bluuebunny/crossref_metadata_2025 huggingface dataset:
Brown tumor of the femur and ulna in a woman with hyperparathyroidism
Authors: Jiang Lu , Huang Yi , Han Yazhou
Published: June 2023

Objective

A typical brown tumor caused by hyperparathyroidism (HPT) is rare. In this report, we describe our pathological findings along with a review of the literature to enhance understanding of the disease and prevent misdiagnosis, as well as to provide evidence for treatment and prognosis.

Methods

We present a case of brown tumor of the left proximal femur and pelvis in a 57-year-old woman who was admitted to our hospital (Dalian Municipal Central Hospital, Dalian, China). Pelvic computed tomography (CT) showed cystic expansile lesions in the left proximal femur and pelvis. Lung and abdominal CT also revealed multiple lytic lesions in the ribs and lumbar spine. X-ray of the left ulna and radius showed that the middle of the left ulna had a fracture caused by a brown tumor. A bone biopsy from the left proximal femur showed focal distribution of giant cells, with hemorrhage and fibrin hyperplasia.

Results

The patient underwent internal fixation of the left intertrochanteric fracture, and postoperative bone biopsy showed focal distribution of giant cells with hemorrhage and fibrin hyperplasia. The patient had a parathyroidectomy 5 months after discharge. Two weeks later, the patient developed a fracture in the right femoral neck and pain in the left forearm. X-ray of the left ulna and radius showed that the middle of the left ulna was affected by a pathological fracture caused by a brown tumor. The patient was debilitated and declined surgical treatment. The patient and her family chose discharge.

Conclusion

Brown tumor of bone, also called osteitis fibrosa cystica, is a rare non-neoplastic lesion that reflects abnormal bone metabolism in patients with HPT. However, with fine needle aspiration cytology in combination with biochemical tests, a correct diagnosis can be reached. The increase in osteoclast activity leads to decalcification and dissolution of bone, and formation of a cystic bone defect with hyperplastic fibrous tissue. This eventually becomes a brown tumor, with deformed and bleeding fibrous tissue. The patient had a typical brown tumor, as well as osteoporosis, anemia, and pathological fractures.
Analysis of clinical efficacy of P-Gemox regimen sandwich radiotherapy, P-Gemox regimen sequential radiotherapy, and radiotherapy alone treatment for extranodal natural killer/T-cell lymphoma*
Authors: Quan Xiaoying , Wang Pinjia , Lei Lei , Chen Xiaoyan , Wu Chunzhi , Ye Bin , Zhang Zhihui
Published: June 2023

Objective

The study aimed to explore the clinical efficacy of P-Gemox regimen sandwich radiotherapy, P-Gemox regimen sequential radiotherapy, and radiotherapy alone in early-stage extranodal natural killer/T-cell lymphoma (ENKTL).

Methods

In total, 124 patients with early-stage ENKTL, from June 2009 to January 2016, were retrospectively analyzed to compare the clinical efficacy of the three regimens.

Results

A total of 46 patients were treated with P-Gemox regimen sandwich radiotherapy, with complete remission (CR) of 91.3%, objective response rate (ORR) of 97.8%, 2-year progression-free survival (PFS) of 76.1%, and 2-year overall survival (OS) of 80.4%. Then, 37 patients received P-Gemox regimen sequential radiotherapy, with CR of 86.5%, ORR of 94.6%, 2-year PFS of 75.7%, and 2-year OS of 81.1%. Finally, 41 patients received radiotherapy alone, with CR of 61.0%, ORR of 80.5%, 2-year PFS of 51.2%, and 2-year OS of 65.9%. When the two groups were compared, significant differences in CR, PFS, and OS were observed among the sandwich radiotherapy, sequential radiotherapy, and radiotherapy alone groups (P < 0.05), respectively. However, no significant difference in CR, ORR, PFS, and OS was observed between the sandwich radiotherapy and sequential radiotherapy groups (P > 0.05). Multivariate analysis revealed that Eastern Cooperative Oncology Group (ECOG), serum lactate dehydrogenase (LDH), platelet-to-lymphocyte ratio (PLR), local tumor invasion, and treatment modalities were independent prognostic factors for PFS (P < 0.05). ECOG, LDH, PLR, local tumor invasion, underlying disease, and treatment modalities were independent prognostic factors for OS (P < 0.05).

Conclusion

P-Gemox regimen combination radiotherapy for patients with early-stage ENKTL was better than the radiotherapy alone.
Metastatic intracranial large-cell neuroendocrine carcinoma: a study of two cases
Authors: Zhan Xiaozhen , Wu Weidong , Wang Xinmin , Wang Kezhen , Leng Jiyong , Cui Chengzhi , Cong Peiyu
Published: June 2023

Objective

The occurrence of large-cell neuroendocrine carcinoma (LCNEC), a kind of neuroendocrine tumor (NET), in the cranium is extremely rare. Here we report two such cases and review the literature in order to improve the diagnosis and treatment of intracranial LCNEC.

Methods

We report two cases of metastatic intracranial LCNEC. In case 1, the patient was diagnosed with lung carcinoma and underwent chemotherapy. Brain metastases were found six months later. The lung and intracranial lesions in case 2 were found at the same time.

Results

Intracranial multiple-tumor resection was performed in case 1 and the patient died 2 months later. Case 2 patient underwent surgery followed by chemotherapy with etoposide and carboplatin. Six months postoperatively, a recurrence lesion was found in the left cerebellar hemisphere. The patient was treated surgically. At present, a year after the diagnosis, the patient is still alive.

