Trastuzumab deruxtecan (DS8201) for advanced non-small cell lung cancer with HER2 exon 20 insertion mutation: a case report.

An antibody-drug conjugate (ADC) of human epidermal growth factor receptor-2 (HER2) provides effective treatment for patients with HER2-positive non-small cell lung cancer (NSCLC). Exon 20 insertion mutations are the most common among HER2 mutations. This mutant subtype is highly drug-resistant, and patients receiving conventional treatment often have a poor prognosis. Trastuzumab deruxtecan (T-DXd), a novel anti-HER2 ADC, has emerged as a novel treatment option for HER2-positive (mutated, expressed, amplified, alternated) NSCLC, based on several studies and reported results. Herein, we report a case of stage IV NSCLC with HER2 exon 20 mutation in a 52-year-old male patient whose tumor recurred after radical resection of pulmonary carcinoma, who could not tolerate chemotherapy, and presented with bone metastasis. After treatment with T-DXd, the tumor significantly regressed and bone metastasis improved, maintaining a state of no progression for 21 months. This case report evidences the use of T-DXd in the treatment of NSCLC with HER2 exon 20 insertion mutation.

RRP12 suppresses cell migration and invasion in colorectal cancer cell via regulation of epithelial-mesenchymal transition.

Background: The survival of patients with advanced colorectal cancer (CRC) is variable. The high rates of recurrence, metastasis, and drug resistance make clinical treatment difficult, which needs to further develop therapeutic and prognostic targets. Ribosomal RNA processing 12 homolog (RRP12), as a nucleolar protein involved in ribosome subunit maturation and export, plays important roles in cell cycle-related processes and the response to DNA damage, and regulates the occurrence and development of various cancers. The primary aim of this study was to identify the function of RRP12 in the process of epithelial-mesenchymal transition (EMT) in CRC. Methods: In this study, the expression of RRP12 in tissue samples and the association with clinicopathological features in CRC was evaluated, and the correlation between RRP12 expression and aggressiveness of CRC was detected. After knockdown of RRP12 gene, the relationship between RRP12 and EMT-related indicators was verified in vivo and in vitro of CRC cells. Identification of RRP12-related genes and pathways through bioinformatic-based analyses was performed to find its potential mechanism. Results: RRP12 is highly expressed in CRC cell lines and clinical samples and is associated with poor survival in CRC patients. RRP12 expression was positively associated with lymph node metastasis, tumor-node-metastasis (TNM) stage, and poor differentiation. Knockdown of RRP12 was found to suppress migration and invasion of CRC cells. RRP12 contributed to the EMT process of CRC cell lines in a ZEB1-mediated manner. RRP12 knockdown was found to reverse metastasis of CRC cells in vivo. Bioinformatic-based analyses indicated that RRP12 could serve as a potential biomarker for prognostic assessment of CRC patients. Conclusions: RRP12 is involved in the tumorigenesis and metastasis of CRC by regulating the EMT process through ZEB1. Thus, RRP12 could be a potential therapeutic target for CRC therapy.

A machine learning prediction model for cancer risk in patients with type 2 diabetes based on clinical tests.

BACKGROUND: The incidence of type 2 diabetes is rapidly increasing worldwide. Studies have shown that it is also associated with cancer-related morbidities. Early detection of cancer in patients with type 2 diabetes is crucial. OBJECTIVE: This study aimed to construct a model to predict cancer risk in patients with type 2 diabetes. METHODS: This study collected clinical data from a total of 5198 patients. A cancer risk prediction model was established by analyzing 261 items from routine laboratory tests. We screened 107 risk factors from 261 clinical tests based on the importance of the characteristic variables, significance of differences between groups (P< 0.05), and minimum description length algorithm. RESULTS: Compared with 16 machine learning classifiers, five classifiers based on the decision tree algorithm (CatBoost, light gradient boosting, random forest, XGBoost, and gradient boosting) had an area under the receiver operating characteristic curve (AUC) of > 0.80. The AUC for CatBoost was 0.852 (sensitivity: 79.6%; specificity: 83.2%). CONCLUSION: The constructed model can predict the risk of cancer in patients with type 2 diabetes based on tumor biomarkers and routine tests using machine learning algorithms. This is helpful for early cancer risk screening and prevention to improve patient outcomes.

