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2023 ◽  
Vol 83 ◽  
Author(s):  
B. Javed ◽  
F. Farooq ◽  
M. Ibrahim ◽  
H. A. B. Abbas ◽  
H. Jawwad ◽  
...  

Abstract The present study was aimed to manifest the antibacterial and antifungal activity of methanolic extracts of Salix alba L. against seven Gram-positive and Gram-negative bacterial pathogens e.g. Streptococcus pyogenes, Staphylococcus aureus (1), S. aureus (2), Shigella sonnei, Escherichia coli (1), E. coli (2) and Neisseria gonorrhoeae and three fungal isolates from the air such as Aspergillus terreus, A. ornatus, and Rhizopus stolonifer. Two different serotypes of S. aureus and E. coli were used. The agar well-diffusion method results showed the dose-dependent response of plant extracts against bacterial and fungal strains while some organisms were found resistant e.g. E. coli (1), S. sonnei, A. terreus and R. stolonifer. The highest antibacterial activity was recorded at 17.000±1.732 mm from 100 mg/mL of leaves methanolic extracts against S. pyogenes while the activity of most of the pathogens decreased after 24 h of incubation. The highest antifungal activity was reported at 11.833±1.0 mm against A. ornatus at 50 mg/mL after 48 h of the incubation period. These experimental findings endorse the use of S. alba in ethnopharmacological formulations and suggest the use of methanolic extracts of the said plant to develop drugs to control the proliferation of resistant disease causing pathogenic microbes.


2022 ◽  
Vol 29 ◽  
Author(s):  
Nadia Zaffaroni ◽  
Giovanni Luca Beretta

Abstract: Lipid peroxidation-driven iron-dependent ferroptosis is a regulated cell death mechanism implicated in numerous disease, such as neurological diseases, kidney injury, ischemia, and tumors, including prostate cancer. The cellular mechanisms of ferrosptosis are strongly associated with iron, reactive oxygen species and aminoacid metabolic pathways. Several compounds, namely ferroptosis inducers, impact on these pathways and trigger ferroptosis by i) inhibiting Xc– transporter system, ii) impairing GPX4 functions and iii) oxidizing iron and polyunsaturated phospholipids. Preclinical studies showed that in combination with conventional anticancer drugs, ferroptosis inducers are effective in prostate cancer and in combating the progression towards the castration resistant disease. This review overviews the mechanisms implicated in ferroptosis and discusses the findings achieved in prostate cancer.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 166
Author(s):  
Maree Pechlivanis ◽  
Bethany K. Campbell ◽  
Christopher M. Hovens ◽  
Niall M. Corcoran

Prostate cancer (PCa) is a hormone driven cancer, characterised by defects in androgen receptor signalling which drive the disease process. As such, androgen targeted therapies have been the mainstay for PCa treatment for over 70 years. High-risk PCa presents unique therapeutic challenges, namely in minimising the primary tumour, and eliminating any undetected micro metastases. Trials of neoadjuvant androgen deprivation therapy aim to address these challenges. Patients typically respond well to neoadjuvant treatment, showing regression of the primary tumour and negative surgical margins at the time of resection, however the majority of patients relapse and progress to metastatic disease. The mechanisms affording this resistance are largely unknown. This commentary attempts to explore theories of resistance more broadly, namely, clonal evolution, cancer stem cells, cell persistence, and drug tolerance. Moreover, it aims to explore the application of these theories in the PCa setting. This commentary also highlights the distinction between castration resistant PCa, and neoadjuvant resistant disease, and identifies the markers and characteristics of neoadjuvant resistant disease presented by current literature.


Author(s):  
Shereen S Katrak ◽  
Rongxia Li ◽  
Sue Reynolds ◽  
Suzanne M Marks ◽  
Jessica R Probst ◽  
...  

