Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κß Signaling Pathway.

BACKGROUND/AIMS: Osteosarcoma, the most common primary bone malignancy, arises from primitive transformed cells of mesenchymal origin with the worldwide increasing morbidity and mortality. Previous studies found apoptosis of osteosarcoma cells was essential for an effective manner to improve the progress of osteosarcoma, and CXCR4 has been demonstrated to be relevant with various tumor progress and metastasis. METHODS: The proliferation of cells transfected with CXCR4 shRNA and control shRNA were measured by BrdU assay. Apoptosis was detected by flow cytometry. Apoptotic protein expression levels were detected by Western blot. Caspase activity was detected by Colorimetric Assay Kits using microplate reader. Activation of NF-κß signaling after CXCR4 down-regulation in osteosarcoma cells was examined by constructing NF-κß promoter luciferase reporter plasmid. The expression and activation of NF-κß Signaling relevant protein were analyzed to investigate the relationship between Akt and NF-κß signaling after the down-regulation of CXCR4 in osteosarcoma cells. RESULTS: Down-regulation of CXCR4 significantly reduced the cell proliferation, while remarkably increased the cell apoptosis and apoptotic protein expression levels in osteosarcoma cells. Furthermore, down-regulation of CXCR4 induced cell apoptosis was caspase dependent in osteosarcoma cells. This study also showed CXCR4 down-regulation induced apoptosis through inhibiting PI3K/Akt/NF-κß signaling pathway. In addition, endoplasmic reticulum stress (ERS) activation was involved in cell apoptosis induced down-regulation of CXCR4. Knockdown of partial ERS relevant proteins followed down-regulation of CXCR4 significantly inhibited cell apoptosis and the apoptotic protein expression levels. CONCLUSIONS: Taken together, the results demonstrated that down-regulation of CXCR4 could induce apoptosis of human osteosarcoma cells through inhibiting PI3K/Akt/NF-κß signaling pathway, indicating that CXCR4 could be vital for the clinical therapy of osteosarcoma.

Uniportal video-assisted thoracoscopic surgery for lung neoplasms with tracheal bronchus: a case report.

A 63-year-old woman came to our department complaint that an abnormal shadow was identified by chest computed tomography (CT). CT revealed a 21 mm × 18 mm solid nodule in the right upper lobe of lung, which was suspected to be lung cancer. We also found a bronchus directly arising from the trachea and running into the right upper lobe, which appeared to be tracheal bronchus (TB). Then she underwent the right upper lobectomy and mediastinal lymph node dissection using uniportal video-assisted thoracic surgery. During the surgery we found two bronchi which were posterior to the pulmonary hilum running into the right upper lobe. And one of them directly branched from the trachea and was thus confirmed to be TB. TB, which may be related to repeated lung infections, is a rare anomaly. The patient underwent surgery and the pathological diagnosis was lung invasive adenocarcinoma, pT1cN0M0 (stage IA3). Then the patient is being followed up outpatient. By doing chest CT before surgery, uniportal video-assisted thoracoscopic surgery (VATS) is safe for lung neoplasms with TB. To our knowledge, this is the first case report of uniportal VATS right upper lobectomy for lung neoplasms with TB.

A comparative study of thoracoscopic sympathectomy for the treatment of hand sweating.

BACKGROUND: To compare postoperative satisfaction, compensatory hyperhidrosis, and the quality of life between thoracoscopic T3 and T4 sympathectomy for the treatment of hand sweating. METHODS: From December 2010 to October 2014, 192 consecutive patients with hand sweating underwent a thoracoscopic bilateral sympathectomy with different planes (T3/T4). The patients were randomly divided into two groups, the T3 and the T4 groups, for those who underwent thoracoscopic T3 and T4 sympathectomy, respectively. All patients underwent double-lumen intubation during the thoracoscopic bilateral sympathectomy. The patients were followed up with by telephone for postoperative evaluation on the safety and effectiveness of the procedure, and the two groups (T3 versus T4) were compared to each other for any potential differences. RESULTS: All of the patients' sweating symptoms improved after the procedure. The incidence of compensatory hyperhidrosis and palm dryness in the T4 group was lower than that in the T3 group (P<0.05). The satisfaction rate and the rate of improvement in sweating and the incidence of palm moisture in the T4 group were higher than those in the T3 group (P<0.05). CONCLUSIONS: Thoracoscopic T3 and T4 sympathectomy are safe and effective methods for the treatment of hand sweating. Lowering the sympathetic chain resection plane can increase patients' satisfaction and enhance improvements in sweating. It can also reduce the incidence of long-term compensatory hyperhidrosis and palm dryness, but it also increases the incidence of palm moisture.

The Ibr-7 derivative of ibrutinib exhibits enhanced cytotoxicity against non-small cell lung cancer cells via targeting of mTORC1/S6 signaling.

