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1.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36835030

RESUMEN

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Pronóstico , Inhibidores de Puntos de Control Inmunológico , Estado Nutricional , Estudios Retrospectivos , Inflamación
2.
Acta Radiol ; 61(8): 1072-1079, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31805769

RESUMEN

Puumala virus (PUUV) is the most common hantavirus in Europe. It is known to cause nephropathia epidemica, which is considered a mild type of hemorrhagic fever with renal syndrome. However, it does not only involve the kidneys and is rarely accompanied by symptomatic hemorrhage. We review the imaging abnormalities caused by PUUV infection, from head to pelvis, emphasizing the broad spectrum of possible findings and bringing further support to a previously suggested denomination "Hantavirus disease" that would encompass all clinical manifestations. Although non-specific, knowledge of radiological appearances is useful to support clinically suspected PUUV infection, before confirmation by serology.


Asunto(s)
Fiebre Hemorrágica con Síndrome Renal/diagnóstico por imagen , Virus Puumala , Abdomen/diagnóstico por imagen , Fiebre Hemorrágica con Síndrome Renal/complicaciones , Humanos , Imagen por Resonancia Magnética , Neurorradiografía , Tórax/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Ultrasonografía
3.
Medicina (Kaunas) ; 55(3)2019 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-30862115

RESUMEN

Lung hyperinflation is a main determinant of dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Surgical or bronchoscopic lung volume reduction are the most efficient therapeutic approaches for reducing hyperinflation in selected patients with emphysema. We here report the case of a 69-year old woman with COPD (GOLD stage 3-D) referred for lung volume reduction. She complained of persistent disabling dyspnoea despite appropriate therapy. Chest imaging showed marked emphysema heterogeneity as well as severe hyperinflation of the right lower lobe. She was deemed to be a good candidate for bronchoscopic treatment with one-way endobronchial valves. In the absence of interlobar collateral ventilation, 2 endobronchial valves were placed in the right lower lobe under general anaesthesia. The improvement observed 1 and 3 months after the procedure was such that the patient no longer met the pulmonary function criteria for COPD. The benefit persisted after 3 years.


Asunto(s)
Neumonectomía/rehabilitación , Prótesis e Implantes/efectos adversos , Implantación de Prótesis/efectos adversos , Implantación de Prótesis/rehabilitación , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Actividades Cotidianas , Anciano , Broncoscopía , Disnea/diagnóstico por imagen , Disnea/fisiopatología , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/cirugía , Pruebas de Función Respiratoria , Fumadores , Tomógrafos Computarizados por Rayos X , Resultado del Tratamiento
4.
Fam Pract ; 34(5): 581-586, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-28472286

RESUMEN

Background: Supplemental health insurances (SHI) cover 38% of the Danish population. SHI can give faster access to, and additional treatment from, private health providers. However, this is contingent on a referral from the general practitioner (GP), further complicating clinical decision-making. Objectives: To describe GPs' attitudes to SHI and their experiences with patients holding SHI. Moreover, we analysed associations between different GP characteristics; e.g. gender, age, practice type, own SHI status and their attitudes to and experiences with SHI. Methods: A questionnaire was mailed to 3321 GPs focusing on three issues: (i) Attitudes towards the public health care system. (ii) Perceptions of the impact of SHI. (iii) Experiences with patients holding SHIs. Results: The response rate was 64%. Overall, GPs found that SHIs contribute to inequality (83%) and overtreatment (90%). However, 46% often feel under pressure to refer SHI patients to specialist care, even though not medically indicated, while 11% always or often refer SHI patients unconditionally. Both groups perceive SHI patients more insistent on getting referrals than patients without SHI. Conclusion: Even though a majority of GPs associate SHI with overtreatment and inequality in health, many GPs feel under pressure to refer patients holding SHI for treatments or examinations that are not medically warranted. Some GPs even refer these patients without further examination or questioning. Insistent SHI patients may partly explain this paradox. Future research should illuminate SHI patients' courses in the private as well as the public healthcare system with regards to medical indications and health outcome measures focusing on inequality and overtreatment.


