Lycopene from tomatoes and tomato products exerts renoprotective effects by ameliorating oxidative stress, apoptosis, pyroptosis, fibrosis, and inflammatory injury in calcium oxalate nephrolithiasis: the underlying mechanisms.

Several mechanisms underlying nephrolithiasis, one of the most common urological diseases, involve calcium oxalate formation, including oxidative stress, inflammatory reactions, fibrosis, pyroptosis, and apoptosis. Although lycopene has strong antioxidant activity, its protective effects against CaOx-induced injury have not yet been reported. This study aimed to systematically investigate the protective effects of lycopene and explore its mechanisms and molecular targets. Crystal deposition, renal function, oxidative stress, inflammatory response, fibrosis, pyroptosis, and apoptosis were assessed to evaluate the renoprotective effects of lycopene against crystal formation in a CaOx rat model and oxalate-stimulated NRK-52E and HK-2 cells. Lycopene markedly ameliorated crystal deposition, restored renal function, and suppressed kidney injury by reducing oxidative stress, apoptosis, inflammation, fibrosis, and pyroptosis in the rats. In cell models, lycopene pretreatment reversed reactive oxygen species increase, apoptotic damage, intracellular lactate dehydrogenase release, cytotoxicity, pyroptosis, and extracellular matrix deposition. Network pharmacology and proteomic analyses were performed to identify lycopene target proteins under CaOx-exposed conditions, and the results showed that Trappc4 might be a pivotal target gene for lycopene, as identified by cellular thermal shift assay and surface plasmon resonance analyses. Based on molecular docking, molecular dynamics simulations, alanine scanning mutagenesis, and saturation mutagenesis, we observed that lycopene directly interacts with Trappc4 via hydrophobic bonds, which may be attributed to the PHE4 and PHE142 residues, preventing ERK1/2 or elevating AMPK signaling pathway phosphorylation events. In conclusion, lycopene might ameliorate oxalate-induced renal tubular epithelial cell injury via the Trappc4/ERK1/2/AMPK pathway, indicating its potential for the treatment of nephrolithiasis.

Current clinical application of lutetium­177 in solid tumors (Review).

Radionuclide-based therapy represents a novel treatment regimen for tumors. Among these therapies, lutetium-177 (177Lu) has gained significant attention due to its stability and safety, as well as its ability to emit both γ and ß rays, allowing for both imaging with single photon emission computed tomography and tumor treatment. As a result, 177Lu can be used for both diagnosis and treatment for diseases such as prostatic and gastric cancer. Therefore, based on the available data, the present review provides a brief overview of the clinical applications of 177Lu-targeted radionuclide therapy in metastatic prostate cancer, neuroendocrine tumors and other types of solid tumors, and highlights the current therapeutic effect, reduction in damage to normal tissues and future research directions, including the development of new nuclides and the application of more nuclides in different tumors. In the future, such treatments could be used in more tumors.

Prognostic value of preoperative serum ferritin in hepatocellular carcinoma patients undergoing transarterial chemoembolization.

The present study investigated the prognostic impact of preoperative serum ferritin (SF) levels on the survival of patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Clinicopathological characteristics and laboratory biomarkers of 223 patients with HCC who underwent TACE were retrospectively reviewed. The Kaplan-Meier method was used to calculate the overall survival (OS), and the log-rank test was used to evaluate statistical significance. Univariate and multivariate analyses were performed using Cox proportional hazards regression to evaluate the prognostic impact of SF in these patients. The present findings identified extrahepatic metastases [hazard ratio (HR)=0.490,95%; confidence interval (CI)=0.282-0.843; P=0.010)] and vascular invasion (HR=0.373; 95% CI=0.225-0.619; P<0.0001) as independent prognostic factors for OS. However, preoperative SF levels could not independently predict OS when compared with other prognostic factors (HR=0.810; 95% CI=0.539-1.216; P=0.309). In conclusion, preoperative SF level is an unreliable biochemical predictor of survival in patients with HCC undergoing TACE.

