Chromoplectic TPM3-ALK rearrangement in a patient with inflammatory myofibroblastic tumor who responded to ceritinib after progression on crizotinib.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRß fusions and may benefit from targeted therapy. PATIENT AND METHODS: We sought to understand the genomic abnormalities of a patient who presented for management of metastatic IMT after progression of disease on crizotinib and a significant and durable partial response to the more potent ALK inhibitor ceritinib. RESULTS: The residual IMT was resected based on the recommendations of a multidisciplinary tumor sarcoma tumor board and analyzed by whole-genome mate pair sequencing. Analysis of the residual, resected tumor identified a chromoplectic TPM3-ALK rearrangement that involved many other known oncogenes and was confirmed by rtPCR. CONCLUSIONS: In our analysis of the treatment-resistant, residual IMT, we identified a complex pattern of genetic rearrangements consistent with chromoplexy. Although it is difficult to know for certain if these chromoplectic rearrangements preceded treatment, their presence suggests that chromoplexy has a role in the oncogenesis of IMTs. Furthermore, this patient's remarkable response suggests that ceritinib should be considered as an option after progression on crizotinib for patients with metastatic or unresectable IMT and ALK mutations.

Wnt signaling pathway pharmacogenetics in non-small cell lung cancer.

Wingless-type protein (Wnt)/ß-catenin pathway alterations in non-small cell lung cancer (NSCLC) are associated with poor prognosis and resistance. In 598 stage III-IV NSCLC patients receiving platinum-based chemotherapy at the MD Anderson Cancer Center (MDACC), we correlated survival with 441 host single-nucleotide polymorphisms (SNPs) in 50 Wnt pathway genes. We then assessed the most significant SNPs in 240 Mayo Clinic patients receiving platinum-based chemotherapy for advanced NSCLC, 127 MDACC patients receiving platinum-based adjuvant chemotherapy and 340 early stage MDACC patients undergoing surgery alone (cohorts 2-4). In multivariate analysis, survival correlates with SNPs for AXIN2 (rs11868547 and rs4541111, of which rs11868547 was assessed in cohorts 2-4), Wnt-5B (rs12819505), CXXC4 (rs4413407) and WIF-1 (rs10878232). Median survival was 19.7, 15.6 and 10.7 months for patients with 1, 2 and 3-5 unfavorable genotypes, respectively (P=3.8 × 10(-9)). Survival tree analysis classified patients into two groups (median survival time 11.3 vs 17.3 months, P=4.7 × 10(-8)). None of the SNPs achieved significance in cohorts 2-4; however, there was a trend in the same direction as cohort 1 for 3 of the SNPs. Using online databases, we found rs10878232 displayed expression quantitative trait loci correlation with the expression of LEMD3, a neighboring gene previously associated with NSCLC survival. In conclusion, results from cohort 1 provide further evidence for an important role for Wnt in NSCLC. Investigation of Wnt inhibitors in advanced NSCLC would be reasonable. Lack of an SNP association with outcome in cohorts 2-4 could be due to low statistical power, impact of patient heterogeneity or false-positive observations in cohort 1.

Author Correction: Achievement of sustainable development goals through the Mediterranean diet.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 89-99-DOI: 10.26355/eurrev_202312_34693 After publication and following some post-publication concerns, the authors have applied the following corrections to the galley proof. -       The conflict of interest section has been amended as follows: M.C. Medori and D. Malacarne are employees at MAGI'S LAB. K. Donato is employee at MAGI EUREGIO and MAGISNAT. M. Bertelli is president of MAGI EUREGIO, MAGISNAT, and MAGI's LAB. E. Borghetti is president at AERSAFE srl. C. Zuccato is researcher at AERSAFE srl. E. Borghetti is patent inventor (IT202100021344A1, IT202100020330A1, WO2021260537A1, WO2022259165A1). M. Bertelli is patent inventor (US20220362260A1, US20230173003A1, WO2022079498A1). D. Malacarne is patent inventor (WO2022079498A1; US20230173003A1). S. Michelini is patent inventor (US20220362260A1). M. Bertelli, S. Michelini, and K. Donato are patent applicants (Application Number: 18/516,241). M. Bertelli and K. Donato are patent applicants (Application Number: 18/466.879). M. Bertelli, K. Donato, and S. Michelini are patent applicants (Application Number: 63/495,155). The remaining authors have no conflict of interest to disclose. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34693.

