Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer.

PURPOSE: This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-na?ve, epidermal growth factor receptor-positive, stage IV non-small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival. PATIENTS AND METHODS: Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week, followed by weekly doses of 250 mg/m2. Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks. Patients were evaluated for tumor response after every two cycles of therapy. RESULTS: The most frequently reported adverse events related to cetuximab included an acne-like rash (88.6%), dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these toxicities were mild to moderate. One patient withdrew from the study because of a grade 3 allergic reaction. Myelosuppression was the most frequently observed toxicity related to chemotherapy. Responses among 35 assessable patients included 10 partial responses (28.6%). Twenty-one patients had stable disease. The median time to progression was 165 days, and the median overall survival was 310 days. CONCLUSION: The combination of cetuximab, carboplatin, and gemcitabine was well tolerated with an acceptable toxicity profile. Most grade 3 adverse events were attributable to chemotherapy. The response rate and median survival are encouraging and warrant additional investigation.     

Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1.

The cytochrome P450 family 1 (CYP1) is considered to be one of the xenobiotic-metabolizing enzyme families and is responsible for oxidative metabolism of polycyclic aromatic hydrocarbons. For example, mouse Cyp1b1 was originally identified as the enzyme responsible for oxidative metabolism of 7,12-dimethylbenz(alpha)anthracene (DMBA). A comparison of the kinetics of this metabolism by mouse and human CYP1B1 orthologs revealed the mouse enzyme to have a more favorable metabolism of DMBA, with a catalytic efficiency ratio (CER) of 0.23. However, CYP1 enzymes are also capable of metabolism of endobiotics, and in the present study, the metabolism of retinoids and lipid endobiotics by human CYP1B1 and mouse Cyp1b1 orthologs was compared. Both hemoproteins oxidized retinol to retinal and retinal to retinoate, but did not oxidize retinoate. The CYP1B1 to Cyp1b1 CERs were 13 and 26 for the two steps, respectively; the Cyp1b1 K(m(app)) values for retinoids were 20-fold higher. Human family 1 cytochromes P450 had unique regional specificities for arachidonate oxidation: the major metabolites of CYP1A1, CYP1A2, and CYP1B1 were 75% terminal hydroxyeicosatetraenoic fatty acids (HETEs), 52% epoxyeicosatrienoic fatty acids (EETs), and 54% mid-chain HETEs, respectively. CYP1A1 and CYP1B1 K(m(app)) values for arachidonate were about 30 microM, whereas CYP1A2 K(m(app)) was 95 microM. The major metabolites of arachidonic acid by Cyp1b1 were EETs (50%) and midchain HETEs (37%). The mouse ortholog had a CER for metabolite production of 64 due to a K(m(app)) of 0.5 mM for arachidonate.     

Microstructure and Mechanical Properties of Metal Foams Fabricated via Melt Foaming and Powder Metallurgy Technique: A Review

Metal foams possess remarkable properties, such as lightweight, high compressive strength, lower specific weight, high stiffness, and high energy absorption. These properties make them highly desirable for many engineering applications, including lightweight materials, energy-absorption devices for aerospace and automotive industries, etc. For such potential applications, it is essential to understand the mechanical behaviour of these foams. Producing metal foams is a highly challenging task due to the coexistence of solid, liquid, and gaseous phases at different temperatures. Although numerous techniques are available for producing metal foams, fabricating foamed metal still suffers from imperfections and inconsistencies. Thus, a good understanding of various processing techniques and properties of the resulting foams is essential to improve the foam quality. This review discussed the types of metal foams available in the market and their properties, providing an overview of the production techniques involved and the contribution of metal foams to various applications. This review also discussed the challenges in foam fabrications and proposed several solutions to address these problems.     

Unusual perineal pain in postpartum period: contribution of perineal ultrasound

We report two cases of persistent [correction of persistant] perineal pain in postpartum period due to transfixation of the anus with a suture and the contribution of perineal ultrasound in the diagnosis of unusual perineal pain.     

以肝脓肿为首发症状的隐匿性结肠癌一例

老年男性,因间断寒战、高热,右上腹痛2个月之主诉入院,无恶心、呕吐、便血、大便次数增多或便秘等表现.查体可见贫血貌,腹部未触及包块,右上腹压痛阳性,肝区叩击痛阳性.血常规示贫血及血象高.粪常规未见隐血.行腹部B超及上腹部CT提示肝右叶脓肿并含气空洞形成,大小约7.4cm×8.9cm×9.0cm.结肠造影示结肠肝曲顶部与肝脓腔相通,形成瘘道.手术探查发现结肠肝曲、十二指肠、胆囊与右肝下间隙界限不清,在肝下形成直径约9cm的脓腔.     

Long-term Survival After An Aggressive Surgical Approach in Patients With Breast Cancer Hepatic Metastases

Background: Metastatic breast cancer is generally believed to be associated with a poor prognosis. Therapeutic advances over the past two decades, however, have resulted in improved outcomes for selected patients with limited metastatic disease. Methods: Between March 1991 and October 2002, 31 patients had hepatic resection for breast cancer metastases limited to the liver. Clinical and pathologic data were collected prospectively from breast and hepatobiliary databases. Results: Median age of patients was 46 years (range, 31 to 70). Liver metastases were solitary in 20 patients and multiple in 11 patients. Median size of the largest liver metastasis was 2.9 cm (range, 1 to 8). Major liver resections (three or more segments resected) were performed in 14 patients, whereas minor resections (fewer than three segments resected) with or without radiofrequency ablation (RFA) were performed in 17 patients. No postoperative mortality occurred. Of the 31 patients, 27 (87%) received either preoperative or postoperative systemic therapy as treatment for metastatic disease. The median survival was 63 months; a single patient died within 12 months of hepatic resection. The overall 2- and 5-year survival rates were 86% and 61%, respectively, whereas the 2- and 5-year disease-free survival rates were 39% and 31%, respectively. No treatment- or patient-specific variables were found to correlate with survival rates. Conclusions: In selected patients with liver metastases from breast cancer, an aggressive surgical approach is associated with favorable long-term survival. Hepatic resection should be considered a component of multimodality treatment of breast cancer in these patients.     

Chemometric Evaluation of Near Infrared,Fourier Transform Infrared,and Raman Spectroscopic Models for the Prediction of Nimodipine Polymorphs

The objective of this study was to assess the performance of the chemometric model to predict the proportion of the recrystallized polymorphs of nimodipine from the cosolvent formulations. Ranging from 100% to 0% (w/w) of polymorph I, the two polymorphs mixtures were prepared and characterized spectroscopically using Fourier transformed infrared spectroscopy (FTIR), near-infrared spectroscopy (NIR), and Raman spectroscopy. Instrumental responses were treated to construct multivariate calibration model using principal component regression (PCR) and partial least square regression approaches. Treated data showed better model fitting than without treatment, which demonstrated higher correlation coefficient (R²) and lower root mean square of standard error (RMSE) and standard error (SE). Multiple scattering correction and standard normal variate exhibited higher R² and lower RMSE and SE values than second derivative. Goodness of fit for FTIR and NIR (R² ~ 0.99) data was better than Raman (R² ~ 0.95). Furthermore, the models were applied on the recrystallized polymorphs obtained by storing nimodipine-cosolvent formulations at selected stability conditions. The relative composition of the polymorphs differed with storage conditions. NIR-chemical imaging on recrystallized sample of nimodipine at 15°C qualitatively corroborated the model-based prediction of the two polymorphs. Therefore, these studies strongly suggest the importance of the potential utility of the chemometric model in predicting nimodipine polymorphs.