Conclusion

NETs of the intracranial region are extremely rare, and hence, most of our knowledge is based on lung NETs, and standard treatment strategies for intracranial NETs remain unclear. Our patients had different survival times probably due to different treatments, indicating that effective surgical resection and subsequent multi-agent chemotherapy should be administered to promote long-term survival of intracranial LCNEC patients.
Intravenous injection of AAV-PHP.eB across the blood-brain barrier in the adult mouse for central nervous system gene therapy*
Authors: Shu Yongwei , Yao Jie , Qu Yang , Zheng Jing , Ding Jing , Zhang Lina , Wang Yefan , Zhao Linlin , Zhang Jingyu , Tang Siqi
Published: June 2023

Objective

To verify the neurotypicality of AAV-PHP.eB after tail vein injection in adult mice and its efficiency in crossing the blood-brain barrier (BBB).

Methods

The rAAV-SYN-GFP plasmid was constructed, and adult C57BL mice were injected with AAV-PHP. eB: SYN-GFP in the tail vein (300 nL, virus titer 3 × 109 vg) and in the prefrontal lobe (50 L, virus titer 5 × 1011 vg). The green fluorescent protein (GFP) signal in the brain was observed at two weeks, while the GFP signal in the peripheral organs was observed at four weeks.

Results

Two weeks after tail vein injection, GFP expression was observed throughout the brain, especially in the cortex, hippocampus, and geniculate nucleus. No GFP signal was observed or detected by western blotting in the peripheral organs after four weeks. GFP signal was observed mainly at the local site after prefrontal lobe injection.

Conclusion

AAV-PHP.eB: SYN-GFP can effectively cross the BBB in adult mice. Using a neuron-specific promoter allows exogenous gene expression in neurons; therefore, AAV-PHP.eB can be used as an effective carrier for studying diseases in the central nervous system (CNS).
Aurora kinases: novel anti-breast cancer targets
Authors: Yiliyaer  , Maimaiti Yusufu
Published: June 2023

Aurora kinases regulate multiple steps of mitotic cell division in eukaryotic cells. Overexpression of aurora kinases has been observed in some tumor cells, which suggests that abnormalities in aurora kinases are closely related to tumorigenesis. In additon, aurora kinases are often amplified or overexpressed in breast cancer cells, leading to chromosomal segregation abnormalities and genomic disorder, and thereby activating oncogenic pathways. Novel Aurora A kinase inhibitors are currently being studied in multiple phase I and II studies. In this review, we describe the biological functions and mechanisms of aurora kinases in breast cancer cells and summarize the preclinical findings related to aurora kinases in breast cancer.
Analyzing proteins in colonic tissues from mice with ulcerative colitis using the iTRAQ technology*
Authors: Chen Na , Zhou Zhongyin
Published: June 2023

Objective

The aim of the study was to investigate the expression of proteins in colonic tissues of mice with ulcerative colitis (UC) by using isobaric tags for relative and absolute quantitation (iTRAQ), probe into the pathogenesis of UC, and find potential biomarkers of UC.

Methods

Forty C57 mice were randomly divided into the control and model groups (20 mice in each group). The mice in the model group were administered dextran sulphate sodium (DSS) for 7 consecutive days ad libitum to induce acute colitis, and the colon tissue was extracted on the 8th day after the successful establishment of the UC model. Proteins were identified by the iTRAQ and tandem mass spectrometry techniques, and the identified proteins were analyzed by bioinformatics.

Results

A total of 4019 proteins were identified among the two groups. Among them, 317 significant differentially expressed proteins (DEPs) were detected according to the screening criteria for selecting DEPs, i.e. fold change ratios ≥ 1.5 or ≤ 0.67 and P-values < 0.05, of which 156 were upregulated and 161 were downregulated. In the Gene Ontology (GO) analysis, the DEPs were classified into 48 functional categories, which contained biological process, cellular component, and molecular function. Based on the 317 DEPs, the KEGG pathway analysis identified 160 vital pathways.

Conclusion

DEPs in colonic tissues of mice with UC were screened using the iTRAQ technique, which laid a foundation for further studies regarding the pathogenesis of UC.
Clinical value of serum pepsinogen levels for the diagnosis of esophageal squamous cell carcinoma
Authors: Rivadeneira D.J. , Luo Hesheng , Tian Jingyuan
Published: June 2023

Objective

Pepsinogens have been previously studied as markers of gastric atrophy. The objective of this study was to investigate the clinical significance of the serum levels of pepsinogen (PG) I and II, as well as the pepsinogen I/II ratio (PGR) in the diagnosis of esophageal squamous cell carcinoma.

Methods

A retrospective data analysis of patients who underwent gastroscopy and PG examination in Renmin Hospital was performed. The subjects were grouped into cancer and healthy control groups, and the differences in the serum levels of PGI and PGII, as well as the PGRs were compared. The receiver operating curve and the area under the curve (AUC) were also compared between the groups.

Results

A total of 351 Chinese patients were enrolled in the study, 209 with esophageal squamous cell carcinoma and 142 healthy controls. Overall, the levels of PGI (P < 0.0001) and PGII (P = 0.0007), as well as the PGR (P = 0.007) of the cancer group were lower than those of the control group. Male subjects in the cancer group had lower PGI (P < 0.0001), PGII (P < 0.0001), and (P = 0.0138). The subjects < 65 years old in the cancer group showed lower PGI (P < 0.0001), PGII (P = 0.001), and PGR (P = 0.0087).Overall, these results show that the levels of PGI (AUC 0.64) and PGII (AUC 0.60) have a predictive ability for discriminating esophageal carcinoma. Moreover, in males < 65 years old, PGI (AUC 0.73) and PGII (AUC 0.69) also showed to have a predictive ability for discriminating esophageal carcinoma.

