Phase II with single-agent docetaxel, in second-line NSCLC, demonstrated an overall response rate of 20%, with a median response duration of 7 months and a median survival time of 9 months. These results suggested that docetaxel had promising activity in patients with platinum-resistant or refractory NSCLC. Phase III studies in this patient population subsequently confirmed this activity; docetaxel prolonged survival when compared to either vinorelbine/ifosfamide or the best supportive care. The phase II studies with docetaxel in first-line NSCLC produced an overall response rate of 30% in evaluable patients, with a median response duration of 6 months and a median survival time of 9 months. A phase III randomized study demonstrated a significant improvement in survival and time to progression with docetaxel, compared to the best supportive care. Based on the activity observed with single-agent docetaxel, combination and multimodality studies with docetaxel have also been conducted. Docetaxel is an active agent in first- and second-line NSCLC. Ongoing studies in the front-line treatment of NSCLC will further define the role of docetaxel in the neo-adjuvant setting. 相似文献
The formation of multiprotein complexes is l'ordre du jour in regulatory pathways. In this issue of Oncogene, Reale et al. report the formation of a particularly sophisticated complex of two important regulatory enzymes, DNMT1 (DNA methyltransferase-1) and PARP-1 (poly(ADP-ribose)polymerase-1). The former evolved with a specific sequence motif binding the enzymatic product of the latter. The product, poly(ADP-ribose), bonds the two partners into a heterodimeric complex and, as a consequence, the catalytic function of DNMT1 is silenced. Thus, PARP-1 becomes a conditional negative regulator of DNMT1. In a larger perspective, Reale et al. highlight the potential role of PARP-1 as a co-regulator of DNA methylation leading to epigenetic reprogramming of cancer cells. 相似文献
Objective To clarify whether CDDP acts as a modulator of 5-FU antitumor action in gastric cancer, patients were treated preoperatively with 5-FU+CDDP (FP) chemotherapy.Patients and methods From September 2000 to November 2001 at Takarazuka Municipal Hospital, 29 patients preoperatively diagnosed with stages II–IV gastric cancer were enrolled. Written informed consent was obtained from all patients. The patients were randomly assigned to two groups: the FU group, in which patients received a continuous intravenous infusion of 5-FU 320 mg/m2 per day over 24 h a day for 5 days beginning 5 days prior to surgery, and the FP group, in which patients received bolus intravenous injections of CDDP 3.5 mg/m2 per day for 5 days prior to surgery in addition to the same infusion of 5-FU as the FU group. As indicators of the intracellular effect of 5-FU treatment, thymidylate synthase (TS) inhibition rates, TS protein levels, TS and dihydropyrimidine dehydrogenase (DPD) activity, and F-RNA concentrations were measured.Results Using Scheffes multiple comparison test, in both treatment groups the tumor regions were found to have significantly higher TS inhibition rates than the nontumor regions (P<0.05). No significant differences in TS protein levels, TS activity, DPD activity or F-RNA concentrations were found between the four regions.Conclusions Our results show that CDDP clinically may act to enhance the antitumor effects of 5-FU in terms of the inhibition of DNA synthesis and could therefore act as a modulator of 5-FU. 相似文献
To compare plasma lysophosphatidic acid (LPA) levels in ovarian cancer patients in women with benign ovarian tumors and in
women with no ovarian pathology. We correlated clinico-pathological parameters with plasma LPA levels. Capillary electrophoresis
with indirect ultraviolet detection was used to analyze the plasma LPA levels of 159 patients (81 patients with ovarian cancer,
27 women without ovarian or uterine pathologies, and 51 patients with benign ovarian tumors) during a 5-year period. Patients
with ovarian cancer had a significantly higher plasma LPA level (n = 81; median (med), 11.53 μmol/l; range, 1.78–43.21 μmol/l) compared with controls with no ovarian pathology (n = 27; med, 1.86 μmol/l; range, 0.94–9.73 μmol/l), and patients with benign ovarian tumor (n = 51; med, 6.17 μmol/l; range, 1.12–25.23 μmol/l; P < 0.001). We found that plasma LPA levels were associated with the International Federation of Gynecology and Obstetrics
stage. The histological subtype and grade of ovarian cancer did not influence the plasma LPA levels in this study. The plasma
LPA level can be a useful marker for ovarian cancer, particularly in the early stages of the disease. 相似文献