Asunto(s)
Actitud del Personal de Salud , Médicos Generales/psicología , Seguro de Salud/estadística & datos numéricos , Derivación y Consulta/estadística & datos numéricos , Adulto , Anciano , Dinamarca , Femenino , Disparidades en el Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Encuestas y Cuestionarios
5.
J Vasc Interv Radiol ; 27(5): 674-81, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27017121

RESUMEN

PURPOSE: To compare the diagnostic accuracy and safety of a 14-gauge core needle versus a 22-gauge fine needle in the evaluation of thoracic lesions by CT-guided percutaneous transthoracic needle biopsy (TTNB). MATERIALS AND METHODS: Medical charts of all patients who underwent CT-guided percutaneous transthoracic core-needle biopsies (CNBs) with a 14-gauge Spirotome device (99 patients, 102 procedures) and fine-needle biopsies (FNBs) with a 22-gauge Rotex needle (92 patients, 102 procedures) between 2007 and 2013 at a single academic institution were retrospectively reviewed. Variables that could influence diagnostic accuracy and safety were collected. RESULTS: The overall and cancer-specific diagnostic accuracy rates were 90% and 94%, respectively, with CNB, versus 82% and 89% with FNB. Precise cancer type/subtype was provided by 97% of CNBs versus 65% of FNBs (P < .001). In patients with lung cancer considered for targeted therapy, biomarker analyses were feasible in 80% of CNBs versus 0% of FNBs (P < .001). The rate of pneumothorax was significantly higher with CNB versus FNB (31% vs 19%; P = .004), but chest tube insertion rates were similar (10% vs 11%, respectively). Major bleeding complications occurred in 1% of CNBs versus 2% of FNBs and were associated with one death in the CNB group. CONCLUSIONS: Percutaneous transthoracic CNB with a 14-gauge Spirotome needle provided better characterization of cancer lesions and allowed biomarker analyses without a significant increase in major procedural complications.


Asunto(s)
Biopsia con Aguja Fina/instrumentación , Biopsia con Aguja Gruesa/instrumentación , Biopsia Guiada por Imagen/instrumentación , Agujas , Radiografía Intervencional/métodos , Enfermedades Torácicas/patología , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina/efectos adversos , Biopsia con Aguja Gruesa/efectos adversos , Biopsia con Aguja Gruesa/mortalidad , Diseño de Equipo , Femenino , Hemorragia/etiología , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/métodos , Biopsia Guiada por Imagen/mortalidad , Masculino , Registros Médicos , Persona de Mediana Edad , Neumotórax/etiología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven
6.
Int J Pharm ; 654: 123954, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38428548

RESUMEN

Calicheamicin is a potent, cell-cycle independent enediyne antibiotic that binds and cleaves DNA. Toxicity has led to its use in a targeted form, as an antibody-drug conjugate approved for the treatment of liquid tumors. We used a reduced calicheamicin to conjugate it to a single cysteine residue at the membrane-inserting end of a pH Low Insertion Peptide (pHLIP) that targets imaging and therapeutic agents to tumors. The cytoplasmic reduction of the disulfide releases the calicheamicin, and activation, DNA binding, and strand scission ensue. We studied the interaction of pHLIP-calicheamicin with liposomal and cellular membranes and demonstrated that the agent exhibits cytotoxic activity both in highly proliferative cancer cells and in non-proliferative immune cells, such as polarized M2 macrophages. In vivo, the agent was effective in inhibiting tumor growth in mice with no signs of toxicity. Biodistribution studies confirmed tumor targeting with no accumulation of the agent in organs and tissues. The agent was found within the tumor mass and tumor-stroma interface. Treatment of tumors led to the depletion of CD206+ M2- tumor-associated macrophages within the tumor core. pHLIP-calicheamicin could be pursued as an effective therapeutic for the treatment of solid tumors.


Asunto(s)
Antineoplásicos , Neoplasias , Animales , Ratones , Calicheamicinas , Distribución Tisular , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , ADN , Concentración de Iones de Hidrógeno
7.
Front Pharmacol ; 15: 1346756, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495104

RESUMEN

Introduction: We have developed a delivery approach that uses two pHLIP peptides that collaborate in the targeted intracellular delivery of a single payload, dimeric STINGa (dMSA). Methods: dMSA was conjugated with two pHLIP peptides via S-S cleavable self-immolating linkers to form 2pHLIP-dMSA. Results: Biophysical studies were carried out to confirm pH-triggered interactions of the 2pHLIP-dMSA with membrane lipid bilayers. The kinetics of linker self-immolation and dMSA release, the pharmacokinetics, the binding to plasma proteins, the stability of the agent in plasma, the targeting and resulting cytokine activation in tumors, and the biodistribution of the construct was investigated. This is the first study demonstrating that combining the energy of the membrane-associated folding of two pHLIPs can be utilized to enhance the targeted intracellular delivery of large therapeutic cargo payloads. Discussion: Linking two pHLIPs to the cargo extends blood half-life, and targeted delivery of dimeric STINGa induces tumor eradication and the development of robust anti-cancer immunity.