Conclusion

Serum PG levels in patients with esophageal squamous cell carcinoma, especially in males aged < 65 years old, are lower than those in healthy people. PGI and PGII are useful for screening esophageal squamous cell carcinoma.
Quantitative monitoring and mutations of ctDNA before and after non-small cell lung cancer radical surgery*
Authors: Chen Xiangqi , Lin Tingyan , Gao Zhisen , Xu Jiangjiang , Feng Rui , Yang Sheng , Chen Shuchen , Kang Mingqiang
Published: June 2023

Objective

The aim of this study was to study the quantitative expression of circulating tumour DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) before and after radical operation and to explore the correlation between gene mutations in non-small cell lung cancer tissues and those in ctDNA.

Methods

We randomly assigned 5 NSCLC patients from the Department of Thoracic Surgery of Fujian Medical University Union Hospital. All the patients had undergone radical surgery. Venous blood samples were collected from the 5 NSCLC patients at two time points (before the operation and 21-37 days after the operation) for monitoring ctDNA levels. This was done by isolating plasma from venous blood using high velocity centrifugation, extracting DNA from the plasma using the QIAamp Circulating Nucleic Acid kit, and then quantifying the ctDNA levels. The results were analyzed using the Wilcoxon Rank Sum Test. Moreover, the ctDNA levels were compared with those of carcinoembryonic antigen (CEA), which was detected simultaneously with the ctDNA. Then, DNA samples from the tumor tissues and peripheral blood cells and ctDNA were sequenced using the Hiseq2000 sequencing platform (Illumina) and the mutant genes were screened out. Mutations that occurred within the tumor tissues were used as positive control, whereas those found in the pre-operative blood cells were used as a negative control. Based on the mutational analysis of ctDNA genes, a total of 508 cancer-related genes were screened.

Results

The median values of the pre- and post-operative ctDNA levels in the 5 patients with NSCLC were 0.612 (0.518-0.876) and 0.430 (0.372-0.612) ng/µL, respectively. There was a significant difference between the two groups (P< 0.05). The pre-operative CEA level was slightly higher than the post-operative level (P> 0.05). In one of the cases, LC tissues showed multiple mutations, consistent with pre-operative ctDNA. Moreover, isogenic mutations of the same type were not detected in post-operative ctDNA or peripheral blood cells.

Conclusion

Mutations found in the lung cancer (LC) ctDNA gene were consistent with the mutation type of LC tissue. Hence, the quantitative and qualitative analysis of ctDNA is a promising novel molecular biomarker for the evaluation of tumor burden changes in NSCLC.
Regulatory mechanisms of long non-coding RNAs
Authors: Luo Zhigang
Published: June 2023

Long non-coding RNAs (lncRNAs) belong to a large and complex family of RNAs, which play many important roles in regulating gene expression. However, the mechanism underlying the dynamic expression of lncRNAs is still not very clear. In order to identify lncRNAs and clarify the mechanisms involved, we collected basic information and highlighted the mechanisms underlying lncRNA expression and regulation. Overall, lncRNAs are regulated by several similar transcription factors and protein-coding genes. Epigenetic modification (DNA methylation and histone modification) can also downregulate lncRNA levels in tissues and cells. Moreover, lncRNAs may be degraded or cleaved via interaction with miRNAs and miRNAassociated protein complexes. Furthermore, alternative RNA splicing (AS) may play a significant role in the post-transcriptional regulation of lncRNAs.
Application of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for the prevention of neutropenia in triple negative breast cancer patients older than 65 years during adjuvant chemotherapy
Authors: Qu Shuxian , Qiu Jianing , Zhang Yidan , Liu Yongming , Zheng Zhendong
Published: June 2023

Objective

The aim of this study was to compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) for the prevention of neutropenia in elderly breast cancer patients during adjuvant chemotherapy.

Methods

A total of 45 oncology inpatients with breast cancer, who received adjuvant chemotherapy and were older than 65 years from May 2017 to October 2018 in the General Hospital of the Northern Theater of the Chinese people's Liberation Army, were included. Epirubivin Cyclophoshamide-Docetaxel (EC-T) sequential adjuvant chemotherapy was chosen. Forty-five patients were randomly divided into two groups; 25 patients in the treatment group were treated with PEG-rhG-CSF and 20 patients in the control group were not treated with PEG-rhG-CSF, but only rhG-CSF. The experimental group was treated with the PEG-rhG-CSF at the end of chemotherapy for 24-48 h, with a 6 mg subcutaneous injection once per chemotherapy cycle. In the control group, rhG-CSF was administered after 48 h of chemotherapy, with a 100 µg subcutaneous injection, 1/d, d 1-7. The dosage could be increased step by step with the exacerbation of neutropenia. The primary aims of this study was to discover the incidence of leukopenia, neutropenia, neutrophilic fever, and adverse reactions in the two groups.

Results

The incidence of neutropenia, neutrophilic fever and adverse reactions decreased in the treatment group compared to the control group, but no significant difference existed between two groups (P > 0.05). Patients in treatment group had a lower, but not statistically significant, incidence of adverse reactions (P > 0.05).

Conclusion

Applying PEG-rhG-CSF could be effective in preventing neutropenia in elderly patients with postoperative adjuvant chemotherapy to treat breast cancer. It may effectively control the occurrence of neutropenia after chemotherapy and reduce the chance of infection. The incidence of side effects, such as fever and bone pain, was low. The adverse drug reactions were well tolerated by patients, which could ensure the smooth progress of chemotherapy.
Association of genetic polymorphisms of GSTM1 and smoking status with lung cancer risk*
Authors: Li Jiaheng , Zhang Lina , Wang Yue , Gu Meng , Wang Ziyu , Li Weiying
Published: June 2023

Objective

Long-term cigarette smoke exposure damages the airway epithelium. However, the correlation among GSTM1 gene polymorphism, smoking status, and lung cancer susceptibility remains unclear. This study aimed to identify the genetic polymorphism of GSTM1 and examine the association of GSTM1 polymorphism and smoking history with lung cancer susceptibility.

