Long noncoding RNA ALOX12-AS1 inhibits cervical cancer cells proliferation via targeting miR-3171.

Cervical cancer is a common female malignancy worldwide, and the molecular mechanism of cervical tumorigenesis remains poorly understood. A large piece of evidence have demonstrated the important roles of long noncoding RNAs (lncRNAs) in tumorigenesis, cancer progression and drug resistance. In this study, we comprehensively analyzed the lncRNAs expression pattern in cervical cancer using RNA sequencing and microarray data from the cancer genome atlas, gene expression omnibus and Genotype Tissue Expression. Moreover, we assessed the correlation between lncRNA expression levels and cervical cancer patient's survival. We uncovered hundreds of lncRNAs that are upregulated or downregulated in cervical cancer tissues. Among these aberrantly lncRNAs, some are significantly associated with cervical patients' poorer prognosis, such as ALOX12-AS1 and LINC00173. ALOX12-AS1 expression is downregulated in cervical cancer, and over-expression of ALOX12-AS1 could inhibit cervical cancer cells proliferation in vitro. Further, mechanistically investigation revealed that ALOX12-AS1 could interact with AGO2 and sponge miR-3171, thereby antagonizing its' repression of tumor suppressor phosphatase and tensin homolog expression in cervical cancer cell. Taken together, this study provides lncRNA candidates in cervical cancer and highlights the critical role of ALOX12-AS1 in cervical cancer.

Microwave ablation plus chemotherapy versus chemotherapy in advanced non-small cell lung cancer: a multicenter, randomized, controlled, phase III clinical trial.

OBJECTIVES: This prospective trial was performed to verify whether microwave ablation (MWA) in combination with chemotherapy could provide superior survival benefit compared with chemotherapy alone. MATERIALS AND METHODS: From March 1, 2015, to June 20, 2017, treatment-naïve patients with pathologically verified advanced or recurrent non-small cell lung cancer (NSCLC) were randomly assigned to MWA plus chemotherapy group or chemotherapy group. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS), time to local progression (TTLP), and objective response rate (ORR). The complications and adverse events were also reported. RESULTS: A total of 293 patients were randomly assigned into the two groups. One hundred forty-eight patients with 117 stage IV tumors were included in the MWA plus chemotherapy group. One hundred forty-five patients with 113 stage IV tumors were included in the chemotherapy group. The median follow-up period was 13.1 months and 12.4 months, respectively. Median PFS was 10.3 months (95% CI 8.0-13.0) in the MWA plus chemotherapy group and 4.9 months (95% CI 4.2-5.7) in the chemotherapy group (HR = 0.44, 95% CI 0.28-0.53; p < 0.0001). Median OS was not reached in the MWA plus chemotherapy group and 12.6 months (95% CI 10.6-14.6) in the chemotherapy group (HR = 0.38, 95% CI 0.27-0.53; p < 0.0001) using Kaplan-Meier analyses with log-rank test. The median TTLP was 24.5 months, and the ORR was 32% in both groups. The adverse event rate was not significantly different in the two groups. CONCLUSIONS: In patients with advanced NSCLC, longer PFS and OS can be achieved with the treatment of combined MWA and chemotherapy than chemotherapy alone. KEY POINTS: • Patients treated with MWA plus chemotherapy had superior PFS and OS over those treated with chemotherapy alone. • The ORR of patients treated with MWA plus chemotherapy was similar to that of those treated with chemotherapy alone. • Complications associated with MWA were common but tolerable and manageable.

Expression of Cytosolic Phospholipase A2 (cPLA2)-Arachidonic Acid (AA)-Cyclooxygenase-2 (COX-2) Pathway Factors in Lung Cancer Patients and Its Implication in Lung Cancer Early Detection and Prognosis.

