We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antiapoptotic factors PED, cFLIP, Bcl-xL and Bcl-2. Furthermore, we provide evidence that exogenous IL-4 was able to upregulate the expression levels of these antiapoptotic proteins and potently stabilized the growth of normal epithelial cells rendering them apoptosis resistant. In conclusion, IL-4 acts as an autocrine survival factor in epithelial cells. Our results indicate that inhibition of IL-4/IL-4R signaling may serve as a novel treatment for epithelial cancers.
Colorectal cancer stem cells (CR-CSC) are responsible for the generation and maintenance of intestinal tumors and are highly resistant to conventional chemotherapeutic agents. Aurora-A, a serine-threonine kinase involved in mitosis regulation, plays multiple key functions in tumor initiation and progression. We found that Aurora-A is overexpressed in primary colorectal tumor cells, in the CR-CSC fraction, and in stem cell-derived differentiated cells, compared with normal colon tissue. Aurora-A expression was functionally linked to centrosome amplification in CR-CSC, as indicated by the decrease in cells with multiple centrosomes that followed Aurora-A silencing. Knockdown of Aurora-A resulted in growth inhibition of CR-CSC, alteration of cell cycle kinetics, and downregulation of the expression levels of antiapoptotic Bcl-2 family members, strongly sensitizing to chemotherapy-induced cell death. Moreover, Aurora-A silencing compromised the ability to form tumor xenografts in immunocompromised mice and reduced the migratory capacity of CR-CSC. Altogether, these results indicate that Aurora-A is essential for CR-CSC regeneration and resistance to cytotoxic stimuli and suggest that therapies directed against Aurora-A may effectively target the stem cell population in colorectal cancer.
The widespread use of imaging examinations has increased the detection of incidental adrenal lesions, which are mostly benign and non-functioning adenomas. The differentiation of a benign from a malignant adrenal mass can be crucial especially in oncology patients since it would greatly affect treatment and prognosis. In this setting, imaging plays a key role in the detection and characterization of adrenal lesions, with several imaging tools which can be employed by radiologists. A thorough knowledge of the imaging features of adrenal masses is essential to better characterize these lesions, avoiding a misinterpretation of imaging findings, which frequently overlap between benign and malignant conditions, thus helping clinicians and surgeons in the management of patients. The purpose of this paper is to provide an overview of the main imaging features of adrenal masses and tumor-like conditions recalling the strengths and weaknesses of imaging modalities commonly used in adrenal imaging.
Following the spread of the infection from the new SARS-CoV2 coronavirus in March 2020, several surgical societies have released their recommendations to manage the implications of the COVID-19 pandemic for the daily clinical practice. The recommendations on emergency surgery have fueled a debate among surgeons on an international level. We maintain that laparoscopic cholecystectomy remains the treatment of choice for acute cholecystitis, even in the COVID-19 era. Moreover, since laparoscopic cholecystectomy is not more likely to spread the COVID-19 infection than open cholecystectomy, it must be organized in such a way as to be carried out safely even in the present situation, to guarantee the patient with the best outcomes that minimally invasive surgery has shown to have.
Since it’s introduction, laparoscopic surgery represented a real revolution in clinical practice. The use of a new generation three-dimensional (3D) HD laparoscopic system can be considered a favorable “hybrid” made by combining two different elements: feasibility and diffusion of laparoscopy and improved quality of vision. In this study we report our clinical experience with use of three-dimensional (3D) HD vision system for laparoscopic surgery. Between 2013 and 2017 a prospective cohort study was conducted at the University Hospital of Palermo. We considered 163 patients underwent to laparoscopic three-dimensional (3D) HD surgery for various indications. This 3D-group was compared to a retrospective-prospective control group of patients who underwent the same surgical procedures. Considerating specific surgical procedures there is no significant difference in term of age and gender. The analysis of all the groups of diseases shows that the laparoscopic procedures performed with 3D technology have a shorter mean operative time than comparable 2D procedures when we consider surgery that require complex tasks. The use of 3D laparoscopic technology is an extraordinary innovation in clinical practice, but the instrumentation is still not widespread. Precisely for this reason the studies in literature are few and mainly limited to the evaluation of the surgical skills to the simulator. This study aims to evaluate the actual benefits of the 3D laparoscopic system integrating it in clinical practice. The three-dimensional view allows advanced performance in particular conditions, such as small and deep spaces and promotes performing complex surgical laparoscopic procedures.
Laparoscopic adrenalectomy offers better surgical outcomes than open adrenalectomy. Size criteria are, at the moment, the main subject discussed for the laparoscopic approach to adrenal tumors. In fact, size is an important variable in predicting malignancy. This experience and the results of literature suggest that laparoscopic approach is safe and feasible for adrenal masses larger than 6 cm with a longer operative time. In presence of local invasion or vascular infiltration laparoscopy is contraindicated.
The widespread use of abdominal imaging techniques has increased the detection of solid renal masses over the past years. Imaging plays a crucial role in the management and surveillance and in determining which lesions need treatment. The "classical angiomyolipoma" is the only benign solid renal mass that can be characterized with confidence by imaging through the detection of a fat-containing lesion without calcifications. There is a large overlap of imaging features between benign and malignant renal masses that often makes difficult a correct characterization of these lesions. In this review, we discuss the imaging features of the main solid renal masses that may suggest a likely benign diagnosis.
Laparoscopic cholecystectomy is a feasible and safe procedure in elderly patients and might be performed during the same hospitalization like definitive treatment of gallstone disease. The old age and subsequent comorbidity are the fundamental predictor of surgical outcomes. Elective treatment should be recommended when repeated gallstone symptoms have occurred in the elderly patient before the development of acute cholecystitis and related complications.
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