Intravaginal Administration of Fc-Fused IL7 Suppresses the Cervicovaginal Tumor by Recruiting HPV DNA Vaccine-Induced CD8 T Cells

Purpose: The induction of tissue-localized virus-specific CD8 T-cell response is essential for the development of an effective therapeutic vaccine against genital diseases, such as cervical cancer and genital herpes. Here, we aimed to elucidate the immunologic role of IL7 in the induction of mucosal cellular immunity. Experimental Design: IL7 was engineered through Fc fusion to enhance mucosal delivery across the genital epithelial barrier. The immunomodulatory role of IL7 was evaluated by monitoring the kinetics of various immune cells and measuring the expression of chemokines and cytokines after intravaginal administration of Fc-fused IL7 (IL7-Fc). The antitumor effects of intramuscular human papillomavirus (HPV) DNA vaccine or topical IL7-Fc alone or in a combinational regimen on mice survival were compared using a orthotopic cervical cancer model. Results: Intravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFN-gamma, TNF alpha, IL6, and IL1 beta), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, gamma delta T cells, and dendritic cells. Importantly, in this murine cervical cancer model, topical administration of IL7-Fc after intramuscular HPV DNA vaccination increases the number of HPV-specific CD8 T cells in the genital mucosa, but not in the spleen, leading to stronger antitumor activity than the HPV DNA vaccine alone. Conclusions: Our findings provide an important insight into the immunomodulatory role of IL7-Fc via topical application and the design of therapeutic vaccine regimen that induces effective genital-mucosal CD8 T-cell responses.1110Ysciescopu

Biologic therapy for amyloid A amyloidosis secondary to rheumatoid arthritis treated with interleukin 6 therapy: Case report and review of literature

INTRODUCTION: Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES: After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION: The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA

Liver X receptors alpha gene (NR1H3) promoter polymorphisms are associated with systemic lupus erythematosus in Koreans.

INTRODUCTION: Liver X receptors are established sensors of lipid and cholesterol homeostasis. Recent studies have reported that these receptors are involved in the regulation of inflammation and immune responses. We attempted to identify single nucleotide polymorphisms (SNPs) of the NR1H3 gene associated with the susceptibility to systemic lupus erythematosus (SLE). METHODS: SNPs were genotyped using SNaPSHOT assay in 300 Korean patients with SLE and 217 normal controls (NC), and in replication samples (160 SLE patients and 143 NC). Also, the functional effects of NR1H3 gene promoter polymorphisms were analyzed using a luciferase assay, real-time polymerase chain reaction, B cell proliferation assay and an electrophoretic mobility shift assay. RESULTS: We identified five polymorphisms: -1851 T > C (rs3758673), -1830 T > C (rs3758674), -1003 G > A (new), -840 C > A (rs61896015) and -115 G > A (rs12221497). There was a significant and reproducible difference in the -1830 T > C, -1003 G > A and -115 G > A polymorphisms between the SLE and the NC. Luciferase activity of the structure containing -1830 C was less enhanced compared to the structure containing -1830 T in basal, GW3965 and T0901317 treated Hep3B cells (P = 0.009, P = 0.034 and P <0.001, respectively). Proliferation of the -1830 TC type was increased compared to the -1830 TT type in basal, GW3965 and T0901317 treated B cells from SLE patients (P = 0.011, P = 0.040 and P = 0.017, respectively). Transcription factor GATA-3 preferentially bound the -1830 T allele in the promoter. CONCLUSIONS: NR1H3 genetic polymorphisms may be associated with disease susceptibility and clinical manifestations of SLE. Specifically, -1830 T > C polymorphism within NR1H3 promoter region may be involved in regulation of NR1H3 expression

Diagnosis and Treatment of Lupus Nephritis: Survey Results on Four Important Issues

Objectives. To investigate the perception of and treatment pattern with regard to the four important issues in the management of lupus nephritis (LN), and to identify which parts of the LN treatment are difficult for physicians to carry out in clinical practice. Methods. Four steps were carried out: pre-survey, LN symposium, post-survey, and meeting after the symposium.The two surveys were conducted with the same contents regarding renal biopsy, induction and maintenance treatment for class III and IV LN, and treatment for class V LN. The results of the first survey and the changes in opinion reflected in the second survey were comparatively analyzed. Results. In the first survey, most of the respondent physicians replied that they would immediately conduct biopsy in the case of significant proteinuria. For the induction treatment of class III and IV LN, most of the respondent physicians selected high-dose cyclophosphamide. Mycophenolate mofetil and steroid combination therapy were selected for the maintenance treatment, and tacrolimus for the treatment of class V LN. There was a controversy in the drug selection, however, especially on the maintenance treatment of class III and IV LN and on the treatment of non-responsive class V LN. Conclusion. Some discrepancies were found in the treatment of LN in the real world. Although no recommendation was made for Korean LN patients in this study, the study results will help physicians select the most reasonable treatment for Korean LN patients based on experts’ experiences and objective evidence

Accuracy of Preoperative Local Staging of Primary Colorectal Cancer by Using Computed Tomography: Reappraisal Based on Data Collected at a Highly Organized Cancer Center

