistant Acid Phosphatase-Expressed Macrophages and Metastatic Breast Cancer Progression.

AbstractInfiltrating neutrophils, lymphocytes, macrophages, and cytokines constitute a state of chronic inflammation within the tumor microenvironment. Tartrate-resistant acid phosphatase 5a (TRACP5a) protein, a novel product of activated macrophage, is postulated to be a biomarker for systemic inflammatory burden in states of chronic inflammation. We aimed to investigate the clinical significance of TRACP5a expression in tumor-infiltrating macrophages and serum TRACP5a in patients with metastatic breast cancer (BC).We retrospectively analyzed the clinical data from 34 BC patients with confirmed skeletal/visceral metastasis upon or during first-line palliative treatment. Patients were stratified into 3 groups based on the therapeutic responses and follow-up disease course. The association of TRACP5a protein with other inflammatory and cancer biomarkers was assessed among the clinically distinct group of patients. Higher TRACP5a protein was significantly correlated with earlier disease progression and survival (Pu200a=u200a0.0045) in comparison to other inflammatory markers, CRP or IL-6. Patients with higher serum TRACP5a level and shorter survival and treatment refractoriness also had more TRACP+ tumor-infiltrating macrophages.Our data support a hypothesis that serum TRACP5a protein can potentially be a predictive and prognostic marker to evaluate disease progression and therapeutic response in BC patients with bone/visceral metastasis. The associations between overall survival and TRACP expression by macrophages require further prospective investigation.