Abstract Background An elevated risk of tuberculosis disease (TB) in persons who have received tumor necrosis factor-alpha inhibitor medications (TNF-α inhibitors) has been reported for nearly two decades, but clinical diagnostic features and outcomes of TB in this population remain poorly described. Methods We analyzed national surveillance data for TB cases among persons aged 15 years and older reported in the United States during 2010–2017 and associated mortality data reported through 2019 to describe the clinical characteristics of those receiving TNF-α inhibitors. Results Of 70,129 TB cases analyzed, 504 (0.7%) of the patients had TNF-α inhibitor use reported at TB diagnosis. Patients with TNF-α inhibitor use at TB diagnosis were more likely than TB patients not receiving TNF-α inhibitors to have TB diagnosed in extrapulmonary sites in conjunction with pulmonary sites (28.8% vs 10.0%, P<0.001). Patients receiving TNF-α inhibitors were less likely to have acid-fast bacilli (AFB) noted on sputum smear microscopy (25.6% vs 39.1%, P=0.04), and more likely to have drug-resistant disease (13.5% vs 10.0%, P<0.001). TB-attributed deaths did not significantly differ between patients receiving and not receiving TNF-α inhibitors (adjusted odds ratio 1.46, 95% confidence interval 0.95-2.26). Conclusions Clinicians evaluating TNF-α inhibitor-treated patients should have a high index of suspicion for TB and be aware that extrapulmonary or sputum smear negative TB disease is more common in these patients. No significantly diminished survival of TB patients treated with TNF-α inhibitor therapy before TB diagnosis was noted.


Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6265
Author(s):  
Fiorella Iglesias Cardenas ◽  
Audrey Mauguen ◽  
Irene Y. Cheung ◽  
Kim Kramer ◽  
Brian H. Kushner ◽  
...  

Beta glucans, complex polysaccharides, prime leukocyte dectin-1 and CR3-receptors and enhance anti-tumor cytotoxicity of complement-activating monoclonal antibodies. We conducted a phase I study (clinicaltrials.gov NCT00492167) to determine the safety of the combination of yeast-derived beta glucan (BG) and anti-GD2 murine monoclonal antibody 3F8 in patients with relapsed or refractory high-risk neuroblastoma. Patients received intravenous 3F8 (fixed dose of 10 mg/m2/day × 10 days) and oral BG (dose-escalated from 10–200 mg/kg/day × 17 days in cohorts of 3–6 patients each). Forty-four patients completed 141 cycles. One patient developed DLT: transient self-limiting hepatic transaminase elevation 5 days after starting BG (120 mg/kg/day). Overall, 1, 3, 12 and 24 evaluable patients had complete response, partial response, stable and progressive disease, respectively, at the end of treatment. Positive human anti-mouse antibody response and dectin-1 rs3901533 polymorphism were associated with better overall survival. BG dose level and serum BG levels did not correlate with response. Progression-free and overall survival at 2 years were 28% and 61%, respectively. BG lacked major toxicity. Treatment with 3F8 plus BG was associated with anti-neuroblastoma responses in patients with resistant disease. Although the maximal tolerated dose for yeast BG was not reached, considering the large volume of oral BG, we recommended 40 mg/kg/day as the phase II dose.


2021 ◽  
Vol 27 ◽  
Author(s):  
Igor Sirák ◽  
Jan Laco ◽  
Hana Vošmiková ◽  
Loren K. Mell ◽  
Fernanda G. Herrera ◽  
...  

Small cell carcinoma of hypercalcemic type (SCCOHT) is a rare gynaecological neoplasm, originating mostly in the ovaries. Cervical origin of this very aggressive malignancy with unknown histogenesis is an extremely rare condition, without published management recommendations. Alterations in SMARCA4 gene are supposed to play the major role in SCCOHT oncogenesis and their identification is crucial for the diagnosis. Adequate genetic counselling of the patients and their families seems to be of great importance. Optimal management and treatment approaches are not known yet but may extremely influence the prognosis of young female patients that suffer from this very resistant disease. Nowadays, a translational research seems to be the key for the further diagnostic and treatment strategies of SCCOHT. The purpose of the case report is to provide practical information and useful recommendations on the diagnosis, management, and treatment of SMARCA4-deficient carcinoma of the uterine cervix resembling SCCOHT.


Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6087
Author(s):  
Gábor Mikala ◽  
Gergely Varga

It was Bart Barlogie who made a clear point by stating in one of his lectures that any myeloma that is not cured will eventually turn into a resistant disease with aggressive clinical behaviour [...]


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Emily A. Kendall ◽  
Hamidah Hussain ◽  
Amber Kunkel ◽  
Rachel W. Kubiak ◽  
Anete Trajman ◽  
...  

