Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer.
4025 Background: B7-H6, also known as NCR3LG1, is a promising molecule in B7 family and a ligand of natural killer (NK) -cell-activating receptor NKp30. B7-H6 can bind NKp30 and induce NK activation and cytokine secretion to exert anti-tumor effects. Studies have reported that the B7-H6 expression is significantly correlated with post-operative prognosis and distant metastasis status in patients with cancer. In patients with gastric cancer, B7-H6 high expression is significantly associated with longer OS. However, the effects of B7-H6 on immunotherapy and immune microenvironment are unknown. Herein, we used the data from TCGA database of gastric cancer to analyze the influence of B7-H6 expression on immune microenvironment. Methods: The gene expression profile and clinical data in gastric cancer were extracted from TCGA database ( http://cancergenome.nih.gov ). According to the previous reported article, 15 was chosen as the cutoff value for the expression of B7-H6, and the expression of B7-H6 is divided into two groups, high group (B7-H6 expression＞15) and low group (B7-H6 expression≤15). Kaplan-Meier analysis was used to verify the influence of B7-H6 expression on OS prognosis. “Cell Type Identification by Estimating Relative Subsets of RNA Transcripts” (CIBERSORT) algorithm was used to analyze the proportion of immune-related cells in the two groups. “Estimation of STromal and Immune cells in Malignant Tumours using Expression data” (ESTIMATE) algorithm was used to analyze stromal and immune scores in the two groups. The differences of immune-related signatures between the two groups were calculated according to previous reports. Results: Kaplan-Meier survival analysis showed that high group was significantly associated with longer overall survival (p value = 0.016), which was consistent with previous reports. The result of CIBERSORT algorithm showed that the proportion of activation immune correlation CD8(+) T cells and NK active cells was significantly higher in low group than in high group (p＜0.05). Meanwhile, the proportion of immune suppressive correlation CD4 resting memory T cell was significantly lower in low group than in high group (p＜0.05). The result of ESTIMATE algorithm showed that the stromal score, immune score, and ESTIMATE score in low group were significantly higher than in high group (p＜0.01). The immune-related signatures, including immune signature, expanded immune signature, TLS signature, myeloid cell chemotaxis, tertiary lymphoid structure, were significantly higher in low group than in high group (p＜0.05). Conclusions: The low B7-H6 expression was correlated with better immune microenvironment. The effect of B7-H6 expression on immunotherapy needs to be further explored.
Background: Carcinoma ex pleomorphic adenoma (CXPA), a very rare malignancy found mostly in the major salivary glands, has no established standardized treatment. Case presentation: This report describes a 67-year-old male with advanced CXPA who was effectively treated by anlotinib. Pleomorphic adenoma of the submandibular gland was first diagnosed in 1976 after a surgical resection of a mass underneath the jaw. The patient underwent re-excision 3 years later due to a recurrent pleomorphic adenoma. CXPA was first diagnosed in 2016 after a surgical removal of the left submandibular mass. A lung nodule was found on a chest CT scan in January 2018. Following a CT-guided lung biopsy that demonstrated findings consistent with pulmonary metastasis, the patient underwent local therapy (microwave ablation and radioactive seed implantation) but suffered a recurrence of disease approximately 6 months later. Anlotinib was administered orally at a dose of 12 mg daily on a 2 weeks on/1 week off schedule. A partial response was observed after two cycles of treatment. The disease remains in continued partial response after completion of his sixth cycle. Conclusion: This is the first report for anlotinib in treating CXPA. Further pre-clinical and clinical studies are needed to validate the efficacy and safety of anlotinib in the treatment of CXPA. Keywords: pulmonary metastasis, chemotherapy, partial response, angiogenesis
Gastric cancer is one of the most common types of human cancer associated with a poor prognosis. MicroRNAs (miRs), a class of non-coding RNAs that are 18-25 nucleotides in length, act as key regulators in gene expression, and have been implicated in various human cancer types. miR-125b has been implicated in the malignant progression of gastric cancer. However, the association between miR-125b expression, clinicopathological characteristics and trastuzumab resistance in human epidermal growth factor receptor 2 (HER2)-positive gastric cancer remains unclear. In the current study, in situ hybridization data demonstrated that 81.8% (108/132) of gastric cancer tissues exhibited positive expression of miR-125b, while only 26.3% (10/38) of non-tumor gastric tissues were miR-125b-positive. Reverse transcription-quantitative polymerase chain reaction data indicated that the expression level of miR-125b was markedly increased in gastric cancer tissues compared with non-cancerous gastric tissues. Furthermore, the miR-125b level was significantly associated with tumor (T) stage, lymph node metastasis, distant metastasis and TNM stage of gastric cancer (P<0.05). Increased miR-125b expression predicated poor prognosis in patients with gastric cancer. For HER2-positive gastric cancer, the upregulation of miR-125b expression was significantly associated with advanced malignant progression, as well as a poor prognosis (P<0.05). Furthermore, data from the present study indicated that the increased miR-125b level was significantly associated with trastuzumab resistance in HER2-positive gastric cancer (P<0.05). Therefore, the current study suggests that miR-125b may become a potential biomarker for predicting prognoses and clinical outcomes in patients with HER2-positive gastric cancer that receive trastuzumab treatment.
