scholarly journals Catheter-Related Sepsis by Candida pararugosa in an Adult Patient under Chemotherapy Regimen

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Gabriella Piatti ◽  
Sara Feltrin ◽  
Emanuela Fellini ◽  
Valentina Barbero ◽  
Alberto Ballestrero
Keyword(s):  
De Novo ◽  
Chemotherapy Regimen ◽  
Stage Iv ◽  
Venous Catheter ◽  
Febrile Episode ◽  
Blood Collection ◽  
Biological Liquids ◽  
High Level ◽  
Inflammation Parameters ◽  
Load Dose

Candida pararugosa is present in animals and humans in different organs and biological liquids, usually as a saprophyte. We report the case of a 61-year-old woman diagnosed with de novo stage IV metastatic lobular breast cancer, carrying a central venous catheter (port-a-cath) and bilateral stents for perirenal infiltration by malignancy. During chemotherapy regimen, a febrile episode occurred, along with a high level of serum glucan. The port-a-cath was removed after blood collection for culture, which gave isolation of Candida pararugosa strains. Given high glucan level and the patient’s frailty, empirical treatment with fluconazole was started with load-dose, 800 mg orally, at day 1 and, afterwards, with 400 mg daily for two weeks. The phenotype of susceptibility to antibiotics of the strain demonstrated lower minimal inhibitory concentration to fluconazole than that reported in the literature. The patient remained asymptomatic, and inflammation parameters showed normalization. Unfortunately, three weeks later, meningeal localization of cancer caused rapid deterioration and death.

Preliminary results of a multicenter phase II trial of vinflunine (with trastuzumab in HER2+ pts) as first-line treatment in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1043-1043 ◽  
Author(s):  
N. W. Peacock ◽  
D. R. Spigel ◽  
M. G. Mainwaring ◽  
D. S. Thompson ◽  
L. Simons ◽  
...  
Keyword(s):  
De Novo ◽  
Vinca Alkaloid ◽  
Metastatic Breast ◽  
Stage Iv ◽  
First Line ◽  
Microtubule Inhibitor ◽  
Level Of Activity ◽  
Significant Efficacy ◽  
High Level ◽  
Ecog Ps

1043 Background: Vinflunine (VFL) is a new and innovative microtubule inhibitor of the vinca alkaloid class that achieves high intracellular concentrations. By inhibition of tubulin polymerization, cell proliferation is arrested leading to apoptotic death. Demonstrating anti- angiogenic and vascular disrupting activities, VFL has demonstrated significant efficacy as 2nd line chemotherapy in MBC (M. Campone, BJC 2006). This trial was designed to evaluate the response rate and safety of VFL as 1st line therapy in MBC as well as its activity in combination with trastuzumab in HER2+ MBC pts. Methods: Eligibility: 0 prior regimens for MBC, > 6 mo from adjuvant therapy, RECIST measurable disease, ECOG PS 0–2, adequate organ function, < G2 neuropathy. Treatment: 320 mg/m2 IV over 20 minutes q3 weeks; 280 mg/m2 with trastuzumab 6 mg/kg q3 weeks in HER2+ pts. Response evaluations q9 weeks; treatment continued until progression or toxicity. A total of 96 pts will be enrolled, 48 pts per each of 2 cohorts, HER2- and HER2+. Results: 18 pts are enrolled, 13 pts evaluable for toxicity and 12 pts for response. 3 pts received VFL monotherapy and 10 pts were treated with VFL + trastuzumab. Median age: 59 years (43–78). ECOG PS 0: 9 pts, 1: 3 pts, 2: 1 pt. Prior adjuvant chemo: 7 pts (54%), with 5 prior anthracyclines and 6 prior taxanes. 2 pts received adjuvant hormonal therapy only. 4 pts presented with de novo stage IV HER2+ MBC. Metastatic disease sites: liver: 6 pts, lung: 7 pts, bone: 5 pts, lymph nodes: 6 pts. 46% had 3 or more sites of organ involvement. Median of 3 cycles (range:1 - 11) was delivered. 7 pts (58%, all HER2+) had a PR and 4 pts (33%) achieved SD. Only 1 pt progressed. Heme toxicity: G3/4 neutropenia: 2 pts (16%); no febrile neutropenia was noted. G3 non-heme toxicity consisted of N/V: 2 pts and myalgia, 2 pts. There were no G4 events. 4 pts were hospitalized (vomiting: 2, cerebro-vascular accident: 1, back pain: 1 pt). 92% of pts remain free of progression at 6 months. Median TTP has not been reached. Conclusions: Vinflunine is a promising new drug with a high level of activity as first line MBC therapy, especially in combination with trastuzumab. VFL is well tolerated in this patient population with a manageable toxicity profile. Accrual to this trial continues. [Table: see text]