Abstract Background Short-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use. Methods We developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens—4 months of rifampicin [4R] or 6 months of isoniazid [6H]—comparing each to a reference of no intervention. Before initiating TPT, TB disease was excluded either through symptom-only screening or with additional radiographic screening that could detect subclinical TB but might limit access to the TPT intervention. TPT’s potential curative effects on both latent and subclinical TB were modeled, as were both acquisitions of resistance and prevention of drug-resistant disease. Although all eligible individuals received the screening and/or TPT interventions, the modeled TB outcomes comprised only those with latent or subclinical TB that would have progressed to symptomatic disease if untreated. Results When prescribed after only symptom-based TB screening (such that individuals with subclinical TB were included among TPT recipients), 4R averted 45 active (i.e., symptomatic) TB cases (95% uncertainty range 24–79 cases or 40–89% of progressions to active TB) per 1000 PWH [17 (9–29, 43–94%) per 1000 HHCs]; 6H averted 37 (19–66, 52–73%) active TB cases among PWH [13 (7–23, 53–75%) among HHCs]. With this symptom-only screening, for each net rifampicin resistance case added by 4R, 12 (3–102) active TB cases were averted among PWH (37 [9–580] among HHCs); isoniazid-resistant TB was also reduced. Similarly, 6H after symptom-only screening increased isoniazid resistance while reducing overall and rifampicin-resistant active TB. Screening for subclinical TB before TPT eliminated this net increase in resistance to the TPT drug; however, if the screening requirement reduced TPT access by more than 10% (the estimated threshold for 4R among HHCs) to 30% (for 6H among PWH), it was likely to reduce the intervention’s overall TB prevention impact. Conclusions All modeled TPT strategies prevent TB relative to no intervention, and differences between TPT regimens or between screening approaches are small relative to uncertainty in the outcomes of any given strategy. If most TPT-eligible individuals can be screened for subclinical TB, then pairing such screening with rifamycin-based TPT maximizes active TB prevention and does not increase rifampicin resistance. Where subclinical TB cannot be routinely excluded without substantially reducing TPT access, the choice of TPT regimen requires weighing 4R’s efficacy advantages (as well as its greater safety and shorter duration that we did not directly model) against the consequences of rifampicin resistance in a small fraction of recipients.


Author(s):  
Arvind Kaul ◽  
Jatin Mistry ◽  
Annamaria Iagnocco ◽  
Xenofon Baraliakos ◽  
Ailsa Bosworth ◽  
...  

Abstract Objectives Advanced therapies (AT) including biologics, biosimilars and JAK inhibitors have dramatically improved the quality of life of patients with Rheumatoid arthritis (RA), Psoriatic Arthritis (PsA) and Axial spondyloarthritis (axSpA). Evidence-based criteria for prescribing these drugs in England and Wales is formulated by the National Institute for Health and Care Excellence (NICE) through Health Technology Appraisals (HTAs) and guidelines with the aim of providing equitable access to AT for patients with severe or resistant disease. Similar bodies exist in some, but not all European countries with disparities in AT access between countries in AT access for RA. We examined whether this disparity was mirrored in England for RA, PsA and axSpA despite the NHS in England and Wales being legally obliged to provide funding for AT recommended by NICE’s HTA board, through commissioning bodies, Clinical Commissioning Groups (CCGs). Methods We requested AT pathways from CCGs in England. Where these were not available, individual hospital Trusts were contacted using Freedom of Information (FOI) requests. Results We found marked variability in the way that CCGs in England interpret NICE guidance. We found 41, 29 and 25 different pathways for RA, PsA and axSpA respectively. Similar disparities existed with sequential prescribing where one AT did not work, with limits on numbers of sequential AT in 54%, 59% and 59% of CCGs for RA, PsA and axSpA respectively, with these limits being different for the same condition between CCGs. Conclusion While patients at identical stages of their disease course should have access to the same NICE approved AT, we found this is not the case for large parts of England. Inequality of access was found between regions mirroring the variability which occurs between countries throughout Europe. Harmonisation of access needs to be addressed by policymakers, ensuring fairness in the way that clinicians and patients can access AT.


2021 ◽  
Vol 22 (22) ◽  
pp. 12095
Author(s):  
Kristin A. Plichta ◽  
Stephen A. Graves ◽  
John M. Buatti

Theranostics, a combination of therapy and diagnostics, is a field of personalized medicine involving the use of the same or similar radiopharmaceutical agents for the diagnosis and treatment of patients. Prostate-specific membrane antigen (PSMA) is a promising theranostic target for the treatment of prostate cancers. Diagnostic PSMA radiopharmaceuticals are currently used for staging and diagnosis of prostate cancers, and imaging can predict response to therapeutic PSMA radiopharmaceuticals. While mainly used in the setting of metastatic, castrate-resistant disease, clinical trials are investigating the use of PSMA-based therapy at earlier stages, including in hormone-sensitive or hormone-naïve prostate cancers, and in oligometastatic prostate cancers. This review explores the use of PSMA as a theranostic target and investigates the potential use of PSMA in earlier stage disease, including hormone-sensitive metastatic prostate cancer, and oligometastatic prostate cancer.


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