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[Anatomical background of low back pain: variability and degeneration of the lumbar spinal canal and intervertebral disc].

The central and lateral lumbar canals constitute complex osteofibrous neurovascular tunnels, allowing movement and deformation of the spine … -individual variation [11], and are particularly susceptible for changes with aging [49]. Articular tropism and other left-right differences may influence their morphology. In the epidural compartments behind the vertebral bodies, a sagittal membrane may totally or partly connect the deeper layer of the posterior longitudinal ligament (PLL) with the poste …

High-Affinity DARPin Allows Targeting of MeV to Glioblastoma Multiforme in Combination with Protease Targeting without Loss of Potency.

Measles virus (MeV) is naturally cytolytic by extensive cell-to-cell fusion. Vaccine-derived MeV is toxic for cancer cells and is clinically tested as oncolytic virus. To combine the potential of MeV with enhanced safety, different targeting strategies have been described. We generated a receptor-targeted MeV by using receptor-blind viral attachment protein genetically fused to designed ankyrin repeat protein (DARPin) binding domains specific for the epidermal growth factor receptor (EGFR). To reduce on-target toxicity for EGFR+ healthy cells, we used an engineered viral fusion protein activat

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… To gain a higher specificity, the natural receptor tropism of H was ablated 9 and substituted by C-terminal fusion of a selected binding domain attaching to the tumor antigen of choice as a target receptor. 10 Resulting recombinant MeVs have a fully retargeted entry tropism solely determined by the targeting … Figure 4 Generation and Tropism of Dual-Targeted Viruses (A) Schematic representation of dual-targeted MeV genome with cloning sites used for exchange of the H and F gene cassette. …

Oncolytic Virus Therapy in a New Era of Immunotherapy, Enhanced by Combination with Existing Anticancer Therapies: Turn up the Heat!

Oncolytic viral therapy is a promising treatment for cancer, where 'cold' tumour cells can become 'hot' to the host immune system. However, with few FDA approved therapies, development of new strategies for more cancer types has been slow and relatively unsuccessful in recent years, Combination therapy has been successful for other types of cancer treatment, therefore, may be a viable alternative to improve the efficacy of oncolytic viral therapy which may reduce some of the adverse events of currently used monotherapies, oncolytic virus therapy and chemotherapy being mutually complimentary wi

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… The tropism of the virus can facilitate entry into specific tissues. 31 , 34 An OV infects tumour cells through the recognition of abnormal surface markers such as CD20 and endothelial growth factor receptors. … Matching target malignant tissue to appropriate viruses is an important element of research, enhancing the tropism of the tumour lysis. …

Gene therapy: principles, challenges and use in clinical practice.

INTRODUCTION: Gene therapy is an emerging topic in medicine. The first products have already been licensed in the European Union for the treatment of immune deficiency, spinal muscular atrophy, hemophilia, retinal dystrophy, a rare neurotransmitter disorder and some hematological cancers, while many more are being assessed in preclinical and clinical trials. OBJECTIVE: The purpose of this review is to provide an overview of the core principles of gene therapy along with information on challenges and risks. Benefits, adverse effects and potential risks are illustrated based on the examples of

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… If given intravenously, the vector will transduce the target cell depending on its tissue tropism. Once bound to the cell via receptors, the virus gets endocytosed. … Analysis of AAV serotypes 1–9 mediated gene expression and tropism in mice after systemic injection. Mol Ther. 2008;16(6):1073–80. 10.1038/mt.2008.76. 65. Castaman G, Matino D. Hemophilia A and B: molecular and clinical similarities and differences. …

Proximal Femur Megaprostheses in Orthopedic Oncology: Evaluation of a Standardized Post-operative Rehabilitation Protocol.

BackgroundReconstructions of the proximal femur after massive resections represent one of the main challenges in orthopedic oncology. Among the possible treatments, megaprostheses represent one of the most used and reliable reconstructive approaches. Although literature about their outcomes has flourished through the last decades, a consensus rehabilitative treatment is still far from being established.Materials and methodsWe evaluated the functional results of all our oncologic cases treated between 2016 and 2022 that could follow our standardized post-operative rehabilitative approach, consi

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… Sites for the reattachment of the gluteal insertion are present in the trochanteric region of the implant The maintenance of good muscular tone and tropism in the months and years that follow surgery might therefore play a pivotal role both in preventing implant dislocations and maximizing the functional … 30° | 0–30° | 0–60° | 0–60° (up to 0–90° in selected cases) Hip brace (time) | Full-time | Full-time | Full-time | Full time for at least 2 months and progressive removal Weight-bearing on operated leg | Toe-touch | Partial | Progressive partial | Full Restoration and maintenance of muscle tone and tropism …

Integrating oncolytic adenoviruses into combination cancer therapy: Mechanisms, advances and clinical outlook.