Unleashing the potential of biotechnology for sustainable development.

The UN Sustainable Development Goals (SDGs) strive to eliminate poverty, preserve the planet, and promote shared prosperity through sustainable and inclusive means by 2030. This requires the implementation of a diverse set of strategies to overcome challenges and foster synergies among different SDG targets, facilitating the achievement of these ambitious goals. The aim of this review is to highlight the world's progress toward SDGs with the utilization of biotechnological advancements, including targets, strategies, synergies, and challenges. We scrutinized published research articles in peer-reviewed journals, UN reports, and scientific books that were relevant to the current topic. We identified some major challenges faced by the countries, especially developing ones, in the way of sustainable progress. These include inadequate governance, fragile states, armed conflicts, rising inequality, limited economic progress, climate change, environmental degradation, and food insecurity. Biotechnological advancements contribute to sustainable resource management, environmental conservation, and ecosystem restoration. Collaboration among countries and organizations is crucial for sharing knowledge and providing technical and financial assistance to developing nations.

Achievement of sustainable development goals through the Mediterranean diet.

The prosperity of our planet relies on the cardinal concept of sustainable development. The dietary choices of humans play a pivotal role in creating a peaceful and contented world. In this context, the Mediterranean diet (MD) has emerged as a valuable approach to accomplishing such progress, wherein the rights of all living beings are equally honored. This review aims to analyze the significance of a plant-based diet, particularly the Mediterranean diet, in attaining sustainable development goals. A comprehensive search of the literature was conducted to gather the most reliable and published scientific evidence from books and papers. Within this research endeavor, specific Sustainable Development Goals (SDGs) are individually addressed in relation to the adoption of the Mediterranean diet as a foundational nutritional paradigm. Our research findings underscore the immense importance of the MD and advocate for its worldwide implementation to accomplish sustainable development objectives. The MD emerges as the most suitable dietary option for fostering sustainability and tranquility in our world. It is crucial to prioritize the global implementation of the MD to genuinely achieve sustainable development.

Genetic variation in glutathione metabolism and DNA repair genes predicts survival of small-cell lung cancer patients.

BACKGROUND: Small-cell lung cancer (SCLC) carries the worst prognosis among lung cancer diagnoses. Combined radiation and chemotherapy is the standard of care; however, treatment outcomes vary. Variability in the rate at which chemotherapy agents are metabolized and in the capacity of repairing DNA damage has been hypothesized to be partly responsible for the treatment response variation. Genes in the glutathione metabolism and DNA repair pathways were tested through tag single-nucleotide polymorphisms (SNPs) to assess their association with survival in SCLC. PATIENTS AND METHODS: Blood DNA from 248 patients with primary SCLC was genotyped for 419 tag SNPs from 49 genes in the glutathione and DNA repair pathways. Association analyses with patient survival were carried out at single-SNP, whole-gene, and haplotype levels after adjusting for age, gender, tumor stage, treatment modalities, and smoking history. RESULTS: Among the 375 SNPs successfully genotyped, 21 SNPs, located on 11 genes, showed significant association with survival. Whole-gene analyses confirmed 3 of the 11 genes: GSS, ABCC2, and XRCC1. Haplotype analyses of these three genes identified haplotype combinations and genomic locations underlying the observed SNP associations. CONCLUSION: Genetic variations in genes involved in the glutathione and DNA repair pathways are associated with SCLC survival.

Optical fiber immunosensor for the detection of IgG antibody to Rift Valley fever virus in humans.

This paper describes the development and evaluation of an optical fiber immunosensor (OFIS) for the detection of IgG antibody to Rift Valley fever virus (RVFV) in humans. The OFIS was based on a sandwich enzyme-linked immunosorbent assay (S-ELISA) format, whereby gamma-irradiated RVFV and control antigens were immobilized on the optical fiber surface coated with a mouse anti-RVFV antibody. Data sets derived from field-collected sera in Africa (n=242) were dichotomized according to the results of a virus neutralization test. Compared to standard colorimetric S-ELISA, the OFIS technique was more sensitive in detecting smaller quantity of specific IgG to RVFV in human sera. At cut-off value selected at a 95% accuracy level by the two-graph receiver operating characteristic analysis, the OFIS diagnostic sensitivity was 97.22% and diagnostic specificity 98.86%. Our results demonstrate that the OFIS technology reported here is highly accurate, simple to perform and has the potential to be used in a portable format.

