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Abstract 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. Methods Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase (HRP) mediated by human telomerase reverse transcriptase (hTERT) promoter (AdhTERTHRP) and murine interleukin-12 (mIL-12) under the control of Cytomegalovirus (CMV) promoter (AdCMVmIL-12) was developed and evaluated against Lewis lung carcinoma (LLC) both in vivo and in vitro. The mechanism of action and systemic toxicities were also investigated. Results The combination of AdhTERTHRP/indole-3-acetic acid (IAA) treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP/IAA alone (tumor volume, 427.4 ± 48.7 mm3 vs 581.9 ± 46.9 mm3, p = 0.005 on day 15; median overall survival (OS), 51 d vs 33 d) or AdCMVmIL-12 alone (tumor volume, 362.2 ± 33.8 mm3 vs 494.4 ± 70.2 mm3, p = 0.046 on day 12; median OS, 51 d vs 36 d). The combination treatment stimulated more CD4+ and CD8+ T lymphocyte infiltration in tumors, compared with either AdCMVmIL-12 alone (1.3-fold increase for CD4+ T cells and 1.2-fold increase for CD8+ T cells, P < 0.01) or AdhTERTHRP alone (2.1-fold increase for CD4+ T cells and 2.2-fold increase for CD8+ T cells, P < 0.01). The apoptotic cells in combination group were significantly increased in comparison with AdCMVmIL-12 alone group (2.8-fold increase, P < 0.01) or AdhTERTHRP alone group (1.6-fold increase, P < 0.01). No significant systematic toxicities were observed. Conclusions Combination gene therapy with AdhTERTHRP/IAA and AdCMVmIL-12 could significantly inhibit tumor growth and improve host survival in LLC model, without significant systemic adverse effects.

To determine the value of radiotherapy in addition to esophagectomy for stage II and III TESCC. We searched the Surveillance, Epidemiology, and End Results (SEER) database for all cases of stage II‐III TESCC. Patients were grouped as those receiving pre‐ or postoperative radiotherapy plus esophagectomy and those receiving esophagectomy alone. Overall survival (OS) and cancer‐specific survival (CSS) were compared between the groups. Among the 3292 patients, multimodality treatments (pre‐ or postoperative radiotherapy plus surgery) were more effective than surgery alone (5‐year, OS: 17.3% vs 7.9%; P < 0.001; CSS: 51.8% vs 34.9%; P < 0.001). Among the patients receiving multimodality treatments, multivariate analyses revealed stage to be the most significant prognostic factor for OS (II vs III, HR, 0.726; P < 0.001), but the sequence of radiotherapy and surgery was only of the marginal significance (pre‐ vs postoperative, HR, 0.875; P = 0.093). Preoperative radiotherapy provided significantly better survival than postoperative radiotherapy in stage III disease (5‐year, OS: 13.0% vs 11.0%, P < 0.04; CSS: 49.2% vs 31.7%, P < 0.003), but not in stage II disease (5‐year OS: 23.5% vs 21.0%, P = 0.519; CSS: 62.0% vs 53.4%, P = 0.075). Radiotherapy in addition to esophagectomy provides better outcomes than esophagectomy alone for in stage II‐III TESCC. Preoperative radiotherapy followed by surgery appears to be the optimal treatment strategy in stage III TESCC. Radiotherapy in addition to esophagectomy provides better outcomes than esophagectomy alone for in stage II‐III TESCC. In high risk of stage III, preoperative radiotherapy followed by surgery is the optimal treatment strategy. [ABSTRACT FROM AUTHOR]

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.Methods: Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase (HRP) mediated by human telomerase reverse transcriptase (hTERT) promoter (AdhTERTHRP) and murine interleukin-12 (mIL-12) under the control of Cytomegalovirus (CMV) promoter (AdCMVmIL-12) was developed and evaluated against Lewis lung carcinoma (LLC) both in vivo and in vitro. The mechanism of action and systemic toxicities were also investigated.Results: The combination of AdhTERTHRP/indole-3-acetic acid (IAA) treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP/IAA alone (tumor volume, 427.4 ± 48.7 mm3 vs 581.9 ± 46.9 mm3, p = 0.005 on day 15; median overall survival (OS), 51 d vs 33 d) or AdCMVmIL-12 alone (tumor volume, 362.2 ± 33.8 mm3 vs 494.4 ± 70.2 mm3, p = 0.046 on day 12; median OS, 51 d vs 36 d). The combination treatment stimulated more CD4+ and CD8+ T lymphocyte infiltration in tumors, compared with either AdCMVmIL-12 alone (1.3-fold increase for CD4+ T cells and 1.2-fold increase for CD8+ T cells, P < 0.01) or AdhTERTHRP alone (2.1-fold increase for CD4+ T cells and 2.2-fold increase for CD8+ T cells, P < 0.01). The apoptotic cells in combination group were significantly increased in comparison with AdCMVmIL-12 alone group (2.8-fold increase, P < 0.01) or AdhTERTHRP alone group (1.6-fold increase, P < 0.01). No significant systematic toxicities were observed.Conclusions: Combination gene therapy with AdhTERTHRP/IAA and AdCMVmIL-12 could significantly inhibit tumor growth and improve host survival in LLC model, without significant systemic adverse effects. [ABSTRACT FROM AUTHOR]

