Horizontal Transfer of Malignant Traits and the Involvement of Extracellular Vesicles in Metastasis.

Metastases are responsible for the vast majority of cancer deaths, yet most therapeutic efforts have focused on targeting and interrupting tumor growth rather than impairing the metastatic process. Traditionally, cancer metastasis is attributed to the dissemination of neoplastic cells from the primary tumor to distant organs through blood and lymphatic circulation. A thorough understanding of the metastatic process is essential to develop new therapeutic strategies that improve cancer survival.

Itraconazole inhibits nuclear delivery of extracellular vesicle cargo by disrupting the entry of late endosomes into the nucleoplasmic reticulum.

Extracellular vesicles (EVs) are mediators of intercellular communication under both healthy and pathological conditions, including the induction of pro-metastatic traits, but it is not yet known how and where functional cargoes of EVs are delivered to their targets in host cell compartments. We have described that after endocytosis, EVs reach Rab7 late endosomes and a fraction of these enter the nucleoplasmic reticulum and transport EV biomaterials to the host cell nucleoplasm. Their entry therein and docking to outer nuclear membrane occur through a tripartite complex formed by the proteins VAP-A, ORP3 and Rab7 (VOR complex).

Oncosuppressor-Mutated Cell-Based Diagnostic Platform for Liquid Biopsy Diagnoses Benign Head and Neck Masses and Predicts Malignancy in Thyroid Nodules: Results from a Consecutive Cohort of Patients.

Background: We reported that a novel oncosuppressor-mutated cell (OMC)-based platform has the potential for early cancer detection in healthy individuals and for identification of cancer patients at risk of developing metachronous metastases.

Objective: Herein, we sought to determine the diagnostic accuracy of this novel OMC-based platform in a consecutive cohort of patients operated for suspicious head and neck masses.

Methods: OMCs (-deficient fibroblasts) were exposed to blood serum from patients with head and neck nodules before surgical removal.

Biomechanical characterization of a chronic type a dissected human aorta.

Aortic dissection is one of the most lethal cardiovascular diseases. A chronic Type A (Stanford) dissected aorta was retrieved for research from a 73-year-old male donor without diagnosed genetic disease. The aorta presented a dissection over the full length, and it reached a diameter of 7.

Colorectal cancer-derived extracellular vesicles induce transformation of fibroblasts into colon carcinoma cells.

Background: We reported that horizontal transfer of malignant traits to target cells is a potential pathway to explain cancer dissemination. Although these results were encouraging, they were never corroborated by data showing the molecular mechanisms responsible for the observed phenomenon.

Methods: In the present study, we exposed BRCA1-KO fibroblasts to extracellular vesicles (EVs) isolated from a colon cancer cell line (HT29) and from sera of patients with colorectal cancer.

Oncosuppressor-Mutated Cells as a Liquid Biopsy Test for Cancer-Screening.

We reported on the ability of immortalized or oncosuppressor-mutated cells (OMCs) to uptake circulating cancer-factors and give tumors when transplanted into mice. This led to the first biological based liquid biopsy test, which we called MATER-D platform. In the present study, we showed for the first time that a different type of OMCs (PTEN-deficient human epithelial MCF10A cells) turn malignant when exposed to cancer patient's sera, confirming the concept that different cells with diverse oncosuppressor mutations can uptake cancer factors and be used in biological based liquid biopsy tests.

Novel blood test to predict neoplastic activity in healthy patients and metastatic recurrence after primary tumor resection.

We reported that single oncosuppressor-mutated (SOM) cells turn malignant when exposed to cancer patients' sera. We tested the possibility to incorporate this discovery into a biological platform able to detect cancer in healthy individuals and to predict metastases after tumor resection. Blood was drawn prior to tumor resection and within a year after surgery.

Exosomes isolated from cancer patients' sera transfer malignant traits and confer the same phenotype of primary tumors to oncosuppressor-mutated cells.