Development of a highly sensitive, field operable biosensor for serological studies of Ebola virus in central Africa.

We describe herein a newly developed optical immunosensor for detection of antibodies directed against antigens of the Ebola virus strains Zaire and Sudan. We employed a photo immobilization methodology based on a photoactivatable electrogenerated poly(pyrrole-benzophenone) film deposited upon an indium tin oxide (ITO) modified conductive surface fiber-optic. It was then linked to a biological receptor, Ebola virus antigen in this case, on the fiber tip through a light driven reaction. The photochemically modified optical fibers were tested as an immunosensor for detection of antibodies against Ebola virus, in animal and human sera, by use of a coupled chemiluminescent reaction. The immunosensor was tested for sensitivity, specificity, and compared to standard chemiluminescent ELISA under the same conditions. The analyte, anti-Ebola IgG, was detected at a low titer of 1:960,000 and 1:1,000,000 for subtypes Zaire and Sudan, respectively. While the same serum tested by ELISA was one order (24 times) less sensitive.

Luminescent yeast cells entrapped in hydrogels for estrogenic endocrine disrupting chemical biodetection.

In the construction of luminescent yeast cell based fibre-optic biosensors, we demonstrate a novel approach for estrogenic endocrine disrupting chemical (EDC) biodetection by entrapping genetically modified Saccharomyces cerevisiae cells, containing the estrogen receptor alpha-mediated expression of the luc reporter gene, in hydrogel matrices based on calcium alginate or PVA. In order to insure a significant signal, an optimal immobilization ratio of 1:2 alginate 3% (w/v): 5 x 10(6) [cells/ml], respectively, was used with the highest 17-beta-estradiol (beta-E2) induction factor after 2.5 h of incubation with 10[nM] beta-E2. It was shown that biocompatible alginate beads, 4.27-4.55 x 10(5) [CFU/bead], which were characterized by a detection limit of 0.08[microg l(-1)] and an EC50 of 0.64[microg l(-1)] for beta-E2, retained their viability for luminescence measurements after 1 month of storage at -80 degrees C slow freeze condition, and thus repeated cell cultivations were not required. The assay reproducibility for each tested EDC, represented by the coefficients of variation (CV), ranged from 4.35 to 18.47%. An alternative immobilization method, based on a room temperature partial drying of polyvinyl alcohol (PVA) solution (LentiKat Liquid) and cell suspension mix, was investigated with only a slightly lower detection limit for beta-E2 than that reported with alginate beads. Alginate yeast based hydrogels may also be applicable to the analysis of environmental water samples since the trend of detected estrogenic activities with alginate beads roughly correlated with LC-MS-MS analytical results.

A Phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity.

Farnesyl protein transferase (FT), an enzyme that catalyzes the first step in the posttranslational modification of ras and a number of other polypeptides, has emerged as an important target for the development of anticancer agents. SCH66336 is one of the first FT inhibitors to undergo clinical testing. We report a Phase I trial to assess the maximum tolerated dose, toxicities, and biological effectiveness of SCH66336 in inhibiting FT in vivo. Twenty patients with solid tumors received 92 courses of escalating SCH66336 doses given orally twice a day (b.i.d.) for 7 days out of every 3 weeks. Gastrointestinal toxicity (nausea, vomiting, and diarrhea) and fatigue were dose-limiting at 400 mg of SCH66336 b.i.d. Moderate reversible renal insufficiency, secondary to dehydration from gastrointestinal toxicity, was also seen. Inhibition of prelamin A farnesylation in buccal mucosa cells of patients treated with SCH66336 was demonstrated, confirming that SCH66336 inhibits protein farnesylation in vivo. One partial response was observed in a patient with previously treated metastatic non-small cell lung cancer, who remained on study for 14 months. This study not only establishes the dose for future testing on this schedule (350 mg b.i.d.) but also provides the first evidence of successful inhibition of FT in the clinical setting and the first hint of clinical activity for this class of agents.