BACKGROUND: Cancer represents a major global public health issue, and recent research has focused on improving the efficacy of existing therapeutic approaches. In this context, oncolytic viruses have emerged as promising treatment options for advanced and treatment-resistant malignancies. Among them, adenoviruses are the most extensively studied due to their favourable safety profile, biological versatility and ease of genetic modification to enhance therapeutic performance. MAIN BODY: Combination-based strategies integrating virotherapy with chemotherapy, radiotherapy or immunotherapy have b

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… ONCOLYTIC ADS IN COMBINATION THERAPY: MECHANISMS, PRECLINICAL AND CLINICAL EVIDENCE Viral engineering strategies Over the years, oncolytic Ads have been modified for better tumour tropism, selectivity and anti‐tumour efficacy, changes that include capsid modifications, small deletions in the pivotal … and improve safety; insertion of hTERT, E2F‐1 and surviving promoters further enable tumour tropism by selective replication in cancer cells with altered molecular pathways. …

Oncolytic Viruses for Cancer Therapy in Dogs.

Cancer remains the leading cause of death in domestic dogs. Conventional therapeutic approaches, including surgery, chemotherapy, and radiotherapy, frequently fail to achieve sustained remission or stabilization. Oncolytic virotherapy, a rapidly advancing therapeutic modality in human oncology, is emerging as a novel strategy in veterinary medicine. This systematic review summarizes current knowledge on the application of oncolytic viruses (OVs) in canine cancer treatment, focusing on their mechanisms of action, safety profiles, and clinical efficacy. We evaluate diverse OV platforms, includin

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… Inactivation of J2R (encoding viral thymidine kinase) reduces VACV’s toxicity, while enhancing its tumor tropism. The I4L and F4L genes encode ribonucleotide reductase-like proteins, modifications that further increase tumor selectivity. … VSV demonstrates preferential tropism for human malignant cells [ 71 ]. The enhanced susceptibility of cancer cells to VSV infection, combined with facile genetic manipulation, renders VSV an attractive oncolytic candidate. …

The Emerging Role of Oncolytic Virotherapy in Glioblastoma Management.

Glioblastoma (GBM) is an aggressive and common form of central nervous system primary malignant tumor in adults. GBM accounts for about half of all gliomas. Despite maximal resection, radiotherapy, and temozolomide, median survival is still 12-15 months because of tumor heterogeneity, diffuse infiltration, and therapeutic resistance. Recurrence is nearly universal, underscoring the need for novel therapies. Oncolytic virotherapy demonstrates a promising strategy that combines direct tumor cell lysis with immune activation. Tumor-selective viruses replicate within malignant cells, induce cell d

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… This results in broad tissue tropism [ 68 ]. Virus exhibits selectivity for cells lacking an antiviral IFN response, which makes it precise to target tumor cells in various tissue types [ 54 ]. … HSV derivatives (G47Δ, G207) exhibit high payload capacity, neuronal tropism compatible with glial tumors, and a favorable safety record after neurovirulence gene deletions [ 25 ]. …

Вирусы и "Мозг-отношение к беде".

Неврологические расстройства, некоторые из которых связаны с вирусными инфекциями, растут из-за старения и увеличения численности населения. Несмотря на крепкую защиту центральной нервной системы, некоторые вирусы эволюционировали, чтобы пробить их, что часто приводит к ужасным последствиям. В этом обзоре мы рассказываем о различных способах проникновения различных вирусов в ЦНС и о последствиях таких вторжений. Последствия могут проявляться в виде острых заболеваний, таких, как энцефалит, менингит, или приводить к долгосрочным последствиям, таким, как нервно - мышечная дисфункция, как это име

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… The reasons for these differences in viral tropism are not fully understood, but herpesviruses always establish a second lifestyle in animals they infect, referred to as latency. … Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can exhibit ocular tropism, permissively infect, and therefore replicate in retinal cells in vitro [ 77 ]. …

Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions.

Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients' quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013.

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… First, certain cell types can enhance the tumor tropism of OVs. Second, these cells can protect OVs from neutralizing antibodies. … These new technologies can overcome neutralizing antibodies, evade liver tropism, enhance tumor targeting of OVs, and reduce innate and adaptive immune responses. …

Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice.

