Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma

Background:Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels.Methods:Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 gm-2 once every 3 weeks. The primary aim of the study was progression-free survival (PFS).Results:No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.Conclusion:NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest

safety of nintedanib plus docetaxel in advanced non squamous nsclc nsnsclc patients the preliminary results of the seneca second line nintedanib in non small cell lung cancer trial

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Diagnosis of American foulbrood in honey bees: A synthesis and proposed analytical protocols

Worldwide, American foulbrood (AFB) is the most devastating bacterial disease of the honey bee (Apis mellifera). Because the distinction between AFB and powdery scale disease is no longer considered valid, the pathogenic agent has recently been reclassified as one species Paenibacillus larvae, eliminating the subspecies designations Paenibacillus larvae subsp. larvae and Paenibacillus larvae subsp. pulvifaciens. The creamy or dark brown, glue-like larval remains of infected larvae continue to provide the most obvious clinical symptom of AFB, although it is not conclusive. Several sensitive and selective culture media are available for isolation of this spore-forming bacterium, with the type of samples that may be utilized for detection of the organism being further expanded. PCR methods for identification and genotyping of the pathogen have now been extensively developed. Nevertheless, biochemical profiling, bacteriophage sensitivity, immunotechniques and microscopy of suspect bacterial strains are entirely adequate for routine identification purposes.Facultad de Ciencias Agrarias y ForestalesCentro de Investigaciones de Fitopatologí

Diagnosis of American foulbrood in honey bees: A synthesis and proposed analytical protocols

Worldwide, American foulbrood (AFB) is the most devastating bacterial disease of the honey bee (Apis mellifera). Because the distinction between AFB and powdery scale disease is no longer considered valid, the pathogenic agent has recently been reclassified as one species Paenibacillus larvae, eliminating the subspecies designations Paenibacillus larvae subsp. larvae and Paenibacillus larvae subsp. pulvifaciens. The creamy or dark brown, glue-like larval remains of infected larvae continue to provide the most obvious clinical symptom of AFB, although it is not conclusive. Several sensitive and selective culture media are available for isolation of this spore-forming bacterium, with the type of samples that may be utilized for detection of the organism being further expanded. PCR methods for identification and genotyping of the pathogen have now been extensively developed. Nevertheless, biochemical profiling, bacteriophage sensitivity, immunotechniques and microscopy of suspect bacterial strains are entirely adequate for routine identification purposes.Facultad de Ciencias Agrarias y ForestalesCentro de Investigaciones de Fitopatologí

Phase Ib study of NGR–hTNF, a selective vascular targeting agent, administered at low doses in combination with doxorubicin to patients with advanced solid tumours

Contains fulltext : 81937timmer-bonte.pdf (publisher's version ) (Closed access)BACKGROUND: Asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF) is a vascular targeting agent exploiting a tumour-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13, overexpressed on tumour blood vessels. Significant preclinical synergy was shown between low doses of NGR-TNF and doxorubicin. METHODS: The primary aim of this phase I trial was to verify the safety of low-dose NGR-hTNF combined with doxorubicin in treating refractory/resistant solid tumours. Secondary objectives included pharmacokinetics (PKs), pharmacodynamics, and clinical activity. In all 15 patients received NGR-hTNF (0.2-0.4-0.8-1.6 microg m(-2)) and doxorubicin (60-75 mg m(-2)), both given intravenously every 3 weeks. RESULTS: No dose-limiting toxicity occurred and the combination was well tolerated. Around two cases of neutropenic fevers, lasting 2 days, and two cases of cardiac ejection-fraction drops, one asymptomatic and the other symptomatic, were registered. Only 11% of the adverse events were related to NGR-hTNF and were short-lasting and mild-to-moderate in severity. There was no apparent PK interaction and the shedding of soluble TNF-receptors did not increase to 0.8 microg m(-2). One partial response (7%), at dose level 0.8 microg m(-2), and 10 stable diseases (66%), lasting for a median duration of 5.6 months, were observed. CONCLUSIONS: NGR-hTNF plus doxorubicin was administered safely and showed promising activity in patients pre-treated with anthracyclines. The dose level of 0.8 microg m(-2) NGR-hTNF plus doxorubicin 75 mg m(-2) was selected for phase II development

Biomarkers of clinical benefit for anti-epidermal growth factor receptor agents in patients with non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) remains by far the major cause of cancer-related death in the Western world in both men and women. The majority of patients will be diagnosed with metastatic disease, and chemotherapy doublets remain the cornerstone of treatment for these patients. However, chemotherapy has a minimal impact on long-term survival and prognosis remains poor for these patients. Further improvement in treatment is likely to require incorporation of novel targeted therapies. Among these agents, inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated significant activity in the first-, second- or third-line treatment of NSCLC. The purpose of current paper is to present the evidence for using several proposed molecular biomarkers as a tool for selection of NSCLC patients for anti-EGFR treatment. According to current data, EGFR mutation status appears to be the strongest predictor for the selection of NSCLC patients to first-line treatment with EGFR tyrosine kinase inhibitors vs chemotherapy. Use of other biomarkers remains investigational

Diagnosis of American foulbrood in honey bees: A synthesis and proposed analytical protocols

Worldwide, American foulbrood (AFB) is the most devastating bacterial disease of the honey bee (Apis mellifera). Because the distinction between AFB and powdery scale disease is no longer considered valid, the pathogenic agent has recently been reclassified as one species Paenibacillus larvae, eliminating the subspecies designations Paenibacillus larvae subsp. larvae and Paenibacillus larvae subsp. pulvifaciens. The creamy or dark brown, glue-like larval remains of infected larvae continue to provide the most obvious clinical symptom of AFB, although it is not conclusive. Several sensitive and selective culture media are available for isolation of this spore-forming bacterium, with the type of samples that may be utilized for detection of the organism being further expanded. PCR methods for identification and genotyping of the pathogen have now been extensively developed. Nevertheless, biochemical profiling, bacteriophage sensitivity, immunotechniques and microscopy of suspect bacterial strains are entirely adequate for routine identification purposes.Facultad de Ciencias Agrarias y ForestalesCentro de Investigaciones de Fitopatologí