Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities.

BACKGROUND: Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted glycoprotein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. RESULTS: We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV-MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. CONCLUSIONS: As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.

Lactadherin immunoblockade in small extracellular vesicles inhibits sEV-mediated increase of pro-metastatic capacities

BACKGROUND: Tumor-derived small extracellular vesicles (sEVs) can promote tumorigenic and metastatic capacities in less aggressive recipient cells mainly through the biomolecules in their cargo. However, despite recent advances, the specific molecules orchestrating these changes are not completely defined. Lactadherin is a secreted 0protein typically found in the milk fat globule membrane. Its overexpression has been associated with increased tumorigenesis and metastasis in breast cancer (BC) and other tumors. However, neither its presence in sEVs secreted by BC cells, nor its role in sEV-mediated intercellular communication have been described. The present study focused on the role of lactadherin-containing sEVs from metastatic MDA-MB-231 triple-negative BC (TNBC) cells (sEV-MDA231) in the promotion of pro-metastatic capacities in non-tumorigenic and non-metastatic recipient cells in vitro, as well as their pro-metastatic role in a murine model of peritoneal carcinomatosis. RESULTS: We show that lactadherin is present in sEVs secreted by BC cells and it is higher in sEV-MDA231 compared with the other BC cell-secreted sEVs measured through ELISA. Incubation of non-metastatic recipient cells with sEV- MDA231 increases their migration and, to some extent, their tumoroid formation capacity but not their anchorage-independent growth. Remarkably, lactadherin blockade in sEV-MDA231 results in a significant decrease of those sEV-mediated changes in vitro. Similarly, intraperitoneally treatment of mice with MDA-MB-231 BC cells and sEV-MDA231 greatly increase the formation of malignant ascites and tumor micronodules, effects that were significantly inhibited when lactadherin was previously blocked in those sEV-MDA231. CONCLUSIONS: As to our knowledge, our study provides the first evidence on the role of lactadherin in metastatic BC cell-secreted sEVs as promoter of: (i) metastatic capacities in less aggressive recipient cells, and ii) the formation of malignant ascites and metastatic tumor nodules. These results increase our understanding on the role of lactadherin in sEVs as promoter of metastatic capacities which can be used as a therapeutic option for BC and other malignancies.

[Acute respiratory failure immediately following surgery for morbid obesity]. / Insuficiencia respiratoria aguda en el postoperatorio inmediato de cirugía por obesidad mórbida.

Patients with sleep apnea-hypopnea syndrome have a higher probability of presenting more postoperative complications, yet early treatment with continuous positive airway pressure can prevent them. We report the case of a patient who underwent surgery for morbid obesity and who developed acute respiratory failure in the immediate postoperative period, requiring readmission to the recovery unit. The patient's condition progressed favorably following treatment with bilevel positive airway pressure. It was subsequently confirmed that the patient suffered from sleep apnea-hypopnea syndrome.

[Miliary dissemination with pulmonary involvement secondary to intravesical immunotherapy with Calmette-Guérin bacillus]. / Diseminación miliar con afectación pulmonar secundaria a inmunoterapia intravesical con bacilo de Calmette-Guérin.

We describe the case of a 67-years-old man who underwent transurethral resection and immunotherapy with Calmette-Guérin bacillus solution (CGB) for superficial transitional carcinoma of the bladder. After a series of intravesical irrigations with CGB, the patient developed fever, asthenia and persistent anorexia and was hospitalized. After testing he was diagnosed of miliary tuberculosis due to CGB and died in spite of tuberculostatic therapy. Hematogenous dissemination, a rare but serious complication of vesical irrigation with CGB, is thought to be more common than previously suspected. It should be suspected in all patients receiving CGB when a compatible clinical picture presents. An understanding of this complication and early establishment of specific treatment is the only wat to improve prognosis.

[Nocardia farcinica pneumoniae in chronic obstructive pulmonary disease patient]. / Neumonía por Nocardia farcinica en paciente con EPOC.