Over the past few decades, there has been growing interest in understanding the molecular mechanisms of cancer pathogenesis and progression, as it is still associated with high morbidity and mortality. Current management of large bone sarcomas typically includes the complex therapeutic approach of limb salvage or sacrifice combined with pre- and postoperative multidrug chemotherapy and/or radiotherapy, and is still associated with high recurrence rates. The development of cellular strategies against specific characteristics of tumour cells appears to be promising, as they can target cancer cel

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… Fig 2 Safety of use of MSCs in proximity to a tumour The unique characteristics of MSCs (self-renewal, differentiation, and tropism to the tumour site) raised expectations of possible therapeutic applications in cancer patients. … MSCs as delivery vehicles of anti-tumor nanoparticles to trigger bone sarcoma cell death The tropism of MSCs to cancer tissue suggests their use as vehicles for local delivery of antineoplastic agents. …

Mesenchymal stem cells in cancer therapy; the art of harnessing a foe to a friend.

For a long time, mesenchymal stem cells (MSCs) were discussed only as stem cells which could give rise to different types of cells. However, when it became clear that their presence in the tumor microenvironment (TME) was like a green light for tumorigenesis, they emerged from the ashes. This review was arranged to provide a comprehensive and precise description of MSCs' role in regulating tumorigenesis and to discuss the dark and the bright sides of cancer treatment strategies using MSCs. To gather the details about MSCs, we made an intensive literature review using keywords, including MSCs,

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… Initially, the high tropism of MSCs to the tumor milieu could be recruited by the therapeutic approaches to deliver anticancer agents into tumor cells directly. … Despite the efficacy, high tumor tropism, low immunogenicity, and safety, it should be noted that most clinical trials evaluating the potential of MSCs in cancer therapeutic approaches did not reach the higher phases. …

Parvovirus B19-induced hemophagocytic lymphohistiocytosis: Case report and review of the literature.

HLH is a catastrophic and likely underdiagnosed pathology with multiple triggers including infection. PVB19 can cause persistent marrow infection leading to HLH despite negative acute serologic markers making timely diagnosis difficult. Increased awareness of PVB19-HLH is warranted given its potentially lethal nature and the careful interpretation required with serologic markers.

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… For example, treatment recommendations for EBV‐VAHS include corticosteroids, IVIG, etoposide, and rituximab. 15 While VAHS is most commonly associated with EBV, other implicated viruses include CMV, HIV, Herpes Simplex, and rarely PVB19. 16 PVB19 is a single‐stranded DNA erythrovirus with a tropism … However, due to PVB19 tropism for the marrow utilization of serum samples to document clearance of infection is considered less sensitive than using bone marrow samples. 18 In a study looking at detection of PVB19 antibodies and DNA in the serum and bone marrow, 112 patients demonstrated IgG positivity …

Bioengineered Mesenchymal Stem/Stromal Cells in Anti-Cancer Therapy: Current Trends and Future Prospects.

Mesenchymal stem/stromal cells (MSCs) are one of the most widely used cell types in advanced therapies due to their therapeutic potential in the regulation of tissue repair and homeostasis, and immune modulation. However, their use in cancer therapy is controversial: they can inhibit cancer cell proliferation, but also potentially promote tumour growth by supporting angiogenesis, modulation of the immune milieu and increasing cancer stem cell invasiveness. This opposite behaviour highlights the need for careful and nuanced use of MSCs in cancer treatment. To optimize their anti-cancer effects,

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… Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging Stem Cells 2009 27 2614 2623 10.1002/stem.187 19650040 PMC4160730 26. Quante M. Tu S.P. Tomita H. Gonda T. Wang S.S. Takashi S. Baik G.H. Shibata W. Diprete B. Betz K.S. … Human mesenchymal stem cells lack tumor tropism but enhance the antitumor activity of oncolytic adenoviruses in orthotopic lung and breast tumors Hum. Gene Ther. 2007 18 627 641 10.1089/hum.2007.034 17604566 172. Yuan X. Zhang Q. Li Z. Zhang X. Bao S. Fan D. Ru Y. Dong S. Zhang Y. Zhang Y. …

Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.

In recent years, the development of chimeric antigen receptor (CAR) technology has greatly promoted the progress of cellular immunotherapy. Among them, CAR-T cell therapy has shown remarkable clinical effects in the treatment of hematological malignancies. However, this therapy still faces a series of challenges, including immunogenicity, toxic side effects, and insufficient maintenance of long-term efficacy. The latest research progress has extended CAR technology to mesenchymal stem cells (MSCs), and the resulting CAR-MSCs combine the precise targeting ability of CAR molecules with the inher

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… Homing effect and tumor tropism: MSCs exhibit homing and tumor tropism, migrating to primary tumors, metastatic sites, and areas of tissue damage or inflammation. This property highlights their potential as a targeted delivery system for anticancer agents. … This tumor tropism may involve three mechanisms, representing the main strategies for enhancing MSC tumor tropism identified in recent research. …

A review of feline infectious peritonitis virus infection.

