scholarly journals Fermentation of Ferulated Arabinoxylan Recovered from the Maize Bioethanol Industry

Processes ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 165
Author(s):  
Mayra A. Mendez-Encinas ◽  
Dora E. Valencia-Rivera ◽  
Elizabeth Carvajal-Millan ◽  
Humberto Astiazaran-Garcia ◽  
Valérie Micard ◽  
...  
Keyword(s):  
Dose Range ◽  
Bifidobacterium Longum ◽  
Short Chain Fatty Acids ◽  
Bifidobacterium Adolescentis ◽  
Inverse Effect ◽  
Antiproliferative Agent ◽  
Health Promoting ◽  
The Media ◽  
Bacteroides Ovatus ◽  
Dose Dependent

Maize by-product from the bioethanol industry (distiller’s dried grains with solubles, DDGS) is a source of ferulated arabinoxylan (AX), which is a health-promoting polysaccharide. In the present study, AX from DDGS was fermented by a representative colonic bacterial mixture (Bifidobacterium longum, Bifidobacterium adolescentis, and Bacteroides ovatus), and the effect of the fermented AX (AX-f) on the proliferation of the cell line Caco-2 was investigated. AX was efficiently metabolized by these bacteria, as evidenced by a decrease in the polysaccharide molecular weight from 209 kDa to < 50 kDa in AX-f, the release of ferulic acid (FA) from polysaccharide chains (1.14 µg/mg AX-f), and the short-chain fatty acids (SCFA) production (277 µmol/50 mg AX). AX-f inhibited the proliferation of Caco-2 cells by 80–40% using concentrations from 125–1000 µg/mL. This dose-dependent inverse effect was attributed to the increased viscosity of the media due to the polysaccharide concentration. The results suggest that the AX-f dose range and the SCFA and free FA production are key determinants of antiproliferative activity. Using the same polysaccharide concentrations, non-fermented AX only inhibited the Caco-2 cells proliferation by 8%. These findings highlight the potential of AX recovered from the maize bioethanol industry as an antiproliferative agent once fermented by colonic bacteria.

scholarly journals Exploring the Diversity of the Bifidobacterial Population in the Human Intestinal Tract

2009 ◽  
Vol 75 (6) ◽  
pp. 1534-1545 ◽  
Author(s):  
Francesca Turroni ◽  
Elena Foroni ◽  
Paola Pizzetti ◽  
Vanessa Giubellini ◽  
Angela Ribbera ◽  
...  
Keyword(s):  
Bifidobacterium Longum ◽  
Bifidobacterium Bifidum ◽  
Selective Medium ◽  
Rrna Gene ◽  
Bifidobacterium Adolescentis ◽  
Fecal Samples ◽  
Bifidobacterium Animalis ◽  
Human Intestinal Microbiota ◽  
Health Promoting ◽  
Internally Transcribed Spacer

ABSTRACT Although the health-promoting roles of bifidobacteria are widely accepted, the diversity of bifidobacteria among the human intestinal microbiota is still poorly understood. We performed a census of bifidobacterial populations from human intestinal mucosal and fecal samples by plating them on selective medium, coupled with molecular analysis of selected rRNA gene sequences (16S rRNA gene and internally transcribed spacer [ITS] 16S-23S spacer sequences) of isolated colonies. A total of 900 isolates were collected, of which 704 were shown to belong to bifidobacteria. Analyses showed that the culturable bifidobacterial population from intestinal and fecal samples include six main phylogenetic taxa, i.e., Bifidobacterium longum, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Bifidobacterium pseudolongum, Bifidobacterium breve, and Bifidobacterium bifidum, and two species mostly detected in fecal samples, i.e., Bifidobacterium dentium and Bifidobacterium animalis subp. lactis. Analysis of bifidobacterial distribution based on age of the subject revealed that certain identified bifidobacterial species were exclusively present in the adult human gut microbiota whereas others were found to be widely distributed. We encountered significant intersubject variability and composition differences between fecal and mucosa-adherent bifidobacterial communities. In contrast, a modest diversification of bifidobacterial populations was noticed between different intestinal regions within the same individual (intrasubject variability). Notably, a small number of bifidobacterial isolates were shown to display a wide ecological distribution, thus suggesting that they possess a broad colonization capacity.

scholarly journals An invitro study of the prebiotic properties of Xylooligosaccharide (XOS) and organoleptic evaluation of XOS added Prawn patia and Black rice kheer.