Efficacy and Safety of Dual Anti-HER2 Blockade and Docetaxel With or Without Carboplatin as Neoadjuvant Regimen for Treatment of HER2-Positive Breast Cancer.

Introduction: This study aimed to compare the efficacy and safety of docetaxel + trastuzumab + pertuzumab and docetaxel + carboplatin + trastuzumab + pertuzumab for treating HER2-positive breast cancer. Method: HER2-positive breast cancer from patients diagnosed between January 2020 and September 2022 were included in this retrospective study. Docetaxel + trastuzumab + pertuzumab or docetaxel + carboplatin + trastuzumab + pertuzumab was selected as the neoadjuvant regimen. The primary endpoint was a complete pathological remission rate. Secondary endpoints were toxicity during neoadjuvant treatment, adjustment of the neoadjuvant therapy scheme, and adjuvant medication. Result: A total of 81 patients were included in this study (38 in the docetaxel + carboplatin + trastuzumab + pertuzumab treatment group and 43 in the docetaxel + trastuzumab + pertuzumab group). The complete pathological remission rates in the docetaxel + carboplatin + trastuzumab + pertuzumab and docetaxel + trastuzumab + pertuzumab groups were 44.7% (95% confidence interval: 30.2%-60.3%) and 51.2% (95% confidence interval: 36.8%-65.4%), respectively. The incidence of grade 3 or higher toxicity in the docetaxel + carboplatin + trastuzumab + pertuzumab group was significantly higher than that in the docetaxel + trastuzumab + pertuzumab group (68.4% vs 39.5%, P = .009). Neutropenia and asthenia were the most common grade 3 or higher toxicities. The incidence of neoadjuvant scheme adjustment was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (26.3% vs 7.0%, P = .039). The proportion of patients who received <6 cycles of neoadjuvant therapy was significantly higher in the docetaxel + carboplatin + trastuzumab + pertuzumab group than in the docetaxel + trastuzumab + pertuzumab group (31.6% vs 4.7%, P = .004). Patients in the docetaxel + carboplatin + trastuzumab + pertuzumab group received higher doses of granulocyte-macrophage colony-stimulating factor. Conclusion: In the neoadjuvant treatment of HER2-positive breast cancer, the docetaxel + trastuzumab + pertuzumab regimen might be more tolerated than the docetaxel + carboplatin + trastuzumab + pertuzumab regimen and did not show a lower complete pathological remission rate. However, our findings require further validation through prospective studies.

Key changes in the future clinical application of ultra-high dose rate radiotherapy.

Ultra-high dose rate radiotherapy (FLASH-RT) is an external beam radiotherapy strategy that uses an extremely high dose rate (≥40 Gy/s). Compared with conventional dose rate radiotherapy (≤0.1 Gy/s), the main advantage of FLASH-RT is that it can reduce damage of organs at risk surrounding the cancer and retain the anti-tumor effect. An important feature of FLASH-RT is that an extremely high dose rate leads to an extremely short treatment time; therefore, in clinical applications, the steps of radiotherapy may need to be adjusted. In this review, we discuss the selection of indications, simulations, target delineation, selection of radiotherapy technologies, and treatment plan evaluation for FLASH-RT to provide a theoretical basis for future research.

Mechanisms of FLASH effect.

FLASH radiotherapy (FLASH-RT) is a novel radiotherapy technology defined as ultra-high dose rate (≥ 40 Gy/s) radiotherapy. The biological effects of FLASH-RT include two aspects: first, compared with conventional dose rate radiotherapy, FLASH-RT can reduce radiation-induced damage in healthy tissue, and second, FLASH-RT can retain antitumor effectiveness. Current research shows that mechanisms of the biological effects of FLASH-RT are related to oxygen. However, due to the short time of FLASH-RT, evidences related to the mechanisms are indirect, and the exact mechanisms of the biological effects of FLASH-RT are not completely clear and some are even contradictory. This review focuses on the mechanisms of the biological effects of FLASH-RT and proposes future research directions.

Research progress on the mechanism of radiation enteritis.

Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. The efficacy of cancer treatment by radiation is often limited by the side effects of Re. Re can be acute or chronic. Treatment of acute Re is essentially symptomatic. However, chronic Re usually requires surgical procedures. The underlying mechanisms of Re are complex and have not yet been elucidated. The purpose of this review is to provide an overview of the pathogenesis of Re. We reviewed the role of intestinal epithelial cells, intestinal stem cells (ISCs), vascular endothelial cells (ECs), intestinal microflora, and other mediators of Re, noting that a better understanding of the pathogenesis of Re may lead to better treatment modalities.

A HALP score-based prediction model for survival of patients with the upper tract urothelial carcinoma undergoing radical nephroureterectomy.

The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP<28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (P<0.001) and progression-free survival (PFS) (P<0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, P=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, P=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.

First demonstration of the FLASH effect with ultrahigh dose rate high-energy X-rays.

PURPOSE: This study aimed to evaluate whether high-energy X-rays (HEXs) of the PARTER (platform for advanced radiotherapy research) platform built on CTFEL (Chengdu THz Free Electron Laser facility) can produce ultrahigh dose rate (FLASH) X-rays and trigger the FLASH effect. MATERIALS AND METHODS: EBT3 radiochromic film and fast current transformer (FCT) devices were used to measure absolute dose and pulsed beam current of HEXs. Subcutaneous tumor-bearing mice and healthy mice were treated with sham, FLASH, and conventional dose rate radiotherapy (CONV), respectively to observe the tumor control efficiency and normal tissue damage. RESULTS: The maximum dose rate of HEXs of PARTER was up to over 1000 Gy/s. Tumor-bearing mice experiment showed a good result on tumor control (p < 0.0001) and significant difference in survival curves (p < 0.005) among the three groups. In the thorax-irradiated healthy mice experiment, there was a significant difference (p = 0.038) in survival among the three groups, with the risk of death decreased by 81% in the FLASH group compared to that in the CONV group. The survival time of healthy mice irradiated in the abdomen in the FLASH group was undoubtedly higher (62.5% of mice were still alive when we stopped observation) than that in the CONV group (7 days). CONCLUSION: This study confirmed that HEXs of the PARTER system can produce ultrahigh dose rate X-rays and trigger a FLASH effect, which provides a basis for future scientific research and clinical application of HEX in FLASH radiotherapy.

Radioimmunotherapy Combined With Low-Intensity Ultrasound and Microbubbles: A Potential Novel Strategy for Treatment of Solid Tumors.

The prognosis of advanced malignant tumors is very poor, and effective treatment is limited. Radioimmunotherapy (RIT) is a novel treatment method. However, its anti-tumor effect is relatively low in solid tumors, which is mainly due to the blood-tumor barrier preventing RIT from penetrating the tumor, resulting in an insufficient dose. Low-intensity ultrasound with microbubbles (USMB) has proven capable of opening the blood-tumor barrier. The combination of the two technologies may overcome the poor anti-tumor effect of RIT and promote the clinical application of RIT in solid tumors. In this article, we reviewed the current research status of RIT in the treatment of solid tumors and the opportunities and challenges of USMB combined with RIT.

Anlotinib Combined with S-1 in Third- or Later-Line Stage IV Non-Small Cell Lung Cancer Treatment: A Phase II Clinical Trial.