BACKGROUND The aim of this study was to elucidate the involvement of cPLA2-AA-COX-2 pathway factors and their potential role in lung cancer early diagnosis and prognosis. MATERIAL AND METHODS We selected 80 lung cancer patients as the cancer group, and 30 normal patients were selected as the normal group. Serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 were measured, and mRNA levels of COX-2, cPLA2, COX-1, and mPGES in serum were determined. Spearman's P-test was used to analyze the correlation between expression of PGI2 and mPGES in serum and the clinical characteristics of these lung cancer patients. The factors affecting the prognosis lung cancer were analyzed by COX regression model. RESULTS The serum contents of COX-2, cPLA2, COX-1, mPGES, PGE2, and PGI2 in the cancer patient group were significantly higher (p<0.05) than in the normal group; after treatment, the serum contents of these factors were significantly decreased (p<0.05). However, distant metastasis had a significant effect on serum contents of mPGES and PGI2 (p<0.05), but not on the other factors. The mRNA levels of COX-2, cPLA2, COX-1, and mPGES in cancer patients were significantly higher than in normal patients. In addition, the 5-year survival rate of patients with high expression of mPGES and/or PGI2 was lower than that of the low expression group. Cox regression analysis showed that the expression of mPGES and PGI2 had statistical significance in predicting the prognosis of lung cancer. CONCLUSIONS The cPLA2-AA-COX-2 pathway is closely associated with lung cancer. These findings are important for clinical diagnosis of lung cancer.

[Inhibitory effect of thalidomide on growth of human hepatoma cell line SMMC-7721 cells].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Anlotinib is effective in the treatment of advanced carcinoma ex pleomorphic adenoma of the submandibular gland.

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.

Cerebral air embolism during percutaneous computed tomography scan-guided liver biopsy.

PURPOSE: The objective of the study is to explore the etiology, clinical manifestations, imaging features, diagnosis, treatment, and prognosis of cerebral air embolism complicated computed tomography (CT) scan-guided percutaneous liver biopsy. MATERIALS AND METHODS: A case of air embolism was developed in the brain during a CT-guided percutaneous needle biopsy of the liver. In addition, retrospective analysis was performed on the previously reported typical cases of cerebral air embolism secondary to CT-guided percutaneous lung biopsy. RESULTS: Cerebral air embolism has been recognized as a potentially fatal but extremely rare complication following CT-guided percutaneous liver or lung biopsy. It was usually caused by cough, positive pressure ventilation, incorrect puncture position, repeated punctures, cavity or cyst in the target sites, and vascular inflammatory lesions. CONCLUSIONS: Clinicians should focus on timely and correct diagnosis of this complication during their interventional procedures. The current main treatment for this complication has been hyperbaric oxygen therapy.

Inhibition of PLA2G4A Reduces the Expression of Lung Cancer-Related Cytokines.

Phospholipase A2-IVA (PLA2G4A) is the most abundant subtype of cytoplasmic phospholipase A2 (cPLA2) and is an important enzyme in tumor development. Our study aimed to explore the role of PLA2G4A in the regulation of lung cancer. The contents of cell-related cytokines (microsomal prostaglandin E synthase-1 [mPGES], PGE2, and prostacyclin [PGI2]) in A549 cells were analyzed by ELISA kits. Cell counting kit-8 (CCK8) was used to detect the effects of inhibitor of cPLA2 (arachidonyl trifluoromethyl ketone [AACOCF3]) on the proliferation of A549 cells. The migration and invasion of A549 cells were tested by cell scratch wound healing assay and transwell assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the effect of inhibitor AACOCF3 on the expression of related mRNA and protein in A549 cells. ELISA result showed that the levels of mPGES, PGE2, and PGI2 in control group were significantly higher than those in the AACOCF3 group. Cell inhibition rate in the control group was significantly lower than that in the AACOCF3 group. The percentage of wound healing in the control group was significantly higher than that in the AACOCF3 group. Meanwhile, the relative invasive number of cells in the control group was significantly higher than those in the AACOCF3 group. The expression levels of related mRNA of PLA2G4A and cyclooxygenase-2 (COX-2) and the expression levels of mPGES, COX-1, and COX-2 protein in the control group were significantly higher than those in the AACOCF3 group. Our research showed that PLA2G4A was involved in migration and invasion of lung cancer cells.

