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Introduction: This multicenter, phase II randomized, non-inferiority study reports from the first prospective two-armed randomized control trial that compared the efficacy, safety, and quality of life (QoL) of pegylated liposomal doxorubicin (PLD)-based and epirubicin-based as adjuvant chemotherapy for stage I-II human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Methods: Patients with stage I/II HER2-negative breast cancer received PLD (37.5 mg/m2, Q3W, 5 cycles, LC arm) plus cyclophosphamide (600 mg/m2) or epirubicin (90 mg/m2, Q3W, 4 cycles, EC arm) plus cyclophosphamide (600 mg/m2). Randomization was stratified by lymph node and ER and PR status. The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS), safety profiles, and QoL. QoL was assessed using the EORTC-QLQ-C30 and QLQ-BR23 questionnaires. Results: A total of 256 patients were assigned to LC (n = 148) and EC (n = 108). There was no difference in 5-year DFS and OS rate between the two groups. LC-based adjuvant regimens had significantly less alopecia and low-grade 3–4 hematologic adverse events (AEs). Significantly improved QoL was observed in the LC arm during and after treatment for symptoms including fatigue, nausea and vomiting, and systemic therapy side effects. Conclusion: Comparable efficacy and safety between adjuvant PLD and epirubicin for stage I-II HER2-negative breast cancer was observed. There was no difference in the 5-year DFS and OS rates between the two treatment arms. However, low-grade 3–4 AEs and a trend of favorable QoL symptom scales were observed in the LC arm, suggesting that PLD-containing regimen could become a new standard treatment for early-stage HER2-negative breast cancer patients. Plain Language Summary: This study compared two chemotherapy treatments for human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer: one using a drug called pegylated liposomal doxorubicin (PLD) and the other using epirubicin. A total of 256 women with stage I or II breast cancer from multiple medical centers in Taiwan were included in this study. They were randomly assigned to receive either PLD or epirubicin along with another drug called cyclophosphamide. Traditional treatments like anthracyclines (including doxorubicin and epirubicin) have been widely used but can have serious side effects. PLD is a newer drug that seems to work as well as traditional anthracyclines but with fewer harmful effects. The study found that both treatments were equally effective in 5-year disease-free survival and overall survival. However, the PLD treatment caused fewer severe side effects, such as hair loss and blood-related problems. Also, patients who received PLD reported feeling better during and after treatment compared to those who received epirubicin. This study is one of the first to directly compare PLD and epirubicin in a randomized trial for HER2-negative early-stage breast cancer patients. The results suggest that PLD could be a treatment option for these patients, offering similar effectiveness with fewer side effects to epirubicin treatments. [ABSTRACT FROM AUTHOR]

1. It has been shown that the antidepressant desipramine is able to induce increases in [Ca2+]i and cell death in MG63 human osteosacroma cells, but whether apoptosis is involved is unclear. In the present study, the effect of desipramine on apoptosis and the underlying mechanisms were explored. It was demonstrated that desipramine induced cell death in a concentration- and time-dependent manner. 2. Cells treated with 100–800 mmol/L desipramine showed typical apoptotic features, including an increase in sub-diploid nuclei and activation of caspase 3, indicating that these cells underwent apoptosis. Immunoblotting revealed that 100 mmol/L desipramine activated extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). Although pretreatment of cells with 20 mmol/L PD98059 (an ERK inhibitor) or 20 mmol/L SP600125 (an inhibitor of JNK) did not inhibit cell death, the addition of 20 mmol/L SB203580 (a p38 MAPK inhibitor) partially rescued cells from apoptosis. Desipramine-induced caspase 3 activation required p38 MAPK activation. 3. Pretreatment of cells with BAPTA/AM (20 mmol/L) to prevent desipramine-induced increases in [Ca2+]i did not protect cells from death. 4. The results of the present study suggest that, in MG63 human osteosarcoma cells, desipramine causes Ca2+-independent apoptosis by inducing p38 MAPK-associated activation of caspase 3. [ABSTRACT FROM AUTHOR]

The effects of econazole, an antifungal drug applied for treatment of keratitis and mycotic corneal ulcer, on cytosolic-free Ca2 + concentrations ([Ca2 +]i) and viability of corneal cells was examined by using SIRC rabbit corneal epithelial cells as model. [Ca2 +]i and cell viability were measured by using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations ≥ 1 μ M increased [Ca2 +]i in a concentration-dependent manner. The Ca2 + signal was reduced partly by removing extracellular Ca2 +. The econazole-induced Ca2 + influx was insensitive to L-type Ca2 + channel blockers and protein kinase C modulators. In Ca2 +-free medium, after pretreatment with 20 μ M econazole, [Ca2 +]i rises induced by 1 μ M thapsigargin (an endoplasmic reticulum Ca2 + pump inhibitor) were abolished. Conversely, thapsigargin pretreatment also abolished econazole-induced [Ca2 +]i rises. Inhibition of phospholipase C with 2 μ M U73122 did not change econazole-induced [Ca2 +]i rises. At concentrations between 10 and 80 μ M, econazole killed cells in a concentration-dependent manner. The cytotoxic effect of 20 μ M econazole was not reversed by prechelating cytosolic Ca2 + with BAPTA. This shows that in SIRC cells econazole induces [Ca2 +]i rises by causing Ca2 + release from the endoplasmic reticulum and Ca2 + influx from unknown pathways. Econazole-caused cytotoxicity was independent from a preceding [Ca2 +]i rise. [ABSTRACT FROM AUTHOR]

