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يتناول كتاب \"ديناميات المجالات الريفية في العالم\" لمجموعة من الباحثين بقيادة دومينيك أندريو التحولات العميقة التي طرأت على الأرياف عالميا، حيث لم تعد تعرف فقط كمجالات زراعية، بل أصبحت فضاءات متعددة الوظائف تشمل السياحة، والخدمات، والحفاظ على البيئة. يسلط الكتاب الضوء على التفاوتات المجالية، والهجرة من وإلى الأرياف، وتأثير السياسات العمومية في دعم التنمية المحلية، كما يناقش التحديات البيئية المتزايدة مثل التغير المناخي والتصحر. ويقدم من خلال أمثلة من مختلف القارات، مما يعكس تنوع التجارب الريفية في ظل العولمة ومتطلبات التنمية المستدامة.

In the decade since the last Lancet Seminar on lung cancer there have been advances in many aspects of the classification, diagnosis, and treatment of non-small-cell lung cancer (NSCLC). An international panel of experts has been brought together to focus on changes in the epidemiology and pathological classification of NSCLC, the role of CT screening and other techniques that could allow earlier diagnosis and more effective treatment of the disease, and the recently introduced seventh edition of the TNM classification and its relation to other prognostic factors such as biological markers. We also describe advances in treatment that have seen the introduction of a new generation of chemotherapy agents, a proven advantage to adjuvant chemotherapy after complete resection for specific stage groups, new techniques for the planning and administration of radiotherapy, and new surgical approaches to assess and reduce the risks of surgical treatment.

Adjuvant cisplatin-based chemotherapy only marginally improves survival in patients with completely resected non-small-cell lung cancer (NSCLC). We have evaluated the predictive value of mutations in TP53, encoding the tumour suppressor p53, in the International Adjuvant Lung Cancer Trial (IALT), a randomized trial of adjuvant cisplatin-based chemotherapy against observation. TP53 (exons 4–8) was sequenced in 524 archived specimens of IALT patients with a median follow-up of 7.5 years. Predictive analyses were based on Cox models adjusted for clinical and pathological variables. P-values ≤0.01 were considered as significant. Mutations were detected in 221 patients (42%) and had no predictive value for the effect of chemotherapy (interaction between TP53 and treatment: p = 0.17 for Overall Survival (OS); p = 0.06 for Disease-Free Interval, (DFS)). However, among patients with mutations, outcome appeared worse in treatment compared to observation arms (HR for OS = 1.36 (95% CI [0.97–1.31), p = 0.08; DFS = 1.40 (95% CI [1.01–1.95]), p = 0.04). When grouping mutations into classes according to predicted effects on protein structure, the tendency towards worse outcomes was restricted to “structure” mutations affecting residues of the hydrophobic core that are not located at the p53 protein-DNA interface (HR for death in this class vs wild-type T53 = 1.66; 95% CI [1.10–2.52], p = 0.02). Overall, TP53 mutations are not significant predictors of outcome in this trial of cisplatin-based chemotherapy, although a specific class of structural mutations may be associated with a tendency towards worse outcomes upon treatment. •Chemotherapy only marginally improves survival in non-small-cell lung cancer.•In a large randomized trial, TP53 mutation does not predict survival.•Patients with mutations have worse survival in treatment than observation.•A class of structural mutations may carry a detrimental effect upon treatment.

Earlier studies suggested that the response to platinum treatment in lung cancer might be predicted according to the presence or absence of the DNA repair enzyme ERCC1. This study shows that the available antibodies do not predict response because they may detect nonfunctional enzymes. In patients with resected stage IB, IIA or IIB, or IIIA non–small-cell lung cancer (NSCLC), platinum-based postoperative chemotherapy is now standard treatment, with an estimated increase in the survival rate of 4 to 5% at 5 years. 1 , 2 The identification of predictive biomarkers of the efficacy of adjuvant chemotherapy could lead to an improved therapeutic index. 3 DNA repair capacity is a major determinant of cisplatin resistance; in particular, the excision repair cross-complementation group 1 (ERCC1) protein plays an essential role in nucleotide excision repair. Together with its partner, xeroderma pigmentosum complementation group F (XPF), ERCC1 cleaves DNA structures near the . . .

Tumor specimens from patients in a trial of cisplatin-based adjuvant chemotherapy for non–small-cell lung cancer were analyzed for the presence of ERCC1, an enzyme that participates in the repair of DNA damage caused by cisplatin. The absence of ERCC1 in the tumor was associated with a survival benefit from cisplatin-based adjuvant chemotherapy, whereas patients whose tumor expressed the enzyme failed to benefit from the chemotherapy. The absence of ERCC1 in the tumor was associated with a survival benefit from cisplatin-based adjuvant chemotherapy, whereas patients whose tumor expressed the enzyme failed to benefit from the chemotherapy. Lung cancer is a leading cause of death from cancer in most industrialized countries. 1 Despite undergoing complete resection of non–small-cell lung cancer, 33% of patients with pathological stage IA die within 5 years, as do 77% of those with pathological stage IIIA. 2 Clinical trials have tested the ability of adjuvant chemotherapy to improve survival after complete resection of non–small-cell lung cancer. The International Adjuvant Lung Cancer Trial (IALT) demonstrated an absolute benefit of 4.1% in 5-year overall survival among 1867 patients who were treated with adjuvant cisplatin-based chemotherapy. 3 Several other randomized studies have confirmed the benefit of postoperative platinum-based therapy . . .