Background: The advent of immunotherapy has changed the landscape of SCLC treatment, although the identification of reliable prognostic biomarkers remains a formidable challenge. Our objective was to investigate the prognostic implications of obesity and body composition in SCLC immunotherapy while seeking a straightforward anthropometric measure., Methods: This retrospective study analyzed data from patients with SCLC who underwent immunotherapy between 2019 and 2023. Body composition and waist circumference (WC) were analyzed using 3D slicer software on baseline CT images. Quantitative measures, including skeletal muscle index (SMI), total adipose tissue index (TATI), and other indicators at the L3 level, along with body shape index (BSI) and additional indicators based on WC, were obtained. The relationships between these indicators, response, PFS, OS, and their interconnections were examined., Results: A total of 145 SCLC patients who received immunotherapy were identified, of whom 133 met the inclusion criteria. In univariate analysis, a BMI≥28 kg/m 2 was associated with a PFS advantage (HR 0.42, p=0.04), but this trend vanished in multivariate analysis. Body measurements exhibited stronger correlations with adipose tissue content, with BSI showing the highest correlation with muscle. In multivariate analysis, lower BSI was associated with poorer OS (HR 1.79, p=0.02). The association between muscle composition and prognosis was robust in univariate analysis but dissipated in multivariate analysis. However, accounting for a high TATI background significantly heightened the adverse effect of SMI on prognosis in the multivariate model., Conclusion: No clear association between BMI and SCLC immunotherapy prognosis was observed. However, high adiposity exacerbated the adverse effects of sarcopenia in SCLC immunotherapy, and BSI demonstrated potential as a straightforward prognostic measure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fang, Yan, Xu, Xu, Gan, Gong, Zhang, Xie and Liao.)

Background: For stage T1b-2N0-1 esophageal cancer, the impact of neoadjuvant therapy plus surgery (NS), surgery alone (SA), and surgery plus adjuvant therapy (ST) on cancer-specific survival (CSS) and overall survival (OS) is uncertain., Methods: Stage T1b-2N0-1 esophageal cancer patients from the SEER database and two Chinese cancer centers were included in this study. The Kaplan-Meier method was used to plot survival curves, which were compared using the log-rank test. Propensity score matching was used to equalize differences between the groups. Cox proportional hazards regression models were used to analyze prognostic factors. A nomogram for OS was developed after screening the variables using the Cox proportional hazards regression model and the least absolute shrinkage and selection operator. The performance of the nomogram was assessed by the Harrell concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve, calibration plots, and decision curve analysis., Results: After propensity score matching analysis, the 3-year CSS and OS rates in the NS group compared to the SA group were 80.3% versus 62.1% (P=0.016) and 75.8% versus 55.5% (P=0.006), the 3-year CSS and OS rates in the NS group compared to the ST group were 71.3% versus 68.3% (P=0.560) and 69.8% versus 62.9% (P=0.330), the 3-year CSS and OS rates in the SA group compared to the ST group were 54.6% versus 66.7% (P=0.220) and 50.2% versus 57.9% (P=0.290), respectively. The predictive nomogram for OS in T1b-2N0-1 patients ultimately incorporated five clinicopathological variables: T stage, N stage, age, examined lymph nodes , and therapy modality. The nomogram C-index for predicting OS was 0.648, 0.663, and 0.666 in the training group, external validation group-1, and external validation group-2, respectively. The 1-, 3-, and 5-year predicted AUC values of the OS prediction model were 0.659, 0.639, and 0.612 for the training group, and 0.786, 0.758, and 0.692 for validation group-1, and 0.805, 0.760, and 0.693 for validation group-2, respectively., Conclusion: For patients with stage T1b-2N0-1 esophageal cancer, neoadjuvant therapy significantly improves prognosis compared to surgery alone, those presenting with positive lymph nodes after upfront surgery can achieve survival benefits from adjuvant therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)