Personalized Estimate of Chemotherapy-Induced Nausea and Vomiting: Development and External Validation of a Nomogram in Cancer Patients Receiving Highly/Moderately Emetogenic Chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) is presented in over 30% of cancer patients receiving highly/moderately emetogenic chemotherapy (HEC/MEC). The currently recommended antiemetic therapy is merely based on the emetogenic level of chemotherapy, regardless of patient's individual risk factors. It is, therefore, critical to develop an approach for personalized management of CINV in the era of precision medicine.A number of variables were involved in the development of CINV. In the present study, we pooled the data from 2 multi-institutional investigations of CINV due to HEC/MEC treatment in Asian countries. Demographic and clinical variables of 881 patients were prospectively collected as defined previously, and 862 of them had full documentation of variables of interest. The data of 548 patients from Chinese institutions were used to identify variables associated with CINV using multivariate logistic regression model, and then construct a personalized prediction model of nomogram; while the remaining 314 patients out of China (Singapore, South Korea, and Taiwan) entered the external validation set. C-index was used to measure the discrimination ability of the model.The predictors in the final model included sex, age, alcohol consumption, history of vomiting pregnancy, history of motion sickness, body surface area, emetogenicity of chemotherapy, and antiemetic regimens. The C-index was 0.67 (95% CI, 0.62-0.72) for the training set and 0.65 (95% CI, 0.58-0.72) for the validation set. The C-index was higher than that of any single predictor, including the emetogenic level of chemotherapy according to current antiemetic guidelines. Calibration curves showed good agreement between prediction and actual occurrence of CINV.This easy-to-use prediction model was based on chemotherapeutic regimens as well as patient's individual risk factors. The prediction accuracy of CINV occurrence in this nomogram was well validated by an independent data set. It could facilitate the assessment of individual risk, and thus improve the personalized management of CINV

Immediate Versus Delayed Topotecan after First-line Therapy in Small Cell Lung Cancer

Background and objective How to prolong progression free survival (PFS) and overall survival (OS) of patients with small cell lung cancer (SCLC) has been one of the hottest issues. We retrospectively reviewed our data to compare the survival of immediate with delayed topotecan after first-line therapy in SCLC. Methods In our retrospective study, 53 patients with SCLC were divided into two groups as follow: patients receiving topotecan-containing regimen as maintenance/consolidation (maintenance/consolidation chemotherapy group) and salvage chemotherapy (salvage chemotherapy group). The Log-rank test was used to assess the difference in OS between two groups. Cox regression model was used for the multivariable analysis of independent prognostic factors. Results Twenty-nine patients received topotecan as maintenance/consolidation treatment, whereas 24 patients salvage chemotherapy. The response rates were 51.7% and 41.7%, respectively. The median survival time were 20 months and 27 months respectively (P=0.89). Multivariate Cox regression analyses identified sex and stage as independent prognostic factors. Conclusion Efficacy of first-line therapy was improved by topotecan maintenance/consolidation treatment, which did not result in any significant survival benefits in SCLC

The Plastic Scintillator Detector at DAMPE

he DArk Matter Particle Explorer (DAMPE) is a general purposed satellite-borne high energy $\gamma-$ray and cosmic ray detector, and among the scientific objectives of DAMPE are the searches for the origin of cosmic rays and an understanding of Dark Matter particles. As one of the four detectors in DAMPE, the Plastic Scintillator Detector (PSD) plays an important role in the particle charge measurement and the photons/electrons separation. The PSD has 82 modules, each consists of a long organic plastic scintillator bar and two PMTs at both ends for readout, in two layers and covers an overall active area larger than 82 cm $\times$ 82 cm. It can identify the charge states for relativistic ions from H to Fe, and the detector efficiency for Z=1 particles can reach 0.9999. The PSD has been successfully launched with DAMPE on Dec. 17, 2015. In this paper, the design, the assembly, the qualification tests of the PSD and some of the performance measured on the ground have been described in detail

A Prospective Randomized Study of the Radiotherapy Volume for Limited-stage Small Cell Lung Cancer: A Preliminary Report