8.
Cancers (Basel) ; 15(15)2023 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-37568692

RESUMEN

BACKGROUND: Interstitial lung disease (ILD) is associated with a higher lung cancer (LC) risk and may impact cancer's clinical characteristics, treatment strategies, and outcomes. This impact's extent is unclear, particularly in Caucasians. METHODS: In this retrospective observational study, we reviewed the files of all LC patients diagnosed in a 38-month period. Expert radiologists reviewed the computed tomography scans performed at diagnosis. Patients with LC and ILD (n = 29, 7%) were compared to those without ILD (n = 363, 93%) for population and cancer characteristics, treatments, and clinical outcomes. RESULTS: Patients with LC and ILD were older (73 ± 8 vs. 65 ± 11 years; p < 0.001). There was no significant difference in LC histology, localization, stage, or treatment modalities. The respiratory complication rate after cancer treatment was significantly higher in the ILD group (39% vs. 6%; p < 0.01). Overall survival rates were similar at 12 (52% vs. 59%; p = 0.48) and 24 months (41% vs. 45%; p = 0.64) but poorer in the ILD group at 36 months, although not statistically significant (9% vs. 39%; p = 0.06). The ILD group had a higher probability of death (hazard ratio (HR) = 1.49 [0.96;2.27]), but this was not statistically significant (p = 0.06). In a Cox regression model, patients with ILD treated surgically had a significantly higher mortality risk (HR = 2.37 [1.1;5.09]; p = 0.03). CONCLUSIONS: Patients with combined LC and ILD have worse clinical outcomes even when similar treatment modalities are offered.

9.
Acta Cardiol ; 77(7): 580-585, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34431450

RESUMEN

INTRODUCTION: A family history of premature CAD may promote enhanced development of coronary atherosclerosis in a sibling population. Baseline CV algorithms may underestimate the risk of coronary incidents in individuals at familial risk. Cardiac CT provides high diagnostic performance for the detection of coronary plaques. There is little data on the use of this technology in the initial diagnostic approach of these patients. The prognostic value of early detection of coronary plaques by cardiac CT remains unknown in this population. OBJECTIVES: The study aimed to estimate the global CV risk and the pre-test probability of CAD in patients with a family history of premature CAD. We investigated the potential role of cardiac CT imaging in the assessment of coronary risk in patients from high-risk families. We sought to remind the 2019 ESC guidelines for screening for CAD in asymptomatic subjects. METHODS: Fifty siblings of patients with premature CAD were investigated. The pre-test probability of CAD was determined with the Clinical Model of the CAD consortium. The risk of CV disease was calculated and compared with three different risk algorithms (SCORE, FRS, PROCAM). All patients underwent cardiac CT with both non-contrast and contrast imaging. Coronary artery calcium (CAC) scoring was calculated and CT angiograms were analyzed. Patients with suspected CT obstructive CAD underwent coronary angiography. Clinical outcomes in terms of treatment were analyzed. RESULTS: The pre-test probability of CAD was low: CAD consortium <10% in 60%, SCORE <5% in 100%, FRS <10% in 88%, CAC scoring <100% in 68%. However, PROCAM was <10% in 16 cases (32%). Only 12 patients (24%) presented normal CCTA findings. In patients with abnormal CCTA findings (n = 38), PROCAM was higher than FRS in 20 patients (53%). Coronary angiography was performed in 31 cases (62%) for suspected CT obstructive CAD. Most patients presented no significant lesions (55%). Revascularization was performed in 8 patients (16%), 6 of them (75%) presented CAC scoring <100, 4 of them (50%) presented CAC scoring <400. After investigation, lipid-lowering therapy was enhanced by 66%. CONCLUSION: Coronary atherosclerotic-phenotyping using cardiac CT may provide discriminatory information allowing earlier identification of patients at familial risk of premature CAD. This diagnostic workup strategy may help to guide and improve the management of these patients. However, there is a paucity of data concerning the prognostic significance of this technology in relatives at familial risk of premature CAD. Therefore, further randomized controlled trials are needed to assess the incremental risk-predictive value of this approach in this population.


