Novel molecular imaging techniques have the potential to significantly enhance the diagnostic and therapeutic approaches for cancer treatment. For solid tumors in particular, novel molecular ...enhancers for imaging modalities such as US, CT, MRI and PET may facilitate earlier and more accurate diagnosis and staging which are prerequisites for successful surgical therapy. Enzymatically activatable “smart” molecular MRI probes seem particularly promising because of their potential to image tumors before and after surgical removal without re-administration of the probe to evaluate completeness of surgical resection. Furthermore, the use of “smart” MR probes as part of screening programs may enable detection of small tumors throughout the body in at-risk patient populations. Dual labeling of molecular MR probes with fluorescent dyes can add real time intraoperative guidance facilitating complete tumor resection and preservation of important structures. A truly theranostic approach with the further addition of therapeutic agents to the molecular probe for adjuvant therapy is conceivable for the future.
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A glowing new era in cancer surgery may be dawning. Using fluorescently labelled markers, surgical molecular navigation means that tumours and nerves can be displayed in real time intra-operatively ...in contrasting pseudocolours, which allows more complete tumour resection while preserving important structures. These advances can potentially cause a paradigm shift in cancer surgery, improving patient outcome and decreasing overall health-care costs.
As the field of international business has matured, there have been shifts in the core unit of analysis. First, there was analysis at country level, using national statistics on trade and foreign ...direct investment (FDI). Next, the focus shifted to the multinational enterprise (MNE) and the parent's firm specific advantages (FSAs). Eventually the MNE was analysed as a network and the subsidiary became a unit of analysis. We untangle the last fifty years of international business theory using a classification by these three units of analysis. This is the country-specific advantage (CSA) and firm-specific advantage (FSA) matrix. Will this integrative framework continue to be useful in the future? We demonstrate that this is likely as the CSA/FSA matrix permits integration of potentially useful alternative units of analysis, including the broad region of the triad. Looking forward, we develop a new framework, visualized in two matrices, to show how distance really matters and how FSAs function in international business. Key to this are the concepts of compounded distance and resource recombination barriers facing MNEs when operating across national borders.
Stem cell-based therapy for human diseases Hoang, Duc M.; Pham, Phuong T.; Bach, Trung Q. ...
Signal transduction and targeted therapy,
08/2022, Letnik:
7, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Abstract
Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human ...pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.
A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates ...for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998-2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998-2002 and 2008-2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes.
We examine the internal equity financing of the multinational subsidiary which retains and reinvests its own earnings. Internal equity financing is a type of firmspecific advantage (FSA) along with ...other traditional FSAs in innovation, research and development, brands and management skills. It also reflects subsidiary-level financial management decision-making. Here we test the contributions of internal equity financing and subsidiary-level financial management decision-making to subsidiary performance, using original survey data from British multinational subsidiaries in six emerging countries in the South East Asia region. Our first finding is that internal equity financing acts as an FSA to improve subsidiary performance. Our second finding is that over 90% of financing sources (including capital investment by the parent firms) in the British subsidiaries come from internal funding. Our third finding is that subsidiary-level financial management decision-making has a statistically significant positive impact on subsidiary performance. Our findings advance the theoretical, empirical and managerial analysis of subsidiary performance in emerging economies.
The literature on the relationship between the degree of multinationality (M) and performance (P) in the context of multinational enterprises (MNEs) has attracted a large volume of research in the ...past 50 years. Yet, the theoretical foundations and the empirical conclusions concerning the nature of M-P relationship vary greatly, thus call for a critical review and assessment. We examine 135 articles in 39 leading scholarly journals and classic books published during the period 1960-2015. We use an inductive approach and a qualitative content analysis methodology for our comprehensive and critical review of the literature. We incorporate international business, finance, and accounting perspectives in our analysis. We review the conceptualization and measurement of M, P, the findings on M-P relationships, methodologies, and geographic focus. We identify six key inconsistencies in the existing research, which cause ambiguity in the relevant findings. We make eight recommendations for future research to address these inconsistencies. Thus, our study contributes to the central debate in this research field.
High-resolution imaging of molecules intrinsically involved in malignancy and metastasis would be of great value for clinical detection and staging of tumors. We now report in vivo visualization of ...matrix metalloproteinase activities by MRI and fluorescence of dendrimeric nanoparticles coated with activatable cell penetrating peptides (ACPPs), labeled with Cy5, gadolinium, or both. Uptake of such nanoparticles in tumors is 4- to 15-fold higher than for unconjugated ACPPs. With fluorescent molecules, we are able to detect residual tumor and metastases as small as 200 μm, which can be resected under fluorescence guidance and analyzed histopathologically with fluorescence microscopy. We show that uptake via this mechanism is comparable to that of other near infrared protease sensors, with the added advantage that the approach is translatable to MRI. Once activated, the Gd-labeled nanoparticles deposit high levels (30-50 μM) of Gd in tumor parenchyma with even higher amounts deposited in regions of infiltrative tumor, resulting in useful T₁ contrast lasting several days after injection. These results should improve MRI-guided clinical staging, presurgical planning, and intraoperative fluorescence-guided surgery. The approach may be generalizable to deliver radiation-sensitizing and chemotherapeutic agents.
We build upon the theoretical framework of firm-specific advantages (FSAs) and country-specific advantages (CSAs) to examine the determinants of the local responsiveness strategy of foreign ...subsidiaries of Chinese multinational enterprises (MNEs). Specifically, we focus on relational assets (R-assets is seen as a unique type of Chinese MNEs’ FSA), the market-seeking foreign direct investment (FDI) and host country institutional environments as drivers of the local responsiveness strategy. We empirically test our hypotheses using a survey data of the foreign subsidiaries of Chinese firms together with other secondary data sources. We find that both Chinese MNEs’ R-assets and the market-seeking oriented FDI are positively related to subsidiaries’ local responsiveness strategy in accommodating local customer needs, government policies, market conditions, and competitive intensity. Moreover, the impact of R-assets in motivating the local responsiveness strategy is stronger in a host country with a weak and underdeveloped institutional environment. While the evidence confirms the existence of the R-assets in influencing subsidiary level strategy, it also casts doubt on such relations-based firm resources in advanced host countries with highly developed institutions.
The completeness of tumor removal during surgery is dependent on the surgeon's ability to differentiate tumor from normal tissue using subjective criteria that are not easily quantifiable. A way to ...objectively assess tumor margins during surgery in patients would be of great value. We have developed a method to visualize tumors during surgery using activatable cell-penetrating peptides (ACPPs), in which the fluorescently labeled, polycationic cell-penetrating peptide (CPP) is coupled via a cleavable linker to a neutralizing peptide. Upon exposure to proteases characteristic of tumor tissue, the linker is cleaved, dissociating the inhibitory peptide and allowing the CPP to bind to and enter tumor cells. In mice, xenografts stably transfected with green fluorescent protein show colocalization with the Cy5-labeled ACPPs. In the same mouse models, Cy5-labeled free ACPPs and ACPPs conjugated to dendrimers (ACPPDs) delineate the margin between tumor and adjacent tissue, resulting in improved precision of tumor resection. Surgery guided by ACPPD resulted in fewer residual cancer cells left in the animal after surgery as measured by Alu PCR. A single injection of ACPPD dually labeled with Cy5 and gadolinium chelates enabled preoperative whole-body tumor detection by MRI, intraoperative guidance by real-time fluorescence, intraoperative histological analysis of margin status by fluorescence, and postoperative MRI tumor quantification. Animals whose tumors were resected with ACPPD guidance had better long-term tumor-free survival and overall survival than animals whose tumors were resected with traditional bright-field illumination only.
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