Ibrutinib is a small molecule drug that targets Bruton's tyrosine kinase in B-cell malignancies and is highly efficient at killing mantle cell lymphoma and chronic lymphocytic leukemia. However, the anti-cancer activity of ibrutinib against solid tumors, such as non-small cell lung cancer (NSCLC), remains low. To improve the cytotoxicity of ibrutinib towards lung cancer, we synthesized a series of ibrutinib derivatives, of which Ibr-7 exhibited superior anti-cancer activity to ibrutinib, especially against epithelial growth factor receptor (EGFR) wild-type NSCLC cell lines. Ibr-7 was observed to dramatically suppress the mammalian target of Rapamycin complex 1 (mTORC1)/S6 signaling pathway, which is only slightly affected by ibrutinib, thus accounting for the superior anti-cancer activity of Ibr-7 towards NSCLC. Ibr-7 was shown to overcome the elevation of Mcl-1 caused by ABT-199 mono-treatment, and thus exhibited a significant synergistic effect when combined with ABT-199. In conclusion, we used a molecular substitution method to generate a novel ibrutinib derivative, termed Ibr-7, which exhibits enhanced anti-cancer activity against NSCLC cells as compared with the parental compound.

Intrapleural perfusion thermo-chemotherapy for pleural effusion caused by lung carcinoma under VATS.

BACKGROUND: The aim of this study was to assess the effectiveness of intrapleural perfusion thermo-chemotherapy (IPTC) under video-assisted thoracoscopic surgery (VATS) for malignant pleural effusion (MPE) caused by lung carcinoma. METHODS: In this retrospective study, fifty-four patients with moderate or large amounts of ipsilateral MPE secondary to non-small cell lung cancer (NSCLC) underwent pleural biopsy and IPTC under VATS. IPTC was performed by perfusing the pleural cavity with 43.0 °C saline solution containing cisplatin (200 mg/m2) using a devised circuit through mechanical circulation for 60 minutes. Blood pressure, heart rate, oxygen saturation (SpO2), and esophageal and rectal temperatures were monitored throughout the surgery. At the end of the perfusion, pleural biopsy was performed again for histological analysis. RESULTS: The temperature at the pleural surface was stabilized at 43 °C, and pleural effusion was controlled in all patients. KPS scores increased in 89.3% of patients. No patient developed bone marrow suppression reactions with noticeable bleeding after treatment, and no liver and kidney malfunctions were observed. Apoptosis was detected by light and electron microscopy after IPTC. CEA markedly decreased in all patients 1 month after IPTC. The median survival time was 21.7 months, with a one-year survival rate of 74.1%. CONCLUSIONS: IPTC under VATS is a new, safe, less invasive and more effective approach for MPE caused by lung carcinoma.

Effect of interleukin-2 treatment combined with magnetic fluid hyperthermia on Lewis lung cancer-bearing mice.

The present study aimed to investigate the therapeutic effect of interleukin-2 (IL-2) treatment combined with magnetic fluid hyperthermia (MFH) on Lewis lung cancer-bearing mice. Magnetic fluids were prepared in vitro and directly injected into the tumors in the mice, which were subjected to an alternating magnetic field. The temperature in the tumor reached 43°C and was maintained by controlling the strength of magnetic field for 30 min. Twenty-four hours later, IL-2 was injected directly into the tumors. Mice were divided into four groups: Group I (control), II (MFH), III (IL-2) and IV (IL-2+MFH). The tumor grew gradually in groups II and IV (both P<0.05) compared to the control group. Histological analysis showed that the tumor cells underwent apoptosis and necrosis. Immunohistochemistry results demonstrated that heat-shock protein 70 and cluster of differentiation (CD) 8-positive and CD4-positive T cells were strongly expressed following hypothermia. Therefore, the present study provided evidence that IL-2 treatment combined with MFH improves the therapeutic effect on lung cancer-bearing mice.

Higher temperature improves the efficacy of magnetic fluid hyperthermia for Lewis lung cancer in a mouse model.

PURPOSE: The aim of this study was to investigate the effect of a higher temperature on the efficacy of magnetic fluid hyperthermia for Lewis lung cancer in a mouse model. MATERIALS AND METHODS: Magnetic fluids were prepared in vitro and directly injected into tumors. Twenty-four hours later, the mice were subjected to an alternating magnetic field. The temperature in the tumor was increased to 46.0°C, higher than the usual temperature used in hyperthermia therapy. The higher temperature was maintained for 30 min with a stable strength of magnetic field. RESULTS: Magnetic fluid hyperthermia with a higher temperature significantly inhibited the growth of the tumors (P < 0.05). The tumors completely regressed in four out of 12 mice. Histological analysis demonstrated that the tumor cells underwent apoptosis and necrosis, and the cells were arrested at the G1/G0 phase of the cell cycle. The lifespan of the treated animals also increased significantly (P < 0.05). CONCLUSIONS: Magnetic fluid hyperthermia with a higher temperature could improve the efficacy of this therapy on lung cancer.

[Effects of magnetic fluid hyperthermia induced by an alternative magnetic field on human carcinoma A549 cell in vitro].