Asunto(s)
Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Humanos , Predisposición Genética a la Enfermedad , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Medición de Riesgo , Factores de Riesgo , Valor Predictivo de las Pruebas
10.
Abdom Radiol (NY) ; 47(7): 2552-2559, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35441863

RESUMEN

BACKGROUND: Previous clinical studies have reported abdominal findings on ultrasonography or MRI in Puumala hantavirus-infected patients. PURPOSE: To determine if abdominal computed tomography (CT) can lead to a diagnosis of Puumala virus infection in the presence of a suggestive clinical picture. MATERIAL AND METHODS: CT findings were studied retrospectively in 30 patients who presented to the emergency department of two (Belgian) hospitals with serologically confirmed Puumala hantavirus infection. RESULTS: The most frequent finding was perirenal fascial thickening (90%), followed by perirenal fat stranding (87%). Retroperitoneal fat stranding was found in 19 patients (64%) in the perivesical spaces along the fascia of the external iliac vessels with or without involvement of the presacral fat. Half of the patients had pelvic ascites, and pleural fluid was found in 7 of them. The right and left mean pole-to-pole kidney's lengths were respectively 125.7 mm and 127.8 mm in 28 patients. CONCLUSION: Retroperitoneal fat stranding, perirenal fascial thickening and/or perirenal fat stranding were found in most patients with acute Puumala virus infection who have undergone CT. Although nonspecific, these findings may help to suggest Puumala hantavirus infection in the right clinical settings.


Asunto(s)
Infecciones por Hantavirus , Fiebre Hemorrágica con Síndrome Renal , Virus Puumala , Fiebre Hemorrágica con Síndrome Renal/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
11.
Front Bioeng Biotechnol ; 10: 1082290, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36686229

RESUMEN

Targeted antigen delivery allows activation of the immune system to kill cancer cells. Here we report the targeted delivery of various epitopes, including a peptide, a small molecule, and a sugar, to tumors by pH Low Insertion Peptides (pHLIPs), which respond to surface acidity and insert to span the membranes of metabolically activated cancer and immune cells within tumors. Epitopes linked to the extracellular ends of pH Low Insertion Peptide peptides were positioned at the surfaces of tumor cells and were recognized by corresponding anti-epitope antibodies. Special attention was devoted to the targeted delivery of the nine residue HA peptide epitope from the Flu virus hemagglutinin. The HA sequence is not present in the human genome, and immunity is readily developed during viral infection or immunization with KLH-HA supplemented with adjuvants. We tested and refined a series of double-headed HA-pHLIP agents, where two HA epitopes were linked to a single pH Low Insertion Peptide peptide via two Peg12 or Peg24 polymers, which enable HA epitopes to engage both antibody binding sites. HA-epitopes positioned at the surfaces of tumor cells remain exposed to the extracellular space for 24-48 h and are then internalized. Different vaccination schemes and various adjuvants, including analogs of FDA approved adjuvants, were tested in mice and resulted in a high titer of anti-HA antibodies. Anti-HA antibody binds HA-pHLIP in blood and travels as a complex leading to significant tumor targeting with no accumulation in organs and to hepatic clearance. HA-pHLIP agents induced regression of 4T1 triple negative breast tumor and B16F10 MHC-I negative melanoma tumors in immunized mice. The therapeutic efficacy potentially is limited by the drop of the level of anti-HA antibodies in the blood to background level after three injections of HA-pHLIP. We hypothesize that additional boosts would be required to keep a high titer of anti-HA antibodies to enhance efficacy. pH Low Insertion Peptide-targeted antigen therapy may provide an opportunity to treat tumors unresponsive to T cell based therapies, having a small number of neo-antigens, or deficient in MHC-I presentation at the surfaces of cancer cells either alone or in combination with other approaches.

12.
Front Oncol ; 12: 1023959, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36330464

RESUMEN

Despite significant progress in the development of novel STING agonists (STINGa), applications appear to be challenged by the low efficiency and poor selectivity of these agents. A pH Low Insertion Peptide (pHLIP) extends the lifetime of a STINGa in the blood and targets it to acidic cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid derived suppressor cells (mMDSCs) and dendritic cells (DCs). CAFs constitute 25% of all live cells within CT26 tumors, and M2-type TAMs and mMDSCs are the most abundant among the immune cells. The resulting activation of cytokines within the tumor microenvironment (TME) triggers the eradication of small (100 mm3) and large (400-700 mm3) CT26 tumors in mice after a single dose of pHLIP-STINGa. The tumor stroma was destroyed (the number of CAFs was reduced by 98%), intratumoral hemorrhage developed, and the level of acidity within the TME was reduced. Further, no tumors developed in 20 out of 25 tumor-free mice re-challenged by an additional injection of cancer cells. The therapeutic effect on CT26 tumors was insignificant in nude mice, lacking T-cells. Thus, targeted delivery of STINGa to tumor stroma and TAMs induces activation of signaling, potentially resulting in the recruitment and infiltration of T-cells, which gain access to the tumor core. The cytotoxic activity of T-cells is not impaired by an acidic environment and immune memory is developed.

