tetrahydrouridine and Prostatic-Neoplasms

Between 82.8% and 92.5% of participants in any BMI group were responders by AS, and between 91.3% and 100% were responders by BBPS in the right colon. Efficacy was consistent across BMI groups, with no clear trends. Greater than 83% of participants in any BMI group found the preparation 'easy' or 'acceptable' to ingest, and the majority (>58%) rated SPMC oral solution as 'better' than a prior bowel preparation. In all BMI groups, safety data were similar to the overall cohort. Commonly reported, drug-related, treatment-emergent AEs were, by ascending BMI group, nausea (1.1%, 5.3%, 1.0%, 5.7%, and 0%) and headache (1.1%, 4.1%, 1.0%, 5.7%, and 0%).. Ready-to-drink SPMC oral solution had consistent, good quality colon cleansing, and favorable tolerability among participants of all BMI groups.. NCT03017235.. The pretreatment serum AST/ALT ratio predicts poor disease outcome and response rate in patients with advanced PDAC treated with gemcitabine/nab-paclitaxel and might represent a novel and inexpensive marker for individual risk assessment in the treatment of pancreatic cancer.. Of the 98 patients included in the study, 58 had CR (59%), 28 had PR (29%), and 12 patients had NR (12%). The percent splenic tissue embolized was significantly greater in the CR group compared to the PR group (P = 0.001). The percent volume of splenic tissue embolized was linearly correlated with the magnitude of platelet increase without a minimum threshold. At least one line of chemotherapy was successfully restarted in 97% of patients, and 41% of patients did not experience recurrence of thrombocytopenia for the duration of their survival. The major complication rate was 8%, with readmission following initial hospitalization for persistent "post-embolization syndrome" symptoms the most common.. In cancer patients with hypersplenism-related thrombocytopenia, PSAE is a safe intervention that effects a durable elevation in platelet counts across a range of malignancies and following the re-initiation of chemotherapy.. Postoperative CRP elevation was a better predictor of prognosis in patients with gastric cancer than the occurrence of intra-abdominal infectious complications.. In clinical practice, mixed-species malaria infections are often not detected by light microscopy (LM) or rapid diagnostic test, as a low number of parasites of one species may occur. Here, we report the case of an 8-year-old girl migrating with her family from Afghanistan with a two-species mixed infection with

Topics: 3-Hydroxybutyric Acid; Acetazolamide; Acrylates; Administration, Intravenous; Adolescent; Adult; Aerosols; Afghanistan; Aflatoxin M1; Agaricales; Aged; Aged, 80 and over; Agricultural Irrigation; Air Pollutants; alpha-L-Fucosidase; Amino Acid Sequence; Androgen Antagonists; Animals; Antibodies, Bacterial; Antigens, Bacterial; Antineoplastic Agents; Antioxidants; Apoptosis; Artifacts; Autophagy; B7-H1 Antigen; Bacterial Proteins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Bile; Bioelectric Energy Sources; Biosensing Techniques; Body Mass Index; Brain; Brazil; Breast Neoplasms; Bufo arenarum; Burkholderia; C-Reactive Protein; Cadmium; Carbon Compounds, Inorganic; Carbon-13 Magnetic Resonance Spectroscopy; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Carcinoma, Transitional Cell; Case-Control Studies; CD4-Positive T-Lymphocytes; Cell Count; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Characiformes; Child; China; Cities; Cobalt; Colonic Neoplasms; Copper Sulfate; Cross-Sectional Studies; Cyclin-Dependent Kinase Inhibitor p16; Cytokines; Deoxycytidine; Diagnosis, Differential; Digestive System; Dihydroxyphenylalanine; Disease Models, Animal; DNA (Cytosine-5-)-Methyltransferase 1; DNA Barcoding, Taxonomic; DNA, Bacterial; Dose-Response Relationship, Drug; Down-Regulation; Edetic Acid; Electrochemical Techniques; Electrodes; Embolization, Therapeutic; Embryo, Nonmammalian; Environmental Monitoring; Enzyme-Linked Immunosorbent Assay; Epithelial-Mesenchymal Transition; Fatty Acids; Feces; Female; Follow-Up Studies; Food Contamination; Forkhead Box Protein M1; Fresh Water; Fungicides, Industrial; Gallium Isotopes; Gallium Radioisotopes; Gastrectomy; Gastric Bypass; Gastric Outlet Obstruction; Gastroplasty; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Bacterial; Genetic Markers; Genome, Bacterial; Genome, Mitochondrial; Glioma; Glycogen Synthase Kinase 3 beta; Goats; Gonads; Guatemala; Halomonadaceae; HEK293 Cells; Helicobacter Infections; Helicobacter pylori; Hepacivirus; Histone-Lysine N-Methyltransferase; Hormones; Humans; Hydroxybutyrate Dehydrogenase; Hypersplenism; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Iran; Japan; Lactuca; Laparoscopy; Larva; Ligands; Liver Neoplasms; Lymphocyte Activation; Macrophages; Malaria; Male; Mercury; Metabolic Syndrome; Metals, Heavy; Mice; Middle Aged; Milk, Human; Mitochondria; Models, Molecular; Molecular Structure; Mothers; Multilocus Sequence Typing; Muscles; Mutation; Nanocomposites; Nanotubes, Carbon; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms; Neoplastic Cells, Circulating; Neoplastic Stem Cells; Neuroimaging; Nitriles; Nitrogen Isotopes; Non-alcoholic Fatty Liver Disease; Nuclear Magnetic Resonance, Biomolecular; Obesity; Obesity, Morbid; Oligopeptides; Oxidation-Reduction; Pancreatic Neoplasms; Particle Size; Particulate Matter; Pepsinogen A; Pesticides; Pharmacogenetics; Phosphatidylinositol 3-Kinases; Phospholipids; Phylogeny; Plasmodium ovale; Plasmodium vivax; Platelet Count; Polyhydroxyalkanoates; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postoperative Complications; Pregnancy; Prevalence; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Domains; Proto-Oncogene Proteins c-akt; Proton Magnetic Resonance Spectroscopy; Pseudogenes; PTEN Phosphohydrolase; Pyrazoles; Pyrimidines; Radiographic Image Interpretation, Computer-Assisted; Radiopharmaceuticals; Rats, Long-Evans; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Receptor, Notch3; Receptors, G-Protein-Coupled; Receptors, Urokinase Plasminogen Activator; Recombinant Proteins; Repressor Proteins; Resveratrol; Retrospective Studies; Risk Assessment; Risk Factors; RNA, Messenger; RNA, Ribosomal, 16S; Salinity; Salvage Therapy; Seasons; Sequence Analysis, DNA; Seroepidemiologic Studies; Signal Transduction; Skin; Snails; Soluble Guanylyl Cyclase; Solutions; Spain; Species Specificity; Spheroids, Cellular; Splenic Artery; Stomach Neoplasms; Streptococcus pneumoniae; Structure-Activity Relationship; Sulfonamides; Sunlight; Surface Properties; Surgical Instruments; Surgical Wound Infection; Survival Rate; Tetrahydrouridine; Thinness; Thrombocytopenia; Tissue Distribution; Titanium; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Turkey; Ubiquinone; Urologic Neoplasms; Viral Envelope Proteins; Wastewater; Water Pollutants, Chemical; Weather; Wnt Signaling Pathway; Xenograft Model Antitumor Assays; Young Adult

