Onkologie最新文献

Academic non-commercial trials are of substantial relevance for both patient care and progress in clinical research. Since the 12th amendment of the German drug law, applications for the initiation of clinical trials at the ethical review boards are much more cost- and time-intensive, particularly for multicenter therapy optimization trials (TOS). To activate a trial, for, e.g., 51 ethical review boards, current curricula vitae (CVs) and certificates on good clinical practice (GCP) and regulations have to be provided for all investigators. After the new amendment of the German drug law in 2012, the process remains complex while the responsibility of the team eligibility has now been transferred to the main investigator at the study site. Therefore, the online database 'QualiPRO' was developed, free of charge and widely accessible for the investigators, their clinical trial units and the coordinating centers of the TOS. Its features ease the process to generate and provide data on the clinical trial activities of any investigator and team member. The database content and architecture follows ethical review board recommendations and the Good Clinical Practice (GCP) of the International Conference on Harmonisation (ICH). After registration of the unit and membership of the team, study staff' members are able to enter and edit data and to print a 'trial' CV. CVs, GCP certificates, licences to practice medicine and more can be uploaded, and, after consent of the investigators, are available to the coordinating centers of TOS. In addition, QualiPRO is an instrument for directors of hospital departments or group leaders to efficiently collect and locally display data on their study activities and on the training status of their staff.

Background: The mortality from non-small cell lung cancer (NSCLC) in China is increasing, and studies about clinical characteristics of recent NSCLC are rare. The primary objective of this study was to explore clinical features in a large general hospital in Northwest China, and to determine risk factors for stage, pathology and survival, with a view to prevention and treatment of NSCLC as well as establishment and improvement of national medical insurance policies.

Patients and methods: We retrospectively analyzed the characteristics of NSCLC patients (n = 274), as well as risk factors for advanced stage and squamous cell carcinoma (SCC). Survival features in different groups were analyzed, as well as risk factors of survival. Follow-up was at least 3 years.

Results: 179 were male (65.3%); 136 had adenocarcinoma (49.6%) and 109 had SCC (39.8%); 186 (67.9%) had advanced-stage disease (IIIB-IV); 130 (47.4%) had smoking habits; 195 came from an urban area (71.2%); 69 had local urban resident basic medical insurance; 58% were younger than 60 years. Female, adenocarcinoma, rural patients were significantly younger than male, SCC, and urban patients. Pathology was the only independent risk factor for advanced stage. Age, sex, and smoking status were independent prognostic factors for SCC. The proportion of male SCC was higher than female SCC even without the influence of smoking. Without local urban resident basic medical insurance, higher stage and not having surgery, but not smoking status, were independent risk factors for lower median progression-free survival (PFS). Patients with adenocarcinoma and SCC in advanced stage accepting EGFR-TKI during treatment had a higher 1-year survival rate and longer overall survival (OS) compared with those never accepting EGFR-TKI. EGFR-TKI treatment and chemotherapy regimen numbers were independent risk factor for median OS in advanced adenocarcinoma and SCC patients.

Conclusion: More prevention and screening should be carried out for the female and rural population. EGFR-TKI could benefit advanced NSCLCs. China's medical insurance policy has some adverse effect on NSCLC survival calling for further improvement.

Background: Colorectal cancer (CRC) plays an important role in cancer mortality and morbidity. This study examined colorectal tissues for RAS, BRAF, and TP53 gene mutations to assess their value as indicators of outcomes of CRC therapy.

Material and methods: DNA was extracted from tissues taken from 165 patients with CRC. RAS gene mutations (exons 2 and 3) were detected by primer extension analysis. BRAF gene mutations (V600E) were detected by high resolution melting (HRM) analysis. TP53 gene mutations (exons 5-8) were detected by direct sequencing.

Results: RAS, BRAF, and TP53 mutations occurred in 36.97% (61/165), 4.24% (7/165), and 37.58% (62/165), respectively. The KRAS mutation is a predictor for poor 5-year survival (p = 0.05), and the co-presence of KRAS and TP53 mutations correlates with lymph node involvement (p = 0.029), tumor stage (p = 0.029), and poor survival (p = 0.021). Multivariate analysis adjusted for tumor size, histologic grade, lymph node metastasis, sex, and age also indicated that KRAS mutations correlate significantly with overall survival (p = 0.036).

