RESUMO
Integrins are necessary for cell adhesion, migration, and positioning. Essential for inducing signalling events for cell survival, proliferation, and differentiation, they also trigger a variety of signal transduction pathways involved in mediating invasion, metastasis, and squamous-cell carcinoma. Several recent studies have demonstrated that the up- and down-regulation of the expression of αv and other integrins can be a potent marker of malignant diseases and patient prognosis. This review focuses on an arginine-glycine-aspartic acid (RGD)-dependent integrin αVß6, its biology, and its role in healthy humans. We examine the implications of αVß6 in cancer progression and the promotion of epithelial-mesenchymal transition (EMT) by contributing to the activation of transforming growth factor beta TGF-ß. Although αvß6 is crucial for proper function in healthy people, it has also been validated as a target for cancer treatment. This review briefly considers aspects of targeting αVß6 in the clinic via different therapeutic modalities.
Assuntos
Integrina alfaV , Neoplasias , Humanos , Ácido Aspártico , Integrinas/metabolismo , Antígenos de Neoplasias/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Neoplasias/terapia , Oligopeptídeos , Arginina , GlicinaRESUMO
Therapeutic antibodies are instrumental in improving the treatment outcome for certain disease conditions. However, to enhance their efficacy and specificity, many efforts are continuously made. One of the approaches that are increasingly explored in this field are pH-responsive antibodies capable of binding target antigens in a pH-dependent manner. We reviewed suitability and examples of these antibodies that are functionally modulated by the tumor microenvironment. Provided in this review is an update about antigens targeted by pH-responsive, sweeping, and recycling antibodies. Applicability of the pH-responsive antibodies in the engineering of chimeric antigen receptor T-cells (CAR-T) and in improving drug delivery to the brain by the enhanced crossing of the blood-brain barrier is also discussed. The pH-responsive antibodies possess strong treatment potential. They emerge as next-generation programmable engineered biologic drugs that are active only within the targeted biological space. Thus, they are valuable in targeting acidified tumor microenvironment because of improved spatial persistence and reduced on-target off-tumor toxicities. We predict that the programmable pH-dependent antibodies become powerful tools in therapies of cancer.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Animais , Humanos , Concentração de Íons de Hidrogênio , CamundongosRESUMO
PURPOSE: We examined renal papillary Hounsfield density in stone formers with all common stone subtypes to further understand the pathophysiology of stone formation. MATERIALS AND METHODS: Using computerized tomography we measured the Hounsfield density of a 0.2 cm(2) renal papillary area in patients with a single renal calyceal stone. Results were compared with those in patients without a nephrolithiasis history who served as controls. Stone composition was determined by stone passage or extraction during endoscopic procedures using infrared spectroscopy and polarized microscopy. We measured the Hounsfield density of the stone bearing calyx and of a single calyx from the upper, middle and lower poles of each kidney. RESULTS: Mean ± SD renal papillary Hounsfield density in controls was 36.2 ± 4.0 HU. In patients with stones Hounsfield density was significantly greater than in controls in stone bearing calyces, nonstone bearing calyces in the affected kidney and calyces in the contralateral nonstone bearing kidney for all stone composition subtypes (range 48.4 to 61.3 HU, each p <0.001). CONCLUSIONS: Patients with kidney stones regardless of composition showed the unique radiographic characteristic of increased renal papillary Hounsfield density. This was true for all calyces and for each kidney in all stone formers with a single renal calyceal stone. This radiographic evidence supports the role of renal papillary deposits or plaques in the pathophysiology of stone formation.
