Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs.
Antiviral Agents/therapeutic use ; Cell- and Tissue-Based Therapy ; DNA Methylation ; Epstein-Barr Virus Infections/*complications ; Genome, Viral ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human/*physiology ; Humans ; Immunotherapy, Adoptive ; Lymphoproliferative Disorders/diagnosis/*etiology/*therapy ; Organ Transplantation/adverse effects ; T-Lymphocytes/immunology ; Transplantation, Homologous ; Virus Latency

The efficacy of intravesical onabotulinumtoxinA (BTXA) in the treatment of overactive bladder (OAB) has been well documented. The use of BTXA injection in orthotopic neobladders is yet to be studied. We present 4 cases of patients injected with intravesical BTXA for overactive orthotopic ileal neobladder. We recorded patient demographics, presenting and follow-up symptoms, urodynamic profiles, and Patient Global Impression of Improvement (PGI-I) scores. The 4 patients reported varying degrees of subjective improvements in the symptoms, including urgency, urge incontinence, and pad usage. Mean follow-up duration was 8.3 months (range, 5-14 months). Average PGI-I score was 3 ("a little better") (range, 2-4). To our knowledge, the current study is the first case series examining BTXA injection for orthotopic neobladder overactivity. BTXA injection yielded varying degrees of objective and subjective improvements, without significant complications. Intravesical BTXA injection is feasible and may be considered as a potential treatment alternative for OAB in orthotopic neobladders, although further study is warranted.
Administration, Intravesical ; Demography ; Follow-Up Studies ; Humans ; Urinary Bladder, Overactive ; Urinary Diversion ; Urinary Incontinence, Urge ; Urinary Reservoirs, Continent ; Urodynamics

Anlotinib has strong antiangiogenic effects and leads to vessel normalization.However,the"window period"characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs.In this study,through RNA sequencing(RNA-seq)and label-free quantitative proteomics analysis,we discovered that anlotinib regulated the expression of components of the extracellular matrix(ECM),leading to a significant reduction in ECM stiffness.Our bioinformatic analysis revealed a potential positive relationship between the ECM pathway and gefitinib resistance,poor treatment outcomes for programmed death 1(PD-1)targeting,and unfavourable prognosis following chemotherapy in lung cancer patients.We administered anlotinib in combination with these antitumour drugs and visualized their distribution using fluorescent labelling in various tumour types.Notably,our results demonstrated that anlotinib prolonged the retention time and distribution of antitumour drugs at the tumour site.Moreover,the combination therapy induced notable loosening of the tumour tissue structure.This reduction was associated with decreased interstitial fluid pressure and tumour solid pressure.Additionally,we observed that anlotinib effectively suppressed the Ras homologue family member A(RhoA)/Rho-associated protein kinase(ROCK)signalling pathway.These findings suggest that,in addition to its antiangiogenic and vessel normalization effects,anlotinib can increase the distribution and retention of antitumour drugs in tumours by modulating ECM expression and physical properties through the RhoA/ROCK signalling pathway.These valuable insights contribute to the development of combination therapies aimed at improving tumour targeting in cancer treatment.