BACKGROUND AND OBJECTIVE: Magnetic fluid hyperthermia (MFH) is a method of heat therapy using nanometer techniques and hyperthermia. It has the advantage of high specificity of targeting. The aim of this study is to detect the effects of MFH induced by an alternating magnetic field on human being carcinoma A549 cells in vitro. METHODS: A human adenocarcinoma cell line A549 was cultured with various concentrations of ferroferric oxide (Fe3O4) magnetic fluid (1.5-6.0) mg/mL and exposed to an alternative magnetic field (AMF) for 30 min. And then the optical density (OD) of viable cell, cytotocixity index, growth curve of cells, morphologic changes of cell, cell cycle and aposptosis were measured. RESULTS: The proliferation of the A549 cells were remarkably inhibited, the OD value of viable cells decreased and cytotoxity index (CI) increased; Apoptosis of the A549 cells were observed to have cell shrinkage, chromatin condensation, margination, unclear fragmentation and intact cell membrane by light and electron microscopy; The cells were inhibited in the stage S. CONCLUSIONS: MFH induced by AMF could inhibit the proliferation, which promotes apoptosis and arrest at S stage of the A549 cells.

Effect of magnetic fluid hyperthermia on lung cancer nodules in a murine model.

The purpose of the present study was to investigate the therapeutic effect of magnetic fluid hyperthermia (MFH) induced by an alternating magnetic field (AMF) on human carcinoma A549 xenograft in nude mice. An animal model of human lung cancer was established by subcutaneous injection of human lung cancer A549 cells in BALB/c nude mice. The xenograft mice were randomly divided into four groups and each group was treated with an injection of a different concentration of magnetic fluid: control, low-dose (67.5 mg/ml), medium-dose (90.0 mg/ml) and high-dose group (112.5 mg/ml), respectively. Following the injection (24 h), the tumor was heated in an AMF for 30 min. Tumor volumes were then measured every week. The therapeutic effect was assessed by measuring the tumor volume and weight. Pathological examination was performed with a light and electronic microscope following treatment. The temperature at the surface of the tumor in the low-, medium- and high-dose groups increased to 41.3, 44.5 and 46.8°C, respectively. The tumor grew significantly slower in the medium- and high-dose groups (both p<0.05) compared to the control group. Cytoclasis and apoptosis were detected under light and electron microscopy. In conclusion, MFH induced by AMF inhibited tumor growth and promoted apoptosis of human carcinoma A549 cells in a xenograft mice model.

Feasibility study of high-temperature thermoseed inductive hyperthermia in melanoma treatment.

Current treatment modalities for melanoma do not offer satisfactory efficacy. We have developed a new, minimally invasive hyperthermia technology based on radio-frequency hyperthermia. Herein, we investigated the feasibility of using a nickel-copper thermoseed for inductive hyperthermia at a relatively high temperature (46-55 ˚C). In vitro, the thermoseed showed good thermal effects and effective killing of B16/F10 melanoma cells. Temperatures of 53.1 ± 0.5 ˚C were achieved for a single thermoseed and 56.5 ± 0.5 ˚C for two in parallel (spacing 5 mm). No B16/F10 melanoma cells survived with heating time longer than 20 min in the parallel thermoseed group. Magnetic fields or thermoseeds alone did not affect the survival rate of B16/F10 cells (P>0.05). In vivo, B16/F10 melanoma cells were subcutaneously injected into the right axilla of C57BL/6 mice. After the tumors grew to ~11-13 mm, two thermoseeds (spacing 5 mm) were implanted into the tumors and the mice were subjected to an alternating magnetic field (100-250 kHz, 15 kA/m) to induce hyperthermia. The temperature at the center of the tumor reached 46 ˚C at 5 min and plateaued at 50 ˚C. Thermoseed treatment produced large necrotic areas, inhibited tumor growth in 60% (6 of 10) of animals and prolonged survival time (P<0.05). Thus, with further optimization and testing, high-temperature thermoseed inductive hyperthermia may have therapeutic potential for melanoma.

Giant cystic hemolymphangioma of the postmediastinum.

Hemolymphangioma of the postmediastinum is very rare. The clinical features and treatment have not been clearly described. We present a case of giant cystic hemolymphangioma of the postmediastinum. A chest roentgenogram revealed an abnormal shadow of the postmediastinum. Computed tomography (CT) of the chest revealed a mediastinal tumor identified a giant non-invasive monomorphic cystic mass, in contact with the tracheal wall, arcus aortae and subclavian artery. The mass had regular borders and spontaneous low density, was homogeneous, and showed no enhancement after administration of contrast medium. Partial excision of the mass was achieved through left thorascopic exploration, Frozen section margin examination suggests hemolymphangioma, which is a benign tumor. Immobilization the surface of remained cyst wall with sclerosing agents. The pathology report was of a hemolymphangioma.

Surgical treatment for recurrent spontaneous pneumothorax during twin pregnancy under video-assisted thoracoscopic surgery (VATS).

Spontaneous pneumothorax during pregnancy is a rare pathological condition. Few cases have been reported previously in the literature. There is no universal guideline for the management of this condition yet. We report a case of recurrent spontaneous pneumothorax during twin pregnancy in a 30-year-old woman. Surgical treatment under video-assisted thoracoscopic surgery (VATS) was successfully performed, without subsequent pneumothorax recurrence.