2020 ◽  
Vol 3 (1) ◽  
pp. 1
Author(s):  
Abnita Thakuria
Keyword(s):  
Acid Tolerance ◽  
Food Products ◽  
Short Chain Fatty Acids ◽  
Probiotic Bacteria ◽  
Black Rice ◽  
Organoleptic Properties ◽  
Organoleptic Evaluation ◽  
Bifidobacterium Adolescentis ◽  
Bile Resistance ◽  
Health Promoting

Background: There is emerging evidence that functional foods ingredients can have an impact on a number of gut related diseases and dysfunctions [1]. A prebiotic is a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers health benefits [2]. Besides providing the health benefits, prebiotics are known to extend technological advantages in favour of improved organoleptic qualities of the food products. Xylooligosaccharides (XOS) is a stable prebiotic which can withstand heat up to 100℃ under acidic conditions (pH=2.5-8) and has a potential to be incorporated into food products [3]. However, its prebiotic properties needs to be established in terms of bile resistance, acid tolerance, fermentability to produce short chain fatty acids (SCFA) and growth of Lactobacillus plantarum and Bifidobacterium adolescentis and Escherichia coli. XOS also needs to be exploited for its potential to be incorporated into various food products and study their organoleptic properties similar to fructooligosaccharides (FOS) which have proven technological benefits in terms of its miscibility and organoleptic qualities.Context and purpose of this study: Several prebiotics such as FOS, GOS, inulin have been recently recognized for their health promoting abilities. XOS is yet another emerging prebiotic that needs to be explored for its prebiotic potential especially in terms of its acid tolerance, bile resistance and ability to get fermented by the probiotic bacteria and produce health promoting short chain fatty acids as well as its potential to be added to food products. Therefore, this study was undertaken to determine the prebiotic properties of XOS invitro and to study the organoleptic properties of XOS upon its addition on a few Indian traditional foods (Prawn patia and Black rice kheer).Results: No degradation of XOS was observed on its exposure to bile at 0h, 1.5h and 3h with bile concentration 0.5%, 1% and 1.5%. XOS recovery was observed to be 100% on its exposure to pH 1.5, 2 and 3 at 0h. At 1.5h it was found to be 98.4%, 98.9% and 97.9% at 1.5pH, 2pH and 3pH respectively and 96.2%, 97.3% and 96.3% upon its exposure to 1.5pH, 2pH and 3pH respectively at 3h. Growth of Lactobacillus plantarum and Bifidobacterium adolescentis was higher (OD 0.71) and (OD 0.75)  up to 2% when compared to glucose (p≤0.01), whereas, growth of Escherichia coli (OD 0.4)  was restricted upon addition of XOS when compared to glucose (p≤0.01). Acetate was produced the most, followed by Propionate and Butyrate. Organoleptic evaluation revealed no significant difference in XOS added Prawn patia and Black rice kheer at all levels of addition (5%, 8% and 10%). Hence, adsition of XOS to these two products were well accepted by the panellists up to 10% level of addition.Conclusions: This study has successfully established the prebiotic potential of XOS in terms of acid tolerance, bile resistance, growth of probiotic bacteria and production of SCFA. XOS was well accepted in both the food products at all the three levels of incorporation, i.e. 5%, 8% and 10%. Limited researches have been conducted on prebiotic XOS. Therefore, for discussion references were taken with regards to other prebiotics such as FOS, inulin etc. Further studies can be undertaken to demonstrate the clinical efficacy of XOS intake with respect to various non communicable diseases.

scholarly journals Lactitol Supplementation Modulates Intestinal Microbiome in Liver Cirrhotic Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Haifeng Lu ◽  
Liang Chen ◽  
Xiaxia Pan ◽  
Yujun Yao ◽  
Hua Zhang ◽  
...  
Keyword(s):  
Bifidobacterium Longum ◽  
Short Chain Fatty Acids ◽  
Intestinal Microbiome ◽  
Klebsiella Pneumonia ◽  
Antibiotic Resistant ◽  
Shotgun Metagenomics ◽  
Pathogenic Genes ◽  
Health Promoting ◽  
Cirrhotic Patients ◽  
Insight Into

