The Effectiveness of Gefitinib on Spinal Metastases of Lung Cancer - Report of Two Cases -

Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Recently, gefitinib, a molecule target therapeutic drug, has offered a new approach for patients with non-small-cell lung cancer (NSCLC). This report describes the effects of gefitinib on bone metastases in two patients with NSCLC. The pain induced by a bone metastasis was relieved after the administration of gefitinib. Furthermore, the radiographs and CT findings showed sclerotic changes that matched those of the metastatic bone tumor after gefitinib administration in both patients. It is believed that gefitinib inhibited tumor cell proliferation and induced normal bone formation. In patients with NSCLC, gefitinib may be effective in the treatment of bone metastases

KRAS early testing. Consensus initiative and cost-effectiveness evaluation for metastatic colorectal patients in an italian setting

KRAS testing is relevant for the choice of the most appropriate first-line therapy of metastatic colorectal cancer (CRC). Strategies for preventing unequal access to the test should be implemented, but their relevance in the practice is related to economic sustainability. The study adopted the Delphi technique to reach a consensus on several topics. Issues related to execution of KRAS testing were identified by an expert's board and proposed to 108 Italian oncologists and pathologists through two subsequent questionnaires. The emerging proposal was evaluated by decision analyses models employed by technology assessment agencies in order to assess cost-effectiveness. Alternative therapeutic strategies included most commonly used chemotherapy regimens alone or in combination with cetuximab or bevacizumab. The survey indicated that time interval for obtaining KRAS test should not exceed 15 days, 10 days being an optimal interval. To assure the access to proper treatment, a useful strategy should be to anticipate the test after radical resection in patients at high risk of relapse. Early KRAS testing in high risk CRC patients generates incremental cost-effectiveness ratios between 6,000 and 13,000 Euro per quality adjusted life year (QALY) gained. In extensive sensitivity analyses ICER's were always below 15,000 Euro per QALY gained, far within the threshold of 60,000 Euro/QALY gained accepted by regulatory institutions in Italy. In metastatic CRC a time interval higher than 15 days for result of KRAS testing limits access to therapeutic choices. Anticipating KRAS testing before the onset of metastatic disease in patients at high risk does not affect the sustainability and cost-effectiveness profile of cetuximab in first-line mCRC. Early KRAS testing may prevent this inequality in high-risk patients, whether they develop metastases, and is a cost-effective strategy. Based on these results, present joined recommendations of Italian societies of Oncology and Pathology should be updated including early KRAS testing

The expanding capability and clinical relevance of molecular diagnostic technology to identify and evaluate EGFR mutations in advanced/metastatic NSCLC.

Epidermal growth factor receptor (EGFR) mutation testing in advanced non-small-cell lung cancer (NSCLC) has evolved rapidly over the past decade, largely triggered by the introduction of the targeted EGFR tyrosine kinase inhibitors (TKIs). Initially used to detect common EGFR mutations and determine the most appropriate first-line therapy at diagnosis, testing methodologies have expanded to test for multiple mutations at multiple time points throughout the disease course. Here we review the current mutation testing approaches, including types of biopsies, and the available assays commonly used in the clinic. Specific application of these approaches in advanced NSCLC, including current guideline recommendations, and potential future developments are discussed

Practical considerations in screening for genetic alterations in cholangiocarcinoma

Cholangiocarcinoma (CCA) encompasses diverse epithelial tumors historically associated with poor outcomes due to an aggressive disease course, late diagnosis, and limited benefit of standard chemotherapy for advanced disease. Comprehensive molecular profiling has revealed a diverse landscape of genomic alterations as oncogenic drivers in CCA. TP53 mutations, CDKN2A/B loss, and KRAS mutations are the most common genetic alterations in CCA. However, intrahepatic CCA (iCCA) and extrahepatic CCA (eCCA) differ substantially in the frequency of many alterations. This includes actionable alterations, such as IDH1 mutations and a large variety of FGFR2 rearrangements, which are found in up to 29% and approximately 10% of patients with iCCA, respectively, but are rare in eCCA. FGFR2 rearrangements are currently the only genetic alteration in CCA for which a targeted therapy, the FGFR1-3 inhibitor pemigatinib, has been approved. However, favorable phase 3 results for IDH1-targeted therapy with ivosidenib in iCCA have been published, and numerous other alterations are actionable by targeted therapies approved in other indications. Recent advances in next-generation sequencing (NGS) have led to the development of assays that allow comprehensive genomic profiling of large gene panels within 2-3 weeks, including in vitro diagnostic tests approved in the US. These assays vary regarding acceptable source material (tumor tissue or peripheral whole blood), genetic source for library construction (DNA or RNA), target selection technology, gene panel size, and type of detectable genomic alterations. While some large commercial laboratories offer rapid and comprehensive genomic profiling services based on proprietary assay platforms, clinical centers may use commercial genomic profiling kits designed for clinical research to develop their own customized laboratory-developed tests. Large-scale genomic profiling based on NGS allows for a detailed and precise molecular diagnosis of CCA and provides an important opportunity for improved targeted treatment plans tailored to the individual patient’s genetic signature

Occurrence of enterotoxic Staphylococcus aureus in raw milk from yaks and cattle in Mongolia.