LESSONS LEARNED: The combination of anlotinib and S-1 exhibited good antitumor activity in third- or later-line treatment for stage IV non-small cell lung cancer (NSCLC). Combination therapy of anlotinib with S-1 has manageable toxicities in patients with NSCLC. BACKGROUND: This study aimed to evaluate the efficacy and safety of anlotinib combined with S-1 as a third- or later-line treatment for patients with stage IV non-small cell lung cancer (NSCLC). Anlotinib was approved in 2018 by the Chinese Food and Drug Administration (FDA) as a third-line treatment for patients with refractory advanced NSCLC and is under study in the U.S. and Europe. METHODS: Simon's phase II clinical trial design with an α error of 5% and a power ß of 80% was used, anticipating a 10% objective response rate (ORR) of anlotinib and a 30% ORR of anlotinib combined with S-1; the required sample size was 29. A total of 29 patients were enrolled in the clinical trial. Patients were treated with anlotinib plus S-1 over a 21-day treatment course until disease progression or unacceptable toxic effects. If the efficacy was assessed as stable disease, partial response, or complete response after six cycles, anlotinib was maintained until disease progression or death. The primary endpoint was the objective response rate. Somatic mutations were not required for study enrollment. RESULTS: The median follow-up time was 11.1 months. Objective responses were observed in 11 of 29 (37.9%) patients making up the intention-to-treat population, which reached the target primary endpoint of 30% ORR. The median overall and progression-free survival were 16.7 and 5.8 months, respectively. The most common grade 3 adverse events (AEs) were gastrointestinal, including nausea, vomiting and diarrhea, fatigue, and hypertension. No grade 4 treatment-related AEs or treatment-related deaths occurred. CONCLUSION: The combination of anlotinib with S-1 in the third- or later-line treatment of stage IV NSCLC shows promising antitumor activity and manageable toxicity in patients with NSCLC; phase III trials will be planned in the future.

FLASH Radiotherapy: History and Future.

The biological effects of radiation dose to organs at risk surrounding tumor target volumes are a major dose-limiting constraint in radiotherapy. This can mean that the tumor cannot be completely destroyed, and the efficacy of radiotherapy will be decreased. Thus, ways to reduce damage to healthy tissue has always been a topic of particular interest in radiotherapy research. Modern radiotherapy technologies such as helical tomotherapy (HT), intensity-modulated radiation therapy (IMRT), and proton radiotherapy can reduce radiation damage to healthy tissues. Recent outcomes of animal experiments show that FLASH radiotherapy (FLASH-RT) can reduce radiation-induced damage in healthy tissue without decreasing antitumor effectiveness. The very short radiotherapy time compared to that of conventional dose-rate radiotherapy is another advantage of FLASH-RT. The first human patient received FLASH-RT in Switzerland in 2018. FLASH-RT may become one of the main radiotherapy technologies in clinical applications in the future. We summarize the history of the development of FLASH-RT, its mechanisms, its influence on radiotherapy, and its future.

Whole-Brain Radiation Therapy With Simultaneous Integrated Boost Versus Whole-Brain Radiation Therapy Plus Stereotactic Radiosurgery for the Treatment of Brain Metastasis From Lung Cancer.

Radiotherapy is one of the most important treatments for brain metastasis (BM). This study aimed to assess whether whole-brain radiation therapy (WBRT) with simultaneous integrated boost (SIB) provided any therapeutic benefit compared to WBRT followed by stereotactic radiosurgery (SRS). Seventy-two consecutive cases of lung cancer with BM treated from January 2014 to June 2020 were analyzed retrospectively. Thirty-seven patients were treated with WBRT (30 Gy in 10 fractions) and SIB (45 Gy in 10 fractions), and 35 patients were treated with WBRT (30 Gy in ten fractions) followed by SRS (16-24 Gy according to the maximum tumor diameter). The primary endpoint was intracranial progression-free survival (PFS). The secondary endpoints were intracranial objective response (partial and complete responses), pattern of intracranial progression, overall survival (OS), and toxicity. The WBRT + SIB group had a significantly longer median intracranial PFS (9.1 vs. 5.9 months, P = 0.001) than the WBRT + SRS group. The intracranial objective response rate was 67.6% and 62.9% in the WBRT + SIB and in WBRT + SRS groups, respectively (P = 0.675). The incidence of progression outside the P-GTV in the WBRT + SIB group was significantly lower than that in the WBRT + SRS group (39.4% vs. 75.0%, P = 0.004). The median OS was 24.3 and 20.3 months in the WBRT + SIB and WBRT + SRS groups, respectively (P = 0.205). There was no significant difference in the incidence of grade 3 or worse adverse reactions between the two groups. Compared to treatment with WBRT + SRS, that with WBRT + SIB for BM appeared to contribute to local control.

Prognostic impact of eosinophils in peripheral blood and tumor site in patients with esophageal squamous cell carcinoma treated with concurrent chemoradiotherapy.