Immune checkpoint inhibitors are effective in the treatment of Epstein-Barr virus-associated gastric cancer: A case report.

RATIONALE: Gastric cancer (GC) is one of the most common malignancies globally, and its occurrence and development are associated with genetic, dietary, biological, and immune factors. Epstein-Barr virus-associated gastric cancer (EBVaGC), as a special subtype of GC, has become a research hotspot in recent years. In patients with advanced GC, Epstein-Barr virus infection is closely related to lymph node metastasis, depth of tumor invasion, and poor prognosis. There is great clinical need for a new treatment modality for EBVaGC. Advances in molecular biology and cancer genetics have led to the development of immune checkpoint inhibitors (ICIs); patients treated with ICIs experience clinical benefit and few adverse effects. PATIENT CONCERNS AND DIAGNOSES: We report a 31-year-old male with advanced EBVaGC and multiple sites of lymph node metastasis who was intolerant to multiple lines of chemotherapy. INTERVENTIONS AND OUTCOME: After immune checkpoint inhibitor treatment, both primary and metastatic tumors shrank significantly without noticeable adverse reactions. After 21 months of progression-free status, the patient underwent R0 resection. LESSONS: This case report provides evidence for the use of ICIs in treating EBVaGC. It also shows that detection of Epstein-Barr virus-encoded small nuclear RNA may be a prognostic factor in gastric cancer.

Significant role of savolitinib in a case of advanced gastric cancer with abnormal mesenchymal-epithelial transition factor (MET): A case report.

RATIONALE: Gastric cancer is a common and lethal malignancy worldwide. It lacks specific clinical symptoms during the early stages, and when detected, the optimal surgical opportunity is lost. Chemotherapy alone offers limited benefits in advanced inoperable disease or postoperative recurrence. Gastric cancer is a heterogeneous tumor involving multiple gene regulations; thus, multi-target combination therapy is the trend in research. The c-MET protein is a tyrosine kinase receptor belonging to the MET family, encoded by the MET proto-oncogene. After binding with its ligand, the hepatocyte growth factor, MET activates cellular signaling pathways in proliferation, motility, migration, and invasion. In addition, it may be abnormally activated in cancers via mutation, amplification, and protein overexpression. PATIENT CONCERNS AND DIAGNOSIS: We report a 35-year-old male with advanced gastric cancer and bone metastasis who was intolerant to chemotherapy. He was in poor general condition, with thrombocytopenia and anemia. INTERVENTIONS AND OUTCOME: Next-generation sequencing (NGS) suggested MET gene amplification in the tumor. After savolitinib treatment, the condition improved significantly without noticeable adverse reactions and maintained a progression-free status for 14 weeks. LESSONS: This case report provides evidence for MET tyrosine kinase inhibitors in treating gastric cancer patients with MET gene amplification. It also shows that MET detection is a target in gastric cancer.

A bioinformatics analysis of zinc finger protein family reveals potential oncogenic biomarkers in breast cancer.

BACKGROUND: Zinc finger protein family is the largest transcription factor family in the human genome. Studies have shown that the aberrant expression of zinc finger protein (ZNF) had a potential role in tumorigenesis. However, due to the high complexity of the ZNF family genes, the role of the ZNF family genes in breast cancer (BRCA) is still lacking in systematic understanding. AIM: In the study, we aim to understand the expression profile, prognostic value, immune invasion pattern, tumor microenvironment, epigenetic and pathway relationships, and drug sensitivity of ZNFs using multi-omics data from public databases. RESULTS: We focused on six members of ZNFs, which were upregulated in a variety of cancers. Notably, ZNF750 and ZNF224 were lower expressed in BRCA, and their expressions were significantly associated with BRCA prognosis. We confirmed the observations obtained by analyzing the clinic-pathological data. Otherwise, the expressions of ZNFs were significantly related to stromal and immune scores, and was significantly different among different immune subtypes in BRCA. Here, we found down-regulated methylation of ZNF217 and ZNF750. The relationship between methylation and survival showed the survival was worse for hypo-methylation of ZNF750 in BRCA, which is consistent with the correlation of high expression of ZNF750 in BRCA with worse survival. CONCLUSIONS: Collectively, our results provide clues for a better understanding of the characterization of ZNF family genes in BRCA from a multi-omics perspective and show their potential for use as new tumor markers and therapeutic targets.