Conclusion: The KRAS mutation is not present in about one-third of CRC patients, and therefore other gene mutations need to be investigated to better understand the molecular mechanisms of CRC and its treatment.

Background: We have analyzed the patient population of one clinic (Charité) over a period of 15 years. Besides the changes in the technical facilities and therapeutical guidelines during these years, this period also reflects the changes in the health system attributable to the reunification of East and West Germany. Until now only few analyses for breast cancer patients from the German speaking area have been reported.

Patients and methods: All 2,062 patients undergoing surgical treatment for breast cancer between 1984 and 1998 were documented and followed up until 2007. The analysis included 1,560 patients with a primary breast cancer who fulfilled certain inclusion criteria. The treatment strategies applied to this population are presented in 3 time periods (1984-1990, 1991-1993, and 1994-1998). The effects of prognostic factors on overall survival were investigated using univariate analyses.

Results: The percentage of pT1 tumors changed from 50.7% in the first period to 63.1% in the third period. The percentage of node-negative patients hardly changed with time (on average 61.6%). However, the percentage of patients with less than 10 assessed nodes decreased from 48.4% to 6.7% and 2.5% for the 3 periods, respectively. Therapeutic strategies changed drastically. Survival rate increased substantially, most likely due to improved therapeutic strategies, but also for other reasons not considered in the analysis.

Background: Accumulating evidence has shown that microRNAs (miRNAs) are aberrantly expressed in human esophageal cancer and crucial to tumorigenesis. Herein, we identified the role of miR-145 in esophageal squamous cell carcinoma (ESCC) development in vitro and in vivo.

Material and methods: miR-145 expression was investigated in 40 ESCC samples as well as 5 ESCC cell lines by real-time polymerase chain reaction. Crystal violet and transwell assays were conducted to explore the effects of miR-145 on the proliferation and invasion of human ESCC cell lines, respectively. The impact of overexpression of miR-145 on putative target c-Myc was subsequently confirmed via Western blot.

Results: miR-145 expression was frequently downregulated in ESCC specimens and cell lines compared with adjacent normal tissues (p < 0.05). Overexpression of miR-145 suppressed (p < 0.05) ESCC cell proliferation and invasion, as well as the growth of xenograft tumors in mice. Overexpression of miR-145 significantly decreased (p < 0.05) the protein level of c-Myc which has previously been identified as a direct target of miR-145.

Conclusion: Our results demonstrate that overexpression of miR-145 inhibits tumor growth in part by targeting c-Myc. Our findings revealed that miR-145 may act as a tumor suppressor in ESCC, and its dysregulation may be involved in the initiation and development of human ESCC.

Background: We assessed the relation between the extent of lymph node (LN) dissection and the prognosis for positron emission tomography-computed tomography (PET-CT)-negative patients with clinical early-stage non-small cell lung cancer (NSCLC), undergoing lobectomy and mediastinal LN dissection.

Methods: 277 patients with clinical stage I/II NSCLC who had undergone a preoperative PET-CT scan followed by lobectomy were analysed retrospectively. The prognostic value of age, maximum standardized uptake value (SUVmax) of the tumour, tumour size, carcinoembryonic antigen and number of dissected LNs was assessed to determine any association with overall survival and disease-free survival.

Results: 31 patients developed postoperative relapse, and multiple logistic regression revealed that the number of dissected LNs was an independent factor predicting relapse. Patients were categorized into groups according to the number of LNs dissected (group I, < 10; group II, ≥ 10). There were no statistical differences between 2 groups but group II patients had a lower relapse rate (6.3%, p = 0.003) and better disease-free survival (74.95 months, p = 0.045).

Conclusions: Mediastinal LN dissection is still important for clinical early-stage NSCLC patients undergoing lobectomy even when the preoperative PET-CT is negative, and results in fewer relapses and improved disease-free survival.