Although kinase inhibitors raise hope for people with cancer, patients and their clinicians are commonly confronted with the cutaneous side-effects that are associated with the use of these drugs. This review is the result of collaborations between dermatologists, medical oncologists, and pathologists, and discusses the cutaneous side-effects seen after treatment with the inhibitors of epidermal-growth-factor receptor (EGFR), imatinib, sorafenib, and sunitinib. Some of the side-effects caused by these agents are very distressing, partly because they are chronic owing to the long duration of treatment. Therefore, patients need early and appropriate dermatological management. Moreover, several studies have reported a link between the antitumour efficacy of EGFR inhibitors and cutaneous side-effects. Elucidation of this connection could lead to the identification of crucial predictive factors for tumour response.

Individual participant data meta-analyses of postoperative chemotherapy have shown improved survival for patients with non-small-cell lung cancer (NSCLC). We aimed to do a systematic review and individual participant data meta-analysis to establish the effect of preoperative chemotherapy for patients with resectable NSCLC. We systematically searched for trials that started after January, 1965. Updated individual participant data were centrally collected, checked, and analysed. Results from individual randomised controlled trials (both published and unpublished) were combined using a two-stage fixed-effect model. Our primary outcome, overall survival, was defined as the time from randomisation until death (any cause), with living patients censored on the date of last follow-up. Secondary outcomes were recurrence-free survival, time to locoregional and distant recurrence, cause-specific survival, complete and overall resection rates, and postoperative mortality. Prespecified analyses explored any variation in effect by trial and patient characteristics. All analyses were by intention to treat. Analyses of 15 randomised controlled trials (2385 patients) showed a significant benefit of preoperative chemotherapy on survival (hazard ratio [HR] 0·87, 95% CI 0·78–0·96, p=0·007), a 13% reduction in the relative risk of death (no evidence of a difference between trials; p=0·18, I2=25%). This finding represents an absolute survival improvement of 5% at 5 years, from 40% to 45%. There was no clear evidence of a difference in the effect on survival by chemotherapy regimen or scheduling, number of drugs, platinum agent used, or whether postoperative radiotherapy was given. There was no clear evidence that particular types of patient defined by age, sex, performance status, histology, or clinical stage benefited more or less from preoperative chemotherapy. Recurrence-free survival (HR 0·85, 95% CI 0·76–0·94, p=0·002) and time to distant recurrence (0·69, 0·58–0·82, p<0·0001) results were both significantly in favour of preoperative chemotherapy although most patients included were stage IB–IIIA. Results for time to locoregional recurrence (0·88, 0·73–1·07, p=0·20), although in favour of preoperative chemotherapy, were not statistically significant. Findings, which are based on 92% of all patients who were randomised, and mainly stage IB–IIIA, show preoperative chemotherapy significantly improves overall survival, time to distant recurrence, and recurrence-free survival in resectable NSCLC. The findings suggest this is a valid treatment option for most of these patients. Toxic effects could not be assessed. Medical Research Council UK.

The majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients. This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR) mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m(2) on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m(2) on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) every 3 weeks. The combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III-IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06), DVT (P = 0.23), proteinuria (P = 0.23), and hypertension (P = 0.11), as well as Grade II alopecia (P = 0.001); however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66), hematological toxicity, febrile neutropenia (P = 1) and fatigue (P = 0.66). Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978). Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89). Bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy in advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation. No significant difference in toxicity was observed between both treatment arms, apart from bevacizumab/carboplatin/paclitaxel-related risks as DVT, hypertension, proteinuria, sensory/motor neuropathy, and alopecia.

Surgery remains the main curative treatment for patients with early-stage non-small-cell lung cancer (NSCLC); however, because many patients probably have undetectable micrometastasis even at diagnosis, adjuvant treatment is usually needed. The results for radiotherapy have mostly been disappointing, and a strong emphasis has, therefore, been placed on chemotherapy as the preferred modality. Adjuvant chemotherapy, and in particular, platinum-based regimens, have been assessed in several studies, but the results have been conflicting. Most trials have included patients with a wide range of disease stages and have shown, at most, only moderate improvements in survival. Thus, although clearly indicated in some patients, whether adjuvant chemotherapy should be used in all patients with resected disease is highly controversial. In this debate, Thierry Le Chevalier and colleagues and Giorgio Scagliotti present opposing arguments for whether this approach should be considered standard.

Exosomes derived from tumours are small vesicles released in vitro by tumour cell lines in culture supematants. To assess the role of these exosomes in vivo, we examined malignant effusions for their presence. We also investigated whether these exosomes could induce production of tumour-specific T cells when pulsed with dendritic cells. We isolated exosomes by ultracentrifugation on sucrose and D 2O gradients of 11 malignant effusions. We characterised exosomes with Western blot analyses, immunoelectron microscopy, and in-vitro stimulations of autologous T lymphocytes. Malignant effusions accumulate high numbers of membrane vesicles that have a mean diameter of 80 nm (SD 30). These vesicles have antigen-presenting molecules (MHC class-I heat-shock proteins), tetraspanins (CD81), and tumour antigens (Her2/Neu, Mart1, TRP, gp100). These criteria, including their morphological characteristics, indicate the similarities between these vesicles and exosomes. Exosomes from patients with melanoma deliver Mart1 tumour antigens to dendritic cells derived from monocytes (MD-DCs) for cross presentation to clones of cytotoxic T lymphocytes specific to Mart1. In seven of nine patients with cancer, lymphocytes specific to the tumour could be efficiently expanded from peripheral blood cells by pulsing autologous MD-DCs with autologous ascitis exosomes. In one patient tested, we successfully expanded a restricted T-cell repertoire, which could not be recovered carcinomatosis nodules. Exosomes derived from tumours accumulate in ascites from patients with cancer. Ascitis exosomes are a natural and new source of tumour-rejection antigens, opening up new avenues for immunisation against cancers.