Interaction between HER2 and ATM predicts poor survival in bladder cancer patients.

Human Epidermal Growth Factor Receptor 2 (HER2) overexpression is considered one of the interesting prognostic biomarkers in bladder cancer. However, the mechanism of bladder cancer development in relation to HER2 status remains to be elucidated. In this study, we investigated HER2-Ataxia telangiectasia mutated (ATM) kinase interaction and their impact on patient survival and cancer aggressiveness. Using the Cancer Genome Atlas (TCGA) cohorts, we demonstrated that ATM expression (protein/mRNA) is increased in HER2 deficient compared with proficient HER2 patients. This finding was then validated using the Gene Expression Omnibus database (GEO). Correlation analysis (using low expression vs high expression as a discriminator) revealed a significant association of ATM low and HER2 high status with several clinicopathological variables such as high tumour grade, late disease stage and tumour shape. Kaplan-Meier survival analysis indicated that ATM low and HER2 high is a powerful prognosticator of both overall survival (OS) and disease-free survival (DFS). Furthermore, using bioinformatics and protein/protein interaction analyses, we identified 66 putative overlapping proteins with direct link between HER2 and ATM most of which are functionally involved in transcription regulation, apoptotic process and cell proliferation. Interestingly, the results showed that these proteins are strongly linked with PI3K-Akt pathway, p53 pathway and microRNAs in cancer. Altogether, our data pinpoint an important biological role of the interconnection between HER2 and ATM. The latter appear to be an independent prognostic biomarker and may serve as targets to develop novel combination therapies to improve the outcome of patients with bladder cancer.

Recruiting Immunity for the Fight against Colorectal Cancer: Current Status and Challenges.

Cancer immunotherapies have changed the landscape of cancer management and improved the standard treatment protocols used in multiple tumors. This has led to significant improvements in progression-free survival and overall survival rates. In this review article, we provide an insight into the major immunotherapeutic methods that are currently under investigation for colorectal cancer (CRC) and their clinical implementations. We emphasize therapies that are based on monoclonal antibodies (mAbs) and adoptive cell therapy, their mechanisms of action, their advantages, and their potential in combination therapy. We also highlight the clinical trials that have demonstrated both the therapeutic efficacy and the toxicities associated with each method. In addition, we summarize emerging targets that are now being evaluated as potential interventions for CRC. Finally, we discuss current challenges and future direction for the cancer immunotherapy field.

Preparing the Bone Tissue Regeneration Ground by Exosomes: From Diagnosis to Therapy.

Bone tissue engineering employs acellular scaffolds or scaffolds, along with cells and growth factors, to provide the mechanical support needed, as well as serve as a delivery vehicle for bioactive molecules to the injury sites. As tissue engineering continues to evolve, it has integrated two emerging fields: stem cells and nanotechnology. A paracrine factor that is found to be responsible for the major regenerative effect in stem cell transplantation is an extracellular vesicle called an 'exosome'. Recent advances in nanotechnology have allowed the 'exosome' to be distinguished from other extracellular vesicles and be polymerized into a well-defined concept. Scientists are now investigating exosome uses in clinical applications. For bone-related diseases, exosomes are being explored as biomarkers for different bone pathologies. They are also being explored as a therapeutic agent where progenitor cell-derived exosomes are used to regenerate damaged bone tissue. In addition, exosomes are being tested as immune modulators for bone tissue inflammation, and finally as a delivery vehicle for therapeutic agents. This review discusses recently published literature on the clinical utilization of exosomes in bone-related applications and the correlated advantages. A particular focus will be placed on the potential utilization of regenerative cell-derived exosomes as a natural biomaterial for tissue regeneration.

Hidden regulators: the emerging roles of lncRNAs in brain development and disease.