13.
Mol Imaging Biol ; 24(6): 874-885, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35604527

RESUMEN

PURPOSE: Acidity can be a useful alternative biomarker for the targeting of metabolically active cells in certain diseased tissues, as in acute inflammation or aggressive tumors. We investigated the targeting of activated macrophages by pH low insertion peptides (pHLIPs), an established technology for targeting cell-surface acidity. PROCEDURES: The uptake of fluorescent pHLIPs by activated macrophages was studied in cell cultures, in a mouse model of lung inflammation, and in a mouse tumor model. Fluorescence microscopy, whole-body and organ imaging, immunohistochemistry, and FACS analysis were employed. RESULTS: We find that cultured, activated macrophages readily internalize pHLIPs. The uptake is higher in glycolytic macrophages activated by LPS and INF-γ compared to macrophages activated by IL-4/IL-13. Fluorescent pHLIPs target LPS-induced lung inflammation in mice. In addition to marking cancer cells within the tumor microenvironment, fluorescent pHLIPs target CD45+, CD11b+, F4/80+, and CD206+ tumor-associated macrophages with no significant targeting of other immune cells. Also, fluorescent pHLIPs target CD206-positive cells found in the inguinal lymph nodes of animals inoculated with breast cancer cells in mammary fat pads. CONCLUSIONS: pHLIP peptides sense low cell surface pH, which triggers their insertion into the cell membrane. Unlike cancerous cells, activated macrophages do not retain inserted pHLIPs on their surfaces, instead their highly active membrane recycling moves the pHLIPs into endosomes. Targeting activated macrophages in diseased tissues may enable clinical visualization and therapeutic opportunities.


Asunto(s)
Sistemas de Liberación de Medicamentos , Neoplasias , Ratones , Animales , Sistemas de Liberación de Medicamentos/métodos , Concentración de Iones de Hidrógeno , Lipopolisacáridos/farmacología , Neoplasias/patología , Péptidos , Macrófagos/patología , Microambiente Tumoral
14.
Diagnostics (Basel) ; 12(11)2022 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-36428830

RESUMEN

D-dimer is a multifaceted biomarker of concomitant activation of coagulation and fibrinolysis, which is routinely used for ruling out pulmonary embolism (PE) and/or deep vein thrombosis (DVT) combined with a clinical pretest probability assessment. The intended use of the tests depends largely on the assay used, and local guidance should be applied. D-dimer testing may suffer from diagnostic errors occurring throughout the pre-analytical, analytical, and post-analytical phases of the testing process. This review aims to provide an overview of D-dimer testing and its value in diagnosing PE and discusses the variables that may impact the quality of its laboratory assessment.

15.
Front Urol ; 22022.
Artículo en Inglés | MEDLINE | ID: mdl-36439552

RESUMEN

Acidity is a useful biomarker for the targeting of metabolically active-cells in tumors. pH Low Insertion Peptides (pHLIPs) sense the pH at the surfaces of tumor cells and can facilitate intracellular delivery of cell-permeable and cell-impermeable cargo molecules. In this study we have shown the targeting of malignant lesions in human bladders by fluorescent pHLIP agents, intracellular delivery of amanitin toxin by pHLIP for the inhibition of urothelial cancer cell proliferation, and enhanced potency of pHLIP-amanitin for cancer cells with 17p loss, a mutation frequently present in urothelial cancers. Twenty-eight ex-vivo bladder specimens, from patients undergoing robotic assisted laparoscopic radical cystectomy for bladder cancer, were treated via intravesical incubation for 15-60 minutes with pHLIP conjugated to indocyanine green (ICG) or IR-800 near infrared fluorescent (NIRF) dyes at concentrations of 4-8 µM. White light cystoscopy identified 47/58 (81%) and NIRF pHLIP cystoscopy identified 57/58 (98.3%) of malignant lesions of different subtypes and stages selected for histopathological processing. pHLIP NIRF imaging improved diagnosis by 17.3% (p < 0.05). All carcinoma-in-situ cases missed by white light cystoscopy were targeted by pHLIP agents and were diagnosed by NIRF imaging. We also investigated the interactions of pHLIP-amanitin with urothelial cancer cells of different grades. pHLIP-amanitin produced concentration- and pH-dependent inhibition of the proliferation of urothelial cancer cells treated for 2 hrs at concentrations up to 4 µM. A 3-4x enhanced cytotoxicity of pHLIP-amanitin was observed for cells with a 17p loss after 2 hrs of treatment at pH6. Potentially, pHLIP technology may improve the management of urothelial cancers, including imaging of malignant lesions using pHLIP-ICG for diagnosis and surgery, and the use of pHLIP-amanitin for treatment of superficial bladder cancers via intravesical instillation.