Staphylococcal food poisoning is considered one of the leading foodborne illnesses in humans worldwide and is associated with contaminated foods of animal origin, such as milk and dairy products. In this study, we investigated the occurrence of staphylococci and the enterotoxigenic properties of Staphylococcus aureus isolated from raw milk from yaks (Bos mutus) and cattle in Mongolia. Staphylococci were isolated from 72 (74%) of the 97 raw milk samples. Of the samples containing staphylococci, 69% (50 of 72) were from yaks and 30.5% (22 of 72) were from cattle. S. aureus was detected in 10% of yak (7 of 72) and 21% of cattle (15 of 72) milk samples. Staphylococcal enterotoxin C was detected in 23% (5 of 22) of the S. aureus strains investigated, based on the reverse passive latex agglutination technique. Three of the five enterotoxigenic strains were from yaks and two were from cattle. None of the S. aureus strains tested produced staphylococcal enterotoxins A, B, or D. To our knowledge, this is the first report of the occurrence of staphylococci and enterotoxigenic S. aureus in milk from yaks and cattle in Mongolia

Thermoelastic signal processing using an FFT lock-in based algorithm on extended sampled data

A fast infrared scanner is used to acquire the thermoelastic effect induced temperature changes along a line on the surface of cyclically loaded tensile samples. The raster scanning movement of the single detector allows the sampling of temperature versus time. This data are then post-processed by means of a lock-in algorithm coupled with 1D and 2D FFT analyses in order to filter out the thermoelastic signal from the noisy measured signal. A data extension algorithm is proposed which uses the information from different acquired frames to extend the data sampling window. The whole signal processing setup is evaluated on experimental data with successful results, proposing a potential tool for low cost Thermoelastic Stress Analysi

Monitoring response to therapy by testing circulating tumor DNA in urine

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Point-of-Care Testing for the Detection of MicroRNAs: Towards Liquid Biopsy on a Chip

Point-of-care (PoC) testing is revolutionizing the healthcare sector improving patient care in daily hospital practice and allowing reaching even remote geographical areas. In the frame of cancer management, the design and validation of PoC enabling the non-invasive, rapid detection of cancer markers is urgently required to implement liquid biopsy in clinical practice. Therefore, focusing on stable blood-based markers with high-specificity, such as microRNAs, is of crucial importance. In this work, we highlight the potential impact of circulating microRNAs detection on cancer management and the development of PoC testing devices, especially for low-income countries. A detailed discussion about the challenges that should be faced to promote the technological transfer and clinical use of these tools has been added, to provide the readers with a complete overview of potentialities and current limitations

Global Emergence of Colistin-Resistant Escherichia coli in Food Chains and Associated Food Safety Implications: A Review

Antimicrobial resistance in bacteria represents one of the most important challenges for public health worldwide. Human infections from antimicrobial-resistant bacteria can be transmitted from person to person, via the environment (especially in the hospital environment), or via handling or eating contaminated foods. Colistin is well known as a last-resort antibiotic for the treatment of human infections; a recent study performed in the People's Republic of China has revealed that colistin resistance is also conferred by the plasmid-mediated mcr-1 gene in Escherichia coli. After that discovery, further plasmid-mediated, colistin resistance genes have been detected. However, to date, only reports on E. coli carrying the mcr-1 gene (E. coli mcr-1+) in foodstuff are available. E. coli mcr-1+ has been isolated from food of animal origin and vegetables; this discovery has opened a debate among food safety experts. This review aims to provide a critical overview of the currently available scientific literature on the presence of the plasmid-mediated, colistin resistance gene E. coli mcr-1 in foodstuffs, focusing on the main implications and future perspectives for food safety

Real-time observation of DNA looping dynamics of Type IIE restriction enzymes NaeI and NarI

Many restriction enzymes require binding of two copies of a recognition sequence for DNA cleavage, thereby introducing a loop in the DNA. We investigated looping dynamics of Type IIE restriction enzymes NaeI and NarI by tracking the Brownian motion of single tethered DNA molecules. DNA containing two endonuclease recognition sites spaced a few 100 bp apart connect small polystyrene beads to a glass surface. The position of a bead is tracked through video microscopy. Protein-mediated looping and unlooping is then observed as a sudden specific change in Brownian motion of the bead. With this method we are able to directly follow DNA looping kinetics of single protein–DNA complexes to obtain loop stability and loop formation times. We show that, in the absence of divalent cations, NaeI induces DNA loops of specific size. In contrast, under these conditions NarI mainly creates non-specific loops, resulting in effective DNA compaction for higher enzyme concentrations. Addition of Ca(2+) increases the NaeI-DNA loop lifetime by two orders of magnitude and stimulates specific binding by NarI. Finally, for both enzymes we observe exponentially distributed loop formation times, indicating that looping is dominated by (re)binding the second recognition site