Nocardia farcinica is an infrequent infection that usually appears in patients with predisposing conditions, especially in immunosuppressed patients, although it has also been found in healthy individuals. Its importance as a new pathogen has been recognized only in recent years. Mainly, it affects the lung, indistinguishable from other types of pneumonia in the clinical and radiological characteristics. The main reason for detection is therapeutic failure.

[Pulmonary diffusion of carbon monoxide in patients with mitral stenosis]. / Estudio de la difusión pulmonar de monóxido de carbono en enfermos con estenosis mitral.

OBJECTIVE: The aim of our work has been the study of CO diffusion capacity in mitral valve stenosis patients. METHOD: We have studied 15 control subjects and 15 patients with mitral valve stenosis. We performed spirometry study and CO pulmonary diffusion tests (DLCO) by single breath method to determine two components: pulmonary capillary blood volume (Vc) and membrane diffusion factor (Dm). In addition, in mitral valve stenosis patients we performed a ecocardiography-doppler study. RESULTS: The mitral valve stenosis group had higher values of DLCO and Vc and a lower ratio of Dm/Vc than the control group. There is a negative correlation between Vc and the mitral valve area (r = -0.63; p = 0.037). We do not find any another correlation between the rest of ecocardiography doppler parameters and lung function test variables that we have measured. We have not found any differences between both groups in Dm. CONCLUSIONS: Mitral valve stenosis patients present a increase of CO pulmonary diffusion capacity and pulmonary capillary blood volume without changes in membrane diffusion factor.

Association of chronic obstructive pulmonary disease and obstructive sleep apnea consequences.

Obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD) are two diseases that often coexist within an individual. This coexistence is known as overlap syndrome and is the result of chance rather than a pathophysiological link. Although there are claims of a very high incidence of OSAS in COPD patients, recent studies report that it is similar to the general population. Overlap patients present sleep-disordered breathing associated to upper and lower airway obstruction and a reduction in respiratory drive. These patients present unique characteristics, which set them apart from either COPD or OSAS patients. COPD and OSAS are independent risk factors for cardiovascular events and their coexistence in overlap syndrome probably increases this risk. The mechanisms underlying cardiovascular risk are still unclear, but may involve systemic inflammation, endothelial dysfunction, and tonic elevation of sympathetic neural activity. The treatment of choice for overlap syndrome in stable patients is CPAP with supplemental oxygen for correction of upper airway obstructive episodes and hypoxemia during sleep.

[Pleural cholesterol: a useful determination]. / Colesterol pleural: una determinación útil.

The difference between exudates and transudates is the first question a clinician must solve when facing a pleural effusion. A great number of parameters have been tried without a definite efficacy of any of them. Cholesterol is an easy, useful determination for distinguishing exudates from transudates. In our series of 86 patients a cholesterol value of 50 mg/dl allowed us to correctly classify 94.2% of effusions. The ratio between pleural fluid cholesterol/serum cholesterol was more efficient because it permitted to correctly classify 97.7% of effusions, in one of those major groups which constitute the binomial exudate/transudate.

[Choroidal metastases as the form of presentation of 2 bronchiolo-alveolar carcinomas]. / Metástasis coroideas como forma de presentación de dos carcinomas bronquioloalveolares.

We report here two cases presenting with visual symptoms secondary to choroidal metastases, without any other remarkable systemic symptom. After an exhaustive investigation in both patients the diagnosis was obtained of bronchoalveolar carcinoma as primary tumor responsible for such lesions. Bronchoalveolar carcinoma is a type of pulmonary adenocarcinoma which rarely begins with clinical symptoms attributable to metastases and even rarer of choroidal location. The presence of such choroidal lesions are usually associated with visual clinical symptoms and they are a diagnostic challenge when manifested as the presenting symptoms. Therapy is directed to the primary tumor usually associated with palliative radiotherapy of choroidal metastases. Their presence implies a poor survival rate.