16.
Front Oncol ; 12: 985446, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36419902

RESUMEN

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK-rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers.

17.
Life (Basel) ; 12(12)2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36556350

RESUMEN

(1) Background: Retinal vascular imaging plays an essential role in diagnosing and managing chronic diseases such as diabetic retinopathy, sickle cell retinopathy, and systemic hypertension. Previously, we have shown that individuals with pulmonary arterial hypertension (PAH), a rare disorder, exhibit unique retinal vascular changes as seen using fluorescein angiography (FA) and that these changes correlate with PAH severity. This study aimed to determine if color fundus (CF) imaging could garner identical retinal information as previously seen using FA images in individuals with PAH. (2) Methods: VESGEN, computer software which provides detailed vascular patterns, was used to compare manual segmentations of FA to CF imaging in PAH subjects (n = 9) followed by deep learning (DL) processing of CF imaging to increase the speed of analysis and facilitate a noninvasive clinical translation. (3) Results: When manual segmentation of FA and CF images were compared using VESGEN analysis, both showed identical tortuosity and vessel area density measures. This remained true even when separating images based on arterial trees only. However, this was not observed with microvessels. DL segmentation when compared to manual segmentation of CF images showed similarities in vascular structure as defined by fractal dimension. Similarities were lost for tortuosity and vessel area density when comparing manual CF imaging to DL imaging. (4) Conclusions: Noninvasive imaging such as CF can be used with VESGEN to provide an accurate and safe assessment of retinal vascular changes in individuals with PAH. In addition to providing insight into possible future clinical translational use.

18.
AJR Am J Roentgenol ; 196(1): 77-86, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21178050

RESUMEN

OBJECTIVE: The right ventricle is often overlooked on chest and even cardiac MDCT studies. This article will review the normal anatomy of the right ventricle on MDCT and the signs of its functional alterations. CONCLUSION: MDCT signs of right ventricular dysfunction should be known and checked in relevant cases, such as pulmonary embolism in particular, and in any disease that affects both the structure and function of the lungs in general.


Asunto(s)
Tomografía Computarizada por Rayos X/métodos , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/fisiopatología , Función Ventricular Derecha/fisiología , Diagnóstico por Imagen , Electrocardiografía , Humanos , Interpretación de Imagen Radiográfica Asistida por Computador
19.
J Belg Soc Radiol ; 105(1): 23, 2021 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-33977221

RESUMEN

Subgaleal lipoma is a benign tumor of adipose tissue. It should be suspected when a semi-spherical avascular mass with well-defined margins, iso- or hyperechoic in most cases, with thin internal echogenic lines parallel to the long axis of the tumor, is observed between the galea aponeurosis and periosteum of the cranial bone. We report a series of cases of three patients who underwent surgical lesion excision and whose histopathological examination findings confirmed the diagnosis of lipoma. MAIN TEACHING POINT: The presence of long continuous echogenic lines within a lens-shaped soft tissue mass located beneath the galea aponeurosis may suggest the diagnosis of subgaleal lipoma.

20.
Clin Nucl Med ; 46(1): 38-39, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33156042

RESUMEN

Myelolipoma is a rare mesenchymal tumor consisting of adipose tissue and hematopoietic cells. Found usually in the adrenal region, however, few cases have been reported in extra-adrenal regions, most frequently in the presacral region. It is important to recognize such tumor, as it can attain massive size and causes pressure symptoms, and needs to be differentiated from malignant tumors, including liposarcomas. Although CT and MRI can suggest a diagnosis of myelolipoma, these are not conclusive. The hematopoietic cells are enhanced by a Tc-albumin nanocolloid scintigraphy and help to distinguish myolipoma from other entities.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Mielolipoma/diagnóstico por imagen , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Cintigrafía
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