Background: Single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be related with susceptibility to several human cancers. We evaluated the associations of rs3746444 in pre-miRNA hsa-mir-499 with the risk of gastric cancer (GC) in the Chinese population.

Patients and methods: The rs3746444 (A>G) SNPs were genotyped in 201 GC and 213 non-cancer subjects in a case-control study by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results: There was no significant overall difference in the genotype distributions of rs3746444 (A>G) SNPs between cases and controls. In the logistic regression analyses, no significantly increased risk of GC was found to be associated with variant genotypes.

Conclusion: The rs3746444 (A>G) SNP is not associated with susceptibility to GC in the Chinese population.

The peroxisome proliferator-activated receptor-γ (PPARγ) belongs to the nuclear hormone receptor superfamily, and is expressed in adipose tissue, skeletal muscle, spleen, heart, liver, placenta, lung, and ovary. PPARγ is a critical regulator of inflammation, adipocyte differentiation, glucose homeostasis, and tumorigenesis. The mechanism of PPARγ on tumor suppression is still unclear, but plenty of evidence shows that PPARγ provides new therapeutic targets for cancer. Here we give a review of how PPARγ and its ligands regulate tumorigenesis by different pathways.

Background: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors.

Methods: In a retrospective study, the data of 225 patients with breast, ovarian and cervical cancer treated in the palliative care unit of a university hospital between 1998 and 2009 were assembled. Clinical aspects and baseline symptoms, laboratory parameters, the clinical course, and outcome were evaluated.

Results: 225 patients (497 cases; cancer diagnoses: breast 79%, ovarian 13%, and cervix 8%) were included in the analysis. The main symptoms were weakness/fatigue (71%), pain (65%), anorexia/nausea (62%), and dyspnea (46%). Pain control was achieved in 85% of all cases, satisfying control of other symptoms in 80%. The median overall survival (OS) was 59 days. 53% of the patients died at the palliative care unit. In the Cox proportional hazards model, 8 parameters indicated an unfavourable outcome: anorexia/nausea, disordered mental status, elevated lactate dehydrogenase, γ-glutamyltransferase, leukocyte count, hypoalbuminaemia, anaemia and hypercalcaemia. Based on these parameters 3 risk groups were defined: low risk (0-2 factors), intermediate risk (3-5 factors), and high risk (6-8 factors). Median survival for high-risk group was 13 days, for intermediate group 61 days, and for low-risk patients 554 days (p < 0.0001).

Conclusion: Weakness/fatigue, pain and anorexia were the main symptoms leading to the hospitalisation of patients with gynaecological malignancies. Symptom and pain control was accomplished in 80% of cases. 8 parameters were identified as indicating a poor outcome, and patients showing at least 6 or more of these factors had a very limited prognosis. Although studied retrospectively, these results may be helpful for individual treatment decisions in patients with advanced gynaecological malignancies. Prospective data and the introduction of documentation systems could help to gain more powerful knowledge about the quality of palliative care.

Background: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors.

Methods: The patients received cisplatin 30 mg/m² and irinotecan 50 mg/m² weekly from week 1 to week 4, with SU5416 at either 65 mg/m² (dose level (DL)1) or 85 mg/m² (DL2) twice weekly for 6 weeks (1 cycle). Serial ¹⁸fluorodeoxyglucose-positron emission tomography (¹⁸FDG-PET) and ¹⁵O-H₂O-PET scans were obtained.

Results: 13 patients were treated (7 on DL1, 6 on DL2); 7 patients completed at least 1 cycle of treatment. 3 patients experienced dose-limiting toxicity (DLT) at DL2 (grade 3 neutropenia and grade 3 thrombocytopenia causing treatment delay, grade 3 nausea/vomiting). No objective responses were observed at DL1, which was determined to be the maximum tolerated dose (MTD). 1 partial response (PR) was observed at DL2. ¹⁸FDG-PET responses were documented but did not predict response according to the Response Evaluation Criteria in Solid Tumors (RECIST).

Conclusions: SU5416 at 65 mg/m² twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity. ¹⁸FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development.