Background and objective Controversies exists with regard to target volumes as far as thoracic radiotherapy (TRT) is concerned in the multimodality treatment for limited-stage small cell lung cancer (LSCLC). The aim of this study is to prospectively compare the local control rate, toxicity profiles, and overall survival (OS) between patients received different target volumes irradiation after induction chemotherapy. Methods LSCLC patients received 2 cycles of etoposide and cisplatin (EP) induction chemotherapy and were randomly assigned to receive TRT to either the post- or pre-chemotherapy tumor extent (GTV-T) as study arm and control arm, CTV-N included the positive nodal drainage area for both arms. One to 2 weeks after induction chemotherapy, 45 Gy/30 Fx/19 d TRT was administered concurrently with the third cycle of EP regimen. After that, additional 3 cycles of EP consolidation were administered. Prophylactic cranial irradiation (PCI) was administered to patients with a complete response. Results Thirty-seven and 40 patients were randomly assigned to study arm and control arm. The local recurrence rates were 32.4% and 28.2% respectively (P=0.80); the isolated nodal failure (INF) rate were 3.0% and 2.6% respectively (P=0.91); all INF sites were in the ipsilateral supraclavicular fossa. Medastinal N3 disease was the risk factor for INF (P=0.02, OR=14.13, 95%CI: 1.47-136.13). During radiotherapy, grade I, II weight loss was observed in 29.4%, 5.9% and 56.4%, 7.7% patients respectively (P=0.04). Grade 0-I and II-III late pulmonary injury was developed in 97.1%, 2.9% and 86.4%, 15.4% patients respectively (P=0.07). Median survival time was 22.1 months and 26.9 months respectively. The 1 to 3-year OS were 77.9%, 44.4%, 37.3% and 75.8%, 56.3%, 41.7% respectively (P=0.79). Conclusion The preliminary results of this study indicate that irradiant the post-chemotherapy tumor extent (GTV-T) and positive nodal drainage area did not decrease local control and overall survival while radiation toxicity was reduced. But the current sample size has not met designed requirements, and further investigation is warranted before final conclusions could be drawn

Docetaxel-loaded M1 macrophage-derived exosomes for a safe and efficient chemoimmunotherapy of breast cancer

The conversion of tumor-promoting M2 macrophage phenotype to tumor-suppressing M1 macrophages is a promising therapeutic approach for cancer treatment. However, the tumor normally provides an abundance of M2 macrophage stimuli, which creates an M2 macrophage-dominant immunosuppressive microenvironment. In our study, docetaxel (DTX) as chemotherapeutic modularity was loaded into M1 macrophage-derived exosomes (M1-Exo) with M1 proinflammatory nature to establish DTX-M1-Exo drug delivery system. We found that DTX-M1-Exo induced naïve M0 macrophages to polarize to M1 phenotype, while failed to repolarize to M2 macrophages upon Interleukin 4 restimulation due to impaired mitochondrial function. This suggests that DTX-M1-Exo can achieve long-term robust M1 activation in immunosuppressive tumor microenvironment. The in vivo results further confirmed that DTX-M1-Exo has a beneficial effect on macrophage infiltration and activation in the tumor tissues. Thus, DTX-M1-Exo is a novel macrophage polarization strategy via combined chemotherapy and immunotherapy to achieve great antitumor therapeutic efficacy

Bibliometric analysis of nutrition in gastric cancer from 2013 to 2023

BackgroundIncreasing evidence suggests that nutrition plays an important role in the treatment of gastric cancer. However, no bibliometrics analysis has been conducted in this field. Our study aimed to conduct a bibliometric study to explore the latest publishing trends and areas of intense activity within the sphere of nutrition in gastric cancer.MethodPublications were extracted from the Web of Science Core Collection. CiteSpace (Version 6.2.4) and VOSviewer (Version 1.6.18) were used for visual analysis.ResultsIn total, there were 441 publications authored by 2,941 authors from 809 organizations and 47 countries, published in 182 journals from 2013 to 2023. The most prolific country was China, and the most productive institution was the Chinese Academy of Medical Sciences. The leading core journal was Nutrients. P Daisuke Kobayashi and Yasuhiro Kodera were the most influential authors. The first highly cited document was published in Gastric Cancer by Kamarajah et al. The hotspots in this field were nutrition treatment and nutritional status. Moreover, research on nutritional status and nutrition-related prognosis in gastric cancer might be a potential trend.ConclusionNutrition in gastric cancer is a burgeoning research field garnering increasing attention. Further investigation is necessary to better understand the impact of nutritional status on the prognosis of gastric cancer

Inflammation-based prognostic system predicts postoperative survival of esophageal carcinoma patients with normal preoperative serum carcinoembryonic antigen and squamous cell carcinoma antigen levels