Objective To make clear of the mechanism of metastasis and recurrence of primary liver cancer, and to make sure of the preventive value of transeatheter arterial immun- ehemoembolization (ICE) in treatment of liver cancer. Methods The study is a double-blinded, controlled, prospective, randomized trial. 146 patients were randomly divided into 3 groups. Group A: regular surgery of primary liver cancer;group B: TACE 1month after surgery, treatment proposal was: ADM + DDP + 5-Fu + LP; group C:transeatheter arterial immun-chemoembolization 1 month after surgery, treatment proposal : ADM + DDP +5-Fu+LP+Octreotide+IFN. Results CD3+, CD4+, CD4+/CD8+ increased 1 month after surgery in group A; In group B: CD3+, CD4+, CD4+/CD8+ decreased but CD8+ increased 1 week after TACE; CD3+, CD4+, CD4+ /CD8+ increased but CD8+ decreased 4 weeks after TACE(P<0.05); In group C: CD3+ , CD4+, CD4+/CD8+ increased slightly 1 week after TACE, but increased significantly 4 weeks later(P<0.05). In group A, the level of VEGF was high before surgery but decreased 1 month after surgery; In group B, the level of VEGF decreased 1 week after TACE, decreased more significantly 4 weeks after TACE than that in group B(P <0.05). 1 year survival rate, 2 year survival rate and 3 year survival rate in group C ware higher than those in group A; 1 year survival rate was higher in group B than that in group A, however, 2 year survival had and 3 year survival rate had no differ-ences between group B and group A. Conclusion Transcatheter arterial ICE can prevent metastasis and recurrence after surgery of primary liver cancer increase the 1,2,3 year survival rate. It not only has the role of TACE,but can increase the immunefunction,and inhibit tumor angiogenesis, then increase the therapeutic effect.
Key words:
Chemoembolization, theraputic; Liver neoplasms; Hepatic artery; Immunotherapy; Octreotide
Sorcin is a soluble resistance‑related calcium‑binding protein, which is expressed in normal mammalian tissues, such as the liver, lungs and heart. It has been observed to be elevated in a number of cancer types, including colorectal, gastric and breast cancer. Its upregulation is usually associated with the development of chemotherapeutic drug resistance. The aim of this study was to evaluate the sorcin expression levels in human serum samples of breast cancer subjects at various stages, and subsequently compare the outcome of neoadjuvant chemotherapy when the sorcin levels fluctuated. In total, 50 subjects were recruited from patients who were admitted to Yantai Yuhunagding Hospital (Yantai, China) and diagnosed with breast cancer. Blood samples prior to and following chemotherapy were assessed using two‑dimensional gel electrophoresis (2‑DE) and western blot analysis. The 2‑DE analysis of the serum samples revealed that sorcin was upregulated in six out of 29 neoadjuvant chemotherapy (NAC)‑sensitive patients and, in those who developed multidrug resistance, sorcin was upregulated in 15 out of 21 patients (P<0.01). The differential expression levels of sorcin were confirmed by western blot and immunohistochemical analysis. In conclusion, sorcin expression in the human serum of breast cancer patients who are resistant to NAC was elevated when compared with that of NAC‑sensitive patients.
