Optimización de cultivos primarios de células de carcinoma renal de células claras como modelo “in vitro” para estudios metabólicos y determinantes de progresión neoplásica

El objetivo del presente estudio fue optimizar la implementación de cultivos primarios a partir de muestras de carcinoma renal de células claras (CRCC) para comprobar la conservación del fenotipo lipogénico contra cortes fijados del mismo origen. Se utilizaron muestras de pacientes con CRCC, evaluándose diversas metodologías y condiciones experimentales de digestión de muestras, adherencia y despegue celular, fenotipo lipogénico, potencial de clonación, proliferación y capacidad de migración. El mayor rendimiento y viabilidad celular se verificó mediante digestión con colagenasa. La adherencia inicial se logró a las 24 hs de incubación, utilizando placas plásticas de cultivo, recubiertas con colágeno comercial y gelatina 0,2% en la mayoría de las muestras analizadas (60% de los casos). Se obtuvieron monocapas, con potencial de migración, en un 40% de los casos, tras 5 ± 1 días de incubación. El promedio de subcultivos fue de 3 ± 1. Este estudio permitió estandarizar cultivos primarios de CRCC comprobándose la conservación de la fenotipia lipogénica, logrando de dicha manera una herramienta importante y útil para el estudio de la biología tumoral y el ensayo de nuevas terapéuticas

Development of a Novel Echocardiography Ramp Test for Speed Optimization and Diagnosis of Device Thrombosis in Continuous-Flow Left Ventricular Assist Devices The Columbia Ramp Study

ObjectivesThis study sought to develop a novel approach to optimizing continuous-flow left ventricular assist device (CF-LVAD) function and diagnosing device malfunctions.BackgroundIn CF-LVAD patients, the dynamic interaction of device speed, left and right ventricular decompression, and valve function can be assessed during an echocardiography-monitored speed ramp test.MethodsWe devised a unique ramp test protocol to be routinely used at the time of discharge for speed optimization and/or if device malfunction was suspected. The patient's left ventricular end-diastolic dimension, frequency of aortic valve opening, valvular insufficiency, blood pressure, and CF-LVAD parameters were recorded in increments of 400 rpm from 8,000 rpm to 12,000 rpm. The results of the speed designations were plotted, and linear function slopes for left ventricular end-diastolic dimension, pulsatility index, and power were calculated.ResultsFifty-two ramp tests for 39 patients were prospectively collected and analyzed. Twenty-eight ramp tests were performed for speed optimization, and speed was changed in 17 (61%) with a mean absolute value adjustment of 424 ± 211 rpm. Seventeen patients had ramp tests performed for suspected device thrombosis, and 10 tests were suspicious for device thrombosis; these patients were then treated with intensified anticoagulation and/or device exchange/emergent transplantation. Device thrombosis was confirmed in 8 of 10 cases at the time of emergent device exchange or transplantation. All patients with device thrombosis, but none of the remaining patients had a left ventricular end-diastolic dimension slope >−0.16.ConclusionsRamp tests facilitate optimal speed changes and device malfunction detection and may be used to monitor the effects of therapeutic interventions and need for surgical intervention in CF-LVAD patients

Mouse mammary tumor virus-like gene sequences are present in lung patient specimens

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like <it>env </it>gene sequences.</p> <p>Results</p> <p>The MMTV-like <it>env </it>gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number <ext-link ext-link-id="AY161347" ext-link-type="gen">AY161347</ext-link>. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the <it>env </it>sequences exhibited disruption of the reading frame due to mutations.</p> <p>Conclusion</p> <p>In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute inflamatory lung infiltrate specimens studied of a Mexican Population.</p

Telomerase and breast cancer

Current therapies for breast cancer include treatments that are toxic and often result in drug resistance. Telomerase, a cellular reverse transcriptase that maintains the ends of chromosomes (telomeres), is activated in the vast majority of breast cancers (over 90% of breast carcinomas) but not in normal adjacent tissues. Telomerase is thus an attractive target for both diagnosis and therapy because of its distinct pattern of expression. We address the use of telomerase in the diagnostics of breast pathology, as well as the use of telomerase inhibitors in the treatment and prevention of breast cancer

