GC-072: A Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat Pathogens.

GC-072: A Novel Therapeutic Candidate for Oral Treatment of Melioidosis and Infections Caused by Select Biothreat Pathogens. Antimicrob Agents Chemother. 2019 Sep 23;: Authors: Shearer JD, Saylor ML, Butler CM, Treston AM, Heine HS, Chirakul S, Schweizer HP, Louie A, Drusano GL, Zumbrun SD, Warfield KL Abstract Burkholderia pseudomallei (B. pseudomallei), the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care, but in the case of septicemia left untreated it can range from 50 - 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for two weeks or longer, followed by oral eradication-phase treatment lasting several months. An effective oral therapeutic for outpatient treatment of acute-phase melioidosis is needed. GC-072 is a potent, 4-oxoquinolizine antibiotic with selective inhibitory activity against bacterial topoisomerases. GC-072 has demonstrated in vitro potency against susceptible and drug-resistant strains of B. pseudomallei and is also active against Burkholderia mallei, Bacillus anthracis, Yersinia pestis, and Francisella tularensis GC-072 is bactericidal both extra- and intracellularly, with rapid killing noted within a few hours and reduced development of resistance compared to ceftazidime. GC-072, delivered intragastrically...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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ConclusionLCH mostly occurs in children. In head and neck it affects principally the mastoid part of the temporal bone. Treatments include surgery, chemotherapy, and irradiation. Most patients enjoy good prognoses. LCH accompanied by TCS is rare and increases the difficulty of diagnosis; molecular data aid in TCS identification.
Source: American Journal of Otolaryngology - Category: Endocrinology Source Type: research
Conclusions 177Lu-PSMA-617 radionuclide therapy is a safe and effective approach to the treatment of mCRPC patients.
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Original Articles Source Type: research
We describe herein the early relapse detection of a hormone-sensitive metastatic upfront PCa treated with docetaxel on 68Ga-PSMA-11 PET/CT before biochemical progression. PSMA PET/CT should be considered to monitor PCa response to chemotherapy to detect early relapse, regardless of prostate-specific antigen levels, increasing the chances of finding low-volume oligoprogressive disease.
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Interesting Images Source Type: research
Authors: Nayak S, Rao GM, Marathe A, Vyshnavi M Abstract BACKGROUND: Mucositis, one of the devastating consequences of chemotherapy and also limits the efficacy of the treatment. At present, there are no antimucositic agents without side effects. Hence, there is a need for better adjuvant therapy using plant or food sources. Here, we have made an attempt to study the effect of Annona muricata (AM) fruit pulp on etoposide-induced mucositis. MATERIALS AND METHODS: The study was conducted at Central Research Laboratory, Kasturba Medical College, Mangalore. The effect of AM fruit pulp (100 mg and 200 mg/kg body wei...
Source: Journal of Carcinogenesis - Category: Cancer & Oncology Tags: J Carcinog Source Type: research
Authors: Jankowska-Polańska B, Polański J, Chabowski M, Rosińczuk J, Mazur G Abstract The purpose of this study was to evaluate the influence of cognitive adjustment to cancer, assessed on the mini-Mental Adjustment to Cancer (mini-MAC) scale, on perception of anxiety and depression, assessed with the Hospital Anxiety and Depression Scale, in patients with non-small cell lung carcinoma (NSCLC). There were 185 patients, grouped according to the score of mini-MAC into constructive coping strategies, balanced coping strategies, and destructive coping strategies. We found that patients with predominantly destructive...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Leimkühler NB, Schneider RK Abstract Self-renewing hematopoietic stem cells and their progeny, lineage-specific downstream progenitors, maintain steady-state hematopoiesis in the bone marrow (BM). Accumulating evidence over the last few years indicates that not only primitive hematopoietic stem and progenitor cells (HSPCs), but also cells defining the microenvironment of the BM (BM niche), sense hematopoietic stress signals. They respond by directing and orchestrating hematopoiesis via not only cell-intrinsic but also cell-extrinsic mechanisms. Inflammation has many beneficial roles by activating the ...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Al-Samkari H, Connors JM Abstract The association between malignancy and thrombosis has been recognized for over a century and a half. Patients with cancer have an elevated risk of both initial and recurrent venous thromboembolism (VTE) compared with patients without cancer owing to cancer- and patient-specific factors. Recurrent VTE is common despite anticoagulation, presenting additional management challenges. Patients with cancer also have an increased risk of bleeding when on anticoagulants compared with patients without cancer. This bleeding risk is heightened by the thrombocytopenia common in patient...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Authors: Richard-Carpentier G, DiNardo CD Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by recurrent genetic, epigenetic, and metabolic abnormalities. As a result of our increasing knowledge of the underlying biology of AML leading to rational drug development, several new targeted agents have been recently added to our therapeutic arsenal. The BCL2 inhibitor venetoclax in combination with low-dose cytarabine (LDAC) or hypomethylating agents (HMAs) is safe and effective in older patients with newly diagnosed AML ineligible for intensive chemotherapy. Glasdegib, a hedgehog pathway...
Source: Hematology ASH Education Program - Category: Hematology Tags: Hematology Am Soc Hematol Educ Program Source Type: research
Abstract To improve the preparedness against exposure to highly pathogenic bacteria and to anticipate the wide variety of bacteria that can cause bloodstream infections (BSIs), a safe, unbiased and highly accurate identification method was developed. Our liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method can identify highly pathogenic bacteria, their near-neighbors and bacteria that are common causes of BSIs directly from positive blood culture flasks. The developed Peptide-Based Microbe Detection Engine (http://proteome2pathogen.com) relies on a two-step workflow: a genus-level search followed...
Source: International Journal of Medical Microbiology - Category: Microbiology Authors: Tags: Int J Med Microbiol Source Type: research
Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) sample preparation methods, including the direct, on-plate formic acid, and ethanol/formic acid tube extraction methods, were evaluated for their ability to render highly pathogenic organisms nonviable and safe for handling in a biosafety level 2 laboratory. Of these, the tube extraction procedure was the most successful, with none of the tested strains surviving this sample preparation method. Tube extracts from several agents of bioterrorism and their near neighbors were analyzed in an eight-laboratory study to examine the u...
Source: Journal of Clinical Microbiology - Category: Microbiology Authors: Tags: Bacteriology Source Type: research
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