Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) have elicited curative effects on patients with advanced non-small celllung cancer and with activating mutations in the EGFR gene. However, acquired resistance to EGFR-TKIs is eventually developed after an initial response is induced;as such, patients with acquired resistance must be treated with more ef-fective strategies to delay or possibly overcome the resistance. This article reviews available data on the treatment of patients who have failed to respond to EGFR-TKI.

Objective To evaluate the impact of comorbidity and age on the tolerance of firstline single-agent chemotherapy in elderly patients with advanced non-small cell lung cancer(NSCLC).Methods Clinical data of 61 elderly patients with advanced NSCLC(aged over 70 years,median age 72 years) receiving first-line single agent chemotherapy were retrospectively analyzed in this study.Performance status(PS) between 0-1 score was in 52 patients,PS 2 score in the other 9 patents.Patients were treated with gemcitabine or docitaxel as the first line chemotherapy,and the median number of chemotherapy cycles was 3.4.Comorbidity was assessed by Charlson comorbidity index (CC1).Patients with CCI equal to 0 were classified as non comorbidity group(n=26),and patients with CCI≥1 were classified as comorbidity group(n=35).Adverse reactions were graded by using the criteria of NCI-CTC v3.0.Results Age and PS could not predict adverse effects of grade 3 or 4.The incidence of hematologic toxicity of grade 3 or 4 was higher in comorbidity group than in noncomorbidity group(40.0％ vs.15.4％,x2 =4.36,P=0.037).The incidences of febrile neutropenia,non hematologic toxicity of grade 3 or 4 and treatment suspension were higher in comorbidity group than in non-comorbidity group.The most common types of comorbidity were diabetes and chronic pulmonary disease.The incidence of non-hematologic toxicity of grade 3 or 4 was increased in patients with chronic pulmonary disease as compared with patients without chronic pulmonary disease(41.4 ％vs.11.5％,x2=6.061,P=0.032).Conclusions The incidences of adverse reactions,especially hematologic toxicity of grade 3 or 4 are significantly increased in patients with comorbidity after singleagent chemotherapy.Evaluation of comorbidity before treatment is helpful to predict the tolerance of single-agent chemotherapy in elderly NSCLC patients.

About half of the elderly patients with advanced non-small cell lung cancer (NSCLC) can not receive effective treatment due to the decreased organ function and complication. Monotherapies using the third generation new drugs have became a standard first-line therapy for NSCLC, as documented by prospective phase 3 clinical trials. Combined chemotherapies that contain platin and single agent are considered optional first- and second-line treatment for patients with good physical performance and few complication. The epidermal growth factor receptor tyrosine kinase inhibitors may become a key therapeutic agent,while the role of anti-vascular endothelial growth factor monoclonal antibody remains unclear. More prospective phase 3 targeting at the elderly patients should be designed and conducted.
Aged ; Antibodies, Monoclonal ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Humans ; Lung Neoplasms ; drug therapy ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors

BACKGROUND: Paraquat (PQ) is a world-wide used herbicide and also a type of common poison for suicide and accidental poisoning. Numerous studies have proved that the concentration of serum PQ plays an important role in prognosis. Spectrophotometry, including common spectrophotometry and second-derivative spectrophotometry, is commonly used for PQ detection in primary hospitals. So far, lack of systematic research on the reliability of the method and the correlation between clinical features of patients with PQ poisoning and the test results has restricted the clinical use of spectrophotometry. This study aimed to evaluate the reliability and value of spectrophotometry in detecting the concentration of serum PQ. METHODS: The wavelengths for detecting the concentration of serum PQ by common and second-derivative spectrophotometry were determined. Second-derivative spectrophotometry was applied to detect the concentration of serum PQ. The linear range and precision for detection of PQ concentration by this method were confirmed. The concentration of serum PQ shown by second-derivative spectrophotometry and HPLC were compared in 8 patients with PQ poisoning. Altogether 21 patients with acute poisoning 4 hours after PQ ingestion treated in the period of October 2008 to September 2010 were retrospectively reviewed. The patients were divided into higher and lower than 1.8 μg/mL groups based on their concentrations of serum PQ measured by second-derivative spectrophotometry on admission. The severity of clinical manifestations between the two groups were analyzed with Student's t test or Fisher's exact test. RESULTS: The absorption peak of 257 nm could not be found when common spectrophotometry was used to detect the PQ concentration in serum. The calibration curve in the 0.4–8.0 μg/mL range for PQ concentration shown by second-derivative spectrophotometry obeyed Beer's law with r=0.996. The average recovery rates of PQ were within a range of 95.0％ to 99.5％, relative standard deviation (RSD) was within 1.35％ to 5.41％ (n=6), and the lower detection limit was 0.05 μg/mL. The PQ concentrations in serum of 8 patients with PQ poisoning shown by second-derivative spectrophotometry were consistent with the quantitative determinations by HPLC (r=0.995, P<0.0001). The survival rate was 22.2％ in patients whose PQ concentration in serum was more than 1.8 μg/mL, and the incidences of acidosis, oliguria and pneumomediastinum in these patients were 55.6％, 55.6％and 77.8％, respectively. These clinical manifestations were different significantly from those of the patients whose PQ concentration in serum was less than 1.8 μg/mL (P<0.05). CONCLUSIONS: For common spectrophotometry, the wavelength at 257 nm was not suitable for detecting serum PQ as no absorbance was shown. Second-derivative spectrophotometry was reliable for detecting serum paraquat concentration. Serum PQ concentration detected by second-derivative spectrophotometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning, and PQ content higher than 1.8 μg/mL 4 hours after ingestion could be an important predictive factor for poor prognosis.

