22 research outputs found
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Ribonucleotide reductase and thymidylate synthase or exogenous deoxyribonucleosides reduce DNA damage and senescence caused by C‐MYC depletion
The down‐regulation of dominant oncogenes, including C‐MYC, in tumor cells often leads to the induction of
senescence via mechanisms that are not completely identified. In the current study, we demonstrate that MYC‐depleted
melanoma cells undergo extensive DNA damage that is caused by the underexpression of thymidylate synthase (TS) and
ribonucleotide reductase (RR) and subsequent depletion of deoxyribonucleoside triphosphate pools. Simultaneous genetic
inhibition of TS and RR in melanoma cells induced DNA damage and senescence phenotypes very similar to the ones
caused by MYC‐depletion. Reciprocally, overexpression of TS and RR in melanoma cells or addition of deoxyribonucleosides
to culture media substantially inhibited DNA damage and senescence‐associated phenotypes caused by C‐MYC
depletion. Our data demonstrate the essential role of TS and RR in C‐MYC‐dependent suppression of senescence in
melanoma cells.Keywords: ribonucleotide reductase, oncogene‐induced senescence, dNTP, myc, melanoma, thymidylate synthas
Principles for developing and adapting clinical practice guidelines and guidance for pandemics, wars, shortages, and other crises and emergencies: the PAGE criteria
Development of international clinical practice guidelines: benefits, limitations, and alternative forms of international collaboration
Use of anticoagulants and antiplatelet agents in stable outpatients with coronary artery disease and atrial fibrillation. International CLARIFY registry
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Merkel Cell Carcinoma and Human Immunodeficiency Virus: More Than a Non-Acquired Immunodeficiency Syndrome-Defining Tumor?
The incidence of non-acquired immunodeficiency syndrome-defining cancers is increasing in human immunodeficiency virus (HIV)-infected persons at a rate that is disproportionate to similar malignancies in the general population. The effect of HIV infection on latent oncogenic viruses and immune surveillance (the latter measured by the absolute CD4 T-cell lymphocyte count) and the role of highly active antiretroviral therapy are considered contributing factors in the development of this epidemiologic trend. Merkel cell carcinoma (MCC), a rare but aggressive cutaneous malignancy, occurs at a disproportionately higher frequency in HIV-infected individuals, even in the context of relatively spared CD4 T-cell lymphocyte counts. A newly identified polyomavirus has been recently isolated from the tumoral genome of MCC, suggesting a viral oncogenic pathogenesis. We report a case of metastatic MCC in an HIV-infected patient that only became clinically evident after he achieved undetectable HIV RNA viral levels for the first time. We review the association of MCC with HIV and discuss the relationship of moderate but prolonged immunosuppression, which results from HIV disease, and its connection with non-acquired immunodeficiency syndrome-defining cancers while suggesting that MCC and other malignancies may need to be reconsidered for classification as acquired immunodeficiency syndrome-defining conditions
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Single-stage total endoscopic resection of a plexiform neurofibroma of the maxillary sinus in a child with type 1 neurofibromatosis
Plexiform neurofibromas are peripheral nerve sheath tumors associated with neurofibromatosis type 1. The maxillary sinus is an extremely rare location of the plexiform neurofibroma and only two adult cases have been previously reported. We report the first case of plexiform neurofibroma of the maxillary sinus occurring in a child with neurofibromatosis type 1. This unusual location presents a management challenge considering the infiltrative nature and the potential malignant degeneration of this type of tumor. MRI is highly valuable to diagnose and plan the surgical approach of the plexiform neurofibroma of the maxillary sinus. Due to the location of the tumor and the patient's age, conservative surgery is highly recommended. We performed an endoscopic total en-bloc resection of the tumor with no recurrence after nine months of follow-up
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Acute Viral Hepatitis A Inducing Autoimmune Hepatitis and Exacerbation of Chronic Hepatitis B 814
Blood Product Utilization Among Trauma and Nontrauma Massive Transfusion Protocols at an Urban Academic Medical Center
Hospital-wide massive transfusion protocols (MTPs) primarily designed for trauma patients may lead to excess blood products being prepared for nontrauma patients. This study characterized blood product utilization among distinct trauma and nontrauma MTPs at a large, urban academic medical center.
A retrospective study of blood product utilization was conducted in patients who required an MTP activation between January 2011 and December 2015 at an urban academic medical center. Trauma MTP containers included 6 red blood cell (RBC) units, 5 plasma units, and 1 unit of apheresis platelets. Nontrauma MTP containers included 6 RBC and 3 plasma units.
There were 334 trauma MTP activations, 233 nontrauma MTP activations, and 77 nontrauma MTP activations that subsequently switched to a trauma MTP ("switched activations"). All nontrauma MTP activations were among bleeding patients who did not have a traumatic injury (100% [233/233]). Few patients with a nontrauma activation required ad hoc transfusion of RBC units (1.3% [95% confidence interval {CI}, 0.3%-3.7%]) or plasma (3.4% [95% CI, 1.5%-6.7%]), and only 45.5% (95% CI, 39.0%-52.1%) required ad hoc transfusion of apheresis platelets. Compared to trauma and switched activations, nontrauma activations transfused a lower median number of RBC, plasma, and apheresis platelet units (P < .001 for all comparisons). There was also a lower median number of prepared but unused plasma units for nontrauma activations (3; [interquartile range {IQR}, 3-5]) compared to trauma (7; [IQR, 5-10]; P < .001) and switched activations (8; [IQR, 5-11]; P < .001). The median number of unused apheresis platelet units was 1 (IQR, 1-2) for trauma activations and 0 (IQR, 0-1) for switched activations. There was a high proportion of trauma and switched activations in which all of the prepared apheresis platelet units were unused (28.1% [95% CI, 23.4%-33.3%] and 9.1% [95% CI, 3.7%-17.8%], respectively).
The majority of initial nontrauma MTP activations did not require a switch to a trauma MTP. Patients remaining under a nontrauma MTP activation were associated with a lower number of transfused and unused plasma and apheresis platelet units. Future studies evaluating the use of hospital-wide nontrauma MTPs are warranted since an MTP designed for nontrauma patient populations may yield a key strategy to optimize blood product utilization in comparison to a universal MTP for both trauma and nontrauma patients