Effects of miR­93 on epithelial­to­mesenchymal transition and vasculogenic mimicry in triple­negative breast cancer cells.

Triple­negative breast cancer (TNBC) is characterized by strong invasiveness, frequent local recurrence and distant metastasis, with poor prognosis. According to tumor angiogenesis theory, tumor cells can obtain blood supply not only by fusing with host blood vessels, but also by constructing a new vascular system through angiogenesis, so as to continuously obtain nutrients and oxygen supply; this is called vasculogenic mimicry (VM). In our previous study, differential expression profiles of miRNAs were examined with gene chip in TNBC and corresponding paracancer tissues, which demonstrated significant up­regulation of microRNA (miR)­93. Bioinformatics found that the target genes of miR­93 were associated with cell proliferation, invasion and migration. The present study investigated the association between miR­93, epithelial­to­mesenchymal transition (EMT) and VM formation in TNBC cell lines. The results indicated that miR­93 depletion suppressed MDA­MB­231 cell viability, invasion and migration (P<0.001). In addition, knockdown of miR­93 significantly upregulated the expression levels of EMT­associated genes such as E­cadherin and occludin, but downregulated the expression levels of vimentin and N­cadherin in MDA­MB­231 cells. VM formation assay showed a significant decrease in microtubule­forming ability of cells following miR­93 knockdown, which was associated with the occurrence of EMT, suggesting that miR­93 may promote the formation of VM via EMT and may be a therapeutic target for the treatment of TNBC.

Metformin suppresses HIF-1α expression in cancer-associated fibroblasts to prevent tumor-stromal cross talk in breast cancer.

The tumor microenvironment (TME) is a crucial factor in cancer progression. In breast cancer, cancer-associated fibroblasts (CAFs) and the derived stromal components have been recognized as comprising the majority of the pathological structure of the TME. In this study, we show that metformin (Met), a diabetes drug, transforms CAFs in the TME. Met disrupts tumor-stromal cross talk by preventing breast cancer cell transforming growth factor-ß (TGF-ß) signaling and the production of stromal-derived factor-1 (SDF-1) and interleukin-8 (IL-8) by CAFs. The suppression of bidirectional signaling between tumor cells and CAFs by Met is attributed to increased phospho-AMP kinase (p-AMPK) levels. By upregulating p-AMPK in CAFs, Met induces prolyl hydroxylases (PHDs), leading to the degradation of hypoxia-inducible factor-1α (HIF-1α) in CAFs. Moreover, interruption of HIF-1α-driven SDF-1 signaling in CAFs by Met leads to decreased breast cancer cell invasion. These findings suggest that Met may be used to target tumor-promoting signaling between CAFs and breast cancer cells in the TME.

Association of genetic and immuno-characteristics with clinical outcomes in patients with RET-rearranged non-small cell lung cancer: a retrospective multicenter study.

BACKGROUND: Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. METHODS: Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). RESULTS: Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6-39.1] vs 24.8 months [95% CI, 11.7-52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9-19.9] vs 4.8 months [95% CI, 4.5-5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). CONCLUSIONS: RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal.

Effects of CCL5 on the biological behavior of breast cancer and the mechanisms of its interaction with tumor­associated macrophages.

The recurrence and metastasis of breast cancer limit the effectiveness of clinical treatments, making them important issues for clinicians to address. Tumor­associated macrophages (TAMs) contribute to regulating the immune system. C­C motif chemokine ligand 5 (CCL5) is an inflammatory chemokine that promotes chemotaxis on cells involved in the immune/inflammatory response. Breast cancer cells that secrete CCL5 act on THP­1 cells, influencing the invasion and metastasis of tumors. However, knowledge remains limited regarding the mechanism underlying the effects of CCL5 on breast cancer cells and TAMs, as well as the mechanisms promoting the migration and invasion of breast cancer. The present study demonstrated that the positive expression of CCL5 was associated with lymph node status and tumor­node­metastasis stage. Treatment with ≥20 ng/ml CCL5 significantly promoted the migration and invasion of MCF­7 and MDA­MB­231 cells. CCL5­small interfering RNA intervention significantly decreased the migration and invasion of the two cell types. In vitro, THP­1 cells were successfully induced to become TAMs, which were then recruited via the chemotactic effects of CCL5. This process was achieved through the co­stimulation of phorbol­12­myristate­13­â€‹acetate, interleukin­4 (IL­4) and IL­13. The nuclear factor­κB (NF­κB) signaling pathway was activated to regulate EMT, as well as the migration and invasion process of MCF­7 cells, when co­cultured with TAMs. We also reported that blocking the expression of CCL5 in vivo may significantly inhibit the growth of human breast cancer xenografts. Therefore, targeting CCL5 may be considered as a novel therapeutic strategy for suppressing the invasion and metastasis of breast cancer.