Methods

The genetic polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR) in 217 lung cancer patients and 198 controls. The demographic data and smoking history of the patients were collected. The age, sex, and residence of the two groups were also obtained.

Results

Significant differences in GSTM1 polymorphism were observed between the case and control groups (P = 0.024). Smoking time and smoking index were significantly different between the case and control groups. With the increase in smoking time and smoking index, the differences became more obvious. There was a synergistic effect between GSTM1 and smoking (S = 3.35). The risk of developing lung cancer increased 4.82 fold in smokers carrying deficient-type GSTM1. Compared with patients carrying wild-type GSTM1, the risk of developing lung cancer was higher in those carrying deficient-type GSTM1 with the increase in smoking time and smoking index. In different pathological types, no significant differences were observed in GSTM1 polymorphism. In different pathological types, the proportions of patients increased with the increase in smoking time and smoking index, especially the proportion of patients with squamous cell carcinoma. Compared with wild-type GSTM1, the proportion of patients with deficient-type GSTM1 increased with the increase in smoking time and smoking index (P = 0.003 and 0.017). This trend was mainly observed in those with squamous cell carcinoma.

Conclusion

GSTM1 mutation is associated with lung cancer susceptibility. Smokers carrying deficient-type GSTM1 are more likely to develop lung cancer. Compared with patients carrying wild-type GSTM1, smokers with deficient-type GSTM1 are more likely develop lung cancer when smoking time is more than 30 years and smoking index is more than 400. In patients carrying deficient-type GSTM1, the risk of developing squamous cell carcinoma increases with an increase in smoking time and smoking dose.
Estimation of the effect of target and normal tissue sparing based on equivalent uniform dose-based optimization in hypofractionated radiotherapy for lung cancer*
Authors: Shao Ying , Zhang Fuli , Wang Shi , Xu Weidong , Jiang Jing
Published: June 2023

Objective

This study aims to investigate the dosimetric differences among four planning methods of physical and biological optimization in hypofractionated radiation therapy for non-small cell lung cancer (NSCLC).

Methods

Ten NSCLC patients receiving radiation therapy were chosen for this retrospective study. Volumetric modulated arc treatment plans for each patient were remade with dose-volume (DV) functions, biological-physical functions, and biological functions, using the same constraint parameters during optimization. The dosimetric differences between the four types of plans were calculated and analyzed.

Results

For the target, equivalent uniform dose (EUD) of the EUD and EUD + DV groups was approximately 2.8%-3.6% and 3.2%-3.7% higher than those of the DV and DV + EUD groups, respectively. The average tumor control probability (TCP) of the EUD and EUD + DV groups was also significantly higher than those of the other two groups (P < 0.05). The difference in heterogeneity index (HI) among the four groups was also statistically significant (P < 0.05), while the difference of conformity index (CI) was not significant (P > 0.05). For the organs at risk, the differences of EUD, V5, V10, V20, V30 of normal lung tissues were not statistically significant (P > 0.05); however, the mean lung dose of the EUD and EUD + DV groups was slightly lower than those of the other two groups.

Conclusion

The biological optimization method has obvious advantages of improving EUD and TCP of the target, while decreasing the exposed dose of normal lung. This result is meaningful in choosing plan optimization methods in routine work.
Expression of HERG in musculoskeletal tumors with different degrees of malignancy*
Authors: Gan Lu , Li Mo , Yang Tongtao , Wu Jin , Du Junjie , Luo Zhuojing , Zhou Yong
Published: June 2023

Objective

The expression of HERG in common bone tumors is scarcely reported and there is a lack of dedicated studies. This study aimed to investigated the expression of HERG in several common musculoskeletal tumors.

Methods

Immunohistochemical staining, RT-PCR, and Western blotting were used to observe HERG expression differences in various tissues and cell lines.

Results

HERG was differentially expressed in different malignant tumors, both at a differential protein level and localization within tumors. HERG was not expressed in normal bone tissue. The HERG inhibitor E-4031 markedly inhibited the proliferation of osteosarcoma cell lines.

Conclusion

HERG was highly expressed in malignant tumors. Blocking of HERG can effectively inhibit the proliferation of bone tumors.
Peritoneal cancer index is a prognostic indicator of survival in advanced gastric cancer with peritoneal carcinomatosis
Authors: Niu Guangcai , Ma Xiangdong
Published: June 2023

Objective

The peritoneal cancer index (PCI) has been used for the detailed evaluation of the peritoneal spread in tumors of a gynecologic origin and has been found to be a prognostic indicator of survival. The aim of this study was to identify the significance of the PCI in advanced gastric cancer (AGC) with peritoneal carcinomatosis (PC).

Methods

From 2010 to 2018, a retrospective analysis was carried out of 60 AGC patients with PC, including 21 patients with a PCI ≤ 13 and 39 with a PCI > 13. All patients were treated with both surgery and intraoperative peritoneal hyperthermic chemotherapy (IPHC). The performance status (Karnofsky performance status), age, sex, Borromann's classification, differentiation, depth of invasion, lymph node metastasis, PCI, extent of gastrectomy, extent of lymph node dissection, and residual tumor volume were retrospectively evaluated and correlated to survival.

Results

The overall 5-year survival rate was 43% and mean survival was (54.47 ± 4.53) months. The favorable clinical prognostic indicators of survival were Borromann's classification, differentiation, depth of invasion, PCI, and residual tumor volume on univariate analyses (P< 0.05). The Cox proportional regression hazard model showed that only the volume of residual tumor and PCI were associated with postoperative survival. The median survival time was 69.76 months for patients with a PCI ≤ 13 and 39.96 months for patients with a PCI > 13. There was a significant difference in survival rate between the two group (P= 0.004). Postoperative major morbidity and mortality rates were 23.81% and 4.76% in the PCI ≤ 13 group and 43.59% and 5.12% in the PCI > 13 group, respectively.

Conclusion

The peritoneal spread in advanced gastric cancer with peritoneal carcinomatosis can be assessed in detail using the PCI. It is also a significant prognostic factor of survival and is useful in identifying subgroups.
Induction of apoptosis in renal cell carcinoma by cinobufotalin through inhibition of Notch1 signal activation*
Authors: Li Qing , Huang Xing
Published: June 2023

Objective

The aim of this study was to investigate the effect of cinobufotalin on apoptosis in renal cell carcinoma and its possible mechanism of action.

Methods

The expression levels of Notch1 in renal cancer cells, as well as in adjacent and normal tissues were assessed in 64 patients with renal cellcarcinoma. The 769-P cells were treated with 0, 10, 20 and 40 mg/L cinobufotalin and the proliferation activity and apoptotic rate of the cells were measured. The expression levels of Notch1, Bcl-2, and Pro-caspase 3 were detected by RT-PCR and Western-blot.

Results

(1) The rates of Notch1 expression in renal cancer cells, adjacent tissues, and normal tissues were 75.0%, 45.3%, and 9.4%, respectively. Notch1 expression had significant effects on tumor, node and metastasis (TNM) staging, Fuhrman grade, and tumor size in patients with renal cell carcinoma (P< 0.05); (2) The inhibition rates of cinobufotalin on 769-P cells were 0%, 6.85%, 11.37%, and 16.33% at 24 h; 0%, 13.57%, 20.14%, and 31.69% at 48 h; 0%, 19.97%, 28.53% and 51.42% at 72 h. At 24 h, the apoptotic rates were 8.2 ± 3.1%, 19.8 ± 5.6%, 33.7 ± 5.0%, and 51.5 ± 6.8%.The effect of cinobufotalin on apoptosis of 769-P cells was dose-dependent; (3) RT-PCR assay showed that protein expression levels for Notch1, Bcl-2, and Pro-caspase 3 were significantly decreased with the increase of drug concentration. Western-blot analysis also showed that Notch1, Bcl-2 and Pro-caspase 3 protein levels showed a significant downward trend with the increase of drug concentration.

Conclusion

Cinobufotalin inhibits the growth of renal cancer cells and induces apoptosis in renal cell carcinoma, which may be related to the inhibition of Notch1 signal activation.
A study on melanoma treatment using dendritic cells loaded with antigens purified from melanoma cell lines*
Authors: Gao Yanwei , Chen Xia , Gao Weishi , Lu Xiangji , Peng Lin
Published: June 2023

Objective

The aim of this study was to purify effective tumor peptide complexes from human melanoma cell lines to enhance the treatment effects on melanoma.

Methods

We purified heat shock protein 70 (HSP70)-peptide complexes (PCs) from human melanoma cell lines A375, A875, M21, M14, WM-35, and SK-HEL-1. We named the purified product as M-HSP70-PCs and determined its immunological activities. Autologous HSP70-PCs purified from primary tumor cells of melanoma patients (9 cases) were used as controls. These two tumor antigenic complexes were loaded into dendritic cells (DCs) and used to stimulate an antitumor response against tumor cells in the corresponding patients.

Results

Mature DCs pulsed with M-HSP70-PCs stimulated autologous T cells to secrete the same levels of type I cytokines as the autologous HSP70-PCs. Moreover, DCs pulsed with M-HSP70-PCs endued CIK cells with an equal ability as autologous HSP70-PCs to kill melanoma cells in the patients.

Conclusion

M-HSP70-PCs may be used as an efficient and generalized tumor antigen in the treatment of DC-based malignant melanoma.
Effect of miR-375 on non-small cell lung carcinoma invasion, migration, and proliferation through the CIP2A pathway
Authors: Wu Junyu , Yuan Weijun , Wang Yuhuan , Zhao Xiaodong
Published: June 2023

Objective

The aim of this study was to study the effect of miR-375 on non-small cell lung carcinoma (NSCLC) invasion, migration, and proliferation through the CIP2A pathway.

Methods

We constructed a stable over-expressing cell line with lentivirus as the experimental group (Lv-miR-375) and transfected the empty vector as the negative control group (Lv-NC). The expression level of miR-375 was detected using real-time fluorescence quantitative PCR (qRT-PCR).Western blots were used to detect the expression levels of cancerous inhibitor of PP2A (CIP2A), MYC, protein kinase B (AKT) and p-AKT in Lv-NC- and Lv-miR-375-transfected cells. Transwell assays were conducted to detect the cell invasion and metastasis ability, and the cell counting kit-8 (CCK8) was used to detect cell proliferation.

Results

qRT-PCR showed that miR-375 was overexpressed in NSCLC. Compared to the Lv-NC-transfected cells, the western blot results showed that CIP2A, MYC and p-AKT were highly expressed in Lv-miR-375-transfected cells. Transwell assays showed that the invasion and migration ability of Lv-miR-375-transfected A549 cells was significantly higher than that of Lv-NC-transfected cells. CCK8 experiments showed that compared to Lv-NC-transfected cells, the cell proliferation ability of the Lv-miR-375-transfected cells increased.

Conclusion

MiR-375 could promote the invasion, migration, and proliferation of NSCLC A549 cells via the CIP2A pathway. MiR-375 is expected to become a new target for the treatment of NSCLC, and may become an important biomarker for the diagnosis, prognosis, and treatment of the disease.
Application of biological optimization of hypofractionated radiotherapy post conservative surgery for breast cancer*
Authors: Shao Ying , Wang Yadi , Zhang Fuli , Wang Shi
Published: June 2023

Objective

The aim of the study was to discuss the application of biological optimization and its difference from physical optimization in hypofractionated radiotherapy for breast cancer after conservative surgery.

Methods

This retrospective study enrolled 15 randomly chosen patients with left-sided breast cancer who received radiotherapy. The volumetric arc therapy (VMAT) technique was used to redesign treatment plans with physical functions (PF) group, biological-physical functions combined (BF + PF and PF + BF) groups, and biological functions (BF) group. The dosimetric differences based on the above four optimization methods were assessed by calculating and analyzing the corresponding dose-volume parameters.

Results

The target parameters of the four groups differed significantly (P < 0.05) except for the conformity index (CI). The tumor control probability (TCP) values in the BF and BF + PF groups were higher than those in the PF and PF + BF groups. Moreover, the dose-volume parameters of the ipsilateral lung in the BF group were less than those of three other groups, while the monitor unit (MU) in the BF group was approximately 16% lower than those of the PF and PF + BF groups.

Conclusion

Biological functions were useful to increase the equivalent uniform dose (EUD) and TCP values of the target, decrease the dose-volume parameters of the organs-at-risk (OARs), and improve treatment efficiency.
The expression of vascular endothelial growth factor (VEGF)/ endostatin (ES) and VEGF receptor 2 (VEGFR2)/ES is associated with NSCLC prognosis*
Authors: Yang Yuan , Lu Baohua , Li Baolan , Li Weiying , Jiang Mei , Yue Wentao , Wang Qunhui , Zhang Tongmei
Published: June 2023

Objective

The aim of our study was to detect the expression of angiogenesis inhibitory proteins and angiogenesis promotive proteins in the postoperative tumor tissue of non-small cell lung cancer (NSCLC) patients. We also investigated the relationship of protein expression with clinical characteristics and prognosis.

Methods

We examined the expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), and endostatin (ES) proteins in 255 specimens resected from NSCLC patients, using immune histochemistry (IHC). We then evaluated the relationships between the expression of the three proteins and clinical characteristics such as stage, histological type, differentiation, gender, tobacco use, and age. According to the value of VEGF/ES, we divided the cohort into angiogenesis-promoting group A, angiogenesis-inhibiting group A, and balance group A. The survival differences in the three groups were evaluated to determine the prognostic value of VEGF/ES. Similarly, we tested the prognostic value of VEGFR2/ES.

Results

VEGF-positive expression was observed in 93 patients (36.4%). VEGF expression was not correlated with the clinical characteristics. VEGFR2-positive expression was observed in 103 patients (40.4%). The expression of VEGFR2 was correlated with the clinical stage (χ
2 = 21.414, P = 0.045) and histological type (χ
2 = 26.911, P = 0.008). ES-positive expression was observed in 140 patients (54.9%). The expression of ES was correlated with the clinical stage (χ
2 = 26.504, P = 0.009). When evaluating the prognostic values of VEGF/ES and VEGFR2/ES, the prognosis of the angiogenesis balance group was similar to that of the angiogenesis-inhibiting group. The minimum survival time was observed in the angiogenesis-promoting group.

Conclusion

VEGF/ES and VEGFR2/ES in resected tumors have prognostic value in postoperative NSCLC patients. The survival time of the population with predominant angiogenic factors was short.

List of abbreviations

VEGF (vascular endothelial growth factor); VEGFR2 (vascular endothelial growth factor receptor 2); ES (endostatin); NSCLC (non-small cell lung cancer); IHC (immunohistochemical); EGFR (epidermal growth factor receptor); ALK (anaplastic lymphoma kinase); ROS1 (c-ros oncogene 1 receptor kinase); TNM (tumor, lymphnode, metastasis); HR (hazard ratio); SCLC (small cell lung cancer); SFDA (State Food and Drug Administration); ERK (extracellular regulated protein kinases); MAPK (mitogen-activated protein kinase)
A case report of double-protein expression in primary uterine cervical diffuse large B cell lymphoma and a review of the literature
Authors: Quan Xiaoying , Zhang Zhihui
Published: June 2023

Primary non-Hodgkin's lymphoma of the uterine cervix is rarely observed. Here, we report a case of “double-protein” expression in a primary uterine cervical diffuse large B-cell lymphoma that was detected based on cervical biopsies at Sichuan Cancer Hospital in December 2016 in a 53-year-old woman with a 1-month history of postmenopausal vaginal bleeding. She was diagnosed with stage IVA cervical cancer after workup and treated with six cycles of rituximab + cyclophosphamide + epirubicin + vindesine + prednisone. She showed a positive partial response after two cycles; however, response assessment revealed a progressive disease after six cycles. Based on the current condition, a treatment regimen comprising a combination of second-line chemotherapy and radiotherapy was advised for the patient. Unfortunately, she discontinued her treatment because of various factors. We conclude that “double-protein” expression in primary uterine cervical diffuse large B-cell lymphoma is difficult to treat and has a poor prognosis. Therefore, improving the diagnosis and treatment of this disease should be considered.
Salvage treatments for prostate-specific antigen relapse of cT3N0M0 prostatic adenocarcinoma after radical prostatectomy combined with neoadjuvant androgen deprivation
Authors: Zhang Lufang , Pan Dongliang , Liu Ludong , Zang Yunjiang , Li Ningchen
Published: June 2023

Objective

The aim of the study was to evaluate the efficiency of salvage treatments for prostate specific antigen (PSA) relapse of cT3N0M0prostatic adenocarcinoma (PCa) after radical prostatectomy (RP) combined with neoadjuvant androgen deprivation (ADT).

Methods

A total of 332 patients with cT3N0M0PCa were enrolled in the prospective study and received RP and pelvic lymph node dissection with neoadjuvant ADT for 3 months. All patients with PSA relapse were treated with salvage external beam radiation therapy (RT) and ADT for 6 months.

Results

The 5-year postoperative PSA relapse rate was 40.96% (136/332). The patients have been divided into the PSA relapse and PSA relapse-free groups in order to compare patient characteristics. The ratio of patients with Gleason score ≥ 8 and positive surgical margin in the PSA relapse group were significantly higher than those of in the PSA relapse-free group (P= 0.01). The mean duration between the start of operative treatment and PSA relapse was 31 months. Salvage treatment to all 136 PSA relapse patients led to favorable outcomes. PSA relapse was not observed after salvage treatment by the end of follow-up. The 5-year overall survival rates of the PSA relapse and PSA relapse-free groups were 94.9% and 93.9%, respectively.

Conclusion

In pursuit of curative treatment, our study showed that RP combined with neoadjuvant ADT is an aggressive multimodality strategy associated with lower PSA relapse and better survival outcomes for stage cT3N0M0PCa patients. Patients with PSA relapse after RP may benefit from early aggressive salvage RT combined with short-term ADT.
Influence of lymph node micrometastasis on the staging system for gastric cancer*
Authors: Gao Lixiong , Ren Xiankun , Li Guiquan , Wu Benhua , Chen Xuan
Published: June 2023

Objective

The aim of this study was to investigate the effect of lymph node micrometastasis on the prognosis of patients with gastric cancer and the necessity of integrating it into the gastric cancer staging system.

Methods

In total, 241 patients with gastric cancer were included. Hematoxylin and eosin staining of lymph nodes was performed, and negative lymph nodes were evaluated by immunohistochemistry to detect micrometastases. Differences in survival rates between stages were evaluated.

Results

(1) A total of 78 patients (32.4%) had lymph node micrometastases. Compared with the group without micrometastases, the overall recurrence rate, lymph infiltration, vascular invasion, and nerve invasion rate in the micrometastasis group were significantly higher (P < 0.05). (2) According to the standard N staging system, the rates of disease-free survival (DFS) for the N0, N1, N2, N3a, and N3b groups were 96.0%, 84.0%, 67.6%, 59.0%, and 21.7%, respectively. There was no significant difference in survival between N2 and N3a. The cumulative survival curves for N2 and N3a intersected. (3) The N stage of 38 patients (15.8%) differed between the traditional system and the new N staging system reflecting micrometastasis. The DFS for N0, N1, N2, N3a, and N3b were 97.0%, 86.3%, 74.2%, 65.4%, and 29.2%, respectively. There was no significant difference in survival between N2 and N3a, but the cumulative survival curves for N2 and N3a did not intersect. (4) Based on a Cox multivariate analysis, various independent risk factors for recurrence were identified (P < 0.05).

Conclusion

Lymph node micrometastasis is an important risk factor for gastric cancer recurrence. Lymph node micrometastasis should be considered in TNM staging to determine prognosis and optimal treatment strategies.
High level of preoperative serum fibrinogen is a predictor of poor prognosis in patients with esophageal squamous cell carcinoma
Authors: Shi Chengcheng , Xu Xiaofeng , Zhang Yuan , Sun Zhanfa , Wang Guangjing
Published: June 2023

Objective

This study aimed to elucidate the association between the level of preoperative serum fibrinogen (PSF) and the prognosis of patients with esophageal squamous cell carcinoma (ESCC).

Methods

From January 2010 to December 2016, all patients diagnosed with ESCC who underwent surgery in Qingdao Municipal Hospital were analyzed retrospectively. Moreover, the fibrinogen levels of all patients were assessed before surgery, and hyperfibrinogenemia was diagnosed when the fibrinogen level was ≥4.0 g/L. The impact of PSF on disease-free survival (DFS) and overall survival (OS) was analyzed using the log-rank method and Cox proportional hazards regression model.Pvalue less than 0.05 was considered statistically significant.

Results

A total of 336 patients were finally analyzed, and approximately 102 patients (30.36%) were diagnosed with hyperfibrinogenemia before surgery. Hyperfibrinogenemia was associated with older age (≥ 70 years) (P= 0.012), advanced pathological T stage (P= 0.003), and lymph node involvement (P= 0.024). Univariate analysis showed that patients with hyperfibrinogenemia had shorter DFS (1.96 yearsvs.3.64 years,P= 0.001) and OS (2.27 yearsvs.4.15 years,P< 0.001) than patients without hyperfibrinogenemia. Multivariate analysis confirmed that PSF was an independent factor affecting DFS (risk ratio [RR]: 1.35, 95% confidence interval [CI]: 1.02-1.79,P= 0.038) and OS (RR: 1.37, 95% CI: 1.03-1.83,P= 0.034) in patients with ESCC.

Conclusion

For patients with operable ESCC, hyperfibrinogenemia had poor prognosis. Moreover, PSF is an independent prognostic factor for operable ESCC.
Multi-disciplinary treatment for hepatocellular carcinoma in primary hospitals in China during the COVID-19 epidemic
Authors: Wu Qing , Wen Shunqian
Published: June 2023

Hepatocellular carcinoma (HCC) is a common malignant tumor in the Chinese population. Due to its high degree of malignancy, rapid progression, and poor prognosis, it mainly requires multi-disciplinary treatment (MDT) in the clinic. In December 2019, COVID-19, a novel coronavirus pneumonia, broke out in Wuhan, China. It has rapidly spread across the country, with various places launching a level I response to major public health emergencies and traffic being restricted. Most patients with HCC were only able to attend primary hospitals, while the MDT model for HCC in provincial hospitals was restricted. Therefore, it was a huge task for clinicians in primary hospitals to ensure MDT was given to patients with HCC during the level I response to major public health emergencies. How to formulate a reasonable MDT mode for patients with HCC according to local conditions was worthy of consideration by hepatobiliary surgeons in primary hospitals.
Intervention for oxaliplatin-induced hypersensitivity in China: a cross-sectional internet-based survey*
Authors: Li Min , Li Wei , Wang Yue , Shangguan Xiaofang , Huang Rui , Liu Dong , Zhang Chengliang
Published: June 2023

Objective

This cross-sectional study aimed at investigating the intervention status and the influence of oncologists on oxaliplatin-induced hypersensitivity reactions (OIHR).

Methods

Snowball sampling was used to send questionnaires to oncologists in various provinces and cities in China, via the internet, to collect data on their socio-demographic characteristics, the occurrence of OIHR, and the current status of interventions. One-way ANOVA and T-test of geographic samples were used to explore the relationship between the incidence of OIHR and intervention measures.

Results

A total of 401 valid questionnaires were collected, most respondents were 30-40 years old, and most oncologists had 5 years of working experience. The proportions of glucocorticoid and H1 receptor antagonist use for OIHR prevention were 67.83% and 38.65%, respectively. The proportion of oncologists with longer working years and higher professional titles who used glucocorticoids for OIHR prevention was higher, and the observed OIHR incidence was lower. Pretreatment with glucocorticoids may be an effective preventive measure and can reduce the incidence of the OXA allergic reactions (P < 0.05).

Conclusion

The risk awareness of junior oncologists to OIHR prevention should be strengthened, and clinical efficacy evaluation of glucocorticoids in OIHR prevention should be further promoted.
CircBAGE2 (hsa_circ_0061259) regulates CCND1 and PDCD10 expression by functioning as an miR-103a-3p ‘sponge’ to alter the proliferation and apoptosis of prostate cancer cells*
Authors: Zhang Chunlei , Liu Dan , Tian Qinqin , Yang Qi , Zi Xiaoyuan , Sun Yinghao
Published: June 2023

Objective

The aim of the article is to explore the function of circBAGE2 (hsa_circ_0061259) in prostate cancer (PCa) cells.

Methods

Sequencing results of circBAGE2 were verified by quantitative RT PCR (qRT-PCR) and Sanger sequencing. Agarose gel electrophoresis was used to detect the resistance of GAPDH, BAGE2, and circBAGE2 to RNase R and their expression as cDNA and gDNAin 22RV1 cells. The biological functions of circBAGE2 were investigated by CCK8 assay and flow cytometry in 22RV1 cells transfected with siRNAs. Multiple databases were used to predict the target binding sites between circRNAs, miRNAs, and mRNAs. Western blotting was used to detect the expression of CCND1 and PDCD10.

Results

CircBAGE2 was significantly upregulated in PCa samples and PCa cells compared to that in matched normal tissues and normal cells, and CircBAGE2 knockdown inhibits cell proliferation and promotes apoptosis. Downregulation of circBAGE2 compromised the expression of CCND1 and PDCD10. The 3′ UTRs of CCND1 and PDCD10 were matched by miR-103a-3p, which shared binding sites with circBAGE2.

Conclusion

CircBAGE2 contributes to PCa progression by upregulating CCND1 and PDCD10 expression through its role as a ‘sponge’ of miR-103a-3p. CircBAGE2 may be a potential therapeutic target for PCa.
Differentially expressed genes analysis and target genes prediction of miR-22 in breast cancer*
Authors: Fan Tao , Wang Chaoqi , Zhang Kun , Yang Hong , Zhang Juan , Wu Wanyan , Song Yingjie
Published: June 2023

Objective

miR-22 is highly active in breast cancer, especially in the luminal B and HER2 subtypes. However, the detailed potential of the use of target genes for miR-22 in breast cancer are still unclear. In this study, we aimed to discover potential genes and the miRNA-DEGs network of miR-22 in breast cancer using bioinformatics approaches.

Methods

Analysis of microarray data GSE17508 (including 3 miR-22 knockout samples and 3 controls) obtained from the Gene Expression Omnibus (GEO) database was performed. Differentially expressed genes (DEGs) between the miR-22 knockout samples and the three control samples were detected using GEO2R. The gene ontology (GO) functional enrichment analysis and protein-protein interaction (PPI) network of DEGs were performed using the online tool Metascape and STRING database, separately. The miR-22 and DEG networks were obtained from the miRNet database. Cytoscape software was used to construct and analyze a merged miRNA-DEG network. The online tools database, mirDIP 4.1, was used to predict miR-22 target genes.

Results

Certain DEGs and miRNAs may be potential targets for predicting and treating miR-22 expressed breast cancer.

Conclusion

We constructed a prognostic model of rectal adenocarcinomas based on four immune-related lncRNAs by analyzing the data based on TCGA database, with high prediction accuracy. We also identified two biomarkers with poor prognosis (PXN-AS1 and AL158152.2) and one biomarker with good prognosis (LINC01871).