Objective: To assess the risk factors that influence mortality from perforated peptic ulcer. Design: Retrospective study. Setting: General hospital, Taiwan. Subjects: 179 patients who had their perforated peptic ulcers operated on and who had minimum follow-up of one year. Main outcome measures: Mortality. Results: The overall mortality was 15% (26/179). Of the 26 patients who died, the cause of death was uncontrolled systemic infection in 21 (81%), hypovolaemic shock in 2, and fatal arrhythmia and heart failure in 1 each. 15 of the patients who died of sepsis did not have fulminant abdominal sepsis. Most deaths occurred early after operation, (range 1-96 days). Old age, preoperative shock, and type of operation seemed to be related to these deaths on univariate analysis, but multivariate analysis showed that coexisting medical illness, delayed treatment, and low albumin concentration were independent risk factors for mortality. Conclusions: To improve the result of treatment of perforated peptic ulcer, the diagnosis and treatment should not be delayed, the associated medical illnesses should be treated, and nutritional support should be given. [ABSTRACT FROM AUTHOR]

Abstract: The effect of diallyl disulfide (DADS) on cytosolic Ca2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells is unclear. This study explored whether DADS changed [Ca2+]i in PC3 cells by using fura-2. DADS at 50–1000μM increased [Ca2+]i in a concentration-dependent manner. The signal was reduced by removing Ca2+. DADS-induced Ca2+ influx was not inhibited by nifedipine, econazole, SK&F96365, and protein kinase C modulators; but was inhibited by aristolochic acid. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitors thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished DADS-induced [Ca2+]i rise. Incubation with DADS inhibited thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter DADS-induced [Ca2+]i rise. At 500–1000μM, DADS killed cells in a concentration-dependent manner. The cytotoxic effect of DADS was partly reversed by prechelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA). Propidium iodide staining suggests that DADS (500μM) induced apoptosis in a Ca2+-independent manner. Annexin V/PI staining further shows that 10μM and 500μM DADS both evoked apoptosis. DADS also increased reactive oxygen species (ROS) production. Collectively, in PC3 cells, DADS induced [Ca2+]i rise probably by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-sensitive channels. DADS induced Ca2+-dependent cell death, ROS production, and Ca2+-independent apoptosis. [Copyright &y& Elsevier]

The effects of econazole, an antifungal drug applied for treatment of keratitis and mycotic corneal ulcer, on cytosolic-free Ca(2+) concentrations ([Ca(2+)](i)) and viability of corneal cells was examined by using SIRC rabbit corneal epithelial cells as model. [Ca(2+)](i) and cell viability were measured by using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations > or = 1 microM increased [Ca(2+)](i) in a concentration-dependent manner. The Ca(2+) signal was reduced partly by removing extracellular Ca(2+). The econazole-induced Ca(2+) influx was insensitive to L-type Ca(2+) channel blockers and protein kinase C modulators. In Ca(2+)-free medium, after pretreatment with 20 microM econazole, [Ca(2+)](i) rises induced by 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) were abolished. Conversely, thapsigargin pretreatment also abolished econazole-induced [Ca(2+)](i) rises. Inhibition of phospholipase C with 2 microM U73122 did not change econazole-induced [Ca(2+)](i) rises. At concentrations between 10 and 80 microM, econazole killed cells in a concentration-dependent manner. The cytotoxic effect of 20 microM econazole was not reversed by prechelating cytosolic Ca(2+) with BAPTA. This shows that in SIRC cells econazole induces [Ca(2+)](i) rises by causing Ca(2+) release from the endoplasmic reticulum and Ca(2+) influx from unknown pathways. Econazole-caused cytotoxicity was independent from a preceding [Ca(2+)](i) rise.

Inflammatory myofibroblastic tumor (IMT) of the alimentary tract often occurs in children or young adults, but may occur at any age. Symptoms are nonspecific and depend on the location of the tumor. The most often involved sites are small bowel mesentery especially the distal ileum, mesotransverse colon, or great omentum. Recurrence appears to be more frequent in the extrapulmonary lesion. Herein we demonstrate a 63-year-old male patient with mesenteric IMT, with an early recurrence after his first operation. We should be aware that if the tumor is larger than 8 cm, multinodular, omental, with ill-defined margin, with pathologically atypia, or ganglion-like cells, a close surveillance after primary surgery with image study might be necessary to detect the tumor recurrence early. Tumor recurrence may be asymptomatic, and it may act like a malignant tumor with a poor prognosis.

Background: Intestinal obstruction has remained one of the most common surgical emergencies, and its clinical spectrum has shifted in past decades. The factors contributing to its surgical mortality were studied in these selected patients with a view to finding pointers which help surgeons to identify patients with high surgical risk of mortality., Methods: Those adult patients who had prior laparotomy for non-malignancy and were operated on for intestinal obstruction were included and studied retrospectively. Thirteen possible risk factors, including co-existing medical illness, tachycardia, preoperative shock, age, bowel ischemia, operative complication, leukocytosis, durations from symptom onset to hospitalization, from hospitalization to operation, and from symptom onset to operation, prior laparotomy number, time interval from last laparotomy to this operation, and operation method, were analyzed using univariate analysis and, then, multivariate analysis to find out the independent risk factors for surgical death., Results: Adhesion-related etiologies were the most common. Still, one-tenth of cases were not adhesion-related. Obstruction in the small bowel (172/176) was more frequent than in the large bowel (4/176). The surgical mortality rate was 6.8% (12/176). The independent risk factors of mortality after surgical treatment were co-existing medical illness, bowel ischemia, preoperative shock, and operative complication. Old age seemed to be a risk factor on univariate anlaysis, but not on multivariate analysis. Duration from symptom onset to hospitalization, from hospitalization to operation, or from symptom onset to operation was not significantly related to surgical mortality., Conclusions: High risk patients could be identified by 4 independent factors: coexisting medical illness, bowel ischemia, preoperative shock, and operative complication. Old age itself was not an independent risk factor.