scholarly journals Genome-Wide Metabolic Reconstruction of the Synthesis of Polyhydroxyalkanoates from Sugars and Fatty Acids by Burkholderia Sensu Lato Species

2021 ◽  
Vol 9 (6) ◽  
pp. 1290
Author(s):  
Natalia Alvarez-Santullano ◽  
Pamela Villegas ◽  
Mario Sepúlveda Mardones ◽  
Roberto E. Durán ◽  
Raúl Donoso ◽  
...  
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
Reducing Power ◽  
Pentose Phosphate ◽  
Fine Tuning ◽  
Metabolic Reconstruction ◽  
Phylogenetic Groups ◽  
Outlier Group ◽  
Pha Genes ◽  
High Level

Burkholderia sensu lato (s.l.) species have a versatile metabolism. The aims of this review are the genomic reconstruction of the metabolic pathways involved in the synthesis of polyhydroxyalkanoates (PHAs) by Burkholderia s.l. genera, and the characterization of the PHA synthases and the pha genes organization. The reports of the PHA synthesis from different substrates by Burkholderia s.l. strains were reviewed. Genome-guided metabolic reconstruction involving the conversion of sugars and fatty acids into PHAs by 37 Burkholderia s.l. species was performed. Sugars are metabolized via the Entner–Doudoroff (ED), pentose-phosphate (PP), and lower Embden–Meyerhoff–Parnas (EMP) pathways, which produce reducing power through NAD(P)H synthesis and PHA precursors. Fatty acid substrates are metabolized via β-oxidation and de novo synthesis of fatty acids into PHAs. The analysis of 194 Burkholderia s.l. genomes revealed that all strains have the phaC, phaA, and phaB genes for PHA synthesis, wherein the phaC gene is generally present in ≥2 copies. PHA synthases were classified into four phylogenetic groups belonging to class I II and III PHA synthases and one outlier group. The reconstruction of PHAs synthesis revealed a high level of gene redundancy probably reflecting complex regulatory layers that provide fine tuning according to diverse substrates and physiological conditions.

scholarly journals Incorporation of biologic factors for the staging of de novo stage IV breast cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Zhen-Yu He ◽  
Chen-Lu Lian ◽  
Jun Wang ◽  
Jian Lei ◽  
Li Hua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Distant Metastasis ◽  
De Novo ◽  
Stage Iv ◽  
Staging System ◽  
Sensitivity Analyses ◽  
Operating Characteristics ◽  
Prognostic Analysis ◽  
Stage Iv Breast Cancer

Abstract This study aimed to investigate the prognostic value of biological factors, including histological grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status in de novo stage IV breast cancer. Based on eligibility, patient data deposited between 2010 and 2014 were collected from the surveillance, epidemiology, and end results database. The receiver operating characteristics curve, Kaplan–Meier analysis, and Cox proportional hazard analysis were used for analysis. We included 8725 patients with a median 3-year breast cancer-specific survival (BCSS) of 52.6%. Higher histologic grade, HER2-negative, ER-negative, and PR-negative disease were significantly associated with lower BCSS in the multivariate prognostic analysis. A risk score staging system separated patients into four risk groups. The risk score was assigned according to a point system: 1 point for grade 3, 1 point if hormone receptor-negative, and 1 point if HER2-negative. The 3-year BCSS was 76.3%, 64.5%, 48.5%, and 23.7% in patients with 0, 1, 2, and 3 points, respectively, with a median BCSS of 72, 52, 35, and 16 months, respectively (P < 0.001). The multivariate prognostic analysis showed that the risk score staging system was an independent prognostic factor associated with BCSS. Patients with a higher risk score had a lower BCSS. Sensitivity analyses replicated similar findings after stratification according to tumor stage, nodal stage, the sites of distant metastasis, and the number of distant metastasis. In conclusion, our risk score staging system shows promise for the prognostic stratification of de novo stage IV breast cancer.

Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10535-10535
Author(s):  
Jessica A Lavery ◽  
Samantha Brown ◽  
Gregory J. Riely ◽  
Philippe L. Bedard ◽  
Ben Ho Park ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Major Mechanism ◽  
First Line Therapy ◽  
Oncogenic Mutation ◽  
Line Therapy ◽  
Response To Chemotherapy

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

scholarly journals Quick and efficient approach to develop genomic resources in orphan species: Application in Lavandula angustifolia

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243853
Author(s):  
Berline Fopa Fomeju ◽  
Dominique Brunel ◽  
Aurélie Bérard ◽  
Jean-Baptiste Rivoal ◽  
Philippe Gallois ◽  
...  
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Rapid Development ◽  
Genetic Distances ◽  
Lavandula Angustifolia ◽  
Distance Analysis ◽  
Alternative Medicines ◽  
Dna And Rna ◽  
Snp Development ◽  
High Level

Next-Generation Sequencing (NGS) technologies, by reducing the cost and increasing the throughput of sequencing, have opened doors to generate genomic data in a range of previously poorly studied species. In this study, we propose a method for the rapid development of a large-scale molecular resources for orphan species. We studied as an example the true lavender (Lavandula angustifolia Mill.), a perennial sub-shrub plant native from the Mediterranean region and whose essential oil have numerous applications in cosmetics, pharmaceuticals, and alternative medicines. The heterozygous clone “Maillette” was used as a reference for DNA and RNA sequencing. We first built a reference Unigene, compound of coding sequences, thanks to de novo RNA-seq assembly. Then, we reconstructed the complete genes sequences (with introns and exons) using an Unigene-guided DNA-seq assembly approach. This aimed to maximize the possibilities of finding polymorphism between genetically close individuals despite the lack of a reference genome. Finally, we used these resources for SNP mining within a collection of 16 commercial lavender clones and tested the SNP within the scope of a genetic distance analysis. We obtained a cleaned reference of 8, 030 functionally in silico annotated genes. We found 359K polymorphic sites and observed a high SNP frequency (mean of 1 SNP per 90 bp) and a high level of heterozygosity (more than 60% of heterozygous SNP per genotype). On overall, we found similar genetic distances between pairs of clones, which is probably related to the out-crossing nature of the species and the restricted area of cultivation. The proposed method is transferable to other orphan species, requires little bioinformatics resources and can be realized within a year. This is also the first reported large-scale SNP development on Lavandula angustifolia. All the genomics resources developed herein are publicly available and provide a rich pool of molecular resources to explore and exploit lavender genetic diversity in breeding programs.

scholarly journals Comparative genomics and pangenome-oriented studies reveal high homogeneity of the agronomically relevant enterobacterial plant pathogen Dickeya solani

2020 ◽  
Author(s):  
Agata Motyka-Pomagruk ◽  
Sabina Zoledowska ◽  
Agnieszka Emilia Misztak ◽  
Wojciech Sledz ◽  
Alessio Mengoni ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Large Scale ◽  
De Novo ◽  
Genetic Material ◽  
Soft Rot ◽  
Potato Production ◽  
Core Gene ◽  
Ecological Niches ◽  
Dickeya Solani ◽  
High Level

