Acute colonic pseudo-obstruction in polytrauma patients.

Background: Acute colonic pseudo-obstruction (ACPO) is characterized by severe colonic distension without mechanical obstruction. It has an uncertain pathogenesis and poses diagnostic challenges. This study aimed to explore risk factors and clinical outcomes of ACPO in polytrauma patients and contribute information to the limited literature on this condition.

Unlocking Translational Potential: Conditionally Reprogrammed Cells in Advancing Breast Cancer Research.

Preclinical in vitro models play an important role in studying cancer cell biology and facilitating translational research, especially in the identification of drug targets and drug discovery studies. This is particularly relevant in breast cancer, where the global burden of disease is quite high based on prevalence and a relatively high rate of lethality. Predictive tools to select patients who will be responsive to invasive or morbid therapies (radiotherapy, chemotherapy, immunotherapy, and/or surgery) are relatively lacking.

Personalized neoantigen cancer vaccines: An analysis of the clinical and commercial potential of ongoing development programs.

Neoantigen cancer vaccines harbor promise as next-generation immuno-oncology therapies, whereby cancer vaccines are tailored to the patient's tumor antigen and represent the future of personalized cancer therapy. While several biotech companies have ongoing development programs, little has been published about the true commercial potential of these innovative therapies and the challenges these products will face upon regulatory approval. In this paper, we provide an overview of neoantigen cancer vaccine development programs and discuss the commercial environment these therapies will face upon launch.

Propagated Circulating Tumor Cells Uncover the Potential Role of NFκB, EMT, and TGFβ Signaling Pathways and in Metastasis.

Circulating tumor cells (CTCs), a population of cancer cells that represent the seeds of metastatic nodules, are a promising model system for studying metastasis. However, the expansion of patient-derived CTCs ex vivo is challenging and dependent on the collection of high numbers of CTCs, which are ultra-rare. Here we report the development of a combined CTC and cultured CTC-derived xenograft (CDX) platform for expanding and studying patient-derived CTCs from metastatic colon, lung, and pancreatic cancers.

Overexpression of the telomerase holoenzyme induces EMT and tumorigenesis of HPV-immortalized keratinocytes.

Cervical cancer is the most frequent malignancy of the female genital tract and is associated with persistent infection of the uterine cervix with high-risk human papillomaviruses (HPV). The two HPV oncoproteins, E6 and E7, cooperatively immortalize cervical cells and are essential but insufficient for inducing tumorigenicity. During the progression of HPV-associated cervical dysplasia to carcinoma, the cellular telomerase reverse transcriptase (TERT) gene is activated and the TERC gene amplified.

Injury patterns, management and outcomes of retroperitoneal haemorrhage caused by lower intercostal arterial bleeding at a level-1 trauma centre: A 10-year retrospective review.

Objective: Haemorrhagic shock is a life-threatening complication of trauma, but remains a preventable cause of death. Early recognition of retroperitoneal haemorrhage (RPH) is crucial in preventing deleterious outcomes including mortality. Injury to the 9-11th intercostal arteries (i.

Ten-year incidence and treatment outcomes of closed degloving injuries (Morel-Lavallee lesions) in a level 1 trauma centre.

Introduction: Morel-Lavallée lesions (MLL), also referred to as closed degloving injuries, result from traumatic shearing forces with separation of the subcutaneous fat from the underlying fascia. The aim of this study was to determine the incidence and treatment of MLLs at a level 1 trauma centre.

Methods: Single-centre retrospective cross-sectional study of consecutive patients with an imaging diagnosis of a Morel-Lavallee lesion from 1/1/2010-31/12/2019.

Identifying drivers of breast cancer metastasis in progressively invasive subpopulations of zebrafish-xenografted MDA-MB-231.

Cancer metastasis is the primary cause of the high mortality rate among human cancers. Efforts to identify therapeutic agents targeting cancer metastasis frequently fail to demonstrate efficacy in clinical trials despite strong preclinical evidence. Until recently, most preclinical studies used mouse models to evaluate anti-metastatic agents.

Two conserved amino acids differentiate the biology of high-risk and low-risk HPV E5 proteins.

The high-risk alpha human papillomaviruses (HPVs) are responsible for 99% of cervical cancers. While the biological functions of the HPV E6 and E7 oncoproteins are well-characterized, the function of E5 has remained elusive. Here, we examined gene expression changes induced by E5 proteins from high-risk HPV-16 and low-risk HPV-6b in multiple pools of primary human keratinocytes.

AIB1 is a novel target of the high-risk HPV E6 protein and a biomarker of cervical cancer progression.

The high-risk human papillomaviruses (HPV-16, -18) are critical etiologic agents in human malignancy, most importantly in cervical cancer. These oncogenic viruses encode the E6 and E7 proteins that are uniformly retained and expressed in cervical cancers and required for maintenance of the tumorigenic phenotype. The E6 and E7 proteins were first identified as targeting the p53 and pRB tumor suppressor pathways, respectively, in host cells, thereby leading to disruption of cell cycle controls.

CLiP, catheter and line position dataset.

Correct catheter position is crucial to ensuring appropriate function of the catheter and avoid complications. This paper describes a dataset consisting of 50,612 image level and 17,999 manually labelled annotations from 30,083 chest radiographs from the publicly available NIH ChestXRay14 dataset with manually annotated and segmented endotracheal tubes (ETT), nasoenteric tubes (NET) and central venous catheters (CVCs).

Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis.

Circulating tumor cells (CTCs) are single cells or clusters of cells within the circulatory system of a cancer patient. While most CTCs will perish, a small proportion will proceed to colonize the metastatic niche. The clinical importance of CTCs was reaffirmed by the 2008 FDA approval of CellSearch, a platform that could extract EpCAM-positive, CD45-negative cells from whole blood samples.

A 10-year retrospective review of management and outcomes of pseudoaneurysms at a tertiary referral centre.

Introduction: Pseudoaneurysms are uncommon but potentially life-threatening. Treatment may involve a variety of interventions including observation, manual compression, ultrasound-guided thrombin injection and a variety of endovascular and surgical techniques. Current treatments are largely based on observational data and there is no consensus on management.

Efficient Propagation of Circulating Tumor Cells: A First Step for Probing Tumor Metastasis.

Circulating tumor cells (CTCs) represent a unique population of cells that can be used to investigate the mechanistic underpinnings of metastasis. Unfortunately, current technologies designed for the isolation and capture of CTCs are inefficient. Existing literature for in vitro CTC cultures report low (6-20%) success rates.

MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer.

Background: Recent studies have suggested that fatty acid oxidation (FAO) is a key metabolic pathway for the growth of triple negative breast cancers (TNBCs), particularly those that have high expression of MYC. However, the underlying mechanism by which MYC promotes FAO remains poorly understood.

Methods: We used a combination of metabolomics, transcriptomics, bioinformatics, and microscopy to elucidate a potential mechanism by which MYC regulates FAO in TNBC.

Conditional Reprogramming for Patient-Derived Cancer Models and Next-Generation Living Biobanks.

Traditional cancer models including cell lines and animal models have limited applications in both basic and clinical cancer research. Genomics-based precision oncology only help 2-20% patients with solid cancer. Functional diagnostics and patient-derived cancer models are needed for precision cancer biology.

High-throughput screening identifies candidate drugs for the treatment of recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a benign neoplasm of the larynx caused mainly by human papillomavirus type 6 or 11 and its standard treatment involves repeated surgical debulking of the laryngeal tumors. However, significant morbidity and occasional mortality due to multiple recurrences occur. Conditional reprogramming (CR) was used to establish a HPV-6 positive culture from an RRP patient, named GUMC-403.

Murine neuroblastoma cell lines developed by conditional reprogramming preserve heterogeneous phenotypes observed in vivo.

Neuroblastoma (NB) is a pediatric tumor of the peripheral nervous system. Treatment of the disease represents an unsolved clinical problem, as survival of patients with aggressive form of NB remains below 50%. Despite recent identification of numerous potential therapeutic targets, clinical trials validating them are challenging due to the rarity of the disease and its high patient-to-patient heterogeneity.

Fidelity of a PDX-CR model for bladder cancer.

Patient-derived xenografts (PDXs) are widely recognised as a more physiologically relevant preclinical model than standard cell lines, but are expensive and low throughput, have low engraftment rate and take a long time to develop. Our newly developed conditional reprogramming (CR) technology addresses many PDX drawbacks, but lacks many in vivo factors. Here we determined whether PDXs and CRCs of the same cancer origin maintain the biological fidelity and complement each for translational research and drug development.

Safety and clinical activity of PD-L1 blockade in patients with aggressive recurrent respiratory papillomatosis.

Background: Recurrent respiratory papillomatosis (RRP) is a human papillomavirus (HPV)-driven disorder that causes substantial morbidity and can lead to fatal distal airway obstruction and post-obstructive pneumonias. Patients require frequent surgical debridement of disease, and no approved systemic adjuvant therapies exist.

Methods: A phase II study was conducted to investigate the clinical activity and safety of programmed death-ligand 1 (PD-L1) blockade with avelumab in patients with RRP.

Long-term expansion of primary equine keratinocytes that maintain the ability to differentiate into stratified epidermis.

Background: Skin injuries in horses frequently lead to chronic wounds that lack a keratinocyte cover essential for healing. The limited proliferation of equine keratinocytes using current protocols has limited their use for regenerative medicine. Previously, equine induced pluripotent stem cells (eiPSCs) have been produced, and eiPSCs could be differentiated into equine keratinocytes suitable for stem cell-based skin constructs.

Δ133p53α, a natural p53 isoform, contributes to conditional reprogramming and long-term proliferation of primary epithelial cells.

We previously developed the technique of conditional reprogramming (CR), which allows primary epithelial cells from fresh or cryopreserved specimens to be propagated long-term in vitro, while maintaining their genetic stability and differentiation potential. This method requires a combination of irradiated fibroblast feeder cells and a Rho-associated kinase (ROCK) inhibitor. In the present study, we demonstrate increased levels of full-length p53 and its natural isoform, Δ133p53α, in conditionally reprogrammed epithelial cells from primary prostate, foreskin, ectocervical, and mammary tissues.

Patient-derived conditionally reprogrammed cells maintain intra-tumor genetic heterogeneity.

Preclinical in vitro models provide an essential tool to study cancer cell biology as well as aid in translational research, including drug target identification and drug discovery efforts. For any model to be clinically relevant, it needs to recapitulate the biology and cell heterogeneity of the primary tumor. We recently developed and described a conditional reprogramming (CR) cell technology that addresses many of these needs and avoids the deficiencies of most current cancer cell lines, which are usually clonal in origin.