Background: Cirrhosis is a common chronic liver disease characterized by irreversible diffuse liver damage. Intestinal microbiome dysbiosis and metabolite dysfunction contribute to the development of cirrhosis. Lactitol (4-β-D-galactopyranosyl-D-glucitol) was previously reported to promote the growth of intestinal Bifidobacteria. However, the effect of lactitol on the intestinal microbiome and fecal short-chain fatty acids (SCFAs) and bile acids (BAs) and the interactions among these factors in cirrhotic patients pre- and post-lactitol treatment remain poorly understood.Methods: Here, using shotgun metagenomics and targeted metabolomics methods.Results: we found that health-promoting lactic acid bacteria, including Bifidobacterium longum, B.pseudocatenulatum, and Lactobacillus salivarius, were increased after lactitol intervention, and significant decrease of pathogen Klebsiella pneumonia and associated antibiotic resistant genes /virulence factors. Functionally, pathways including Pseudomonas aeruginosa biofilm formation, endotoxin biosynthesis, and horizontal transfer of pathogenic genes were decreased in cirrhotic patients after 4-week lactitol intervention compared with before treatment.Conclusion: We identified lactitol-associated metagenomic changes, and provide insight into the understanding of the roles of lactitol in modulating gut microbiome in cirrhotic patients.

scholarly journals A Novel Non-Digestible, Carrot-Derived Polysaccharide (cRG-I) Selectively Modulates the Human Gut Microbiota while Promoting Gut Barrier Integrity: An Integrated In Vitro Approach

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1917 ◽  
Author(s):  
Pieter Van den Abbeele ◽  
Lynn Verstrepen ◽  
Jonas Ghyselinck ◽  
Ruud Albers ◽  
Massimo Marzorati ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Bifidobacterium Longum ◽  
Short Chain Fatty Acids ◽  
In Vitro Models ◽  
Peripheral Blood Mononuclear ◽  
Bifidobacterium Adolescentis ◽  
Pectic Polysaccharide ◽  
Barrier Integrity ◽  
Rhamnogalacturonan I

Modulation of the gut microbiome as a means to improve human health has recently gained increasing interest. In this study, it was investigated whether cRG-I, a carrot-derived pectic polysaccharide, enriched in rhamnogalacturonan-I (RG-I) classifies as a potential prebiotic ingredient using novel in vitro models. First, digestion methods involving α-amylase/brush border enzymes demonstrated the non-digestibility of cRG-I by host-derived enzymes versus digestible (starch/maltose) and non-digestible controls (inulin). Then, a recently developed short-term (48 h) colonic incubation strategy was applied and revealed that cRG-I fermentation increased levels of health-promoting short-chain fatty acids (SCFA; mainly acetate and propionate) and lactate comparable but not identical to the reference prebiotic inulin. Upon upgrading this fermentation model by inclusion of a simulated mucosal environment while applying quantitative 16S-targeted Illumina sequencing, cRG-I was additionally shown to specifically stimulate operational taxonomic units (OTUs) related to health-associated species such as Bifidobacterium longum, Bifidobacterium adolescentis, Bacteroides dorei, Bacteroides ovatus, Roseburia hominis, Faecalibacterium prausnitzii, and Eubacterium hallii. Finally, in a novel model to assess host–microbe interactions (Caco-2/peripheral blood mononuclear cells (PBMC) co-culture) fermented cRG-I increased barrier integrity while decreasing markers for inflammation. In conclusion, by using novel in vitro models, cRG-I was identified as a promising prebiotic candidate to proceed to clinical studies.

scholarly journals Coculture Fermentations of Bifidobacterium Species and Bacteroides thetaiotaomicron Reveal a Mechanistic Insight into the Prebiotic Effect of Inulin-Type Fructans