ABSTRACT: To date, no effective biological markers have been identified for predicting the prognosis of esophageal cancer patients. Recent studies have shown that eosinophils are independent prognostic factors in some cancers. This study aimed to identify the prognostic impact of eosinophils in esophageal squamous cell carcinoma patients treated with concurrent chemoradiotherapy (CCRT).This study enrolled 136 patients who received CCRT for locally advanced unresectable esophageal squamous cell carcinoma (ESCC). We evaluated the survival time and clinical pathological characteristics of eosinophils. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used for univariate analysis and the Cox proportional hazards regression model was used to conduct a multivariate analysis.Kaplan-Meier analysis revealed that high eosinophil infiltration correlated with better overall survival (OS) (P = .008) and better progression-free survival (PFS) (P = .015). The increase in absolute eosinophil count after CCRT also enhanced OS (P = .005) and PFS (P = .007). The PFS and OS in patients with high blood eosinophil count before CCRT (>2%) was better than those with low blood eosinophil count(<2%) (P = .006 and P = .001, respectively). Additionally, the multivariate analysis revealed that disease stage and high eosinophil infiltration, increased peripheral blood absolute eosinophil count after CCRT, and high peripheral blood eosinophil count before CCRT were independent prognostic indicators.High eosinophil count of tumor site, increased peripheral blood absolute eosinophil count after CCRT, and high peripheral blood eosinophil count before CCRT are favorable prognostic factors for patients with ESCC treated with CCRT.

Association of preoperative systemic Immune-inflammation Index and Prognostic Nutritional Index with survival in patients with Upper Tract Urothelial Carcinoma.

Background: Both systemic inflammation response and malnutrition are closely related to poor prognosis in patients with certain types of solid tumor. This study investigated the prognostic value of the preoperative combination of systemic immune-inflammation index and prognostic nutritional index (SII-PNI) in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Methods: The predictive ability of SII-PNI was developed and further validated in a cohort of 525 UTUC patients (253 in the training cohort and 272 in the validation cohort) who received RNU. Results: Survival analysis indicated that a SII ≥672.44 was significantly associated with worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) while a PNI ≥47.83 was associated with better survival outcomes (All P-values < 0.05). The combination of simultaneously SII ≥672.44 and PNI <47.83 was a powerful independent risk factor for OS, CSS, and RFS (P < 0.05). The SII-PNI had the largest area under the curve (AUC) compared to that for SII or PNI alone and other clinical factors, indicating its superior for predicting survival. In addition, the incorporation of the SII-PNI into established nomograms or current clinical parameters such as pathologic T stage and N stage, achieved higher c-indexes or larger AUC than without, indicating that adding SII-PNI helped predict prognosis. All results were found in the training cohort and confirmed in the validation cohort. Conclusions: SII-PNI was a strong independent predictor of UTUC patients after RNU.

Distribution of brain metastases: low-risk metastasis areas may be avoided when treating with whole-brain radiotherapy.

OBJECTIVE: Previous work has demonstrated that metastases are not uniformly distributed across the brain. This study aims to determine there are low-risk brain metastasis (BM) areas that may be avoided during whole-brain radiotherapy (WBRT) to reduce neurocognitive toxicity. METHODS: Clinical and magnetic resonance imaging (MRI) data of 991 metastases in 192 patients with advanced cancer were analyzed retrospectively. Eleven anatomically defined regions of interest (ROIs) were contoured, and the locations of the BMs were recorded. Using the same definition, ROIs were contoured in 20 healthy volunteers.The proportions of patients with BMs in different ROIs, proportion of BMs, and proportion of different ROI volumes relative to the total volume were calculated. RESULTS: The proportion of observed BMs was lower than expected in the brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary gland. The proportion of BMs was significantly higher than expected in the parietal lobe, occipital lobe, and cerebellum. For those patients with single BM, there was very low rate of low-risk ROIs involvement (0%), with 2-4 BMs, 6-13% of the patients had low-risk ROIs involvement, with ≥5 BMs, significant (> 30%) of the patients had low-risk ROIs involvement. CONCLUSION: The brainstem, insula, diencephalon and internal structures, corpus callosum, and pituitary gland demonstrate low risk for metastatic involvement. Involvement of low risk areas occurs in patients with more than 1 BM.

