Anti-cytokine autoantibodies are ubiquitous in healthy individuals

AbstractAnti-cytokine autoantibodies in healthy individuals have been widely reported but the occurrence is variable and inconstant. We hypothesized that cytokine-binding in vivo may explain their variable and infrequent detection. Therefore, we focused on the detection of the cytokine-autoantibody complexes and found that anti-cytokine autoantibody to IL-2, IL-8, tumor necrosis factor-α, vascular endothelial growth factor and granulocyte-colony stimulating factor were present in all 15 individuals evaluated, while those to IL-3, osteopontin and macrophage-colony stimulating factor were not detected in anyone. Autoantibodies against IL-4, IL-6, IL-10, and interferon-gamma were variously detected. Thus, we discovered that anti-cytokine autoantibodies to multiple cytokines are ubiquitous in healthy individuals

Pretreatment glasgow prognostic score predicts survival among patients administered first-line atezolizumab plus carboplatin and etoposide for small cell lung cancer

BackgroundThere are no established predictive biomarkers for the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with small-cell lung cancer (SCLC). Therefore, the current study aimed to investigate whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can predict the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with extensive-disease SCLC.MethodsWe reviewed data from 84 patients who received first-line atezolizumab plus carboplatin and etoposide therapy for SCLC at nine Japanese institutions between August 2019 and May 2021. Further, we evaluated the prognostic value of the GPS, NLR, and BMI. The Kaplan–Meier and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). Moreover, the GPS, NLR, and BMI consisted of C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively.ResultsThe response rate was 72.6% (95% confidence interval: 63.0–82.1%). The median PFS and OS from the initiation of treatment were 5.4 (95% CI: 4.9–5.9) months and 15.4 (95% CI: 11.4–16.8) months, respectively. The GPS independently predicted the effectiveness of first-line atezolizumab plus carboplatin and etoposide treatment, as a favorable GPS (GPS 0–1) was correlated with significantly better PFS and OS rates compared to a poor GPS (GPS 2) (PFS: 5.8 vs. 3.8 months, p = 0.0005; OS: 16.5 vs. 8.4 months, p<0.0001).ConclusionsThis is the first analysis to evaluate the association between the GPS, NLR, and BMI and the treatment effectiveness of survival among patients receiving first-line atezolizumab plus carboplatin and etoposide therapy for SCLC. Among patients receiving this treatment for SCLC, GPS was significantly associated with the PFS and OS rates, suggesting that GPS might be useful for evaluating therapeutic outcomes in these patients

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2^ndEGFR-TKI administration.</p> <p>Methods</p> <p>We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.</p> <p>Results</p> <p>Three patients (27%) were treated with gefitinib as the 2^ndEGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2^ndEGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2^ndEGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2^ndEGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.</p> <p>Conclusions</p> <p>Our results indicate that a 2^ndEGFR-TKI treatment can be an effective treatment option for gefitinib responders.</p

Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>Gefitinib was the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Few treatment options are available for NSCLC patients who have responded to gefitinib treatment and demonstrated tumor progression. The present study was conducted to evaluate the efficacy and toxicity of the 2^ndEGFR-TKI administration.</p> <p>Methods</p> <p>We retrospectively analyzed 11 patients who had obtained a partial response (PR) or stable disease (SD) with gefitinib treatment and were re-treated with EGFR-TKI after failure of the initial gefitinib treatment.</p> <p>Results</p> <p>Three patients (27%) were treated with gefitinib as the 2^ndEGFR-TKI, and 8 patients (73%) received erlotinib. Only one patient (9%) showed PR, 7 (64%) achieved SD, and 3 (27%) had progressive disease. The disease control rate was 73% (95% CI, 43% - 91%) and the median progression-free survival was 3.4 months (95% CI, 2 - 5.2). The median overall survival from the beginning of the 2^ndEGFR-TKI and from diagnosis were 7.3 months (95% CI, 2.7 - 13) and 36.7 months (95% CI, 23.6 - 43.9), respectively. No statistical differences in PFS or OS were observed between gefitinib and erlotinib as the 2^ndEGFR-TKI (PFS, P = 0.23 and OS, P = 0.052). The toxicities associated with the 2^ndEGFR-TKI were generally acceptable and comparable to those observed for the initial gefitinib therapy.</p> <p>Conclusions</p> <p>Our results indicate that a 2^ndEGFR-TKI treatment can be an effective treatment option for gefitinib responders.</p

