Predicting chemotherapy response to paclitaxel-based therapy in advanced non-small-cell lung cancer with P-glycoprotein expression

BACKGROUND: It was reported that multidrug resistance gene 1 (MDR1) encoding human P-glycoprotein (Pgp) may play an important role in multidrug resistance of lung cancer. Therefore, before initiating chemotherapy, it is important to accurately determine the presence of Pgp in lung cancer, to achieve a satisfactory chemotherapy response. OBJECTIVES: The aim of this study was to compare immunohistochemical analyses of Pgp expression and response to paclitaxel in non-small-cell lung cancer (NSCLC). METHODS: Before chemotherapy with paclitaxel, 50 patients with stage IIIb or IV NSCLC were enrolled in this study. Immunohistochemical analyses were performed on multiple nonconsecutive sections of the biopsy specimens to determine Pgp expression. Chemotherapy response was evaluated in the 3rd month after completion of treatment by clinical and radiological methods. RESULTS: All of the 28 (100%) cases with good response had negative Pgp expression and 15 of the 22 (68%) cases with poor response had positive Pgp expression (p < 0.05). No significant differences were found for other prognostic factors (age, sex, body weight loss, performance status, tumor cell type, and tumor stage) between good response and poor response groups. CONCLUSIONS: Although Pgp expression in NSCLC does not fully predict chemotherapy response to paclitaxel-based therapy, detection of Pgp expression will aid in planning paclitaxel-based therapy for patients with advanced NSCLC. Further studies with a larger number of patients and a longer time of follow-up are necessary to confirm our findings.     

内皮祖细胞在急性肺损伤中的应用

急性肺损伤(acute lung injury,ALI)是临床常见危重症,目前缺乏有效的治疗手段,病死率高达40%[1].内皮细胞的损伤和活化在ALI发病机制中占有极其重要的地位[2].     

Increased circulating endothelial progenitor cells are associated with survival in acute lung injury

RATIONALE: Repair of damaged endothelium is important in recovery from acute lung injury. In animal models, bone marrow-derived endothelial progenitor cells differentiate into mature endothelium and assist in repairing damaged vasculature. OBJECTIVES: The quantity of endothelial progenitor cells in patients with acute lung injury is unknown. We hypothesize that increased numbers of circulating endothelial progenitor cells will be associated with an improved outcome in acute lung injury and the acute respiratory distress syndrome. METHODS: Peripheral blood mononuclear cells from the buffy coat of patients with early acute lung injury (n=45), intubated control subjects (n=10), and healthy volunteers (n=7) were isolated using Ficoll density gradient centrifugation, and plated on fibronectin-coated cellware. After 24 hours, nonadherent cells were removed and replated on fibronectin-coated cellware at a concentration of 1x10(6) cells/well. Colony-forming units were counted after 7 days' incubation. MEASUREMENTS/MAIN RESULTS: Endothelial progenitor cell colony numbers were significantly higher in patients with acute lung injury compared with healthy control subjects (p<0.05), but did not differ between patients with acute lung injury and intubated control subjects. However, in the 45 patients with acute lung injury, improved survival correlated with a higher colony count (p<0.04). Patients with acute lung injury with a colony count of >or= 35 had a mortality of 30%, compared with 61% in those with colony counts <35 (p<0.03), results that persisted in a multivariable analysis correcting for age, sex, and severity of illness. CONCLUSIONS: An increased number of circulating endothelial progenitor cells in acute lung injury is associated with improved survival.     

Endothelial progenitor cells are reduced in refractory hypertension

Circulating endothelial progenitor cells (EPCs) play a key role in the maintenance of endothelial homoeostasis and promote vascular repair. They may also be of predictive value for cardiovascular events. Reduced EPC number and functional activity have been associated with several cardiovascular risk factors, but their relationship with hypertension remains unclear. The objective of this study was to investigate if number and function of circulating EPCs are reduced in patients with refractory hypertension (RHT). Circulating EPCs (CD34+ CD133+/CD45+) were isolated from peripheral blood by flow cytometry in 39 RHT and 30 normotensive controls. EPC number was also determined in vitro after 7 days in culture. After age adjustment, EPC concentration was significantly reduced in RHT as compared with controls (mean (95% CI), 33.8 (18.1-49.6) vs 69.1 (50.7-87.5) EPCs per 10(5) peripheral mononuclear cells (MNCs), respectively; P=0.014). After in vitro culture, EPCs were also reduced in patients as compared with controls (mean (95% CI), 142.3 (49.5-235.0) vs 611.0 (480.2-741.8) EPCs per field, respectively, P<0.001). In multiple linear regression analysis, circulating EPCs were significantly reduced by 56.3% in RHT as compared with control (P=0.006), independently of all other known risk factors. Moreover, RHT had a high independent predictive value for lower EPC proliferation. The number of EPCs per field was reduced by 76.7% in RHT with respect to controls (P<0.001). In summary, the number of circulating EPCs after culture is reduced in patients with RHT, which may be related to the increased rate of endothelial dysfunction, atherosclerotic disease and cardiovascular events observed in this population.     