Abstract Background: Dickeya solani is an important plant pathogenic bacterium causing severe losses in European potato production. This species draws a lot of attention due to its remarkable virulence, great devastating potential and easier spread in contrast to other Dickeya spp. In view of a high need for extensive studies on economically important soft rot Pectobacteriaceae , we performed a comparative genomics analysis on D. solani strains to search for genetic foundations that would explain the differences in the observed virulence levels within the D. solani population. Results: High quality assemblies of 8 de novo sequenced D. solani genomes have been obtained. Whole-sequence comparison, ANIb, ANIm, Tetra and pangenome-oriented analyses performed on these genomes and the sequences of 14 additional strains revealed an exceptionally high level of homogeneity among the studied genetic material of D. solani strains. With the use of 22 genomes, the pangenome of D. solani , comprising 84.7% core, 7.2% accessory and 8.1% unique genes, has been almost completely determined, suggesting the presence of a nearly closed pangenome structure. Attribution of the genes included in the D. solani pangenome fractions to functional COG categories showed that higher percentages of accessory and unique pangenome parts in contrast to the core section are encountered in phage/mobile elements- and transcription- associated groups with the genome of RNS 05.1.2A strain having the most significant impact. Also, the first D. solani large-scale genome-wide phylogeny computed on concatenated core gene alignments is herein reported. Conclusions: The almost closed status of D. solani pangenome achieved in this work points to the fact that the unique gene pool of this species should no longer expand. Such a feature is characteristic of taxa whose representatives either occupy isolated ecological niches or lack efficient mechanisms for gene exchange and recombination, which seems rational concerning a strictly pathogenic species with clonal population structure. Finally, no obvious correlations between the geographical origin of D. solani strains and their phylogeny were found, which might reflect the specificity of the international seed potato market.

scholarly journals Impact of Primary Site Surgery on Survival of Patients with de novo Stage IV Breast Cancer

2021 ◽  
Vol Volume 13 ◽  
pp. 319-327
Author(s):  
Zhen Huang ◽  
Qixing Tan ◽  
Qinghong Qin ◽  
Qinguo Mo ◽  
Changyuan Wei
Keyword(s):  
Breast Cancer ◽  
De Novo ◽  
Stage Iv ◽  
Primary Site ◽  
Stage Iv Breast Cancer

scholarly journals Capture-based enrichment of Theileria parva DNA enables full genome assembly of first buffalo-derived strain and reveals exceptional intra-specific genetic diversity

2020 ◽  
Author(s):  
Nicholas C Palmateer ◽  
Kyle Tretina ◽  
Joshua Orvis ◽  
Olukemi O Ifeonu ◽  
Jonathan Crabtree ◽  
...  
Keyword(s):  
Vaccine Development ◽  
De Novo ◽  
High Specificity ◽  
Theileria Parva ◽  
Nucleotide Polymorphisms ◽  
Specificity And Sensitivity ◽  
Genome Wide ◽  
Dna Capture ◽  
High Level ◽  
Genome Assemblies

AbstractTheileria parva is an economically important, intracellular, tick-transmitted parasite of cattle. A live vaccine against the parasite is effective against challenge from cattle-transmissible T. parva but not against genotypes originating from the African Cape buffalo, a major wildlife reservoir, prompting the need to characterize genome-wide variation within and between cattle- and buffalo-associated T. parva populations. Here, we describe a capture-based target enrichment approach that enables, for the first time, de novo assembly of nearly complete T. parva genomes derived from infected host cell lines. This approach has exceptionally high specificity and sensitivity and is successful for both cattle- and buffalo-derived T. parva parasites. De novo genome assemblies generated for cattle genotypes differ from the reference by ∼54K single nucleotide polymorphisms (SNPs) throughout the 8.31 Mb genome, an average of 6.5 SNPs/kb. We report the first buffalo-derived T. parva genome, which is larger than the genome from the reference, cattle-derived, Muguga strain. The average non-synonymous nucleotide diversity (πN) per gene, between buffalo-derived T. parva and the Muguga strain, was 1.3%. This remarkably high level of genetic divergence is supported by an average FST, genome-wide, of 0.44, reflecting a degree of genetic differentiation between cattle- and buffalo-derived T. parva parasites more commonly seen between, rather than within, species, with clear implications for vaccine development. The DNA capture approach used provides clear advantages over alternative T. parva DNA enrichment methods used previously and enables in-depth comparative genomics in this apicomplexan parasite.

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