Identification of new cancer stem cell markers and signaling pathways in HER­2­positive breast cancer by transcriptome sequencing.

Human epidermal growth factor receptor (HER)­2­positive breast cancer accounts for ~25% of all breast cancer cases, has a high propensity for relapse, metastasis and drug resistance, and is associated with a poor prognosis. Therefore, it is necessary to develop more effective therapeutic targets for the treatment of HER­2­positive breast cancer. CD44+/CD24­/low is currently the most commonly used marker for breast cancer stem cells (CSCs), which are considered the main cause of drug resistance, relapse and metastasis. In the present study, the ratio of CD44+/CD24­/low cells was almost zero in SK­BR­3 cells; however, it was >90% in MDA­MB­231 cells, as determined by flow cytometry. Since SK­BR­3 and MDA­MB­231 cells both exhibit a strong propensity for invasion and migration, it was hypothesized that there may be other markers of CSCs in SK­BR­3 cells. Therefore, transcriptome sequencing was performed for SK­BR­3 and MDA­MB­231 cells. It was observed that several leukocyte differentiation antigens and other CSC markers were significantly more highly expressed in SK­BR­3 cells. Furthermore, the expression of aldehyde dehydrogenase (ALDH)1A3, CD164 and epithelial cell adhesion molecule (EpCAM) was higher in SK­BR­3 cells compared with in other subtypes of breast cell lines, as determined by reverse transcription­polymerase chain reaction and western blot analysis. In addition, the expression levels of ALDH1A3, ALDH3B2 and EpCAM were higher in HER­2­positive breast cancer compared with in paracancerous tissues and other subtypes of breast cancer, as determined by immunohistochemistry. The expression of ß­catenin in the Wnt signaling pathway was lower in SK­BR­3 cells compared with in MDA­MB­231 cells, which may be used as a prognostic indicator for breast cancer. These findings may help identify novel CSC markers and therapeutic targets for HER­2­positive breast cancer.

Ribosome display and selection of single-chain variable fragments effectively inhibit growth and progression of microspheres in vitro and in vivo.

Distinguishing the surface markers of cancer stem cells (CSCs) is a useful method for early diagnosis and treatment of tumors, as CSCs may participate in tumorigenesis and metastasis by migrating into the circulatory system. However, the potential targets of CSCs are expressed at low levels in the natural state and are always changing. Thus, dynamic screening has been reported to be an effective measure for exploring CSC markers. In recent years, diverse single-chain variable fragments (scFvs) have been widely used in immunotherapy. In this study, we determined that the scFvs, screened using RD, had a high affinity to microspheres and could inhibit their progression. We also observed that the selected scFvs underwent evolution in vitro, and antitumor-associated proteins were successfully expressed. Combined with chemotherapy, the scFvs had a synergistic effect on the inhibition of the microspheres' progression in vitro and in vivo, which could be ascribed to their high affinity for stem-like cells and the inhibition of the microspheres' collective behaviors. In addition, proteins inhibiting CD44+ /CD24+ and MAPK were involved. Our data indicated that dynamic screening of the scFvs in a natural state was of great significance in the inhibition of the microspheres in vitro and in vivo.

Association of multiple genetic variants with breast cancer susceptibility in the Han Chinese population.