用吉非替尼或化疗治疗有EGFR突变的非小细胞肺癌

背景 有表皮生长因子受体（EGFR）敏感性突变的非小细胞肺癌,对EGFR酪氨酸激酶抑制剂（例如吉非替尼）高度敏感,但对其与标准化疗相比的疗效和安全性特征知之甚少。     

用吉非替尼或化疗治疗有EGFR突变的非小细胞肺癌

背景 有表皮生长因子受体（EGFR）敏感性突变的非小细胞肺癌,对EGFR酪氨酸激酶抑制剂（例如吉非替尼）高度敏感,但对其与标准化疗相比的疗效和安全性特征知之甚少。     

Patients preferences in chemotherapy for advanced non-small-cell lung cancer

OBJECTIVE: To determine how Japanese patients with lung cancer weigh potential survival, chemotherapy response rate, and symptom relief against the potential toxicity of different treatments in cancer chemotherapy. METHODS AND PATIENTS: We used a questionnaire describing a hypothetical situation about stage IV non-small-cell lung cancer. Seventy-three patients with lung cancer who had received chemotherapy and 120 patients with other respiratory disease as the control group were asked to rate the minimal benefit that would make two hypothetical treatments acceptable. For "chance of cure," "response but not cure," and "symptom relief," the subjects could give answers from 1% to 100% and for prolonging life could give answers from 1 to 60 months. RESULTS: Patients with lung cancer were significantly more likely than were patients with other respiratory diseases to accept either intensive or less-intensive treatments for a potentially small benefit for "chance of cure," "response but not cure," and "symptom relief". The degree of survival advantage that patients require before accepting cancer treatment with its associated toxicity varied widely. If their lives were prolonged 3 months, 19% and 21% of patients with lung cancer would choose to receive intensive and less-intensive treatment, respectively. When the chance of symptom relief was 70%, 73% of patients with lung cancer were willing to choose intensive chemotherapy. Factor associated with patients' choice of chemotherapy in both groups was age. CONCLUSION: Oncologists must consider the substantial range of attitudes to chemotherapy among patients when making treatment decisions and they must give patients the opportunity to be included in this process.     

Endothelial progenitor cells are suppressed in anemic patients with acute coronary syndrome

ObjectiveAnemia is an independent predictor of poor prognosis in acute coronary syndrome. Endothelial progenitor cells are bone marrow-derived cells that are mobilized into the circulation in response to ischemia. The number of circulating endothelial progenitor cells increases within days of acute coronary syndrome. There is no confirmation regarding the correlation between the occurrence of anemia and the deficiency in endothelial progenitor cells in patients with acute coronary syndrome. The correlation between chronic anemia and endothelial progenitor cells in patients with acute coronary syndrome was investigated.MethodsEndothelial progenitor cells were examined in 26 patients with acute coronary syndrome. Fifteen patients had chronic nonprogressive anemia, and 11 patients had a normal blood count. Blood samples were drawn on the first day of admission and 4 to 7 days later. Mononuclear cells were separated and cultured on fibronectin-coated plates with EndoCult medium (StemCell Technologies, Vancouver, BC, Canada) for 5 days. Colony forming unit count and a migration assay were performed at each time point.ResultsBaseline colony forming unit in the non-anemic group was higher than in the anemic group (P < .0001). There was a highly significant correlation between admission hemoglobin and colony forming unit count (R = 0.83, P < .0001). Colony forming units increased in both groups on the second measurement but to a lower extent in the anemic group (P = .0004). The migration assay in the non-anemic group was higher than in the anemic group at baseline (P = .017) and 4 to 7 days later (P = .0054).ConclusionPatients with acute coronary syndrome with anemia demonstrate a reduced number of peripheral endothelial progenitor cells with impaired function, possibly representing a lower capacity for vascular healing. These phenomena may partly explain the poor prognosis observed in patients with acute coronary syndrome and anemia.     

Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer

Purpose  

Although there are several reports concerning gemcitabine-induced interstitial lung disease (ILD), the risk factors for ILD are not well known. In addition, data comparing the incidence and pattern of ILD associated with gemcitabine treatment in patients with non-small-cell lung cancer (NSCLC) versus those with pancreatic cancer are scarce.     

Multiagent neoadjuvant chemotherapy and tumor response are associated with improved survival in pancreatic cancer

Background

Neoadjuvant therapy (NT) for borderline resectable pancreatic cancer (BRPC) has evolved to include multi-agent regimens and chemoradiation. We report our experience and compare outcomes of initially resectable pancreatic cancer (IRPC) vs BRPC receiving NT across two eras of chemotherapy regimens.

Combination chemotherapy with carboplatin and docetaxel for elderly patients with non-small-cell lung cancer

The efficacy and toxicity of treatment with carboplatin (AUC= 5)+ docetaxel (70mg/m2) were analyzed retrospectively in 27 elderly patients with advanced non-small-cell lung cancer (NSCLC) aged 70 years or more. The median age of the patients was 74 years (range, 70-83 years). The performance status (ECOG), clinical stage, and tumor histology in the patients were as follows: PS: PS 0, 12 patients; PS 1, 11 patients; PS 2, 4 patients; disease stage: stage IIIA, 5 patients; stage IIIB, 11 patients; stage IV, 11 patients; tumor histology: adenocarcinoma, 18 patients; squamous cell carcinoma, 9 patients. The median number of treatment cycles administered was 4. The median survival time was 11.1 months and the 1-year survival rate was 40.7%. The response rate was 33.3%. The major toxicities were leukopenia and neutropenia; grade 3/4 neutropenia occurred in 22 patients (81.5%). Nonhematologic toxicities were generally mild, including grade 3 anorexia in 13 patients (48.1%) and grade 3 febrile neutropenia in 9 patients (33.3%). No treatment-related deaths were observed. Thus, it was concluded that the combination of carboplatin + docetaxel is a feasible, well-tolerated, and effective regimen for fit elderly patients with NSCLC. Prospective studies comparing carboplatin + docetaxel with third-generation single-agent chemotherapy or non-platinum-based combination chemotherapy are needed to confirm the efficacy and safety of this drug combination.