Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK), whose biological activity is tightly regulated by its cellular abundance. Recent studies have revealed that ERK3 is upregulated in multiple cancers and promotes cancer cell migration/invasion and drug resistance. Little is known, however, about how ERK3 expression level is upregulated in cancers. Here we have identified the oncogenic polycomb group protein BMI1 as a positive regulator of ERK3 level in head and neck cancer cells. Mechanistically, BMI1 upregulates ERK3 expression by suppressing the tumor suppressive microRNA (miRNA) let-7i which directly targets ERK3 mRNA. ERK3 then acts as an important downstream mediator of BMI1 in promoting cancer cell migration. Importantly, ERK3 protein level is positively correlated with BMI1 level in head and neck tumor specimens of human patients. Taken together, our study revealed a molecular pathway consisting of BMI1, miRNA let-7i and ERK3 which controls the migration of head and neck cancer cells, and suggests that ERK3 kinase is a potential new therapeutic target in head and neck cancers, particularly those with BMI1 overexpression.
Cystoisospora belli, previously known as Isospora belli, is an obligate intracellular coccidian parasite that is most often associated with gastrointestinal disease in immunocompromised patients. In this study, we detail the clinicopathologic features of 18 cases of Cystoisospora infection affecting the gallbladder in immunocompetent individuals and compare them with a control group. Each case was reviewed for cholecystitis (none, acute, chronic), epithelial disarray, presence of intraepithelial lymphocytes (none, rare [≤5 per 20 epithelial cells], present [>5 per 20 epithelial cells]), architectural distortion, intramucosal eosinophilia, and mural thickening/serositis. The mean age of patients with Cystoisospora infection was 33 years and the male to female ratio 1:4.3. Cholecystectomy was performed for biliary dyskinesia (n=7), abdominal pain (n=7), suspected cholelithiasis (n=5), and cholecystitis (n=3). In 2 cases, Cystoisospora was found in donor gallbladders resected at the time of liver transplantation. Each case was characterized by eosinophilic, oval or banana-shaped intraepithelial parasites within perinuclear parasitophorous vacuoles. Most cases showed epithelial disarray and minimal intraepithelial lymphocytosis. Of the 11 cases with an average follow-up of 15 months, none had evidence of disease related to Cystoisospora infection within the biliary tract or elsewhere in the gastrointestinal tract. We present the largest series of gallbladder cystoisosporiasis in immunocompetent patients to date. Cystoisospora infection is underrecognized in the gallbladders of immunocompetent patients, in part due to the subtle findings in routine cholecystectomy specimens. On the basis of the clinical follow-up, gallbladder cystoisosporiasis in immunocompetent individuals appears to be a self-limited infection.
In 2007, a 47-year-old African American man presented with gradual progressive shortness of breath and recurrent pneumonia. His medical history was significant and included pulmonary hypertension treated with bosentan (Tracleer; Actelion, San Francisco, Calif) and sildenafil citrate (Revatio; Pfizer, New York, NY), as well as coronary artery disease, for which he underwent placement of a right coronary artery stent. He also had a history of heavy smoking, with cessation in 2008 and occasional relapses until he arrived at our center in 2009 for evaluation for lung transplantation. A review of his vital signs revealed a respiratory rate of 15 breaths per minute at rest and resting oxygen saturation of 90% in room air, with desaturation to 72% with short-distance walking despite administration of 6 L of oxygen with a nasal cannula. Mean pulmonary arterial pressure was 30 mm Hg. Computed tomography (CT) of the chest depicted multiple small thinwalled cysts with upper lobe predominance, as well as a few scattered small nodules. Given the patient's clinical history, pulmonary Langerhans cell histiocytosis (PLCH) was suspected, and the patient subsequently underwent double lung transplantation. Pathologic findings confirmed the diagnosis.
Context.-New molecular diagnostic tests are attractive because of the potential they hold for improving diagnostics in microbiology. The value of these tests, which is often assumed, should be investigated to determine the best use of these potentially powerful tools.Objective.-To investigate the usefulness of broad-range polymerase chain reaction (PCR), followed by sequencing, in mycobacterial infections.Design.-We reviewed the test performance of acid-fast bacilli (AFB) PCR and traditional diagnostic methods (histopathology, AFB smear, and culture). We assessed the diagnostic effect and cost of the unrestricted ordering of broad-range PCR for the detection and identification of mycobacteria in clinical specimens.Results.-The AFB PCR was less sensitive than culture and histopathology and was less specific than culture, AFB smear, and histopathology. During 18 months, $93 063 was spent on 183 patient specimens for broad-range PCR and DNA sequencing for mycobacteria to confirm one culture-proven Mycobacterium tuberculosis infection that was also known to be positive by AFB smear and histopathology. In this cohort, there was a false-negative AFB PCR for M tuberculosis and a false-positive AFB PCR for Mycobacterium lentiflavum.Conclusion.-Testing of AFB smear-negative specimens from patients without an inflammatory response supportive of a mycobacterial infection is costly and has not been proven to improve patient care. Traditional diagnostics (histopathology, AFB smear, and culture) should remain the primary methods for the detection of mycobacteria in clinical specimens.(Arch Pathol Lab Med. 2015;139:1020-1023; doi: 10.5858/arpa.2013-0705-OA) S election of the optimum tests for a specimen becomes more challenging as newer testing methods become increasingly available for the detection of microorganisms. Polymerase chain reaction (PCR)-based methods for microorganism detection and identification are attractive given the sensitivity and speed of many of these assays. 1,2Broad-range PCR assays (ie, PCR assays that detect large groups of microorganisms) have been used successfully as an antecedent to DNA sequencing for the detection and identification of a variety of microorganisms. [3][4][5] This has been used after cultivation to identify microorganisms when traditional methods fail. 6 Additionally, it has been used directly on clinical specimens that contain evidence of infection (ie, microorganisms in an appropriate inflammatory response) when traditional methods of culture are unproductive. 5,7,8 However, the reported advantages of these assays such as speed and sensitivity make them prone to misuse. For example, broad-range PCR for bacteria, fungi, and mycobacteria has been used as a more expensive replacement for the inefficient practice of ''pan-culture'' that preceded it.9 Unfortunately, this approach (which we will demonstrate) is equally unsound and significantly more expensive for the detection of mycobacteria in clinical specimens and should be reconsidered in an era of health care reform when cost-effe...
Overall, the evidence does not support using probiotics to treat Clostridium difficile-associated diarrhea (CDAD). More studies are needed to determine if they are helpful and, if so, which ones and at what dosages.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.