Patient survival in head and neck squamous cell cancer (HNSCC) has not changed significantly in many years, despite progress in surgical, radiotherapy and chemotherapy techniques. Immunotherapy, a rapidly progressing alternative cancer treatment, aims to prompt or assist the body's immune system to combat the disease itself. A number of strategies exist including the use of dendritic cells, natural antigen presenting cells capable of stimulating an anti-tumor immune response. Encouraging work has been performed using these cells as vaccines against a number of tumors especially melanoma. Work with head and neck cancer is also encouraging, but less advanced. Dendritic cell presence in head and neck squamous cell cancers is associated with an improved prognosis, however due to immunosuppression, the exact mechanism of which remains poorly understood, these cells do not function efficiently. This prevents the stimulation of an effective anti-tumor immune response by the patient and allows tumor growth to continue. This review summarises the current level of understanding of dendritic cells and their relationship with HNSCC. It briefly summarises work with dendritic cells and other cancers where relevant to HNSCC; dendritic cells and head and neck cancer; the possible causes of dendritic cell impairment; the techniques used to restore their function and the methods used to prime the dendritic cells prior to their use as vaccines for the stimulation of an anti-tumor response. 相似文献
The usefulness of placental alkaline phosphatase (PLAP) as a tumour marker was assessed in 1578 serum samples from 236 patients with seminoma. Smoking habits were known for all but 7 patients (22 samples). Smoking was associated with significantly higher mean levels of PLAP in disease-free patients (28.8[S.E. 2.1]U/l vs. 15.9[1.3] U/l in non-smokers). Mean PLAP levels were higher in patients with active disease (78.6 [23.5] U/l in non-smokers and 47.2 [18.5] U/l in smokers). The median values showed a similar trend. However, there was considerable overlap between the various groups and differences between mean and median values indicated that PLAP values were distributed asymmetrically. The predictive value of PLAP as a tumour marker was consequently much less than superficial inspection of these values might suggest. In 97 patients on surveillance, only 2 out of 11 patients who relapsed had elevated PLAP at the time of clinically detectable relapse. With the upper limit of normal PLAP quoted by our laboratory (35 U/l), specificity and sensitivity were, respectively, 88% and 45% (all patients) and 96% and 47% (non-smokers). The sensitivity and specificity of PLAP were assessed in more detail for a series of threshold values (normal vs. abnormal) with a graphical method. Only in non-smokers did PLAP seem useful and even in this group the positive predictive value of an “abnormal” test may be low; less than 50% in clinically relevant circumstances. Serum PLAP assay cannot usefully stand alone as a marker for seminoma and its routine estimation contributes little to follow-up. 相似文献
Autoimmune phenomena may complicate the course of myelodysplastic syndromes (MDS) but large vessel arteritis is a rare event. We report a case of large vessel arteritis in a patient with MDS. A 62-year-old male presented with thrombocytopenia and was diagnosed with low-risk MDS, (<5% blasts in his bone marrow and a normal karyotype). Shortly thereafter he developed large vessel (Takayasu's) arteritis (TA) that responded well to oral corticosteroid and methotrexate therapy. Ten months later the MDS transformed into acute myeloid leukemia (AML). After a successful induction course with cytarabine and daunorubicin he underwent allogeneic transplantation from a matched unrelated donor with reduced-intensity conditioning. The transplantation was complicated by systemic cytomegalovirus (CMV) disease and he died 6 weeks post transplantation. Takayasu's arteritis is an uncommon form of vasculitis affecting primarily young women and is atypical for elderly males. Though autoimmune manifestations in MDS occur in 10%-18.5% of patients, usually large vessels are spared. In MDS, activated T cells are thought to mediate bone marrow failure via overproduction of proinflammatory cytokines that cause stem cell apoptosis. These T cells may also mediate the autoimmune phenomena in MDS. The prognostic significance of autoimmunity in the course of MDS is not yet determined. Some reports suggest worse prognosis. The case illustrates a possible association between MDS and large vessel vasculitis and suggests a possible relationship between the presence of autoimmune syndromes and the outcome of patients with MDS. 相似文献
Encouraged by recent studies on the MTHFR 677C>T polymorphism and breast cancer risk that suggested an association of the
677 TT genotype with increased breast cancer susceptibility in premenopausal women, we performed an analysis of the relationship
between breast cancer risk and the MTHFR 677C>T polymorphism in 210 premenopausal breast cancer patients and sex- and agematched
healthy control subjects. Our data show a trend for a higher MTHFR 677T allele frequency in breast cancer cases (61.9%) than
in controls (51.5%, P = 0.082) supporting the results of previous studies. 相似文献
Chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK) are rare oncogenic events found in 3–5% of non-small-cell lung cancers (NSCLC). Limited data have been published on the management of these patients outside clinical trials.