Long non-coding RNAs (lncRNAs) have emerged as critical players in brain development and disease. These non-coding transcripts, which once considered as "transcriptional junk," are now known for their regulatory roles in gene expression. In brain development, lncRNAs participate in many processes, including neurogenesis, neuronal differentiation, and synaptogenesis. They employ their effect through a wide variety of transcriptional and post-transcriptional regulatory mechanisms through interactions with chromatin modifiers, transcription factors, and other regulatory molecules. Dysregulation of lncRNAs has been associated with certain brain diseases, including Alzheimer's disease, Parkinson's disease, cancer, and neurodevelopmental disorders. Altered expression and function of specific lncRNAs have been implicated with disrupted neuronal connectivity, impaired synaptic plasticity, and aberrant gene expression pattern, highlighting the functional importance of this subclass of brain-enriched RNAs. Moreover, lncRNAs have been identified as potential biomarkers and therapeutic targets for neurological diseases. Here, we give a comprehensive review of the existing knowledge of lncRNAs. Our aim is to provide a better understanding of the diversity of lncRNA structure and functions in brain development and disease. This holds promise for unravelling the complexity of neurodevelopmental and neurodegenerative disorders, paving the way for the development of novel biomarkers and therapeutic targets for improved diagnosis and treatment.

Homologous recombination mRNAs (RAD21, RAD50 and BARD1) have a potentially poor prognostic role in ERBB2-low bladder cancer patients.

Human epidermal growth factor receptor 2 (HER2/ERBB2) factor is known to be implicated in many malignancies and the potential of it as a prognostic biomarker was reported years ago. Molecular subtypes of HER2/ERBB2 negative and positive with distinct clinical outcomes have been identified in recent years; however, it is still under investigation for bladder cancer. This study evaluates the biological and prognostic significance of RAD21, RAD50 and BARD1 (homologous recombination biomarkers) mRNA levels with ERBB2 low and high expression to explore their impact on bladder cancer patient survival and cancer aggressiveness. The expression of ERBB2, RAD21, RAD50 and BARD1 mRNA levels was assessed in The Cancer Genome Atlas (TCGA) bladder cancer dataset along with four validation cohorts. Outcome analysis was evaluated using disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analysis were used to evaluate the relationship between RAD21, RAD50, BARD1 and ERBB2 expression and clinicopathological variables. A significant increase in mRNA expression levels of RAD21, RAD50 and BARD1 was noticed in ERBB2-low patients compared to ERBB2-high patients. This overexpression of the homologous recombination repair transcripts was associated with poor outcome in ERBB2-low tumors, not in ERBB2-high tumors. Furthermore, the combined expression of high RAD21/RAD50, high RAD21/BARD1 or high RAD50/BARD1 were significantly associated with worse DFS and a better outcome for those with low co-expression in the ERBB2-low cohort. High expression of either RAD21/RAD50 or RAD21/BARD1 in ERBB2-low cohort associated with higher chance of metastasis. In addition, gene expression of BARD1 alone or in combination with RAD50 acted as an independent prognostic factor for worst survival. The data presented in this study reveal a connection between RAD21, RAD50, BARD1 and ERBB2 and patient survival. Importantly, it provided novel findings and potential prognostic markers, particularly in ERBB2-low bladder cancer.

The impact of the COVID-19 pandemic on rehabilitation services provided for cochlear implant recipients in Saudi Arabia.

OBJECTIVE: This study examines the impact of the COVID-19 pandemic on cochlear implantation (CI) recipients in Saudi Arabia. The impact was measured using the results of an online survey that investigated challenges related to access to re/habilitation and programming services, increased dependence on virtual interaction, and emotional impact. METHODS: The cross-sectional online survey reached 353 pediatric and adult CI recipients between April 21st and May 3rd 2020, during the first weeks of implementing the lockdown strategy and the transitioning to virtual settings. RESULTS: It was revealed that overall access to aural re/habilitation was considerably affected during the pandemic, and that the impact of this disruption was significantly greater for pediatric recipients than for adults. On the other hand, overall access to programming services was not affected. Results also revealed that CI recipients' performance at school or work was negatively impacted by the transition to a virtual communication. In addition, participants noticed a decline in their auditory performance, language skills, and speech understanding. They also registered feelings of anxiety, social isolation, and fear related to sudden changes in their CI function. Finally, the study revealed a gap between CI clinical/non-clinical support provided during the pandemic and the expectations of CI recipients. CONCLUSION: Collectively, outcomes from this study highlight the importance of shifting towards a more patient -centered model that offers empowerment and self-advocacy. In addition, the outcomes also emphasize the importance of developing and adapting emergency protocols. This will ensure continuation of services provided to CI recipients during scenario disasters like a pandemic.Key messagesPediatric aural re/habilitation was subjected to a significantly greater interruption, compared to adult aural re/habilitation, duringthe COVID-19 shutdown.Cochlear Implant (CI) recipients expressed feelings of anxiety, social isolation, and fear. These feelings were related to sudden changes in their CI functioning, caused by interruption of support services during the pandemic.Patient -centered model can offer emergency protocols that ensure a smooth continuation of cochlear implant-related re/habilitation and services during disaster scenarios such as the COVID-19 pandemic.