Feline infectious peritonitis (FIP) is an infectious disease characterized by non-specific laboratory changes and clinical signs. Clinical symptoms include anorexia, jaundice, fever, and weight loss. Moreover, some lesions are found in the digestive and respiratory systems. FIP, whose virulence varies, cannot be distinguished using several diagnostic methods. Moreover, feline coronaviruses (FCoVs) can be classified into two serotypes based on differences in their amino acid sequences, spike (S) protein sequences, and antibody (Ab) neutralization. There are two pathotypes, namely those caused b

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… It has been established that the S glycoprotein of FCoV controls host cell entry, and mutations in the S gene affect cell tropism. … They continually evolve into new hosts, readily combining with closely related species to create novel viruses and can also change cell tropism and pathogenicity within the same host. …

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to

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… It was also hypothesized that passaging in purified cancer cells would decrease tropism for healthy cells or avoid it altogether [ 100 , 101 ]. … Instead, it was suggested that tropisms for other tissues could be interfered with by other viruses or chemicals. …

Improved oncolytic and immunostimulatory activity of the spontaneous jin-3 reovirus mutant in preclinical bladder cancer models.

Immunotherapy has emerged as a promising strategy for treatment of urothelial carcinoma of the bladder (UCB) but not all patients show clinically desirable responses upon treatment with immune-checkpoint inhibition. Oncolytic viruses may unleash the full potential of immunotherapy. Besides tumor-lysing properties, oncolytic viruses can induce durable and systemic anti-viral and anti-tumor immune responses. Here, we evaluated and compared oncolytic and immunostimulatory properties of wild-type reovirus (R124) and the junction-adhesion molecule-independent mutant reovirus (jin-3) in preclinical

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… We previously demonstrated that jin-3 reoviruses display extended tumor tropism compared to the wild-type reovirus. 44 , 45 Interestingly, this JAM-A protein is involved in various biological processes including tight junctions involved in epithelial barrier function. 46 Expression levels of JAM-A in … Additionally, jin-3 has an extended tropism compared to the wild-type reovirus because these viruses can infect cells independently of JAM-A expression on the tumor cell surface. …

pIL6-TRAIL-engineered umbilical cord mesenchymal/stromal stem cells are highly cytotoxic for myeloma cells both in vitro and in vivo.

BackgroundMesenchymal/stromal stem cells (MSCs) are favorably regarded in anti-cancer cytotherapies for their spontaneous chemotaxis toward inflammatory and tumor environments associated with an intrinsic cytotoxicity against tumor cells. Placenta-derived or TRAIL-engineered adipose MSCs have been shown to exert anti-tumor activity in both in-vitro and in-vivo models of multiple myeloma (MM) while TRAIL-transduced umbilical cord (UC)-MSCs appear efficient inducers of apoptosis in a few solid tumors. However, apoptosis is not selective for cancer cells since specific TRAIL receptors are also ex

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… By evaluating the GFP expression in several ex vivo organs, we found that the accumulation of pIL6-TRAIL + -GFP + -UC-MSCs occurred in tibiae as well as in lung, heart, and renal glomeruli, thus supporting the typical tropism also to the tumor sites ascribed to MSCs [ 27 ]. … Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells. 2009;27:2614–23. doi: 10.1002/stem.187. 7. de Melo SM, Bittencourt S, Ferrazoli EG, da Silva CS, da Cunha FF, da Silva FH, et al. …

Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.

In a precision medicine perspective, among the biomarkers potentially useful for early diagnosis of cancers, as well as to define their prognosis and eventually to identify novel and more effective therapeutic targets, there are the long non-coding RNAs (lncRNAs). The term lncRNA identifies a class of non-coding RNA molecules involved in the regulation of gene expression that intervene at the transcriptional, post-transcriptional, and epigenetic level. Metastasis is a natural evolution of some malignant tumours, frequently encountered in patients with advanced cancers. Onset and development of

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… The authors suggested that the lncRNA HOXA11-AS, together with its transcription factor HOXB13, regulates the bone tropism of prostate cancer cells through specific downstream cytokine and integrin signals ( 65 ). … Knockdown of MAYA in breast cancer cells with bone tropism (BoM-1833 cells) counteracts connective growth factor (CTGF) secretion and cancer cell-induced osteoclast differentiation and, consequently, limits the potential for osteolytic bone metastasis. …