Objective
To investigate the clinical characteristics and management of patients with NSCLC harboring ALK translocations (ALK+) in a real-life setting in France.
Methods
This multicenter, observational, retrospective study included all NSCLC patients harboring ALK translocations diagnosed in participating centers between January 2012 and December 2014. Patient data include clinical characteristics, disease management, and outcomes [progression-free survival (PFS) and overall survival (OS)].
Results
The 31 participating centers reported data on 132 patients, of whom 51% (n = 67) were male. The median age was 60.1 ± 14.5 (standard deviation) years; 89% (n = 106/119) had performance status 0/1 at diagnosis; 79% (n = 103/130) were non- or former smokers; 93% (n = 120/129) had adenocarcinomas and 74%(n = 97)/19%(n = 25)/7%(n = 10) had disease stages IV/III/I-II at diagnosis, respectively; co-mutations included EGFR (n = 2), BRAF (n = 2), KRAS (n = 1), and HER2 (n = 1). Of the patients with stage IV NSCLC (n = 97), 96% received first-line treatment [75% chemotherapy-based, 21% ALK tyrosine kinase inhibitor (TKI)], with an associated response rate (RR), disease-control rate (DCR), and PFS of 42%, 64%, and 7.5 [95% confidence interval (CI) 5.9–9.5] months, respectively; 62% received second-line treatment (28% chemotherapy, 72% ALK TKI) with an associated RR, DCR, and PFS of 43.4%, 70%, and 4.7 (95% CI 4.0–8.1) months, respectively. The 2-year OS was 56.7% (95% CI 45.5–70.4%); median OS was not reached.
Conclusion
The results of this real-life analysis suggest that the prognosis of NSCLC patients with theALK translocation may be better than that of the overall NSCLC population, but the outcomes were poorer than those of ALK+ NSCLC patients included in clinical studies.
Birt-Hogg-Dubé (BHD) syndrome is characterized by the development of pneumothorax, hair folliculomas and renal tumors and the responsible BHD gene is thought to be a tumor suppressor. The function of folliculin (Flcn), encoded by BHD, is totally unknown, although its interaction with Fnip1 has been reported. In this study, we identified a novel protein binding to Flcn, which is highly homologous to Fnip1, and which we named FnipL (recently reported in an independent study as Fnip2). The interaction between FnipL/Fnip2 and Flcn may be mediated mainly by the C-terminal domains of each protein as is the case for the Flcn-Fnip1 interaction. FnipL/Fnip2 and Flcn were located together in the cytoplasm in a reticular pattern, although solely expressed Flcn was found mainly in the nucleus. Cytoplasmic retention of Flcn was canceled with C-terminal truncation of FnipL/Fnip2, suggesting that FnipL/Fnip2 regulates Flcn distribution through their complex formation. By the employment of siRNA, we observed a decrease in S6K1 phosphorylation in the BHD-suppressed cell. We also observed a decrease in S6K1 phosphorylation in FNIP1- and, to a lesser extent, in FNIPL/FNIP2-suppressed cells. These results suggest that Flcn-FnipL/Fnip2 and Flcn-Fnip1 complexes positively regulate S6K1 phosphorylation and that FnipL/Fnip2 provides an important clue to elucidating the function of Flcn and the pathogenesis of BHD. 相似文献