2009 ◽  
Vol 75 (8) ◽  
pp. 2312-2319 ◽  
Author(s):  
Gwen Falony ◽  
Thomas Calmeyn ◽  
Frédéric Leroy ◽  
Luc De Vuyst
Keyword(s):  
Bifidobacterium Longum ◽  
Fermentation Medium ◽  
Bacteroides Thetaiotaomicron ◽  
Bifidobacterium Adolescentis ◽  
Breakdown Mechanism ◽  
High Fructose ◽  
Degradation Rates ◽  
Health Promoting ◽  
The Moment ◽  
Insight Into

ABSTRACT Four bifidobacteria, each representing a cluster of strains with specific inulin-type-fructan degradation capacities, were grown in coculture fermentations with Bacteroides thetaiotaomicron LMG 11262, a strain able to metabolize both oligofructose and inulin. In a medium for colon bacteria with inulin as the sole added energy source, the ability of the bifidobacteria to compete for this substrate reflected phenotypical variation. Bifidobacterium breve Yakult, a strain that was not able to degrade oligofructose or inulin, was outcompeted by B. thetaiotaomicron LMG 11262. Bifidobacterium adolescentis LMG 10734, a strain that could degrade oligofructose (displaying a preferential breakdown mechanism) but that did not grow on inulin, managed to become competitive when oligofructose and short fractions of inulin started to accumulate in the fermentation medium. Bifidobacterium angulatum LMG 11039T, a strain that was previously shown to degrade all oligofructose fractions simultaneously and to be able to partially break down inulin, was competitive from the beginning of the fermentation, consuming short fractions of inulin from the moment they appeared. Bifidobacterium longum LMG 11047, representing a cluster of bifidobacteria that shared both high fructose consumption and oligofructose degradation rates and were able to perform partial breakdown of inulin, was the dominating strain in a coculture with B. thetaiotaomicron LMG 11262. These observations indicate that distinct subgroups within the large-intestinal Bifidobacterium population will be stimulated by different groups of prebiotic inulin-type fructans, a variation that could be reflected in differences concerning their health-promoting effects.

scholarly journals Prebiotic Effect of Lycopene and Dark Chocolate on Gut Microbiome with Systemic Changes in Liver Metabolism, Skeletal Muscles and Skin in Moderately Obese Persons

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Maria Wiese ◽  
Yuriy Bashmakov ◽  
Natalia Chalyk ◽  
Dennis Sandris Nielsen ◽  
Łukasz Krych ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Bifidobacterium Longum ◽  
Health Benefit ◽  
Liver Metabolism ◽  
Systemic Effect ◽  
Dark Chocolate ◽  
Bifidobacterium Adolescentis ◽  
Dose Dependent

Lycopene rich food and dark chocolate are among the best-documented products with a broad health benefit. This study explored the systemic effect of lycopene and dark chocolate (DC) on gut microbiota, blood, liver metabolism, skeletal muscle tissue oxygenation and skin. 30 volunteers were recruited for this trial, 15 women and 15 men with a mean age of 55 ± 5.7 years and with moderate obesity, 30 < BMI < 35 kg/m2. They were randomized and divided into five equal interventional groups: three received different formulations of lycopene, one of them with a 7 mg daily dose and two with 30 mg; another group was given 10 g of DC with 7 mg lycopene embedded into its matrix, and the last group received 10 g DC. The trial was double-blinded for the three lycopene groups and separately for the 2 DC groups; the trial lasted for 1 month. By the end of the trial there were dose-dependent changes in the gut microbiota profile in all three lycopene groups with an increase of relative abundance of, e.g.,Bifidobacterium adolescentisandBifidobacterium longum. This was also accompanied by dose-dependent changes in the blood, liver metabolism, skeletal muscle and skin parameters. Consumption of DC resulted in increased relative abundance of, e.g.,Lactobacillusand a reduction of corneocyte exfoliation. This is the first study which reports the prebiotic potential of lycopene and DC.