Assuntos
Cálculos Renais/química , Cálculos Renais/patologia , Medula Renal/patologia , Adulto , Feminino , Humanos , Cálculos Renais/diagnóstico por imagem , Medula Renal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: We compared infection rates after percutaneous nephrolithotomy in a group of patients without a history of infection or struvite calculi who received 24 hours or less of antibiotics postoperatively (ie compliance with AUA guidelines) vs a group that received 5 to 7 days of antibiotics postoperatively. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive percutaneous nephrolithotomy procedures in patients without a history of urinary tract infection. Group 1 received 24 hours or less of antibiotics postoperatively and group 2 received a mean of 6 days of antibiotics postoperatively. RESULTS: A total of 52 patients in group 1 (24 hours or less of antibiotics) and 30 in group 2 (mean 6 days of antibiotics) met study inclusion criteria. In 5 group 1 patients (9.6%) fever developed within 72 hours of percutaneous nephrolithotomy but none demonstrated bacteriuria or bacteremia on cultures. No patient in group 1 was treated for urinary tract infection on postoperative days 3 to 14. In 4 group 2 patients (13.3%) fever developed within 72 hours of percutaneous nephrolithotomy. A single patient showed bacteriuria (less than 10,000 cfu mixed gram-positive bacteria) on culture while no patient demonstrated bacteremia. No patient in group 2 was treated for urinary tract infection on postoperative days 3 to 14. There was no difference in stone-free rates or the need for additional procedures between the 2 groups. CONCLUSIONS: In this pilot series compliance with AUA guidelines for antibiotic prophylaxis did not result in higher rates of infection than in a comparable group of 30 patients who received approximately 6 days of antibiotics postoperatively.
Assuntos
Antibacterianos/uso terapêutico , Fidelidade a Diretrizes , Nefrostomia Percutânea , Cuidados Pós-Operatórios/normas , Infecções Urinárias/epidemiologia , Infecções Urinárias/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sociedades Médicas , Estados Unidos , UrologiaRESUMO
With all the current misinformation on social media platforms about the COVID-19 vaccine and its potential effects on fertility, it is essential for healthcare providers to have evidenced-based research to educate their patients, especially those who are trying to conceive, of the risks to mothers and fetuses of being unvaccinated. It is well known that COVID-19 infection puts pregnant women at higher risk of complications, including ICU admission, placentitis, stillbirth, and death. In February of 2021, the American College of Obstetricians and Gynecologists (ACOG), the American Society for Reproductive Medicine (ASRM), and the Society for Maternal-Fetal Medicine (SMFM) released a statement denying any link between COVID vaccination and infertility. ASRM later confirmed and stated that "everyone, including pregnant women and those seeking to become pregnant, should get a COVID-19 vaccine". In this review, we aim to provide a compilation of data that denies any link between vaccination and infertility for healthcare providers to be able to educate their patients based on evidence-based medicine. We also reviewed the effect of COVID-19 virus and vaccination on various parameters and processes that are essential to obtaining a successful pregnancy.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Pessoal de Saúde , Saúde Reprodutiva , Humanos , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Feminino , COVID-19/prevenção & controle , Gravidez , Vacinação/efeitos adversos , SARS-CoV-2/imunologia , Complicações Infecciosas na Gravidez/prevenção & controleRESUMO
The rare occurrence of an inflammatory mucocele in a pneumatized anterior clinoid process is described. The patient, a 20-year-old woman, presented with a severe visual field defect in her right eye associated with abnormality in the right anterior clinoid process identified on computed tomography and magnetic resonance imaging. Initially, surgical intervention was recommended for resection of a possible neoplasm. The patient's clinical history, however, was significant for sinusitis accompanied by sore throat and right ear infection that resolved with oral antibiotic therapy. When her condition was evaluated approximately 1 month after the onset of her visual symptoms, the patient had regained full visual acuity in the affected eye. Surgical exploration was not required, and the patient's optic neuropathy reversed with appropriate antibiotic therapy.
Assuntos
Mucocele/complicações , Mucocele/tratamento farmacológico , Neuropatia Óptica Isquêmica/tratamento farmacológico , Neuropatia Óptica Isquêmica/etiologia , Adulto , Antibacterianos/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética , Sinusite/etiologia , Sinusite/terapia , Tomografia Computadorizada por Raios X , Testes Visuais , Campos Visuais/fisiologiaRESUMO
Acoustophoresis is a method well suited for cell and microbead separation or concentration for downstream analysis in microfluidic settings. One of the main limitations that acoustophoresis share with other microfluidic techniques is that the separation efficiency is poor for particle-rich suspensions. We report that flow laminated liquids can be relocated in a microchannel when exposed to a resonant acoustic field. Differences in acoustic impedance between two liquids cause migration of the high-impedance liquid towards an acoustic pressure node. In a set of experiments we charted this phenomenon and show herein that it can be used to either relocate liquids with respect to each other, or to stabilize the interface between them. This resulted in decreased medium carry-over when transferring microbeads (4% by volume) between suspending liquids using acoustophoresis. Furthermore we demonstrate that acoustic relocation of liquids occurs for impedance differences as low as 0.1%.