Purpose: In patients with colorectal cancer, preoperative staging using various imaging technologies is important for establishing the treatment plan and predicting the prognosis. Although computed tomography (CT) has been used most widely, the versatility of CT accuracy was primarily because of the lack of specialization. In this study, we aimed to identify whether any advancement in abdominal CT accuracy in the prediction of local staging has occurred. Methods: Between December 2014 and November 2015, patients with colorectal cancer were retrospectively enrolled. All CT findings were retrospectively reported. A total of 285 patients were included, and their retrospectively collected data were retrospectively reviewed, focusing on a comparison between preoperative and postoperative staging. Results: The overall prediction accuracy of the T stage was 55.1%, with overstaging occurring in 63 (22.1%) and understaging in 65 patients (22.8%). The sensitivity and specificity were 90.0% and 68.4%, respectively. The overall prediction accuracy of the N stage was 54.7%, with overstaging occurring in 89 (31.2%) and understaging in 40 patients (14.1%). The sensitivity and specificity were 71.9% and 63.2%, respectively. The CT accuracies by pathologic stage were 0%, 62.2%, 25.3%, and 81.2% for stages 0 (Tis N0), I, II, and III, respectively. Conclusion: CT has good sensitivity for detecting colon cancers with tumor invasion beyond the bowel wall. However, detection of nodal involvement using CT is unreliable. In our opinion, abdominal CT alone has limitations in predicting the local staging of colorectal cancer, and additional technologies, such as CT plus positron emission tomography and/or colonography, will improve its accuracy

E-commerce ethics and its impact on buyer repurchase intentions and loyalty: an empirical study of small and medium Egyptian businesses

The theoretical understanding of e-commerce has received much attention over the years; however, relatively little focus has been directed towards e-commerce ethics, especially the SMEs B2B e-commerce aspect. Therefore, the purpose of this paper is to develop and empirically test a framework that explains the impact of SMEs B2B e-commerce ethics on buyer repurchase intentions and loyalty. Using SEM to analyse the data collected from a sample of SME e-commerce firms in Egypt, the results indicate that buyers’ perceptions of supplier ethics construct is composed of six dimensions (security, non-deception, fulfilment/reliability, service recovery, shared value, and communication) and strongly predictive of online buyer repurchase intentions and loyalty. Furthermore, our results also show that reliability/fulfilment and non-deception are the most effective relationship-building dimensions. In addition, relationship quality has a positive effect on buyer repurchase intentions and loyalty. The results offer important implications for B2B e-commerce and are likely to stimulate further research in the area of relationship marketing

Minimally invasive surgery for radical hysterectomy in women with cervical cancer: Korean Society of Gynecologic Oncology, Korean Society of Obstetrics and Gynecology, and Korean Society of Gynecologic Endoscopy and Minimally Invasive Surgery position statement

On the basis of emerging data and the current understanding of minimally invasive surgery (MIS) for radical hysterectomy (RH) in women with cervical cancer, the Korean Society of Gynecologic Oncology, Korean Society of Obstetrics and Gynecology, and Korean Society of Gynecologic Endoscopy and Minimally Invasive Surgery support the following recommendations: According to the recently published phase III Laparoscopic Approach to Cervical Cancer (LACC) trial-a prospective randomized clinical trial-disease-free survival and overall survival rates of MIS RH are significantly lower than those of open RH. Gynecologic oncologists should be aware of the emerging data on MIS RH for early-stage cervical cancer. The results of the LACC trial, together with institutional data, should be discussed with patients before choosing MIS RH. MIS RH should be performed for optimal candidates according to the current practice guidelines by gynecologic oncologists who are skilled at performing MIS

Efficacy and Safety of Rituximab in Korean Patients with Refractory Inflammatory Myopathies

BACKGROUND: Rituximab (RTX), a monoclonal antibody that selectively binds to CD20+ B cells, showed favorable outcomes in patients with idiopathic inflammatory myopathies (IIM) in small case series, but the evidence is still not enough. Our goal was to determine the efficacy and safety of RTX for Korean patients with refractory IIM. METHODS: We retrospectively analyzed the medical records of 16 patients with refractory IIM treated with RTX in seven tertiary rheumatology clinics in the Korea. The efficacy of RTX was evaluated with the improvement of serum creatine phosphokinase (CPK) level and physician's global assessment (PGA), and daily corticosteroid dose reduction. A &gt; 25% decrease in CPK level, corticosteroid dose, or PGA was considered significant. A complete response (CR) was designated by meeting three efficacy criteria and a partial response (PR) by only two criteria. RESULTS: Sixteen patients with IIM were evaluated (13 female; median age, 51.8 years). All patients had received at least one conventional immunosuppressive agent (median, 3.6 [2.0-5.0]) and concomitant corticosteroids. The median CPK level and median dose of prednisolone was 421.0 units/L and 20.0 mg/day respectively. Eleven patients were treated with intravenous immunoglobulin. Seven patients received 2,000 mg of RTX and the others received lower dose. Twenty-four weeks after RTX treatment, 11 patients achieved a &gt; 25% reduction in corticosteroid dose and CPK levels, and nine showed improved PGA. The overall response rate was 68.8% (11 patients). At the end of follow-up (median 24 weeks), 12 (75.0%) patients responded overall: four (25.0%) and eight (50.0%) patients achieved CR and PR, respectively. Baseline muscle enzyme levels were higher in responders than non-responders, but disease duration, RTX dose, ESR and serum CRP were not significantly different between the two groups. The rate of adverse event was 25.4/1,000 person-years. CONCLUSION: RTX could be an effective and relatively safe therapeutic option in patients with refractory IIM

Impact of PARP inhibitor maintenance therapy in newly diagnosed advanced epithelial ovarian cancer: A meta-analysis

Objectives: This meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients. Methods/materials: A systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis. Results: The two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63). Conclusions: In patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy

Clinical guidelines for ovarian cancer: the Korean Society of Gynecologic Oncology guidelines

Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC