bluuebunny/crossref_metadata_2025_split huggingface dataset:
Research progression of PD-1/PD-L1 in non-small cell lung cancer
Authors: Liu Xing , Xie Xiaodong 
Published: June 2023

AbstractLung cancer is the leading cause of cancer-related mortality worldwide. Despite great progress in the development of target agents, most people who do not harbor a mutation do not benefit from these agents. Immunotherapy, which stimulates the body’s immune system to improve the anti-tumor immunity effect, is a new therapeutic method for non-small cell lung cancer (NSCLC). Programmed cell death 1 (PD-1) and its ligand (PD-L1) belong to the CD28/B7 immunoglobulin super-family and are co-stimulatory molecules that show negative regulation effects. Combined with its ligand, PD-1 can modulate the tumor microenvironment, enabling tumor cells to escape host immune surveillance and elimination and play a key role in the clinical significance of NSCLC. An increasing number of clinical trials have suggested that immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 monoclonal antibodies, are beneficial and safe for NSCLC. Here, we review the brief history of PD-L1 as a biomarker, mechanism of action, and critical role of PD-1/PD-L1 in the treatment of NSCLC as well as the current research status and future directions.
Effect of etoposide plus thalidomide as maintenance therapy on progression-free survival of elderly patients with advanced non-small cell lung cancer
Authors: Ge Yanan , Zheng Zhendong , Liu Zhaozhe , Qiu Jianing , Xie Xiaodong 
Published: June 2023

Abstract

Objective
The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer (NSCLC) without disease progression after first-line chemotherapy.

Methods
After four to six cycles of platinum-based first-line therapy, 64 elderly patients with advanced NSCLC without disease progression who were treated in the General Hospital of Shenyang Military Region (China) from 2014 to 2016 were enrolled in this study. According to the different maintenance treatment methods, patients were divided as having received etoposide plus thalidomide therapy (treatment group, n = 32) and best supportive care (control group, n = 32). Disease control and progression-free survival (PFS) were compared between the two groups.

Results
The recent curative effect objective response rates of the treatment group and the control group were 31.3% and 3.1%, respectively, and the disease control rates were 71.9% and 31.3%, respectively. The Kaplan-Meier survival curves of the two groups were significantly different (χ2 = 26.532, P = 0.001). The median PFS for the treatment group and control group was 6.0 months [95% confidence interval (CI) = 4.3-7.9 months] and 3.2 months (95% CI = 2.6-3.8 months), respectively. The side effects in the treatment group included hematologic abnormalities, gastrointestinal toxicity, and impaired liver function, which were relieved after symptomatic support therapy and drug withdrawal.

Conclusion
Etoposide plus thalidomide as maintenance therapy is associated with a significantly longer PFS with tolerable toxicity for elderly patients with advanced NSCLC.
Efficacy of pemetrexed combined with erlotinib/gefitinib in advanced non-small cell lung cancer patients during tyrosine kinase inhibitor treatment ⁎
Authors: Zhang Guanzhong , Liu Zhaozhe , Han Tao , Xie Xiaodong , Jiao Shunchang 
Published: June 2023

Abstract

Objective
We aimed to evaluate the efficacy and safety of pemetrexed combined with erlotinib/gefitinib in advanced non-small cell lung cancer (NSCLC) patients during tyrosine kinase inhibitor (TKI) treatment.

Methods
Thirty-two patients with advanced NSCLC were divided into two groups. Patients in the control group received continuous daily epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment, and patients in the experimental group received continuous daily EGFR-TKI along with pemetrexed treatment, which was administered on day 1 at 500 mg/m2. Erlotinib (150 mg) or gefitinib (250 mg) was administered daily from day 1 to day 21, with a cycle of every 21 days. Dexamethasone, folic acid, and vitamin B12 were also administered during the treatment. The endpoint of the primary study was the disease control rate.

Results
The objective response rate was 21.9% (95% CI: 7.6% to 36.3%) in the control group, whereas the disease control rate was 84.4% (95% CI: 71.8% to 97.0%) in the experimental group. The median progression-free survival was 6.2 (95% CI: 2.4 to 10.0). Grades 3 or 4 adverse effects of leucopenia (15.6%), neutropenia (12.5%), anemia (3.1%), and nausea or vomiting (3.1%) were found in the experimental group.

Conclusion
The administration of pemetrexed combined with erlotinib or gefitinib showed a higher efficacy in TKI-resistant NSCLC patients. Further, the adverse effects of this drug combination were well tolerated by the patients. Pemetrexed combined with TKI treatment might provide a satisfactory therapeutic strategy for advanced NSCLC patients after TKI treatment.
The role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis in lung cancer with c-Met amplification ⁎
Authors: Zhou Shaozhang , Dong Zhixin , Lv Jinyi , Zeng Aiping , Wang Huilin , Ning Ruiling , Song Xiangqun 
Published: June 2023

Abstract

Objective
This study aimed to study the role of the HGF/c-Met signaling pathway in crizotinib-induced apoptosis of various lung adenocarcinoma cell lines and xenograft tumor models.

Methods

In vitro, H2228, H1993, and A549 cells were treated with crizotinib. The inhibition of proliferation was quantitated by a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was quantified by flow cytometry. Expression of key proteins of the HGF/c-Met signaling pathway was examined by western blotting. In vivo, H1993 and A549 tumor cell xenograft models were established. Immunohistochemical analysis was used to determine protein expression of HGF and c-MET and the amount of phospho-c-MET (p-c-Met). Real-time quantitative polymerase chain reaction (PCR) was applied to examine the messenger RNA (mRNA) expression of c-MET and serine/ threonine protein kinase (AKT). The expression and activation of the key proteins were evaluated by western blotting.

Results

In vitro, the growth of H1993, H2228, and A549 cells was inhibited after crizotinib treatment for 72 h. Apoptotic rates of H1993 and H2228 cells increased with the crizotinib concentration and exposure time. In vivo, the growth-inhibitory rate of crizotinib for H1993 xenografts was 72.3%. Positive expression rates of HGF and c-MET in H1993 xenografts were higher than those in A549 xenografts; the p-c-MET amount was the largest in H1993 xenograft control but the lowest in the H1993 xenograft with crizotinib treatment. The mRNA expression levels of c-MET and AKT in H1993 xenografts were higher than those of A549 xenografts. The protein levels of c-MET, AKT, and extracellular regulated protein kinases (ERK) in H1993 xenografts were higher than those in A549 xenografts; the p-AKT amount was higher in H1993 xenograft control than in A549 xenografts; the largest amount of p-c-MET was detected in H1993 xenograft control; the amount of p-ERK was the lowest in the H1993 xenograft with crizotinib treatment.

Conclusion
The HGF/c-Met signaling pathway may mediate crizotinib-induced apoptosis and inhibition of proliferation of lung adenocarcinoma cells.
Expression of CXCL12-CXCR4 in osteosarcoma and its correlation with angiogenesis
Authors: Han Lu , Shen Yangyang , Zhao Wenhua , Sun Baoyong , Zhang Xin , Cui Kai , Zhou Lei , Li Sheng 
Published: June 2023

Abstract

Objective
The expression of CXCL12 (stromal cell-derived factor-1)-CXCR4 (chemokine receptors-4) in osteosarcoma and its role in angiogenesis were examined.

Methods
The expression of CXCR4 and CXCL12 in 40 cases of osteosarcoma was detected by immunohistochemistry and real-time fluorescence quantitative PCR. The expression of CD34 in osteosarcoma was detected by immunohistochemistry. Morphometric image analysis was performed to measure microvessel density (MVD). Additionally, the relationship between CXCL12 and CXCR4 expression and MVD of osteosarcoma and pulmonary metastasis were analyzed.

Results
The positive rates of CXCL12 and CXCR4 protein expression in osteosarcoma were 40.0% (16/40) and 60.0% (24/40), respectively. Fluorescence quantitative real-time PCR indicated that the expression level of CXCR4 mRNA in pulmonary metastatic osteosarcoma was higher than that in non-pulmonary metastatic osteosarcoma (P < 0.01). The level of MVD in pulmonary metastatic osteosarcoma was higher than that in non-pulmonary metastatic osteosarcoma (P < 0.01).

Conclusion
The expression level of CXCR4 was significantly associated with pulmonary metastasis and angiogenesis of osteosarcoma.
Function and clinical significance of SUMOylation in type I endometrial carcinoma
Authors: Cui Xin , Zhang Caixin , Li Yunhui , Qi Yongyun , Ding Xiaoyan , Hei Shumin , Huang Weiqing 
Published: June 2023

Abstract

Objective
This study elucidated the function and role of SUMOylation in type I endometrial carcinoma.

Methods
Fifty type I endometrial carcinoma cases and para-cancer tissue samples were collected. The expression levels of ubiquitin-conjugating enzyme E2 I (Ube2i, Ubc9) and small ubiquitin-like modifier 1 (SUMO1)/sentrin-specific peptidase 1 (SENP1) proteins were examined using immunohistochemistry and the correlation with clinicopathological parameters was analyzed.

Results
Ubc9 expression in type I endometrial carcinoma tissues was significantly higher than that in the para-cancer tissues; in contrast, the expression of the SENP1 protein was markedly lower than that in the para-cancer tissues. Ubc9 and SENP1 expression levels were negatively correlated and were associated with tumor differentiation, but not age, depth of invasion, tumor stage, and lymph node metastasis.

Conclusion
SUMOylation modification plays a major role in the pathogenesis and development of type I endometrial carcinoma. Thus, it could be a potential target for the treatment of endometrial cancer.
Complete transthoracic resection of giant posterior mediastinal goiter: A case report and review of the surgical approaches
Authors: Lin Gaoyang , Gao Dadeng , Yuan Fang , Lv Yingyi , Liu Zhenbo 
Published: June 2023

Abstract
Intrathoracic goiter (IG) is commonly located in the anterior mediastinum. Here, we report the case of a 54-year-old Chinese woman with successful removal of an intrathoracic goiter and improvement of dyspnea by a right posterolateral thoracotomy approach. Conclusion: Posterior mediastinal thyroid goiter with mediastinal compressive symptoms is an indication for surgery.
Risk factors for anastomotic leakage after low anterior resection without diversional stomas*
Authors: Chen Xiaolong , Feng Libo , Liu Yu , Wu Xiaolong , Xu Jie , Chen Peng , Zuo Zhonglin , Liu Yi , Zou Qingwei , Liu Qing , Xia Dong 
Published: June 2023

AbstractObjectiveThe most important complication after low anterior resection (LAR) for mid-low rectal cancer is symptomatic anastomotic leakage (AL). More than one-third of patients with rectal cancer who underwent LAR will have functional stomas during primary operation. The aim of this retrospective study was to evaluate the risk factors associated with clinical AL following LAR without diversional stomas.MethodsBetween 2012 and 2017, information about 578 consecutive patients with rectal tumors less than 12 cm from the anal verge who underwent LAR without diversional stomas by the same surgical team was collected retrospectively. A standardized extraperitonealized anastomosis and pelvic drainage were conducted for all patients during primary operations, and the outcome of interest was clinical AL. The associations between AL and 14 patient-related and surgical variables were examined by both univariate chi-square test and multivariate logistic regression analysis.ResultsThe AL rate was 7.27% (42 of 578). Univariate and multivariate analyses showed that male sex (P= 0.018), mid-low rectal cancer (located 10 cm or less above the anal verge) (P= 0.041), presence of diabetes (odds ratio = 2.117), longer duration of operation (odds ratio = 1.890), and intraoperative contamination (odds ratio = 2.163) were risk factors of AL for LAR without diversional stoma and independently predictive of clinical AL. Nearly 83.3% (35 of 42) of leakage could be cured by persistent pelvic irrigation-suction-drainage without surgical intervention. Only 7 patients (16.7%) with severe complications, such as peritonitis, and fistula, required reoperation, and functional stoma was used as a salvage treatment.ConclusionFrom the findings of this retrospective survey, we identified that mid-low rectal cancer and male sex were independent risk factors for developing clinical AL after LAR without diversional stomas, as well as longer duration of operation, presence of diabetes, and contamination of the operative field. Moreover, we deemed that LAR without diversional stomas for mid-low rectal cancers was safe, effective, and feasible. Extraperitonealized anastomosis and pelvic drainage obtained a relatively low rate of AL and avoided unnecessary functional stomas. Pelvic irrigation-suction-drainage was an effective procedure to resolve AL, and functional stoma was potentially used as a salvage modality for serious leakage.
A pulmonary metastatic breast phyllodes tumor and clinicopathology analysis
Authors: Li Jia , Li Gang , Xing Yixiang , Kang Min , Xu Xianjie 
Published: June 2023

AbstractObjectiveBreast phyllodes tumors (PTs) are rare fibroepithelial tumors that are characterized by formation of foliation patterns. Behaviorally, only relatively poor prediction of PTs is possible based on their histological appearance. PTs are frequently misdiagnosed because they are difficult to differentiate from soft tissue tumors. In this report, we describe the pathological features of a rare case of PT and review the relevant literature, summarizing the essentials of the diagnosis and differential diagnosis, while attempting to avoid misdiagnosis or missed diagnosis of the tumor to the best of our abilities.MethodsWe present a case of pulmonary metastatic lobular tumor, analyzing the morphological [hematoxylin-eosin (HE) staining] and immunohistochemical (streptavidin perosidase method, SP) features of the tissue.ResultsLong spindle-shaped tumor cells were observed using microscopy. The cells were arranged in bundles, with a whirlpool pattern, and braided. The proliferation of the spindle cells was markedly atypical and karyokinesis was elevated. Residual ductal epithelium was detected in some areas, and the margins of the tumor tissues showed invasive growth. Immunohistochemical studies of the spindle-shaped tumor cells were positive for actin, PR, CD10, SMA, Bcl-2, and negative for CKP, S-100, CD34, ER. The Ki-67 index was 40%.ConclusionThe spindle cell tumor identified in the lung should first be considered as a metastatic neosplasm, because most soft-tissue sarcomas commonly metastasize through the bloodstream to the lungs. Although malignant breast PTs are rare, a detailed medical history that includes prior surgical history is required to avoid wrongful or missed diagnosis.
Predictive value of serum levels of transforming growth factor beta 1 for the short-term effects of radiotherapy and chemotherapy in patients with esophageal cancer
Authors: Gao Fei , Jia Lin , Han Jianjun , Wang Jisheng , Wang Yun 
Published: June 2023

Abstract

Objective
To investigate variation in levels of transforming growth factor beta 1 (TGF-β1) before and after radiotherapy in patients with esophageal cancer in order to evaluate the predictive value of TGF-β1 for the effects of radiotherapy

Methods
A total of 140 patients with esophageal squamous carcinoma undergoing radical radiation therapy in the Department of Oncology from March 2015 to December 2017 were enrolled. The patients were divided into the effective (115 cases) and ineffective (25 cases) groups according to World Health Organization (WHO) criteria for the evaluation of solid tumors (2009 RECIST standard). TGF-β1 levels were measured in all patients by using enzyme-linked immunosorbent assay (ELISA). Multiple-factor analysis of the predictive value of the treatment efficacy was performed by Cox regression analysis.

Results
After radiotherapy, 36, 79, and 25 cases experienced complete response (CR), partial response (PR), and no response (NR), respectively, with a total effective rate of 82.14%. The TGF-β1 level was significantly lower in the effective group than that in the ineffective group (P < 0.05) and covariance analysis revealed significantly reduced TGF-β1 level in esophageal cancer patients following radiotherapy. The multi-factor Cox regression model revealed that the predictive value of TGF-β1 for the effect of radiotherapy was largest, with a hazard ratio [HR] of 1.955 (P = 0.002), followed by exposure dose, with (HR = 1.367; P = 0.035).

Conclusion
Serum TGF-β1 level can serve as a predictor for the short-term effects of radiotherapy in patients with esophageal cancer.
Nutritional status changes in patients with advanced non-small cell lung cancer receiving first-line chemotherapy
Authors: Sun Wei , Liu Shunfang , Peng Ping , Liu Dongbo 
Published: June 2023

Abstract

Objective
This study aimed to assess the real-life nutritional status changes and gastrointestinal symptoms in patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.

Methods
A total of 104 patients with metastatic NSCLC receiving first-line chemotherapy were included in this study. Unintentional weight loss, body mass index (BMI) changes, and gastrointestinal symptoms were recorded and evaluated. Biochemical parameters [hemoglobin (Hb) and albumin levels] were compared before and after two chemotherapy cycles using SPSS software.

Results
Of these patients, 65.38% (68/104) experienced unintentional weight loss, whereas 30.77% and 12.5% presented with ≥ 5% and ≥ 10% degrees of weight loss, respectively, within 6 months before first-line chemotherapy was administered. Then, 48.08% (50/104) of the patients experienced unintentional weight loss after two chemotherapy cycles. The mean body weight after chemotherapy was 61.47 ± 10.37 kg, which was significantly decreased relative to that before chemotherapy (P < 0.05). The mean BMI after chemotherapy was 22.66 ± 3.34 kg/m2, which was also significantly diminished with respect to that during the previous chemotherapy cycle (P < 0.05). The most common gastrointestinal symptoms reported among all the study patients were anorexia (80/104, 76.92%), nausea (53/104, 50.96%), constipation (49/104, 47.12%), vomiting (48/104, 46.15%), taste disorders (40/104, 38.46%), and early satiety (32/104, 30.77%). The mean Hb levels after chemotherapy were 117.06 ± 16.67 g/L, which were significantly lower than those before chemotherapy (132.73 ± 16.42 g/L) (P < 0.05). No significant difference was noted between the mean albumin levels before and after chemotherapy (38.29 ± 4.22 g/L vs 38.17 ± 4.54 g/L; P = 0.798).

Conclusion
Weight loss history, gastrointestinal symptoms, and Hb level decreases are determinant factors of nutritional status in patients with advanced NSCLC and must be included in the screening, evaluation, and treatment of lung carcinoma.
Establishment and characterization of an oxaliplatin-resistant hepatic cancer cell line*
Authors: Qiu Ping , Chen Gang , Dai Yuhong , Qiu Hong 
Published: June 2023

AbstractObjectiveThe aim of the current study was to establish an oxaliplatin-resistant hepatoma cell line (HepG2/OXA) and investigate the potential mechanisms of its drug resistance.MethodsThe hepatoma cell subline, HepG2/OXA, resistant to oxaliplatin (OXA), was established from a parent cell line HepG2, by stepwise exposure to gradually increasing concentrations of OXA over a half-year period. Chemosenstivity of the cytotoxic drugs, OXA, cisplatin (CDDP), adriamycin (ADM), and 5-fuorouracil (5-FU), was determined in HepG2 and HepG2/OXA cells, by the Cell counting kit-8 (CCK8) assay. Cell cycle distribution of HepG2 and HepG2/OXA cells was analyzed by Flow cytometry (FCM). The expression levels of several drug resistance-related proteins, such as P-glycoprotein (P-gp), multidrug resistant protein 1 (MRP1), and excision repair-cross complementing 1 (ERCC1) protein in the two cell lines were tested by the western blot assay.ResultsThe IC50 of OXA in HepG2/OXA and HepG2 were 136.84 µmol/L and 23.86 µmol/L, respectively. The resistance index (RI) was 5.34. HepG2 was also demonstrated to be cross-resistant to other anti-tumor agents, such as 5-FU, ADM, and CDDP. The percentage of HepG2/OXA cells in the S phase was significantly decreased compared to HepG2 cells (25.58% ± 2.36% vs 14.37% ± 2.54%,P< 0.05), while the percentage of cells in the G0/G1 and G2/M phases showed no statistical difference (respectively 55.29% ± 4.98% vs 56.73% ± 4.56%,P> 0.05, and 24.63% ± 4.81% vs 28.26% ± 3.82%,P> 0.05). The ERCC1 was found to be over expressed in HepG2/OXA cells, while there was no difference in the expressions of P-gp and MRP1 between the multiple drug resistance (MDR) phenotype cell line and its parental cell line.ConclusionHepG2/OXA showed an MDR ability; the over expression of ERCC1 might be associated with the platinum resistance of the cells, but P-gp and MRP1 are not.
The efficacy of capecitabine and temozolomide against neuroendocrine carcinomas
Authors: Gao Yanwei , Luan Wei , Li Wenxin , Jia Baoqing 
Published: June 2023

Abstract

Objective
Neuroendocrine carcinomas (NECs) are resistant to currently available chemotherapy agents, and its therapeutic options are limited. Preclinical data have suggested synergy between capecitabine and temozolomide (CAPTEM). Therefore, we evaluated the efficacy and safety of CAPTEM in patients with metastatic NECs who have failed prior therapies.

Methods
A retrospective review was conducted on seven patients with metastatic NECs for whom platinum-based chemotherapies and hepatic chemoembolization failed. Patients received capecitabine (1000 mg twice daily on days 1-14) and temozolomide (150-200 mg/m2 once daily on days 10-14) every 28 days. Tumor assessments were performed every two cycles.

Results
Among the seven patients treated, two achieved partial remission and four achieved stable disease. The total response rate was 29%, and the clinical benefit was 86%. Median progression-free survival was 10 (range: 8-14) months. The most common toxicities were grade 1 and 2 neutropenia, grade 1 fatigue, and grade 1 and 2 hand-foot syndrome. No grade 4 toxicities or treatment-related deaths were observed.

Conclusion
Our study showed that the CAPTEM regimen is an effective and well-tolerated salvage option for NECs. Further prospective studies are warranted to evaluate optimal combinations of the CAPTEM regimen for NECs.