The synergistic mechanisms of propofol with cisplatin or doxorubicin in human ovarian cancer cells.

BACKGROUND: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. METHODS: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. RESULTS: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. CONCLUSION: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.

Factors affecting the expression and stability of full-length and truncated SRSF3 proteins in human cancer cells.

Alternative splicing plays a crucial role in increasing the diversity of mRNAs expressed in the genome. Serine/arginine-rich splicing factor 3 (SRSF3) is responsible for regulating the alternative splicing of its own mRNA and ensuring that its expression is balanced to maintain homeostasis. Moreover, the exon skipping of SRSF3 leads to the production of a truncated protein instead of a frameshift mutation that generates a premature termination codon (PTC). However, the precise regulatory mechanism involved in the splicing of SRSF3 remains unclear. In this study, we first established a platform for coexpressing full-length SRSF3 (SRSF3-FL) and SRSF3-PTC and further identified a specific antibody against the SRSF3-FL and truncated SRSF3 (SRSF3-TR) proteins. Next, we found that exogenously overexpressing SRSF3-FL or SRSF3-PTC failed to reverse the effects of digoxin, caffeine, or both in combination on this molecule and its targets. Endoplasmic reticulum-related pathways, transcription factors, and chemicals such as palmitic acid and phosphate were found to be involved in the regulation of SRSF3 expression. The downregulation of SRSF3-FL by palmitic acid and phosphate was mediated via different regulatory mechanisms in HeLa cells. In summary, we provide new insights into the altered expression of the SRSF3-FL and SRSF3-TR proteins for the identification of the functions of SRSF3 in cells.

Antitumorigenic Effect of Tramadol and Synergistic Effect With Doxorubicin in Human Breast Cancer Cells.

BACKGROUND: Breast cancer in women is one of the leading causes of cancer mortality worldwide, and curative therapy is the main focus of clinical treatment. Anesthetic-analgesic techniques might alter stress responses and immunity and thereby influence outcomes in cancer patients. This study investigated the effect of tramadol on breast cancer progression and metastasis. METHODS: The effects of tramadol on two different subtypes of human breast adenocarcinoma cell lines, MDA-MB-231 and MCF-7, were studied with regard to cell growth, migration, colony formation and invasion and normoxic or hypoxic microenvironment for the expression of hypoxia-inducible factor-1α, reactive oxygen species, epithelial-mesenchymal transition related and cyclin-related proteins. The co-administration of tramadol and doxorubicin was studied to determine whether the effective doxorubicin dose might be reduced in combination with tramadol. RESULTS: The results showed that tramadol inhibited cell growth at concentrations more than 0.5 and more than 1.0 mg/mL in MDA-MB-231 and MCF-7 cells, respectively. Additionally, cell migration, colony formation and invasion were inhibited in a dose-dependent manner by tramadol in both cell lines. The combination of tramadol and doxorubicin induced synergistic effects in MDA-MD-231 cells and, with specific dosage combinations in MCF-7 cells. CONCLUSIONS: Tramadol may regulate epithelial-mesenchymal transition and possess cytotoxic effects in breast cancer cells. Tramadol inhibits the progression of breast cancer cells and might be a candidate for combination therapy, especially for triple-negative breast cancer, and is a promising treatment strategy for breast cancer.

Midterm results of vascular ring connector in open surgery for aortic dissection.

OBJECTIVES: This study observed midterm results of vascular ring connectors in surgery for aortic dissection. METHODS: Vascular ring connectors were used as stents in vascular grafts to achieve quick, sutureless anastomoses. Tapes were used to secure ringed vascular grafts from outside the aorta. RESULTS: From November 2007 to February 2011, 113 consecutive patients with aortic dissection, except 3 in preoperative profound shock, underwent open surgery. All underwent aortic reconstruction with vascular grafts and vascular ring connectors: ascending aorta in 29, descending thoracic aorta in 20, distal hemiarch plus descending thoracic aorta in 22, total arch in 14, ascending aorta plus total arch in 12, total arch plus descending thoracic aorta in 7, ascending aorta plus arch plus descending thoracic aorta in 8, and thoracoabdominal aorta in 1. Concomitant operations were 19 Bentall procedures, 14 coronary bypasses, 2 mitral valve replacements, 1 aortic valve replacement, and 1 heart transplant. We used sternotomy to repair 77% of type B dissections, 83% with elephant trunks. Time to extubation was 9.0 ± 6.2 hours. Average blood loss was 345 ± 195 mL. Half the patients needed no blood transfusion. In-hospital mortality was 5.3%; late mortality was 2.7%. CONCLUSIONS: Use of vascular ring connectors in surgical repair for aortic dissection might reduce risks and improve early and midterm results. With addition of elephant trunk, most type B dissections could be repaired through sternotomy. With the improved surgical results, we can suggest open repair for most uncomplicated type B dissections; however, more long-term follow-up is needed.