Mouse mammary tumor-like virus (MMTV) is present in human breast tissue before development of virally associated breast cancer

© 2017 The Author(s). Background: There is substantial evidence that a virus homologous to mouse mammary tumor virus (MMTV) may have a role in human breast cancer. The present study indicates that those who developed breast cancer associated with an MMTV-like virus had this virus in their non-cancerous breast tissues years before the cancer developed. Methods: Polymerase chain reaction (PCR) techniques and sequencing were used to identify MMTV-like envelope gene sequences (MMTV-like env sequences) in Australian benign breast biopsy specimens from women who several years later developed breast cancer. Murine contamination was excluded by stringent laboratory procedures, and the absence of intracisternal A particle sequences and mitochondrial cyclooxygenase sequences. Results: MMTV-like env sequences (also called HMTV sequences to denote their source) were found in 9 of 25 breast cancer specimens (36%). Among 25 non-cancerous breast biopsies of these same patients taken 1 to 11 years earlier, six contained MMTV-like sequences (24%). Five of the six were among the nine virally-associated breast cancers. In two pairs of specimens, benign and malignant, env sequences were 97% identical. Conclusions: The identification of MMTV (MMTV-like) sequences in breast tissues prior to the development of MMTV positive breast cancer fulfills a key criterion for a possible causal role for the MMTV-like virus in human breast cancer

Left Ventricular Assist Device Implantation in Hypertrophic and Restrictive Cardiomyopathy: A Systematic Review

Left ventricular assist device (LVAD) implantation in patients with advanced heart failure due to hypertrophic or restrictive cardiomyopathy (HCM/RCM) presents technical and physiologic challenges. We conducted a systematic review of observational studies to evaluate the utilization and clinical outcomes associated with LVAD implantation in patients with HCM/RCM and compared these to patients with dilated or ischemic cardiomyopathy (DCM/ICM). We searched MEDLINE, EMBASE, and Scopus from inception through May 2019 and included appropriate studies describing the use of an LVAD in patients with HCM/RCM. We identified six studies with a total of 2,766 patients with HCM/RCM and advanced heart failure, among whom 338 patients (12.2%) underwent LVAD implantation. In patients listed for transplant, the rate of LVAD implantation was significantly lower in patients with HCM/RCM compared to that in patients with DCM/ICM (4.4% vs. 18.2%, p \u3c 0.001). Adverse clinical outcomes were significantly higher in HCM/RCM than in DCM/ICM, including operative/short-term mortality (14.0% vs. 9.0%), right ventricular failure (50.0% vs. 21.0%), infection (15.5% vs. 11.2%), bleeding (40.2% vs. 12.5%), renal failure (15.0% vs. 5.1%), stroke (5.0% vs. 2.4%), and arrhythmias (18.0% vs. 7.7%) (all p values \u3c0.001)

Obesity and Outcomes Following Cardiogenic Shock Requiring Acute Mechanical Circulatory Support

BACKGROUND: The association of obesity on outcomes in patients with cardiogenic shock requiring acute mechanical circulatory support has not been thoroughly investigated. METHODS: We evaluated the National Readmission Database for adults with either acute myocardial infarction or heart failure complicated by cardiogenic shock requiring acute mechanical circulatory support between January 2016 and November 2017. Exposure was assessed using RESULTS: The survey-weighted sample included a total of 35 555 hospitalizations with a mean age of 65.4±0.2 years and 29.8% females. Obesity was associated with higher in-hospital mortality (no obesity, 26.4% [BMI, 20.0-29.9] versus class I obesity, 25.0% [BMI, 30.0-34.9] versus class II obesity, 28.7% [BMI, 35.0-39.9] versus class III obesity, 34.9% [BMI, ≥40]; CONCLUSIONS: Among adults with acute myocardial infarction or acute heart failure resulting in cardiogenic shock requiring acute mechanical circulatory support, younger adults with class II and class III obesity and older patients with class III obesity have a higher risk of in-hospital mortality compared with nonobese patients