Upregulation of miR-125b is associated with poor prognosis and trastuzumab resistance in HER2-positive gastric cancer.

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.

Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo.

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.

The therapy of gefitinib towards breast cancer partially through reversing breast cancer biomarker arginine.

BACKGROUND: Breast cancer remains the leading reason of cancer death among women worldwide, and gefitinib is the efficient drug for breast cancer. AIMS: To use targeted metabolomics method to elucidate the therapeutic mechanism of gefitinib through profiling the amino acids. METHODS: Healthy women (n=56) and women with breast cancer (n=60) were enrolled in Affiliated Yuhuangding hospital, medical college of Qingdao University from 2012-2014. API 3200 triple quadrupole mass spectrometer was used to analyze the serum samples. RESULTS: The concentration of amino acids was compared between healthy women and women with breast cancers. Compared with the healthy women, the concentration of arginine in breast cancer women significantly decreased (p<0.0001). To show the representative capability of arginine towards the pathogenesis of breast cancers, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to be 0.96 ± 0.02, indicating the high predictive capability of arginine for breast cancer . The reversing ability of gefitinib towards the level of arginine was further determined, and 1 month treatment of gefitinib (500 mg/day) significantly reversed the arginine level of breast cancer patients (p<0.0001). CONCLUSION: The therapy of gefitinib towards breast cancer through reversing breast cancer biomarker arginine was demonstrated.

A rare case of primary paranasal sinus angiosarcoma with pulmonary metastasis detected by 18F-FDG PET/CT.

The study reports a rare case of primary paranasal sinus angiosarcoma with pulmonary metastases detected by 18F-FDG PET/CT. A 29-year-old woman presented with nasal congestion and rhinorrhea for 6 months. CT scanning showed a large mass in the right maxillary sinus, which had infiltrated the surrounding tissues. Subsequent evaluation by 18F-FDG PET/CT indicated numerous nodules in the lung, in addition to the paranasal sinus mass, which exhibited elevated FDG activity. Histologic examination after nasal endoscopic biopsy confirmed the diagnosis as primary paranasal sinus angiosarcoma with pulmonary metastases.

EGFR mutation L747P led to gefitinib resistance and accelerated liver metastases in a Chinese patient with lung adenocarcinoma.

BACKGROUND: Mutations in the epidermal growth factor receptor gene (EGFR) are found in around half of Asian patients with non-small cell lung cancer (NSCLC). For this reason, EGFR tyrosine kinase inhibitors (TKI) are often prescribed depending on the EGFR status. Two common EGFR mutations, a deletion in exon 19 and L858R in exon 21, demonstrate a positive response to gefitinib, the first approved EGFR TKI. However, T790M and an insertion in EGFR exon 21 are resistant to EGFR TKI treatment. The relationships between the EGFR mutation type and response to the target drug have not been fully investigated. CASE PRESENTATION: We describe a 66-year-old Chinese male diagnosed with stage IV lung adenocarcinoma based on evidence from a computed tomography (CT) scan and histological features of a biopsy taken during fiberoptic bronchoscopy surgery. Molecular analysis of EGFR exons 19 and 21 revealed the presence of only one mutation in exon 19: L747P (2239-2240 TT>CC). The patient requested gefitinib treatment for 2 weeks but his response was poor. A CT scan revealed that the number and relative volume of the liver metastases had increased after treatment. CONCLUSION: L747P (2239-2240 TT>CC) in exon 19 is a rare EGFR mutation that appears to lead to gefitinib resistance and might accelerate liver metastases.

Primary Testicular Serous Papillary Carcinoma With Extensive Calcification on CT and FDG PET/CT.

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.

Overexpression of sorcin in multidrug-resistant human breast cancer.

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.