The study's goals were as follows: (1) to extend our past findings with rodent tumors to human tumors in nude mice, (2) to determine if the drug protocol could be simplified so that only CldC and one modulator, tetrahydrouridine (H4U), would be sufficient to obtain efficacy, (3) to determine the levels of deoxycytidine kinase and dCMP deaminase in human tumors, compared to adjacent normal tissue, and (4) to determine the effect of CldC on normal tissue radiation damage to the cervical spinal cord of nude mice.. The five human tumors used were as follows: prostate tumors, PC-3 and H-1579; glioblastoma, SF-295; breast tumor, GI-101; and lung tumor, H-165. The duration of treatment was 3-5 weeks, with drugs administered on Days 1-4 and radiation on Days 3-5 of each week. The biomodulators of CldC were N-(Phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartyl transcarbamoylase, 5-fluorodeoxycytidine (FdC), resulting in tumor-directed inhibition of thymidylate synthetase, and H4U, an inhibitor of cytidine deaminase. The total dose of focused irradiation of the tumors was usually 45 Gy in 12 fractions.. Marked radiosensitization was obtained with CldC and the three modulators. The average days in tumor regrowth delay for X-ray compared to drugs plus X-ray, respectively, were: PC-3 prostate, 42-97; H-1579 prostate, 29-115; glioblastoma, 5-51; breast, 50-80; lung, 32-123. Comparative studies with PC-3 and H-1579 using CldC coadministered with H4U, showed that both PALA and FdC are dispensable, and the protocol can be simplified with equal and possibly heightened efficacy. For example, PC-3 with X-ray and (1) no drugs, (2) CldC plus the three modulators, (3) a high dose of CldC, and (4) escalating doses of CldC resulted in 0/10, 3/9, 5/10, and 6/9 cures, respectively. The tumor regrowth delay data followed a similar pattern. After treating mice only 11/2 weeks with CldC + H4U, 92% of the PC-3 tumor cells were found to possess CldU in their DNA. The great majority of head-and-neck tumors from patient material had markedly higher levels of dC kinase and dCMP deaminase than found in adjacent normal tissue. Physiologic and histologic studies showed that CldC + H4U combined with X-ray, focused on the cervical spinal cord, did not result in damage to that tissue.. 5-CldC coadministered with only H4U is an effective radiosensitizer of human tumors. Ninety-two percent of PC-3 tumor cells have been shown to take up ClUra derived from CldC in their DNA after only 11/2 weeks and 2 weeks of bolus i.p. injections. Enzymatic alterations that make tumors successful have been exploited for a therapeutic advantage. The great electronegativity, coupled with the relatively small Van der Waal radius of the Cl atom, may result in CldC's possessing the dual advantageous properties of FdC on one hand and BrdU and IdU on the other hand. These advantages include autoenhancing the incorporation of CldUTP into DNA by not only overrunning but also inhibiting the formation of competing TTP pools in tumors. A clinical trial is about to begin, with head-and-neck tumors as a first target of CldC radiosensitization.

Topics: Animals; Breast Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; DCMP Deaminase; Deoxycytidine; Deoxycytidine Kinase; Female; Glioblastoma; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplasm Proteins; Neoplasms; Prostatic Neoplasms; Radiation-Sensitizing Agents; Radiotherapy Dosage; Spinal Cord; Tetrahydrouridine