The Impact of COVID-19 Infection on Patients with Chronic Diseases Admitted to ICU: a Cohort Retrospective Study.

The coronavirus disease (COVID-19) infection is causing significant morbidity and mortality rates worldwide. A comprehensive investigation of the disease characteristics, especially among vulnerable disease groups, could help better manage the disease and reduce the pathogen's effect. This retrospective study examined the impact of COVID-19 infection on three groups of patients with chronic diseases. We investigated the clinical characteristics and outcomes of 535 COVID-19 patients with cardiovascular diseases (CVD), chronic kidney diseases (CKD), and Cancer that were admitted to the Intensive Care Unit (ICU). Of the total cases, 433 patients (80.93%) were discharged from the ICU, and 102 patients (19.06%) were declared dead. Patients' symptoms, their clinical laboratory findings, number and type of medications, length of ICU stay, and outcome were collected and analyzed. Most COVID-19 patients included in our study were associated with other comorbidities such as diabetes mellitus, hypertension, and heart disease and failure. Upon ICU admission, the main COVID-19-related symptoms in CVD, CKD, and cancer patients were cough (55.73, 50.42, and 50.5%, respectively), Shortness of Breath (SOB) (59.38, 43.1, and 43.7%, respectively), and fever (41.15%, 48.75%, and 28.2%, respectively). In terms of lab findings, D-dimer, LDH, and inflammatory markers, in particular, were outside the normal range. Treatment options for patients with COVID-19 in ICU were mainly antibiotics, synthetic glucocorticoids, and Low Molecular Weight Heparin (LMWH). Furthermore, CKD patients had a longer ICU stay (13.93 ± 15.87 days) which illustrates the poorer outcome in this group of patients compared with the others. In conclusion, our results highlighted the significant risk factors among COVID-19 patients within the three groups. This can guide physicians in prioritizing ICU admission and help in the management of critically ill patients with COVID-19.

Nanotechnology: A revolutionary approach to prevent breast cancer recurrence.

Breast cancer is the most prevalent malignancy in women worldwide and one of the deadliest after lung cancer. Currently, standard treatment approaches for breast cancers are surgery accompanied by chemotherapy or radiotherapy. Cancer local recurrence after mastectomy is commonly considered as being a poor prognostic predictor. There have been advancements in the procedures utilized for breast reconstruction following mastectomy, much as there have been advancements in the early diagnosis and treatment of breast cancer. For the last decade, developing nanotechnology applications for cancer therapies has had much focus. The benefits granted by nanotechnologies via enhancing biological processes and promoting better biomaterial compatibility, as well as generating functionalized tissues, transpire exciting possibilities. Modified nanomedicine may introduce tremendous improvements to the fields of breast cancer recurrence through implants. It can modify the surfaces of implants to optimize tissue growth, thus minimizing inflammation and unsatisfactory results. Here we discuss new nanotechnology advancements and incorporate them into breast reconstruction surgeries following mastectomy or lumpectomy. In addtion, we repurpose old technologies, like growth factor therapies using nanotechnology for more efficient delivery.

Stem cells and the pursuit of youth, a tale of limitless possibilities and commercial fraud.

This article examines the hype generated around the term "stem cell", and the capitalization of the stem cell craze by the cosmetic industry. It started by introducing product lines containing active ingredients derived from plant stem cells. Then, evolved to using own cells for skin regeneration and hair loss treatment, and allogenic cells for the manufacturing of stem cell-derived products. This article also discusses the missing links for safe and reliable stem cell applications in cosmetics, and why local regulatory bodies, members of the industry and consumers must all work together to stop the illegitimate use of the "stem cell" good name in unsafe or fraudulent commercial practices.