Background: Horizontal transfer of malignant traits from the primary tumor to distant organs, through blood circulating factors, has recently become a thoroughly studied metastatic pathway to explain cancer dissemination. Recently, we reported that oncosuppressor gene-mutated human cells undergo malignant transformation when exposed to cancer patients' sera. We also observed that oncosuppressor mutated cells would show an increased uptake of cancer-derived exosomes and we suggested that oncosuppressor genes might protect the integrity of the cell genome by blocking integration of cancer-derived exosomes.

Transfer of malignant traits as opposed to migration of cells: A novel concept to explain metastatic disease.

Metastatic disease is believed to develop following dissemination of cells to target organs. Inability of this theory to effectively explain certain phenomena such as patterns of metastatic spread, late metastasis formation, different gene patterns between primary cancer and metastasis have brought forward the need for alternative models. Recent discoveries have strengthened the validity of theories supporting a humoral transfer of malignant traits as opposed to migration of malignant cells to explain metastatic disease in cancer patients.

Reprogramming Malignant Cancer Cells toward a Benign Phenotype following Exposure to Human Embryonic Stem Cell Microenvironment.

The embryonic microenvironment is well known to be non-permissive for tumor development because early developmental signals naturally suppress the expression of proto-oncogenes. In an analogous manner, mimicking an early embryonic environment during embryonic stem cell culture has been shown to suppress oncogenic phenotypes of cancer cells. Exosomes derived from human embryonic stem cells harbor substances that mirror the content of the cells of origin and have been reported to reprogram hematopoietic stem/progenitor cells via horizontal transfer of mRNA and proteins.

Transfer of malignant trait to BRCA1 deficient human fibroblasts following exposure to serum of cancer patients.

Background: It was reported that metastases might occur via transfer of biologically active blood circulating molecules from the primary tumor to distant organs rather than only migration of cancer cells. We showed in an earlier study that exposure of immortalized human embryonic kidney cells (HEK 293) to cancer patient sera, induce their transformation into undifferentiated cancers due to a horizontal transfer of malignant traits. In the present work, we tested the hypothesis that even other human cells as long as they are deficient for a single oncosuppressor gene might undergo malignant transformation when exposed to human cancer serum.

Prevention of perineal hernia after laparoscopic and robotic abdominoperineal resection: review with illustrative case series of internal hernia through pelvic mesh.

This review is intended to raise awareness of placing a pelvic mesh to prevent perineal hernias in cases of minimally invasive (MIS) abdominoperineal resections (APR) and, in doing so, causing internal hernias through the mesh. In this article, we review the published literature and present an illustrative series of 4 consecutive cases of early internal hernia through a pelvic mesh defect. These meshes were placed to prevent perineal hernias after laparoscopic or robotic APRs.

Transfer of malignant trait to immortalized human cells following exposure to human cancer serum.

Background: Human cancer cells can transfer signaling molecules to neighboring and distant cells predisposing them to malignant transformation. This process might contribute to tumor progression and invasion through delivery of oncogenes or inhibitors of tumor suppressor genes, derived from the primary tumor cells, to susceptible target cells. The oncogenic potential of human cancer serum has been described in immortalized mouse fibroblasts but has not been shown yet in human cells.

Total sacrectomy for recurrent rectal cancer - A case report featuring technical details and potential pitfalls.

Introduction: Total sacrectomy for recurrent rectal cancer is controversial. However, recent publications suggest encouraging outcomes with high sacral resections. We present the first case report describing technical aspects, potential pitfalls and treatment of complications associated with total sacrectomy performed as a treatment of recurrent rectal cancer.

Cerebrospinal fluid drainage to prevent paraplegia during thoracic and thoracoabdominal aortic aneurysm surgery: a systematic review and meta-analysis.

Objectives: We undertook a quantitative systematic review of randomized controlled trials (RCTs) and observational studies to determine the effectiveness of cerebrospinal fluid (CSF) drainage to prevent paraplegia in thoracic aneurysm (TA) and thoracoabdominal aortic aneurysm (TAAA) surgery.

Methods: We included RCTs and cohort studies that met the following criteria: elective or emergent aneurysm surgery involving the thoracic or thoracoabdominal aorta, documentation of postoperative neurologic deficits, and patient age older than 18 years. We excluded studies that reported results in 10 or fewer patients and duplicate publications.