BACKGROUND: The Glasgow Prognostic Score (GPS) is an established inflammation-based system that is used to predict the prognosis for several types of malignancies. In this retrospective study, we assessed the postoperative survival of 725 patients with non-metastatic esophageal squamous cell carcinoma who had normal preoperative serum tumor marker levels according to the GPS. METHODS: Among 1394 patients who underwent esophagectomy between August 2006 and December 2010, 725 with normal preoperative serum levels of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were enrolled. All demographic, pathologic, and survival data were analyzed retrospectively. Uni- and multivariate analyses were performed to evaluate the relationship with overall survival. The Kaplan–Meier analysis and log-rank tests were used to compare the survival curves between patients with GPS 0 (group A) and 1 or 2 (group B). RESULTS: Patients in group A exhibited significantly better 3- and 5-year cancer-specific survival (CSS) rates (0.780 and 0.759, respectively) than those in group B (0.624 and 0.605, respectively). Multivariate Cox regression analysis revealed that age, tumor length, pathological tumor-node-metastasis (pTNM) stage, venous invasion, lymph node metastasis, serum albumin and C-reactive protein levels, and GPS were associated with postoperative survival of these patients. Further multivariate analysis confirmed that GPS was an independent prognostic factor. The Kaplan–Meier analysis and log-rank tests demonstrated a significant difference in CSS between groups A and B (P = 0.001). CONCLUSIONS: GPS may be a valuable prognostic indicator for esophageal cancer patients with normal preoperative CEA and SCC-Ag serum levels

Protection of Bovine Mammary Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Cell Damage by Resveratrol

The mammary epithelial cells (MECs) of high-producing dairy cows are likely to be subject to oxidative stress (OS) due to the intensive cell metabolism. The objectives of this study were to investigate the cytoprotective effects of resveratrol against hydrogen peroxide- (H2O2-) induced OS in cultured bovine MECs (MAC-T). Pretreatment of MAC-T cells with resveratrol could rescue the decrease in cell viability and resulted in lower intracellular reactive oxygen species (ROS) accumulation after H2O2 exposure. Resveratrol helped MAC-T cells to prevent H2O2-induced endoplasmic reticulum stress and mitochondria-related cell apoptosis. Moreover, resveratrol induced mRNA expression of multiple antioxidant defense genes in MAC-T cells under normal/oxidative conditions. Nuclear factor erythroid 2-related factor 2 (Nrf2) was required for the cytoprotective effects on MAC-T cells by resveratrol, as knockdown of Nrf2 significantly abolished resveratrol-induced cytoprotective effects against OS. In addition, by using selective inhibitors, we further confirmed that the induction of Nrf2 by resveratrol was mediated through the prolonged activation of PI3K/Akt and ERK/MAPK pathways but negatively regulated by p38/MAPK pathway. Overall, resveratrol has beneficial effects on bovine MECs redox balance and may be potentially used as a therapeutic medicine against oxidative insult in lactating animals

Bone-protective effects of deer-hide gelatin in cyclophosphamide-induced osteoporosis rats

Chemotherapy is a cornerstone of cancer treatment, but its adverse effects, particularly those related to the cardiovascular and skeletal systems, are drawing more attention. According to studies, the PI3K/AKT signaling pathway may be involved in myelosuppression and cardiotoxicity, two types of multi-organ damage caused by chemotherapy. Despite the absence of thorough research, deer hide gelatin (DHG), a traditional Chinese medicine high in collagen, has shown promise in the prevention and treatment of skeletal and hematological disorders. This study aimed to evaluate the protective effects of DHG on chemotherapy-induced osteoporosis (OP) in rat bone tissue, as well as the material basis and mechanisms of its anti-OP activity. The results showed that DHG reversed the decrease in bone mineral density induced by chemotherapy, improved bone biomechanical properties, and ameliorated bone microstructure. DHG promoted the expression of the osteoblast-related indicators BALP and P1NP while suppressing the expression of the osteoclast-related marker TRACP-5b. Protein mass spectrometry screening was used to find putative anti-OP bioactive peptides. According to network pharmacology predictions, the PI3K signaling pathway may be the mechanism by which the active peptides in DHG produce their anti-OP actions. Additionally, immunofluorescence investigation demonstrated that DHG inhibited MMP9 expression while increasing RUNX2 expression. In vitro experiments also confirmed that DHG active peptides promoted bone formation by activating the PI3K/AKT/ERK signaling pathway, upregulating RUNX2 protein expression, and promoting osteoblast differentiation and mineralization. In conclusion, DHG has protective benefits against OP caused by chemotherapy. This also raises the possibility that DHG could be useful in the broader management of chemotherapy side effects (e.g., potentially related to cardio-oncology, considering the pathway’s important role in organs like the heart), warranting further investigation