Successful intraoperative identification of an anomalous origin of the left coronary artery from the pulmonary artery using real time three-dimensional transesophageal echocardiography.

Anomalous origin of the left coronary artery (LCA) from the pulmonary artery (ALCAPA) is a rare congenital defect that presents only infrequently in adults. An adult diagnosed with ALCAPA, heart failure, and mitral regurgitation underwent surgical ligation of the anomalous origin of the LCA from the pulmonary artery (PA) and coronary artery bypass grafting (CABG). The anomalous origin in the PA and proximal segment of the left anterior descending artery (LAD) was successfully delineated via real time, three-dimensional transesophageal echocardiography during surgery. This modality allows for fast assessment and novel views of complex cardiac abnormalities and can aid in perioperative monitoring.

Emergent bedside real-time three-dimensional transesophageal echocardiography in a patient with cardiac arrest following a caesarean section.

Post-caesarean pulmonary embolism (PE) is associated with significant peri-operative morbidity and mortality. This report describes a case of sudden cardiac arrest 2 days post-caesarean due to massive PE diagnosed via bedside transesophageal echocardiography (TEE). Recognition of the PE at the bifurcation of the right and left pulmonary arteries was achieved by real-time three-dimensional TEE, but not two-dimensional TEE. Extracorporeal membrane oxygenation was immediately established and emergent pulmonary thromboembolectomy was performed. The patient was discharged without residual deficits on Day 22 of hospitalization.

Live three-dimensional transesophageal echocardiography in an unusual case of aorto-left ventricular tunnel with a large interventricular septal aneurysm.

Aorto-left ventricular tunnel (ALVT) is a rare congenital malformation. We report an unusual case of ALVT with a large interventricular septal aneurysm causing severe aortic regurgitation and left ventricular outflow obstruction diagnosed with real time three-dimensional transesophageal echocardiography (3D TEE). Real time 3D TEE allows for assessment and novel views of complex cardiac abnormalities and can aid in perioperative monitoring.

The routine use of live three-dimensional transesophageal echocardiography in mitral valve surgery: clinical experience.

BACKGROUND: Perioperative monitoring of mitral valve (MV) anatomy, function, and pathology is essential for surgical management of different MV disease. AIMS: To overcome the several potential pitfalls of two-dimensional transesophageal echocardiography (2D TEE) and offline 3D TEE. METHODS: Live 3D TEE was used to assess 73 patients (44 men and 29 women) with Carpentier type II MV regurgitation undergoing MV surgery perioperatively. RESULTS: The isolated segment most frequently involved was A2/P2, but A1or P1 rarely was involved in an isolated lesion or combined lesions. The agreement between 3D TEE finding and surgery was 88% (64/73). In nine patients, the live 3D TEE images revealed more segments or scallops with prolapse than the surgeon noted intraoperatively. CONCLUSIONS: Live 3D TEE allows more sensitivity and was feasible identification of prolapse or flail of individual segments of MV leaflets during surgery. We conclude that live 3D TEE should be regarded as an important adjunct to the standard 2D TEE examination in making decisions about MV surgery.

Live/Real time three-dimensional transthoracic echocardiographic assessment of pericardial disease.

We studied 19 patients with pericardial disease using two-dimensional and three-dimensional transthorathic echocardiography (2DTTE and 3DTTE, respectively) in order to determine whether 3DTTE provides incremental value on top of 2DTTE in the evaluation of these patients. With 3DTTE a more comprehensive assessment of pericardial effusion can be made and both the parietal and visceral layers of the pericardium can be visualized en face and examined for pathologies and fibrin deposits. In our series of patients, 3DTTE was superior to 2DTTE in uncovering mass lesions involving the pericardium such as tuberculous granulomas and metastatic disease. Furthermore, it provided a better assessment of the nature of pericardial lesions, such as pericardial and mediastinal hematomas, pericardial cysts, and metastatic disease to the pericardium by sequential cropping of the 3D data sets and visualizing the interior of the lesions in a manner not possible with 2DTTE. It was also valuable in determining the extent of pericardial calcification in pericardial constriction and in measuring the size of pericardial masses. These preliminary results suggest the superiority of 3DTTE over 2DTTE in the evaluation of pericardial diseases and that it provides incremental knowledge to the echocardiographer.

A new vascular ring connector in surgery for aortic dissection.

OBJECTIVE: To improve the surgical results of aortic dissection, we used a novel vascular ring connector for anastomosis. METHODS: The vascular ring connector is a titanic ring used as a stent in the vascular graft to achieve a quick, blood-sealed, and sutureless anastomosis. From November 2007 to December 2008, 19 consecutive patients (age range 36-77 years; 16 male and 3 female) with aortic dissection underwent open surgery. All patients received aortic reconstruction with vascular grafts (including 5 cases of arch replacement). The combined procedures were 5 Bentall and 4 coronary artery bypass graft operations. RESULTS: There were no significant blood leaks from the anastomotic sites. The time required for each anastomosis was 1 to 2 minutes. All patients were discharged uneventfully and are still doing well after a follow-up period of 1 to 12 months. CONCLUSION: The vascular ring connector may improve the early surgical results of aortic dissection by reducing both the time for anastomosis and the risk of bleeding and may be an alternative technique for aortic reconstruction. Its usefulness in the routine treatment of aortic dissection warrants further evaluation.