Perspective of Immune Checkpoint Inhibitors in Thymic Carcinoma

Thymic carcinoma is a rare neoplasm with a dismal prognosis, and there are no established therapeutic regimens for metastatic or recurrent disease. Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are widely approved in several human cancers, contributing to prolonging survival in thoracic tumors. Thymic carcinoma exhibits histologic properties of squamous cell carcinoma (SQC), and resembles the SQC of the lung. ICIs are not approved in thymic carcinoma. Thus, several clinical trials have been undertaken to demonstrate if they are therapeutically effective for patients with thymic carcinoma. In our review, three prospective phase II studies and several case series were discussed in thymic carcinoma. We found that the objective response rate, disease control rate, and progression-free survival in PD-1 blockade monotherapy were approximately 20%, 73%, and four months, respectively. Two exploratory investigations indicated that PD-L1 within tumor cells exhibits a possibility of the therapeutic prediction of PD-1 blockade in thymic carcinoma. Several case reports, alongside their treatment content, have also been reviewed. The therapeutic efficacy of PD-1 blockade monotherapy is still limited in patients with thymic carcinoma. Future perspectives focus on the therapeutic implication of tyrokinase inhibitors plus ICIs or new experimental agents plus ICIs alongside several ongoing experimental studies

Perspective of Immune Checkpoint Inhibitors in Thymic Carcinoma

Thymic carcinoma is a rare neoplasm with a dismal prognosis, and there are no established therapeutic regimens for metastatic or recurrent disease. Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are widely approved in several human cancers, contributing to prolonging survival in thoracic tumors. Thymic carcinoma exhibits histologic properties of squamous cell carcinoma (SQC), and resembles the SQC of the lung. ICIs are not approved in thymic carcinoma. Thus, several clinical trials have been undertaken to demonstrate if they are therapeutically effective for patients with thymic carcinoma. In our review, three prospective phase II studies and several case series were discussed in thymic carcinoma. We found that the objective response rate, disease control rate, and progression-free survival in PD-1 blockade monotherapy were approximately 20%, 73%, and four months, respectively. Two exploratory investigations indicated that PD-L1 within tumor cells exhibits a possibility of the therapeutic prediction of PD-1 blockade in thymic carcinoma. Several case reports, alongside their treatment content, have also been reviewed. The therapeutic efficacy of PD-1 blockade monotherapy is still limited in patients with thymic carcinoma. Future perspectives focus on the therapeutic implication of tyrokinase inhibitors plus ICIs or new experimental agents plus ICIs alongside several ongoing experimental studies

Advanced Research on Immune Checkpoint Inhibitor Therapy

The human body has an inherent immune surveillance mechanism that eliminates cancer cells and suppresses the development of cancer [...

Development of N2O emission factors derived from nitrification of treated sewage water in rivers

Because treated sewage water contains nitrogen compounds such as NH4-N and NO2+3-N, nitrous oxide (N2O) which is one of the greenhouse gases is generated by nitrification and denitrification reactions in rivers. This study aimed to develop a method for estimating the amount of N2O generated from the nitrification of residual N compounds in treated sewage water by subtracting the amount of residual N2O dissolved in the treated sewage water. A year-round field survey of dissolved N2O (D-N2O) in the treated sewage water and river water showed that nitrification proceeded in the downstream direction in the rivers following the discharge of the treated sewage water, thereby generating N2O. The deaeration rate of N2O dissolved in the river water was obtained from a laboratory experiment. The N2O emission factor that can be applied to in-river nitrification of NH4-N contained in the treated sewage water was calculated to be 0.0025 kgN2O-N kgNH4-N-1. HIGHLIGHTS N2O emissions derived from the nitrification of treated sewage water in rivers were investigated in Japan.; The laboratory experiment revealed the deaeration rates for D-N2O present in the rivers and treated sewage water.; N2O emission factor was developed for the nitrification of treated sewage water in rivers.

Salvage Chemotherapy in Patients with Previously Treated Thymic Carcinoma

Thymic carcinoma is a rare neoplasm, and it is difficult to achieve complete remission with systemic chemotherapy. In advanced or recurrent thymic carcinoma, platinum-based chemotherapy is chosen as the first-line setting; however, it remains unclear which regimen is better to improve its outcome. It remains unknown whether salvage chemotherapy should be administered to patients with platinum-based chemotherapy-refractory thymic carcinoma. Currently, several clinical studies have investigated the efficacy of second-line settings for advanced thymic carcinoma. As cytotoxic agents, S-1, amrubicin, pemetrexed, docetaxel, paclitaxel, and gemcitabine have been reported as prospective phase II studies or retrospective studies. The overall response rates (ORRs) of S-1, amrubicin, and pemetrexed were 25–50%, 11–44.4%, and 9–10%, respectively. Molecular targeting drugs, such as sunitinib, everolimus, and lenvatinib, also provide clinical effectiveness with tolerability after the failure of platinum-based regimens. Based on the results of the prospective phase II study, the ORR, median progression-free survival, and median overall survival were 16.6% and 5.6 months, respectively, in everolimus, 26% and 7.2 months, respectively, in sunitinib, and 38% and 9.3 months, respectively, in lenvatinib. Although it is difficult to compare each study, lenvatinib appears to be better in increasing efficacy as a second-line setting. However, each study had a small sample size, which may have biased the results of their studies. Further investigation is warranted to elucidate the therapeutic significance of salvage chemotherapy in advanced thymic carcinoma in a large-scale study