Cancer Subclones Derived from the Patient's Head and Neck Squamous Cell Carcinoma Tumor Stem Cells for the Screening of Personalized Antitumor Immunotherapy and Chemotherapy.

Studying on subclonal evolution of cancer stem cells can help illustrate how the immune system recognizes tumor cells, leading to subclonal treatment by immune-based therapies. Here, we discuss that cancer subclones derived from the patient's head and neck squamous cell carcinoma tumor stem cells can be used for the screening of personalized antitumor immunotherapy and chemotherapy, to maximize benefits and to minimize the adversary effects, toward personalized or precision medicine. We propose a "wait-and-watch" scheme for monitoring a lifetime cancer stem cell subclonal development evolved with local environments to cancer

Spatiotemporal switching signals for cancer stem cell activation in pediatric origins of adulthood cancer: Towards a watch-and-wait lifetime strategy for cancer treatment.

Pediatric origin of cancer stem cell hypothesis holds great promise and potential in adult cancer treatment, however; the road to innovation is full of obstacles as there are plenty of questions left unanswered. First, the key question is to characterize the nature of such stem cells (concept). Second, the quantitative imaging of pediatric stem cells should be implemented (technology). Conceptually, pediatric stem cell origins of adult cancer are based on the notion that plasticity in early life developmental programming evolves local environments to cancer. Technologically, such imaging in children is lacking as all imaging is designed for adult patients. We postulate that the need for quantitative imaging to measure space-time changes of plasticity in early life developmental programming in children may trigger research and development of the imaging technology. Such quantitative imaging of pediatric origin of adulthood cancer will help develop a spatiotemporal monitoring system to determine cancer initiation and progression. Clinical validation of such speculative hypothesis-that cancer originates in a pediatric environment-will help implement a wait-and-watch strategy for cancer treatment

Cancer Niche as a Garbage Disposal Machine: Implications of TCM-Mediated Balance of Body-Disease for Treatment of Cancer.

Cancer epidemic led to worldwide to search for a new "game changer" concept to govern cancer research and cancer treatment. Western medicine-based cancer research has been extending the impasse without resolution in sigh for improving survival of patients with solid malignant tumors in the last four decades due to heterogeneity in cancer tissues. Such a deadlock charts a course to learn lessons from the developing countries, directly or indirectly to complement the exhausted Western medicine. We propose a new concept of "Cancer niche as a garbage disposal machine" with implications of traditional Chinese medicine-mediated restoration of normal balance between body and disease to bring the fight against cancer under control

Implementation and Validation of the Roche Light Cycler 480 96-Well Plate Platform as a Real-Time PCR Assay for the Quantitative Detection of Cytomegalovirus (CMV) in Clinical Specimens Using the Luminex MultiCode ASRs System.

Allogenic stem-cell therapies benefit patients in the treatment of multiple diseases; however, the side effects of stem-cell therapies (SCT) derived from the concomitant use of immune suppression agents often include triggering infection diseases. Thus, analysis is required to improve the detection of pathogen infections in SCT. We develop a polymerase chain reaction (PCR)-based methodology for the qualitative real-time DNA detection of cytomegalovirus (CMV), with reference to herpes simplex virus types 1 (HSVI), Epstein-Barr virus (EBV), and varicella-zoster virus (VZV) in blood, urine, solid tissues, and cerebrospinal fluid. This real-time PCR of 96-well plate format provides a rapid framework as required by the Food and Drug Administration (FDA) for clinical settings, including the processing of specimens, reagent handling, special safety precautions, quality control criteria and analytical accuracy, precisely reportable range (analyst measurement range), reference range, limit of detection (LOD), analytical specificity established by interference study, and analyte stability. Specifically, we determined the reportable range (analyst measurement range) with the following criteria: CMV copies ≥200 copies/mL; report copy/mL value; CMV copies ≤199 copies/mL; report detected but below quantitative range; CMV copies = 0 with report <200 copies/mL. That is, with reference range, copy numbers (CN) per milliliter (mL) of the LOD were determined by standard curves that correlated Ct value and calibrated standard DNA panels. The three repeats determined that the measuring range was 1E2~1E6 copies/mL. The standard curves show the slopes were within the range -2.99 to -3.65 with R2 ≥ 0.98. High copy (HC) controls were within 0.17-0.18 log differences of DNA copy numbers; (2) low copy (LC) controls were within 0.17-0.18 log differences; (3) LOD was within 0.14-0.15 log differences. As such, we set up a fast, simple, inexpensive, sensitive, and reliable molecular approach for the qualitative detection of CMV pathogens. Conclusion: This real-time PCR of the 96-well plate format provides a rapid framework as required by the FDA for clinical settings

A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors

Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent stem cell population based on their capacity of targeting brain tumors. A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors is proposed to fill the gap in the current work flow of stem cell-based therapy. The organotypic slice platform has advantages of being mimic in vivo model, easier to manipulate to optimize parameters than in vivo models such as rodents and primates. This model serves as a framework to address the discrepancy between anticipated in vivo results and actual in vivo results, a critical barrier to timely progress in the field of the use of stem cells for the treatment of neurological disorders

The Differentiation Balance of Bone Marrow Mesenchymal Stem Cells Is Crucial to Hematopoiesis.