The Measurement of Heparin and Other Therapeutic Sufphated Polysaccharides in Plasma, Serum and Urine

1985 ◽  
Vol 54 (03) ◽  
pp. 630-634 ◽  
Author(s):  
J Dawes ◽  
C V Prowse ◽  
D D Pepper
Keyword(s):  
Biological Fluids ◽  
Anticoagulant Activity ◽  
Dose Range ◽  
Plasma Concentrations ◽  
Heparin Therapy ◽  
Competitive Binding Assay ◽  
First Order Kinetics ◽  
Activity Measurements ◽  
Heparin Activity ◽  
Dose Dependent

SummaryThe competitive binding assay described will specifically and accurately measure concentrations of administered heparin in biological fluids with a sensitivity of 60 ng ml-1. Neither endogenous glycosaminoglycans, nor plasma proteins such as ATIII and PF4 interfere in the assay. Semi-synthetic highly sulphated heparinoids and LMW heparin can also be measured. Using this assay heparin clearance followed simple first-order kinetics over the dose range 100-5,000 units, but the half-life was strongly dose-dependent. There was good correlation with heparin activity measurements by APTT and anti-Xa clotting assays. Plasma concentrations were measurable for at least 5 h following subcutaneous injection of 10,000 units of heparin. Excretion in the urine could be followed after all but the lowest intravenous dose. This assay, used in conjunction with measurements of heparin anticoagulant activity, will be valuable in the elucidation of mechanisms of action of heparin and the heparinoids, and in the assessment and management of problems related to heparin therapy.

scholarly journals Fate of fructo-oligosaccharides in the human intestine

1996 ◽  
Vol 76 (2) ◽  
pp. 211-221 ◽  
Author(s):  
Martine S. Alles ◽  
Joseph G. A. J. Hautvast ◽  
Fokko M. Nagengast ◽  
Ralf Hartemink ◽  
Katrien M. J. Van Laere ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Total Concentration ◽  
Latin Square ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Colonic Fermentation ◽  
Faecal Samples ◽  
Faecal Weight ◽  
Dose Dependent ◽  
Chain Fatty Acids

There is a need for studies on colonic fermentation in order to learn more abouthealth and diseases of the colon. The aim of the present study was to evaluate the fate of twodifferent doses of fructo-oligosaccharides (5 and 15 g/d) v. glucose in the intestine of healthy men. Twenty-four volunteers participated in a 5-weekstudy. The study was a completely balanced multiple crossover trial using an orthogonal Latin-square design for three periods, with supplement periods of 7 d and two 7 d wash-out periods. Breath samples and faecal samples were collected. There was a clear gaseous response to the consumption of fructo-oligosaccharides. The highest dose significantly increased 24 h integratedexcretion of breath H2 (P < 0·05). Breath H2 excretion after ingestion of 5 g fructo-oligosaccharides was higher than control, but did not reach significance. No effects on the total concentration of short-chain fatty acids in faeces were observed, no modification of the molar proportions of the various short-chain fatty acids was observed. The faecal pH did not change. No changes in faecal weight were observed. No fructo-oligosaccharides were recovered in faeces. We conclude that fructo-oligosaccharides added to the diet of young Western subjects are fully metabolized in the large intestine. The level of fermentation seems to be dose-dependent.

scholarly journals Identification, Detection, and Enumeration of Human Bifidobacterium Species by PCR Targeting the Transaldolase Gene

2002 ◽  
Vol 68 (5) ◽  
pp. 2420-2427 ◽  
Author(s):  
Teresa Requena ◽  
Jeremy Burton ◽  
Takahiro Matsuki ◽  
Karen Munro ◽  
Mary Alice Simon ◽  
...  
Keyword(s):  
Real Time ◽  
16S Rdna ◽  
Quantitative Pcr ◽  
Gene Sequence ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Bifidobacterium Longum ◽  
Bifidobacterium Adolescentis ◽  
Fecal Samples ◽  
Real Time Quantitative Pcr ◽  
Pcr Targeting