We selected 13 tag single nucleotide polymorphisms (tSNPs) to investigate whether they were associated with breast cancer risk in the Chinese Han population. Upon statistical analyses of clinical data from 551 patients and 577 controls, we found that six of the 13 SNPs were associated with breast cancer; namely, rs4973768(Odds ratio (OR) = 1.30, 95% confidence interval (CI) =1.01-1.67), rs981782(OR =1.30, 95% CI=1.01-1.66), rs1432679(OR =0.84, 95% CI=0.70-0.99), rs10759243(OR=1.30, 95%CI=1.09-1.55), rs10822013(OR =1.18, 95% CI=1.00-1.39) and rs704010(OR =1.63, 95% CI=1.04-2.56). When stratified based on breast cancer subtype, our analyses revealed that three SNPs (rs981782, rs10759243 and rs704010) correlated with ER+ breast cancer, while another three (rs4973768, rs1432679 and rs10822013) correlated with ER- breast cancer. We obtained similar results while investigating the correlation of SNPs with PR status or clinical stage. Our results suggest that associations identified between SNPs and breast cancer through genome-wide association studies (GWAS) may not always be generalizable across races.

Down-regulation of deacetylase HDAC6 inhibits the melanoma cell line A375.S2 growth through ROS-dependent mitochondrial pathway.

Previous studies have shown that histone deacetylase 6 (HDAC6) plays critical roles in many cellular processes related to cancer. However, its biological roles in the development of melanoma remain unexplored. Our aim was to investigate whether HDAC6 has a biological role in human melanoma development and to understand its underlying mechanism. In the present study, HDAC6 expression was up-regulated in melanoma tissues and cell lines. Knockdown of HDAC6 significantly inhibited the proliferation and colony formation ability of A375.S2 cells, promoted cell arrest at G0/G1 phase and apoptosis. Additionally, western blotting assay showed that HDAC6 silencing suppressed Bcl-2 level and enhanced Bax level, then activated caspase-9 and caspase-3, and further activated the release of cytochrome c from mitochondria to cytoplasm, finally induced cell apoptosis involving the mitochondrial pathway. Knockdown of HDAC6 triggered a significant generation of ROS and disruption of mitochondrial membrane potential (MMP). Furthermore, ROS inhibitor, NAC reduced HDAC6 siRNA-induced ROS production, and blocked HDAC6 siRNA-induced loss of MMP and apoptosis. NAC also significantly blocked HDAC6 siRNA-induced mtDNA copy number decrease and mitochondrial biogenesis and degradation imbalance. In conclusion, the results showed that knockdown of HDAC6 induced apoptosis in human melanoma A375.S2 cells through a ROS-dependent mitochondrial pathway.

Ocular albinism type 1-induced melanoma cell migration is mediated through the RAS/RAF/MEK/ERK signaling pathway.

Malignant melanoma has the highest risk of mortality among all types of skin cancer due to its highly metastatic potential. The ocular albinism type 1 (OA1) protein is a pigment cell­specific glycoprotein, which shares significant structural and functional features with G protein­coupled receptors. However, the role of OA1 in melanoma has yet to be elucidated. The present study aimed to investigate whether OA1 is involved in melanoma cell migration. OA1 was found to stimulate cell migration in a dose­dependent manner in cultured human melanoma cells. Furthermore, knockdown of OA1 using small interfering RNA was observed to significantly inhibit melanoma cell migration. In addition, the mechanism underlying OA1­induced melanoma cell migration was investigated. Stimulation of the RAS/RAF/mitogen activated protein kinase kinase (MEK)/extracellular signal­regulated kinase (ERK) pathway using growth factors enhanced OA1 expression and melanoma cell migration, whereas inhibition of this pathway using U0126 was observed to markedly decrease OA1 expression and the number of migrated cells. These findings indicate that OA1 is involved in melanoma cell migration and that OA1­induced melanoma cell migration is mediated through the RAS/RAF/MEK/ERK signaling pathway. Therefore, OA1 may serve as a novel therapeutic target for melanoma.

Consideration of dual characters of exosomes in the tumour immune response.

Efforts to get a strong and sustained anti-tumour immune response induced by a tumour specific antigen have failed, but sipuleucel-T has been approved by the US Food and Drug Administration (FDA). We noticed that exosomes secreted by tumour cells or immune cells may be crucially involved in the tumour immune response, whereas others have had inconsistent findings on exosome involvement. Based on immune network theory, we summarise research advances of exosomes and speculate that in the tumour immune response exosomes follow the immune response curve hypothesis. Exosomes activate simultabeously both immune activation and immune tolerance, but at different intensities. To obtain a desired anti-immune response, the initial point of immunity should be determined to achieve the strongest anti-tumour response, and repeated in vitro to extend and enhance this response. As a result, our hypothesis proposes that studies should now be directed at determining the exact time of exosome activity in maintaining a viable anti-tumour immune response in vivo.

