The Effect of Physical Therapy on Somatosensory Tinnitus.

Objective: The objective of this work was to assess the effect of physical therapy in patients with somatosensory tinnitus (ST) and explore the influence of physical therapy on clinical variables obtained before treatment. Methods: A total of 43 patients with ST were randomized to the immediate-start group (n = 20) and delayed-start group (n = 23). All patients received physical therapy for 1 week (seven sessions). Each session lasted 60 min. The Visual Analogue Scale (VAS), Tinnitus Handicap Inventory (THI), and numerical pain rating scale (NPRS) scores were documented at baseline and after treatment (week 1) for all patients. For subjects in the immediate-start group, the THI, VAS, and NPRS scores were measured after therapy (weeks 6, 9, and 12, respectively). Medical history characteristic functional activity scale (HCFA) scores were measured at baseline to assess the association between somatic symptoms and tinnitus. Results: At week 1, VAS, THI, and NPRS scores of patients in the immediate-start group were improved by 1.25 ± 1.59, 11.10 ± 15.10, and 0.95 ± 1.54 points, respectively, and were significantly higher than those in the delayed-start group (p < 0.05). The change in VAS, THI, and NPRS scores in the treatment group was significantly positively correlated with the scores of the HCFA before treatment (r = 0.786, p < 0.001; r = 0.680, p = 0.001; r = 0.796, p < 0.001). There was no significant difference in THI, VAS, and NPRS scores among patients in the immediate-start group between weeks 1, 6, 9, and 12 after treatment (p > 0.05). Conclusions: Although more participants were necessary in the further study, the study implies that physical therapy can reduce physical pain, improve tinnitus symptoms, and quality of life in ST patients without hearing loss, and the short-term curative effect is stable, especially for tinnitus patients with clear somatic symptoms.

Anti-tumor effects of gene therapy with GALV membrane fusion glycoprotein in lung adenocarcinoma.

This study examined the efficacy of gene therapy of lung adenocarcinoma using specifically controlled type I herpes simplex virus recombinant vector expressing Gibbon ape leukemia virus membrane fusion glycoprotein gene (GALV.fus). Recombinant HSV-I plasmid carrying target transgene was constructed, and recombinant viral vector was generated in Vero cells using Lipofectamine transfection. Viral vector was introduced into lung adenocarcinoma A549 cells or human fetal fibroblast HFL-I GNHu 5 cells, or inoculated into human lung adenocarcinoma xenografts in nude mice. The anti-tumor and cytotoxic effects of GALV-FMG, the transgene, were examined in these cell and animal models. Expression of GALV-FMG in xenographs achieved 100 % tumorigenicity. Recombinant HSV-I viral vector also exhibited significant tumor cell killing effect in vitro. Relative survival rates of tumor cells treated with GALV-FMG or control vectors were, respectively, 20 and 70 %. GALV.fus has a potent anti-tumor effect against lung cancer both in vitro and in vivo. This anti-tumor potential provides foundation for further studies with this vector.

Gene therapy of lung adenocarcinoma using herpes virus expressing a fusogenic membrane glycoprotein.

The aim of this study is to observe the in vitro-targeted destruction of lung adenocarcinoma using recombinant Type I herpes simplex virus (HSV-I)-mediated gibbon ape leukemia virus envelope glycoprotein (GALV.fus), controlled by UL38 promoter and cytomegalovirus promoter (CMVP). A recombinant HSV-I plasmid encoding the GALV.fus was transfected into green monkey kidney cells, the lung adenocarcinoma line A549, and the human fetal fibroblast cell line HFL-I GNHu5 in various doses. The effects and expression of in vitro GALV.fus were observed using an inverted microscope. Enhanced green fluorescence protein expression served as the contro1 for GALV.fus. Recombinant HSV-I virus was produced. Fusogenic recombinant virus infection led to cell fusions in A549 in a dose-dependent manner. Nonfusogenic viruses only produced conventional cytotoxic effects. Recombinant HSV-I with the CMVP initiated cell fusions in HFL-1 GNHu5 cells with arrested cell cycles or as quiescence. HSV-I regulated by UL38p caused cell fusion only in growing cells. Protein expression of GALV.fus was confirmed by Western Blot in infected A549 and HFL-1 GNHu5. Delivery and tumor-specific expression of GALV.fus gene can selectively and safely target lung cancer in vitro, and may prove to be a novel gene therapy for lung cancer.

[The construction of recombinant type I herpes simplex virus carrying GALV.fus gene and its antitumor effect in nude mice].

OBJECTIVE: To observe the killing effect of recombinant type I herpes simplex virus (HSV-I) with Gibbon ape leukemia virus membrane fusion glycoprotein (GALV.fus) gene on lung adenocarcinoma in vitro and in vivo. METHODS: Recombinant HSV-I plasmids (HSV-UL38P-GALV.fus, HSV-CMVP-GALV.fus, HSV-CMVP-EGFP) was introduced into green monkey kidney cells (Vero) by liposome to amplify the virus, which were propagated in Vero cells and purified by cesium chloride density purification, titrated by TCID50 method. The three recombinant viruses were named as Synco-2, Synco-1 and Baco-1 respectively, and were transfected into lung adenocarcinoma cell line A549 cell and human lung adenocarcinoma xenografts which were established in nude mice subcutaneously to observe the expression and transfection of recombinant plasmids; mice model was divided to A (Control) group, B (Baco-1) group, C (Synco-1) group, D (Synco-2) group and E (Synco-2) group. The antitumor and cytotoxic effects of the virus in vitro or in vivo were investigated simultaneously. RESULTS: Recombinated HSV-I virus were packed successfully, the titre of Baco-1, Synco-1 and Synco-2 were 3 x 10(10) pfu/mL, 1X 10(11) pfu/mL and 4 x 10(10) pfu/mL respectively. The virus produced clear antitumor effects in vitro, the oncolytic activity of Synco-2 and Synco-1 was superior to that of Baco-1 (P < 0.01). The striking antitumor effect was seen when the virus was given subcutaneously in established xenografts in the animals. Tumor volume in Group C and D decreased significantly compared those in Group A and B (P < 0.01). The same result was observed in tumour weight (P < 0.01), and we also find that there was statistical significance between Group C and D in tumour quality at last two weeks (P < 0.01). CONCLUSIONS: The three recombinant HSV-I were packaged, amplificated and purified successfully. Recombinant GALV. fus gene system controlled by special promoter and mediated by available carrier has potent activity against lung cancer both in vitro or in vivo, and maybe a new promising candidate for investigative gene therapy of this malignancy.