High-output heart failure resulting from an obscure traumatic arteriovenous fistula.

Traumatic arteriovenous fistula (AVF) is not an uncommon disorder, but late discovery and the presentation of high-output heart failure is very rare. This patient did not know that he had traumatic AVF after a gunshot injury in the left thigh 14 years ago. The major presentation of the AVF was signs of heart failure. We performed surgical repair after making the diagnosis. The patient recovered with an uneventful course. This report stresses the importance of history-taking and physical examination in making the diagnosis of traumatic AVF.

Long-term survival and prognostic implications after coronary artery bypass grafting in Chinese patients with coronary artery disease.

OBJECTIVES: This hospital-based study was conducted to determine the survival rates of patients after coronary artery bypass grafting (CABG) surgery and the associated prognostic factors related to all-cause mortality during a 7-year follow-up in Taiwan. METHODS AND RESULTS: Between January 1997 and December 2003, the medical records of 1877 patients who underwent primary, isolated CABG surgery were studied. The Kaplan-Meier method was used to estimate survival. Multiple Cox regression was used to investigate the independence of prognostic factors associated with all-cause mortality. Of the 1877 patients who underwent CABG surgery, 192 expired during the 7-year study period. The overall patient survival rate was 85.96% (95% CI: 83.74-88.16). Using multiple Cox regression analysis, in addition to female gender, older age at surgery, pulmonary oedema, longer ischaemic time, longer cardiopulmonary bypass time, and poorer postoperative left ventricular ejection fraction were significant factors associated with all-cause mortality for both men and women. Associated prognostic factors varied by gender. For men, smoking (RR = 2.82, 95% CI: 1.06-4.16), respiratory failure (RR = 6.88, 95% CI: 3.29-14.40) and cardiogenic shock (RR = 4.04, 95% CI: 2.13-7.67) were significantly related to all-cause mortality, but not for women. Sepsis (RR = 8.97,95% CI: 1.19-19.81) and ICU stay (RR = 1.03,95% CI: 1.01-1.05) were significantly related to all-cause mortality among female patients only. CONCLUSIONS: Several gender-related differences were noted pertaining to all-cause mortality and the relationships between smoking, sepsis, respiratory failure, cardiogenic shock, and ICU stay.

Cardiopulmonary resuscitation in prone position: a simplified method for outpatients.

BACKGROUND: The efficacy of cardiopulmonary resuscitation (CPR) is vital for saving lives of victims with sudden cardiac arrest. In 1960, Kuowenhoven and colleagues proposed the method that has become standard for CPR. Despite vast input of resources for public education and training of this procedure, its success rate outside hospitals remains poor to dismal. During CPR, restoration of respiration is as important as circulation. But opening the airway and giving effective mouth-to-mouth respiration is difficult for lay people to learn. Furthermore, most bystanders are reluctant to do mouth-to-mouth respiration because of the risk of infection. Therefore, the general population needs a more simplified CPR method for outpatients. The practice of CPR in the prone position, first proposed by McNeil in 1989, has not been adopted, despite the fact that it meets the desirable requirements of ideal resuscitation: simultaneous restoration of circulation and respiration with a very simple maneuver. METHODS: Part 1 (circulation test): Eleven patients who expired in the intensive care unit (ICU), with arterial lines attached, received standard pre-cordial cardiac massage, and the generated blood pressure (BP) was recorded. They were then turned to the prone position, with the head turned to one side. We compressed the patient's thoracic spine with the same force used in standard CPR (rhythm of approximately 60 per minute each time when the back bounces back), and the BP was also recorded. Part 2 (ventilation test): Ten healthy volunteers (5 doctors and 5 nurses) were enlisted for respiratory assessment during compression on the back. With the nose clipped and spontaneous breathing held, the volunteer's exhaled tidal volume upon compression was measured with a spirometer. RESULTS: Standard external cardiac massage of the cadavers generated BPs of 55 +/- 20/13 +/- 7 mmHg; however, external compression on the back of the cadavers generated higher BP of 79 +/- 20/17 +/- 10 mmHg (p = 0.028, Wilcoxon signed-rank analysis). External compression on the back of the volunteers generated mean tidal volumes of 399 +/- 110 mL. CONCLUSION: Our study revealed that prone CPR provides good respiratory and circulatory support at the same time. It is easy to perform and it may be a good alternative way for bystanders to perform CPR in public surroundings. We recommend that more investigators do further studies on this topic.