Reduction of the HIV-1 reservoir in resting CD4+ T-lymphocytes by high dosage intravenous immunoglobulin treatment: a proof-of-concept study

Background  

The latency of HIV-1 in resting CD4⁺ T-lymphocytes constitutes a major obstacle for the eradication of virus in patients on antiretroviral therapy (ART). As yet, no approach to reduce this viral reservoir has proven effective.     

Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

Background  

Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap.     

Gene therapy with tumor-specific promoter mediated suicide gene plus IL-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma

Background  

Gene therapy is a promising therapeutic approach for cancer. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. This study is to establish a more effective and less toxic gene therapy of cancer.     

A functional PTPN22 polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population

Background  

The 1858C/T SNP of the PTPN22 gene has been associated with many autoimmune diseases, suggesting the existence of an inflammatory process common to all of them. We studied the association of that polymorphism with immunoglobulin A deficiency (IgAD) following a double approach: a case-control and a TDT study.     

The identification of unique serum proteins of HIV-1 latently infected long-term non-progressor patients

Background  

The search for disease biomarkers within human peripheral fluids has become a favorable approach to preventative therapeutics throughout the past few years. The comparison of normal versus disease states can identify an overexpression or a suppression of critical proteins where illness has directly altered a patient's cellular homeostasis. In particular, the analysis of HIV-1 infected serum is an attractive medium with which to identify altered protein expression due to the ease and non-invasive methods of collecting samples as well as the corresponding insight into the in vivo interaction of the virus with infected cells/tissue. The utilization of proteomic techniques to globally identify differentially expressed serum proteins in response to HIV-1 infection is a significant undertaking that is complicated due to the innate protein profile of human serum.     

Assessment of HIV-1 entry inhibitors by MLV/HIV-1 pseudotyped vectors

Background  

Murine leukemia virus (MLV) vector particles can be pseudotyped with a truncated variant of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) and selectively target gene transfer to human cells expressing both CD4 and an appropriate co-receptor. Vector transduction mimics the HIV-1 entry process and is therefore a safe tool to study HIV-1 entry.     

A novel scoring system for selecting the target patients of COVID-19 convalescent plasma therapy: A hypothesis

The primary cause of mortality in patients of coronavirus disease 2019 (COVID-19) is the cytokine storm and not directly due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Therefore, it is being stressed by transfusion medicine specialists to use COVID-19 convalescent plasma (CCP) therapy early in the course of the disease, preferably within 72 h of diagnosis. The authors herein, propose a scoring system for the rapid assessment of the patients who have tested positive for SARS-CoV-2. Therefore, a systematic approach may be followed where the patients are categorised into two groups, namely, the low-risk group [LRG; score < 5] and the high-risk group [HRG; score ≥ 5] based on this scoring system. Those classified as an HRG should be administered CCP therapy within 72 h of a confirmed diagnosis of COVID-19 to neutralise the SARS-CoV-2 virus and prevent the occurrence of the cytokine storm. This in turn could help reduce the overall mortality in the recipients.     

Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy

Background  

Adoptive cell therapy with allogenic NK cells constitutes a promising approach for the treatment of certain malignancies. Such strategies are currently limited by the requirement of an efficient protocol for NK cell expansion. We have developed a method using synthetic nanosized phosphonate-capped dendrimers allowing such expansion. We are showing here that this is due to a specific inhibitory activity towards CD4⁺ T cell which could lead to further medical applications of this dendrimer.     

Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

Background  

Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM). We have reported a promising complete remission (CR) rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT) while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT.     

Exposing Viruses: RNA Patterns Sensed by RIG-I-like Receptors

Introduction  

Virus infection triggers a multitude of innate immune pathways that limit viral replication, restrict viral spread and coordinate antigen-specific, adaptive immune responses. Type-I interferons (IFNs) play a crucial role in these events. Innate receptors expressed by the host cell recognize virus presence and signal for rapid IFN induction following infection.     

Status of proinflammatory and anti-inflammatory cytokines in different brain regions of a rat model of Japanese encephalitis

Objectives  

This study evaluated cytokines and chemokine in different regions of the rat brain at different time points following Japanese encephalitis virus (JEV) infection.     

Expenditures for the care of HIV-infected patients in rural areas in China's antiretroviral therapy programs

Background  

The Chinese government has provided health services to those infected by the human immunodeficiency virus (HIV) under the acquired immunodeficiency syndrome (AIDS) care policy since 2003. Detailed research on the actual expenditures and costs for providing care to patients with AIDS is needed for future financial planning of AIDS health care services and possible reform of HIV/AIDS-related policy. The purpose of the current study was to determine the actual expenditures and factors influencing costs for untreated AIDS patients in a rural area of China after initiating highly active antiretroviral therapy (HAART) under the national Free Care Program (China CARES).     