The Fib-PNI-MLR Score, an Integrative Model of Coagulation Cascades, Nutrition Status, and Systemic Inflammatory Response, Predicts Urological Outcomes After Surgery in Patients With Non-Metastatic Renal Cell Carcinoma.

Cancer-associated inflammation, activation of coagulation cascades, and malnutrition are closely related to the prognosis of patients with malignancy, including renal cell carcinoma (RCC). This study aimed to investigate the prognostic value of a combination of preoperative plasma fibrinogen, prognostic nutritional index, and monocyte-to-lymphocyte ratio (Fib-PNI-MLR) in patients with non-metastatic RCC undergoing nephrectomy. We retrospectively collected medical data from 829 of the 1,019 cases of RCC. The optimal cutoff values of fibrinogen (≥3.54 vs. <3.54, mg/dl), PNI (<47.03 vs. ≥47.03), and MLR (≥0.29 vs. <0.29) were defined using receiver operating characteristic (ROC) analysis and the Fib-PNI-MLR score (range, 0-3) was determined as the sum of points (0 or 1) assigned to each indicator. As a result, Fib-PNI-MLR was an independent risk factor for overall survival (OS), cancer-specific survival (CSS), and metastatic-free survival (MFS) (all P < 0.05). The concordance-index and area under the curve (AUC) were larger for the Fib-PNI-MLR score than that for other clinical parameters. Subgroup analysis (Fuhrman grade G1+G2 and Fuhrman grade G3+G4; pathologic T1, T2, and T3-4 stage) revealed the significant association of a higher Fib-PNI-MLR score with poor urological outcomes (all P < 0.05). Data indicated that patients with higher Fib-PNI-MLR might benefit from partial nephrectomy. The Fib-PNI-MLR score might serve as a promising prognostic factor in patients with non-metastatic RCC.

Efficient inhibition of cervical cancer by dual drugs loaded in biodegradable thermosensitive hydrogel composites.

BACKGROUND AND PURPOSE: We aimed to explore the anti-tumor effect and mechanism of the combination of cisplatin (DDP)-containing thermosensitive hydrogel (PEG-PCL-PEG, or PECE) and paclitaxel (PTX)-loaded MPEG-PCL polymeric micelles called PDMP on human cervical carcinoma (HeLa) cell. In our previous studies, we found that PDMP in situ treatment of lung cancer will be liable to have potential in Lung cancer patients. RESULTS: Compared with other treatments, PDMP was most effective in prolonging survival time (P < 0.05), inhibiting tumor growth (P < 0.05), decreasing expression of CD133 (P < 0.05), CD31 (P < 0.05), and aldehyde dehydrogenase 1 (ALDH1) (P > 0.05), inducing G1 phase arrest (P < 0.05), increasing the apoptosis rate (P < 0.05), and in expressing ATM and γ-H2AX (P < 0.05). CONCLUSIONS: PDMP is regarded as a promising anti-tumor reactant, when it comes to the treatment of cervical carcinoma. METHODS: we used a xenograft cervical cancer model to verify the anti-tumor activity of PDMP and to explore its mechanism of action. Mice were intratumorally administered with NS, PECE, PTX+DDP or PDMP. After two days of treatment, three mice per group were sacrificed and tumor tissue was harvested. Levels of histone H2AX phosphorylation (γ-H2AX) were determined by immunohistochemistry and ataxia telangiectasia mutated(ATM) protein levels were measured by western blot analysis. In addition, it would sacrifice each of group of three mice through 10 days' treatment, what's more, it would harvest tumor by virtue of flow cytometry and immunohistochemical analysis. It would like to use there maining mice to analyze tumor growth and survival. The remaining mice were analyzed for tumor growth and survival.

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

BACKGROUND: Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. METHODS: This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. RESULTS: In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. CONCLUSION: The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.