The aim of this study was to investigate the effect of thalidomide on the growth of human hepatoma cell line SMMC-7721 cells in vitro, and to explore the curative possibility of hepatocellular carcinoma with thalidomide.SMMC-7721 cells were treated with Thalidomide at different concentrations. The cell growth and proliferation was assessed by MTT assay. DNA ladder, apoptosis rate and changes of cell nuclei were studied by agarose electrophresis, fluorescence microscopy and flow cytometry, respectively. The expression of caspase-3 was analyzed with flow cytometry. The VEGF content of SMMC-7721 cells in culture medium was tested by ELSIA.When the concentration of Thalidomide solution was increased from 3.125 microg/ml to 200 microg/ml, the cell growth was inhibited by from 11.7% to 34.2%. Compared with the control group, the thalidomide solution at a concentration of 25, 50, 100 and 200 microg/ml solution significantly inhibited the proliferation of SMMC-7721 cells (P < 0.05). A ladder pattern of DNA fragments appeared after SMMC-7721 cells exposed to 200 microg/ml thalidomide for 24 h, especially for 48 h. Fluorescence microscopy revealed that the cell nuclei were condensed and fragmented after the cells were exposed to 200 microg/ml thalidomide for 48 h. In cells treated with 200 microg/ml thalidomide for 12, 24, 48 and 72 h, the apoptotic rate was 3.1% +/- 0.5%, 8.4% +/- 1.3%, 19.4% +/- 3.5% and 25.8% +/- 2.1%, respectively, significantly higher than that in the negative control group 1.6% +/- 0.6%. The cells treated with thalidomide at a concentration of 50, 100, 200 microg/ml for 48 h, the apoptotic rate was 8.7% +/- 1.2%, 16.8% +/- 2.5% and 25.4% +/- 4.5%, respectively, increasing in a dose-dependent manner, also significantly than that in the cells of control group 2.1% +/- 0.5%, (all were P < 0.05). The caspase-3 positivity of SMMC-7721 cells treated with thalidomide was increasing along with the increase of treatment time or drug concentration, but not in the control cells. The VEGF content in SMMC-7721 cells was lowering when thalidomide was used in an increasing concentration.Under the conditions used in this study, thalidomide can inhibit the proliferation of SMMC-7721 cells in vitro. Induction of apoptosis and inhibition of angiogenesis may be possibly two mechanisms for its anticancer action.
A 67-year-old man with a swollen right testicle also had dry cough for 3 months. Computed tomography of the chest showed multiple calcified lung nodules and lymph nodes in the hilum. FDG PET/CT revealed elevated FDG activity not only in the right testicle mass but also calcified thoracic lesions. Histologic examination after testicle biopsy demonstrated primary testicular papillary serous carcinoma.
e22500 Background: Breast cancer susceptibility genes BRCA1 and 2 are tumor suppressor genes and they play an important role in DNA damage response and repair during homologous recombination. Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant disease due to BRCA1 and 2 germline mutation. Germline mutations of BRCA1 and 2 genes significantly increase the risk of developing breast cancer, ovarian cancer, prostate cancer and a broad range of cancers. PARP inhibitor (PARPi) monotherapy and combinations have shown promising efficacy against a variety of cancer types with BRCA mutations. Nevertheless, the knowledge of incidence of BRCA1 and 2 germline mutations in solid tumor remains poorly understood. Herein, next generation sequencing of 539-gene profiling was performed to explore the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors. Methods: We retrospectively analyzed the BRCA1 and BRCA2 germline mutations from a comprehensive 539-gene profiling of 8535 Chinese patients with pan-cancer. 539-gene profiling contains the somatic mutations in tumor tissue or blood ctDNA and the germline mutations in blood leukocyte. We screened out the pathogenic and likely pathogenic mutations in BRCA germline mutations, and calculated the mutation frequency and the median age in every cancer type. Results: In 8535 patients with pan-cancer, 110 patients were found pathogenic or likely pathogenic germline mutations in BRCA gene and the mutation frequency was 1.29%, of which 40 BRCA1 mutations and 70 BRCA2 mutations were found in patients, respectively. The total median age was 58.15. Eliminated a few types of cancers that had a smaller number (less than 50), the higher frequency of mutations contained ovarian cancer (14.78%, media age 58), prostatic cancer (6%, media age 58.33), breast cancer (5.2% media age 57.33). The details of the top 8 cancer types with mutation frequency and media age were shown in Table. Conclusions: This was the first report of the incidence of BRCA1 and 2 germline mutations in Chinese solid tumors, which expanded the understanding of BRCA1/2 and provided a direction for clinical trial design of PARPi monotherapy and combinations.[Table: see text]
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)