The effect of an Internet-based cognitive behavioral therapy intervention on social support in disaster evacuees

Introduction

Both exposure to a natural disaster and psychological symptoms may lead to decreases in social support. Few studies have examined ways to improve social support among victims of natural disasters.

Aims

The objective of the study was to assess emotional and tangible support following a 12-session Internet-based cognitive behavioral therapy (ICBT) targeting posttraumatic stress (PTS), insomnia, and depression symptoms and to examine the association between posttreatment symptoms and emotional and tangible support.

Materials and Methods

One hundred and seventy-eight wildfire evacuees with significant PTS, depression and/or insomnia symptoms were given access to the ICBT. They completed questionnaires at pre- and posttreatment to measure social support and symptom severity.

Results

Results show that completion of the treatment led to an improvement in emotional support. Lower posttreatment PTS and insomnia symptoms were associated with higher posttreatment emotional support.

Conclusion

ICBT may contribute to enhance emotional support through symptom improvement and probably more so when social support is address directly in treatment.     

Tailored antiplatelet therapy can overcome clopidogrel and aspirin resistance - The BOchum CLopidogrel and Aspirin Plan (BOCLA-Plan) to improve antiplatelet therapy

Background  

Dual antiplatelet therapy using acetylsalicylic acid (ASA, aspirin) and clopidogrel is of great importance following coronary stenting. However, the variable platelet inhibitory effectiveness compromises the antithrombotic advantages provided by dual antiplatelet therapy. The aim of this single-center prospective study was to reduce the low response incidence of dual antiplatelet therapy with ASA and clopidogrel according to a prespecified therapy algorithm.     

Acceptability of a novel suicide prevention psychological therapy for people who experience non-affective psychosis

Objectives

Suicide is a leading cause of death worldwide. People experiencing psychosis are at increased risk of death by suicide. Talking therapies can alleviate suicidal thoughts, plans, and attempts. Therapies need to also be acceptable to recipients. The aim of this study was to investigate the views on psychological therapy for people experiencing psychosis and suicidality using the Theoretical Framework of Acceptability.

Design

Qualitative interview study.

Methods

Participants were recruited from a randomised controlled trial comparing suicide prevention psychological therapy with treatment as usual. Individuals had a diagnosis of non-affective psychosis and experience of suicidal thoughts, plans and/or attempts. To assess the acceptability of the therapy, semi-structured interviews were conducted with 20 participants randomised to receive therapy. Data were deductively analysed using an adaptation of the Theoretical Framework of Acceptability.

Results

Interviews (Mean = 45 min) were conducted and audio recorded with 21 participants. Data were organised into six themes: 1. Affective attitude, 2. Burden, 3. Alliance, 4. Intervention coherence, 5. Perceived effectiveness, and 6. Self-efficacy. There was no evidence of issues relating to domains of ethicality and opportunity costs associated with receiving therapy.

Conclusions

Talking about suicide was difficult and, at times, distressing, but it was perceived to be useful for understanding experiences. To be acceptable, it is important for therapists to ensure that clients' understanding of therapy aligns with expectations of effectiveness and to invest in building strong therapeutic alliances. Future research will benefit from examining therapists' experiences of delivering therapy through different modes (e.g. online, telephone).     

Acupressure for smoking cessation – a pilot study

Background  

Tobacco smoking is a serious risk to health: several therapies are available to assist those who wish to stop. Smokers who approach publicly funded stop-smoking clinics in the UK are currently offered nicotine replacement therapy (NRT) or bupropion, and group behaviour therapy, for which there is evidence of effectiveness. Acupuncture and acupressure are also used to help smokers, though a systematic review of the evidence of their effectiveness was inconclusive. The aim of this pilot project was to determine the feasibility of a study to test acupressure as an adjunct to one anti-smoking treatment currently offered, and to inform the design of the study.     

Pathology of rituximab-induced Kaposi sarcoma flare

Background

Kaposi sarcoma (KS) flare may occur following therapy with corticosteroids, as part of the immune reconstitution inflammatory syndrome seen with highly active antiretroviral therapy (HAART), and after rituximab therapy. The exact mechanism responsible for iatrogenic KS flare is unclear.

Methods

A case of AIDS-associated cutaneous KS flare following rituximab therapy was compared to similar controls by means of immunohistochemistry using vascular makers (CD34, CD31), monoclonal antibodies to Human Herpesvirus 8 (HHV8) gene products (LNA-1, K5), as well as B-lymphocyte (CD20) and T-lymphocyte (CD3, CD4, CD8) markers.