ABSTRACT Methods that enabled the identification, detection, and enumeration of Bifidobacterium species by PCR targeting the transaldolase gene were tested. Bifidobacterial species isolated from the feces of human adults and babies were identified by PCR amplification of a 301-bp transaldolase gene sequence and comparison of the relative migrations of the DNA fragments in denaturing gradient gel electrophoresis (DGGE). Two subtypes of Bifidobacterium longum, five subtypes of Bifidobacterium adolescentis, and two subtypes of Bifidobacterium pseudocatenulatum could be differentiated using PCR-DGGE. Bifidobacterium angulatum and B. catenulatum type cultures could not be differentiated from each other. Bifidobacterial species were also detected directly in fecal samples by this combination of PCR and DGGE. The number of species detected was less than that detected by PCR using species-specific primers targeting 16S ribosomal DNA (rDNA). Real-time quantitative PCR targeting a 110-bp transaldolase gene sequence was used to enumerate bifidobacteria in fecal samples. Real-time quantitative PCR measurements of bifidobacteria in fecal samples from adults correlated well with results obtained by culture when either a 16S rDNA sequence or the transaldolase gene sequence was targeted. In the case of samples from infants, 16S rDNA-targeted PCR was superior to PCR targeting the transaldolase gene for the quantification of bifidobacterial populations.

PF-06939999, a potent and selective PRMT5 inhibitor, in patients with advanced or metastatic solid tumors: A phase 1 dose escalation study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3019-3019
Author(s):  
Jordi Rodon Ahnert ◽  
Cesar Augusto Perez ◽  
Kit Man Wong ◽  
Michael L. Maitland ◽  
Frank Tsai ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Dose Escalation ◽  
Urothelial Cancer ◽  
Phase 1 ◽  
Dose Range ◽  
Median Number ◽  
Splicing Factor ◽  
Dose Escalation Study ◽  
Study Objective ◽  
Dose Dependent

3019 Background: Protein arginine methyltransferase 5 (PRMT5) methylates multiple substrates known to be dysregulated in cancer, including components of the spliceosome machinery. PF-06939999 is a selective small-molecule inhibitor of PRMT5. Here we report the safety, PK, PD, and preliminary activity of PF-06939999 in patients (pts) with selected advanced/metastatic solid tumors. Methods: This phase 1 dose escalation trial (NCT03854227) enrolled pts with solid tumor types marked by potential frequent splicing factor mutations, including advanced/metastatic endometrial cancer, head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), urothelial cancer, cervical cancer, or esophageal cancer. PF-06939999 monotherapy was continuously administered orally QD or BID in 28-day cycles. A Bayesian Logistic Regression Model was used to inform dose level decisions. Primary objectives were to assess dose limiting toxicities (DLTs), AEs and laboratory abnormalities. Tumor response was assessed using RECIST v1.1. PK and PD were assessed by determining PF-06939999 plasma concentration after dosing and changes in plasma levels of symmetric di-methyl arginine (SDMA), the product of PRMT5 enzymatic activity. Results: 28 pts received PF-06939999 at doses from 0.5-12 mg daily (QD or BID) during dose escalation. Median number of cycles was 2 (range, 1-13). Most were female (54%) with a median age of 61.5 (range, 32-84) y. Median number of prior therapies was 4. Overall, 4/24 (17%) pts reported DLTs: thrombocytopenia (n=2, 6 mg BID); anemia (n=1, 8 mg QD); and neutropenia (n=1, 6 mg QD). Treatment-related AEs occurred in 24 (86%) pts. Most common (≥20%) treatment-related AEs across all cycles were anemia (43%), thrombocytopenia (32%), dysgeusia, fatigue and nausea (29% each). Grade ≥3 treatment-related AEs included anemia (25%), thrombocytopenia (21%), fatigue, neutropenia and lymphocyte count decreased (4% each). One pt (6mg BID) had Grade 4 treatment-related thrombocytopenia. All cytopenias were dose-dependent and reversible with dose modification. No pts discontinued treatment for treatment-related toxicity. There were no treatment-related deaths. Exposure to PF-06939999 increased with doses in the dose range tested. Plasma SDMA was reduced at steady state (58.4-87.5%), indicating robust PD target inhibition. Two pts had confirmed partial response (HNSCC and NSCLC). 6 mg QD was identified as the recommended monotherapy dose for expansion. Conclusions: PF-06939999 showed dose-dependent and manageable toxicities in this phase 1 dose escalation study. Objective tumor responses were observed in pts with HNSCC and NSCLC. Analysis of archival tissue for the presence of splicing factor mutations and other potential predictive biomarkers is ongoing. Enrollment to part 2 dose expansion is ongoing in pts with NSCLC, HNSCC and urothelial cancer. Clinical trial information: NCT03854227.

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