Adolescent ; Child ; Child, Preschool ; Cytomegalovirus Infections ; complications ; Female ; Humans ; Kidney Diseases ; etiology ; Kidney Glomerulus ; pathology ; Male

Adult ; Female ; Helicobacter Infections ; complications ; Helicobacter pylori ; Humans ; Hyperemesis Gravidarum ; etiology ; Pregnancy

UNLABELLEDOBJECTIVE To study the clinical and biological characteristics and prognosis of t(8;21)/AML1-ETO-positive childhood acute myeloid leukemia (AML).

METHODSThe clinical data of 55 children who were diagnosed as t (8; 21)/AML1-ETO-positive AML were retrospectively studied. Event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) rates were estimated by the Kaplan-Meier method. Prognostic factors were evaluated by COX regression analysis software.

RESULTSOf the 55 patients, 4 patients gave up treatment after the diagnosis was confirmed and 4 patients were lost to follow-up after the first chemotherapy course. The remaining 47 patients received a double-induction therapy. The total complete remission (CR) rate was 71% and 94% after the first and second chemotherapy course, respectively. The disease was relapsed in 10 patients (21%). The 5-year EFS, DFS and OS rates were (56.1 ± 7.9)%, (59.8 ± 8.1)%, and (72.0 ± 8.1)%, respectively. Multivariate analysis showed that age was an independent risk factor for the long-term prognosis. The older children had a greater risk of experiencing an accident or death (P<0.05). The 5-year OS rate in 27 patients with regular consolidation chemotherapy was significantly higher than 13 patients with irregular chemotherapy after CRz [(47.5 ± 17.1)% vs (38.9 ± 17.3)%; P<0.01].

CONCLUSIONSChildhood t(8;21)/AML1-ETO-positive AML is a highly heterogeneous disease, with a high CR rate and a good long-term prognosis. Age is one of the important factors affecting the long-term therapeutic effect. Regular consolidation chemotherapy applied after CR usually is helpful.

Adolescent ; Bone Marrow Examination ; Child ; Child, Preschool ; Chromosomes, Human, Pair 21 ; Chromosomes, Human, Pair 8 ; Core Binding Factor Alpha 2 Subunit ; analysis ; Female ; Humans ; Leukemia, Myeloid, Acute ; genetics ; mortality ; Male ; Oncogene Proteins, Fusion ; analysis ; Prognosis ; RUNX1 Translocation Partner 1 Protein ; Translocation, Genetic

OBJECTIVETo retrospectively analyze the treatment outcomes and side effects of childhood acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) or ATRA + arsenic trioxide (As2O3).

METHODSFrom 1992 to 2006, 45 patients with newly diagnosed APL were enrolled. All of them were PML-RAR alpha positive. 24 patients were induced with ATRA (group A) and 21 with ATRA + As2O3 (group B). The remission rate and side effects were observed.

RESULTS1) 19 (79.2%) patients in group A achieved CR, while 21(100%) patients in group B achieved CR. The CR rate in group A was lower than that in group B (P=0.027). 2) The recovery time of coagulation parameters and PLT count in group B was shorter than that in group A. 3) The overall survival (OS) and event-free survival(EFS) in group A were 77.8% and 66.9% at 41 months of follow-up, and in group B were 100% and 100% respectively at 34 months of followup. Group A had a significant lower EFS (P=0.0357)than group B. 4) The time of PML-RAR alpha fusion gene converting to negative in group A was longer (P=0.026) than that in group B.