Results

CD20+ B-cell depletion with rituximab in KS flare occurred concomitantly with activation of the HHV8 immediate early gene protein K5. KS flare in this patient was successfully treated with liposomal doxorubicin and valganciclovir.

Conclusion

Rituximab-induced KS flare appears to be related to HHV8 activation. Effective management of iatrogenic KS flare therefore depends upon the control of HHV8 viremia in conjunction with specific chemotherapy for KS.     

The endogenous soluble VEGF receptor-2 isoform suppresses lymph node metastasis in a mouse immunocompetent mammary cancer model

Background  

Cancer metastasis contributes significantly to cancer mortality and is facilitated by lymphangiogenesis and angiogenesis. A new splicing variant, endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2) that we recently identified is an endogenous selective inhibitor of lymphangiogenesis. To evaluate the antimetastatic potential of esVEGFR-2, gene therapy with vector expressing esVEGFR-2 (pesVEGFR-2) or endostatin (pEndo) as a positive control was conducted on murine metastatic mammary cancer.     

The use of microarray technologies in clinical oncology

Purpose

Based on previous studies that demonstrated the safety profile and preliminary clinical activity of prostate specific antigen (PSA) targeted therapeutic vaccines, as well as recent laboratory data supporting the value of the addition of co-stimulatory molecules B7-1, ICAM-1, and LFA-3 (designated TRICOM?) to these vaccines, we conducted a Phase I study to evaluate the safety and immunogenicity of a novel vaccinia and fowlpox vaccine incorporating the PSA gene sequence and TRICOM.

Methods

In this study, ten patients with androgen independent prostate cancer with or without metastatic disease were enrolled. Patients were treated with 2 × l0⁸ pfu of a recombinant vaccinia virus vaccine (PROSTVAC-V) followed by 1 × 10⁹ pfu of the booster recombinant fowlpox virus (PROSTVAC-F) both with gene sequences for PSA and TRICOM. The mean age of patients enrolled in the study was 70 (range 63 to 79). The mean PSA at baseline was 434 (range 9 – 1424).

Results

There were no deaths, and no Grade 3 or 4 adverse events. The most commonly reported adverse events, regardless of causality, were injection site reactions and fatigue. One serious adverse event (SAE) occurred that was unrelated to vaccine; this patient developed progressive disease with a new sphenoid metastasis. PSA was measured at week 4 and week 8. Four patients had stable disease (with less than 25% increase in PSA) through the week 8 study period. Anti-PSA antibodies were not induced with therapy: however, anti-vaccinia titers increased in all patients.

Conclusion

This study demonstrated that vaccination with PROSTVAC-V and PROSTVAC-F combined with TRICOM is well-tolerated and generated an immune response to vaccinia. Therefore, PROSTVAC-VF/TRICOM represents a feasible therapeutic approach for further phase II and III study in patients with prostate cancer.     

Generation of Full-Length Functional Antibody against PreS2 of Hepatitis B Virus in Hepatic Cells In Vitro from Bicistrons Mediated by Gutless Adenovirus

Background

Monoclonal antibodies (mAbs) have been developed as effective therapeutics for a wide variety of diseases. Delivery of mAbs by gene transfer provides an option for overcoming the difficulties in mAb production and manufacturing processes. However, for the polymeric structure of full-length mAbs, it is important to design an optimal gene transfer system for mAb generation.

Methods

Gutless adenovirus and liver-specific promoter transthyretin (TTR) were combined to deliver bicistronic mAb genes in human hepatic cell lines. In order to optimize the bicistrons for mAb generation, four bicistrons were designed and compared, and the most efficient one was selected. ELISA and Western blot were conducted to evaluate mAb products in the supernatants.

Results

Our data showed that all of four gutless adenoviruses elicited liver-specific mAb production in HepG2 and Hep3B hepatic cell lines. It was observed that the L2AH bicistron construct (comprising an immunoglobulin light-chain cDNA situated 50 of a heavy-chain cDNA, with a foot-and-mouth disease virus 2A cleavage site in the middle, subcloned into the helper-dependent adenovirus plasmid pGL) could induce the highest level expression of mAb (about 5.0 μg/mL in Hep3B) among these four constructs. Importantly, the mAb products by gene transfer methods retained specific antigen-binding activity.

Conclusion

Our studies gave further evidence that it was feasible to produce active full-length mAb in human hepatic cell lines in vitro by a special gene delivery system. Moreover, we developed an optimized bicistron gene transfer system for future gene therapy research, which may also be of use in industrial mAb production.