Bone marrow mesenchymal stem cells (BMSCs), the important component and regulator of bone marrow microenvironment, give rise to hematopoietic-supporting stromal cells and form hematopoietic niches for hematopoietic stem cells (HSCs). However, how BMSC differentiation affects hematopoiesis is poorly understood. In this review, we focus on the role of BMSC differentiation in hematopoiesis. We discussed the role of BMSCs and their progeny in hematopoiesis. We also examine the mechanisms that cause differentiation bias of BMSCs in stress conditions including aging, irradiation, and chemotherapy. Moreover, the differentiation balance of BMSCs is crucial to hematopoiesis. We highlight the negative effects of differentiation bias of BMSCs on hematopoietic recovery after bone marrow transplantation. Keeping the differentiation balance of BMSCs is critical for hematopoietic recovery. This review summarises current understanding about how BMSC differentiation affects hematopoiesis and its potential application in improving hematopoietic recovery after bone marrow transplantation

Breathing Signature as Vitality Score Index Created by Exercises of Qigong: Implications of Artificial Intelligence Tools Used in Traditional Chinese Medicine.

Rising concerns about the short- and long-term detrimental consequences of administration of conventional pharmacopeia are fueling the search for alternative, complementary, personalized, and comprehensive approaches to human healthcare. Qigong, a form of Traditional Chinese Medicine, represents a viable alternative approach. Here, we started with the practical, philosophical, and psychological background of Ki (in Japanese) or Qi (in Chinese) and their relationship to Qigong theory and clinical application. Noting the drawbacks of the current state of Qigong clinic, herein we propose that to manage the unique aspects of the Eastern 'non-linearity' and 'holistic' approach, it needs to be integrated with the Western "linearity" "one-direction" approach. This is done through developing the concepts of "Qigong breathing signatures," which can define our life breathing patterns associated with diseases using machine learning technology. We predict that this can be achieved by establishing an artificial intelligence (AI)-Medicine training camp of databases, which will integrate Qigong-like breathing patterns with different pathologies unique to individuals. Such an integrated connection will allow the AI-Medicine algorithm to identify breathing patterns and guide medical intervention. This unique view of potentially connecting Eastern Medicine and Western Technology can further add a novel insight to our current understanding of both Western and Eastern medicine, thereby establishing a vitality score index (VSI) that can predict the outcomes of lifestyle behaviors and medical conditions

Crif1 Promotes Osteoporosis in Mice after Radiation

Abstract Radiation induces rapid bone loss and enhances bone resorption and RANKL expression. RANKL provides the crucial signal to induce osteoclast differentiation and plays an important role in bone resorption. However, the mechanisms of radiation-induced osteoporosis are not fully understood. Here, we show that Crif1 expression increases in bone marrow cells after radiation. Conditional Crif1 deletion in bone marrow cells causes decreases in RANKL expression and the RANKL/OPG ratio, and relieves bone loss after radiation in mice. We further demonstrated in vitro that Crif1 promotes RANKL secretion via the cAMP/PKA pathway. Moreover, protein-protein docking screening identified five compounds as Crif1 inhibitors; these compounds dramatically suppressed RANKL secretion and CREB phosphorylation when cells were exposed to forskolin. This study enriches current knowledge of the pathogenesis of osteoporosis and provides insights into potential therapeutic strategies for osteoporosis treatment

Single-cell transcriptomes reveal the mechanism for a breast cancer prognostic gene panel.

The clinical benefits of the MammaPrint® signature for breast cancer is well documented; however, how these genes are related to cell cycle perturbation have not been well determined. Our single-cell transcriptome mapping (algorithm) provides details into the fine perturbation of all individual genes during a cell cycle, providing a view of the cell-cycle-phase specific landscape of any given human genes. Specifically, we identified that 38 out of the 70 (54%) MammaPrint® signature genes are perturbated to a specific phase of the cell cycle. The MammaPrint® signature panel derived its clinical prognosis power from measuring the cell cycle activity of specific breast cancer samples. Such cell cycle phase index of the MammaPrint® signature suggested that measurement of the cell cycle index from tumors could be developed into a prognosis tool for various types of cancer beyond breast cancer, potentially improving therapy through targeting a specific phase of the cell cycle of cancer cells

A Biological Global Positioning System: Considerations for Tracking Stem Cell Behaviors in the Whole Body

Many recent research studies have proposed stem cell therapy as a treatment for cancer, spinal cord injuries, brain damage, cardiovascular disease, and other conditions. Some of these experimental therapies have been tested in small animals and, in rare cases, in humans. Medical researchers anticipate extensive clinical applications of stem cell therapy in the future. The lack of basic knowledge concerning basic stem cell biology-survival, migration, differentiation, integration in a real time manner when transplanted into damaged CNS remains an absolute bottleneck for attempt to design stem cell therapies for CNS diseases. A major challenge to the development of clinical applied stem cell therapy in medical practice remains the lack of efficient stem cell tracking methods. As a result, the fate of the vast majority of stem cells transplanted in the human central nervous system (CNS), particularly in the detrimental effects, remains unknown. The paucity of knowledge concerning basic stem cell biology—survival, migration, differentiation, integration in real-time when transplanted into damaged CNS remains a bottleneck in the attempt to design stem cell therapies for CNS diseases. Even though excellent histological techniques remain as the gold standard, no good in vivo techniques are currently available to assess the transplanted graft for migration, differentiation, or survival. To address these issues, herein we propose strategies to investigate the lineage fate determination of derived human embryonic stem cells (hESC) transplanted in vivo into the CNS. Here, we describe a comprehensive biological Global Positioning System (bGPS) to track transplanted stem cells. But, first, we review, four currently used standard methods for tracking stem cells in vivo: magnetic resonance imaging (MRI), bioluminescence imaging (BLI), positron emission tomography (PET) imaging and fluorescence imaging (FLI) with quantum dots. We summarize these modalities and propose criteria that can be employed to rank the practical usefulness for specific applications. Based on the results of this review, we argue that additional qualities are still needed to advance these modalities toward clinical applications. We then discuss an ideal procedure for labeling and tracking stem cells in vivo, finally, we present a novel imaging system based on our experiments