Nanogenomics and Artificial Intelligence: A Dynamic Duo for the Fight Against Breast Cancer.

Application software is utilized to aid in the diagnosis of breast cancer. Yet, recent advances in artificial intelligence (AI) are addressing challenges related to the detection, classification, and monitoring of different types of tumors. AI can apply deep learning algorithms to perform automated analysis on mammographic or histologic examinations. Large volume of data generated by digitalized mammogram or whole-slide images can be interoperated through advanced machine learning. This enables fast evaluation of every tissue patch on an image, resulting in a quicker more sensitivity, and more reproducible diagnoses compared to human performance. On the other hand, cancer cell-exosomes which are extracellular vesicles released by cancer cells into the blood circulation, are being explored as cancer biomarker. Recent studies on cancer-exosome-content revealed that the encapsulated miRNA and other biomolecules are indicative of tumor sub-type, possible metastasis and prognosis. Thus, theoretically, through nanogenomicas, a profile of each breast tumor sub-type, estrogen receptor status, and potential metastasis site can be constructed. Then, a laboratory instrument, fitted with an AI program, can be used to diagnose suspected patients by matching their sera miRNA and biomolecules composition with the available template profiles. In this paper, we discuss the advantages of establishing a nanogenomics-AI-based breast cancer diagnostic approach, compared to the gold standard radiology or histology based approaches that are currently being adapted to AI. Also, we discuss the advantages of building the diagnostic and prognostic biomolecular profiles for breast cancers based on the exosome encapsulated content, rather than the free circulating miRNA and other biomolecules.

Cancer of Unknown Primary Site: Real Entity or Misdiagnosed Disease?

Metastasis is a late event in the progression of any tumour. However, invasive cancers are occasionally detected in the form of metastatic lesions without a clearly detectable primary tumour. Cancer of unknown primary site (CUP) is defined as a confirmed metastatic tumour, with unknown primary tumour site, despite the standardized diagnostic approach that includes clinical history, routine laboratory tests, and complete physical examination. Due to the lack of basic research on its primary causes, CUP is appropriately termed an 'orphan' cancer. Nevertheless, CUP accounts for 2-5% of diagnosed malignancies. To date, it is unclear whether CUP is an entity with primary dormancy as its hallmark or an entity with genetic abnormalities that cause it to manifest as a primary metastatic disease. In this review, we discuss different aspects of CUP, including its current diagnostic methods, angiogenesis effectors, relationship with cancer stem cells and current treatments.

Establishment and characterization of fetal and maternal mesenchymal stem/stromal cell lines from the human term placenta.

INTRODUCTION: Human placental mesenchymal stem/stromal cells (MSC) are an attractive source of MSC with great therapeutic potential. However, primary MSC are difficult to study in vitro due to their limited lifespan and patient-to-patient variation. METHODS: Fetal and maternal MSC were prepared from cells of the chorionic and basal plates of the placenta, respectively. Fetal and maternal MSC were transduced with the human telomerase reverse transcriptase (hTERT). Conventional stem cell assays assessed the MSC characteristics of the cell lines. Functional assays for cell proliferation, cell migration and ability to form colonies in soft agar were used to assess the whether transduced cells retained properties of primary MSC. RESULTS: Fetal chorionic and maternal MSC were successfully transduced with hTERT to create the cell lines CMSC29 and DMSC23 respectively. The lifespans of CMSC29 and DMSC23 were extended in cell culture. Both cell lines retained important MSC characteristics including cell surface marker expression and multipotent differentiation potential. Neither of the cell lines was tumourigenic in vitro. Gene expression differences were observed between CMSC29 and DMSC23 cells and their corresponding parent, primary MSC. Both cell lines show similar migration potential to their corresponding primary, parent MSC. DISCUSSION: The data show that transduced MSC retained important functional properties of the primary MSC. There were gene expression and functional differences between cell lines CMSC29 and DMSC23 that reflect their different tissue microenvironments of the parent, primary MSC. CMSC29 and DMSC23 cell lines could be useful tools for optimisation and functional studies of MSC.