Anti-angiogenesis effect of generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide on breast cancer in vitro.

OBJECTIVE: To study the effects of the generation 4 polyamidoamine/vascular endothelial growth factor antisense oligodeoxynucleotide (G4PAMAM/VEGFASODN) compound on the expressions of vascular endothelial growth factor (VEGF) and its mRNA of breast cancer cells and on the inhibition of vascular endothelial cells. METHODS: We examined the morphology of G4PAMAM/VEGFASODN compound and its pH stability, in vitro transfection efficiency and toxicity, and the expressions of VEGF and its mRNA. Methyl thiazolyl tetrazolium assay was used to detect the inhibitory function of the compound on vascular endothelial cells. RESULTS: The compound was about 10 nm in diameter and was homogeneously netlike. From pH 5 to 10, it showed quite a buffered ability. The 48-h transfection rate in the charge ratio of 1:40 was 98.76%, significantly higher than that of the liposome group (P<0.05). None of the transfection products showed obvious toxicity on the cells. The expressions of both VEGF protein and its mRNA after G4PAMAM/VEGFASODN transfection decreased markedly. CONCLUSION: With a low toxicity, high safety, and high transfection rate, G4PAMAM/VEGFASODN could be a promising gene vector. Specifically, it inhibits VEGF gene expression efficiently, laying a basis for further in vivo animal studies.

Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer.

AIM: To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer (ESCC) and the survival of the patients. METHODS: Sixty-four patients (median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m(2) intravenously on day 1 and capecitabine 1000 mg/m(2) orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy. Each patient received at least two cycles of treatment. The efficacy, side effects and patient survival were evaluated. RESULTS: The partial response (PR) rate was 43.8% (28/64). Stable disease (SD) rate was 47.9% (26/64), and disease progression rate was 15.6% (10/64). The clinical benefit rate (PR + SD) was 84.4%. The main toxicities were leukopenia (50.0%), nausea and vomiting (51.6%), diarrhea (50.0%), stomatitis (39.1%), polyneuropathy (37.5%) and hand-foot syndrome (37.5%). No grade 4 event in the entire cohort was found. The median progression-free survival was 4 mo, median overall survival was 10 mo (95% CI: 8.3-11.7 mo), and the 1- and 2-year survival rates were 38.1% and 8.2%, respectively. High Karnofsky index, single metastatic lesion and response to the regimen indicated respectively good prognosis. CONCLUSION: Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients. The regimen has improved the survival moderately and merits further studies.

[Anti-angiogenesis effect of G4PAMAM/VEGFASODN on breast cancer in vitro].

OBJECTIVE: To investigate the effect of G4PAMAM/VEGFASODN compound on expression of VEGF and VEGF mRNA in MDA-MB-231 breast cancer cells and the growth inhibition of vascular endothelial cells. METHODS: The diameter of G4PAMAM/VEGFASODN granule was measured by transmission electron microscopy, and its stability under different pH was also observed. The efficiency of transfection in vitro was detected by flow cytometer and the positively transfected cells were detected by laser scanning confocal microscope. The survival rate and the inhibitory rate of vascular endothelial cells were determined by MTT assay. The expression of protein VEGF was detected by immunohistochemical method and the expression of VEGF mRNA was detected by RT-PCR. RESULT: The diameter of G4PAMAM/VEGFASODN granules was about 10 nm and it arranged as homogeneous netlike. Under pH 5-10 G4PAMAM/VEGFASODN presented highly stable and no dissociation was observed with different charge ratios. The 48-hour transfection rate of G4PAMAM/VEGFASODN in charge ratio of 1:40 was significantly higher than that of the lipofectamine group. None of the transfection products in each group showed cell toxicity. The staining of VEGF protein in the cytoplasm of MDA-MB-231 cells after G4PAMAM/ASODN transfection weakened markedly, and the positive expression rate decreased. Meanwhile, the VEGF mRNA expression was also decreased. CONCLUSION: With good stability and transfection rate, compound G4PAMAM/VEGFASODN can be a promising new nanometer vector of gene transfer system. The G4PAMAM/VEGFASODN can inhibit the expression of VEGF gene specifically and efficiently, which may be used for in vivo animal experiment.