CONCLUSIONSATRA + As2O3 for patients with newly diagnosed childhood APL is a feasible treatment with higher CR rate, less side effects and longer long-term survival.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; administration & dosage ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; genetics ; Male ; Oncogene Proteins, Fusion ; genetics ; Oxides ; administration & dosage ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; administration & dosage

This study was aimed to investigate the expressions of adhesion molecules such as CD54, CD49d and CD62L by CD34(+) cells sampled from different stages of bone marrow (BM) and peripheral blood (PB) before/after G-CSF mobilization and after transplantation through the direct labeling with three colour-immunofluorescence and flow cytometry, and to explore the differences in expression of adhesion molecules on CD34(+) cells from different origins and their clinical significance. Mononuclear cells collected from BM and PB before mobilization, after collection of stem cells and hematopoietic recostruction of BM at the end of transplantation were marked with CD54-FITC, CD49d-FITC and CD62L-FITC separately, as well as CD34-PE and CD45PerCE. 3-color fluorescene analysis was carried out by FACS. The expression differences of CD34(+) and adhesion molecules between BM and APBSC were compared. The results showed that expression differences of CD54, CD49d and cd62Lon CD34(+) cells belore mobilization, after collection and reconstraction of transplantation were not statiscally significant, the difference of CD54, CD49d and CD62L on CD34(+) between 1st and 2nd collections of hematopoietic stem cells also were not statiscally significant. In the collected APBSC, the expression level of CD34(+) CD49d(+) was significantly lower than those in BM before mobilization (P = 0.001). It is concluded that the method of chemotherapy combined with G-CSF mobilization can down-regulate CD49d expression in BM CD34(+) cells, thus can mobilize and move theirs into peripheral blood. After the reconstitution by transplantation, the expression of CD49d on CD34(+) cells tends to normal, the clinical significance needs to be elucidated by accumulation of much more cases.
Adolescent ; Adult ; Antigens, CD ; blood ; Antigens, CD34 ; blood ; Antigens, Neoplasm ; blood ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Bone Marrow Cells ; immunology ; CD52 Antigen ; Cell Adhesion Molecules ; blood ; Combined Modality Therapy ; Female ; Flow Cytometry ; Glycoproteins ; blood ; Hematopoietic Stem Cells ; immunology ; Humans ; Integrin alpha4 ; blood ; L-Selectin ; blood ; Leukocytes, Mononuclear ; immunology ; Lymphoma ; blood ; immunology ; therapy ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; methods ; Transplantation, Autologous

OBJECTIVETo investigate the therapeutic effects of hemin, an inducer of heme oxygenase, in a rat model of gestational hypertension and explore the possible mechanism.

METHODSEighteen pregnant SD rats at day 12 of gestation were randomized equally into gestational hypertension model group, hemin treatment group, and normal pregnancy (control) group. In the former two groups, the rats were subjected to daily nitro-L-arginine methyl ester (L-NAME, 80 mg/kg) gavage since gestational day 14 for 7 consecutive days to induce gestational hypertension; saline was administered in the same manner in the control rats. The rats in hemin group received daily intraperitoneal injection of hemin (30 mg/kg) starting from gestational day 16. HO activity and carboxyhemoglobin (COHb) level in rat placental tissue were detected with spectrophotometric method, and soluble vascular endothelial growth factor receptor-1 (sFlt-1) and vascular endothelial growth factor (VEGF) level in the placental tissue homogenate supernatant were detected using ELSIA.

RESULTSAt gestational day 20, the blood pressure and 24-h urinary protein were significantly higher in the model group than in the other two groups (P<0.05), and were higher in hemin group than in the control group (P<0.05); HO activity and COHb content in the placenta tissue were the lowest in the model group (P<0.05), and was lower in hemin group than in the control group (P<0.05). The level of sFlt-1 was significantly higher and VEGF level significantly lower in the model group than in the other two groups (P<0.05); sFlt-1 level remained higher and VEGF lower in hemin group than in the control group (P<0.05).

CONCLUSIONHemin can reduce blood pressure and urinary protein in rats with gestational hypertension possibly by up-regulating HO activity, enhancing carbon monoxide production, reducing sFlt-1 and increasing VEGF in the placental tissue.

Animals ; Blood Pressure ; Carbon Monoxide ; metabolism ; Disease Models, Animal ; Female ; Heme Oxygenase (Decyclizing) ; Hemin ; pharmacology ; Hypertension, Pregnancy-Induced ; drug therapy ; Placenta ; drug effects ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism