Preliminary clinical study of weekly recombinant human endostatin as a hypoxic tumour cell radiosensitiser combined with radiotherapy in the treatment of NSCLC

2012 ◽  
Vol 14 (6) ◽  
pp. 465-470 ◽  
Author(s):  
Xiao-Dong Jiang ◽  
Yun Qiao ◽  
Peng Dai ◽  
Jin Wu ◽  
Da-An Song ◽  
...  
Keyword(s):  
Clinical Study ◽  
Tumour Cell ◽  
Recombinant Human Endostatin ◽  
Hypoxic Tumour Cell

scholarly journals Evaluation of intravitreal topotecan dose levels, toxicity and efficacy for retinoblastoma vitreous seeds: a preclinical and clinical study

2021 ◽  
pp. bjophthalmol-2020-318529
Author(s):  
Carley M Bogan ◽  
Jessica V Kaczmarek ◽  
Janene M Pierce ◽  
Sheau-chiann Chen ◽  
Kelli L Boyd ◽  
...  
Keyword(s):  
Cohort Study ◽  
Clinical Study ◽  
Tumour Cell ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Rabbit Model ◽  
Retinal Toxicity ◽  
Apoptosis Induction ◽  
Dose Levels ◽  
Vitreous Seeds

BackgroundCurrent melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in our rabbit model and patient cohort.MethodsRabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction. Patients: retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.ResultsIntravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC90 across the rabbit vitreous. Three weekly topotecan injections (either 15 µg or 30 µg) caused no retinal toxicity in rabbits, whereas melphalan 12.5 µg (equals 25 µg in humans) reduced ERG amplitudes 42%–79%. Intravitreal topotecan 15 µg was equally effective to melphalan to treat WERI-Rb1 cell xenografts in rabbits (96% reduction for topotecan vs saline (p=0.004), 88% reduction for melphalan vs saline (p=0.004), topotecan vs melphalan, p=0.15). In our clinical study, patients received 881 monotherapy injections (48 topotecan, 833 melphalan). Patients receiving 20 µg or 30 µg topotecan demonstrated no significant ERG reductions; melphalan caused ERG reductions of 7.6 μV for every injection of 25 µg (p=0.03) or 30 µg (p<0.001). Most patients treated with intravitreal topotecan also received intravitreal melphalan at some point during their treatment course. Among those eyes treated exclusively with topotecan monotherapy, all eyes were salvaged.ConclusionsTaken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.

scholarly journals Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10

2020 ◽  
Author(s):  
Fangyu Chen ◽  
Bing Xu ◽  
Jie Li ◽  
Xi Yang ◽  
Junjie Gu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Cell ◽  
Therapeutic Option ◽  
In Vitro Assays ◽  
Luciferase Reporter ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Potential Biomarker ◽  
Hypoxic Tumour Cell

Abstract Background: Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear. Methods: Exo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter.Results: Hypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis. Conclusions: Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.

scholarly journals Hypoxic Tumour Cell-derived Exosomal miR-340-5p Promotes Radioresistance of Oesophageal Squamous Cell Carcinoma via KLF10

2020 ◽  
Author(s):  
Fangyu Chen ◽  
Bing Xu ◽  
Jie Li ◽  
Xi Yang ◽  
Junjie Gu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Cell ◽  
Clinical Samples ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Potential Biomarker ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Hypoxic Tumour Cell

Abstract Background: Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communications between hypoxic cells and aerobic cells via exosomes during radiation resistance remain unclear. Methods: We previously detected miR-340-5p is highly expressed in hypoxic OSCC exosomes by RNA-seq. The effects and mechanisms of hypoxic EVs and miR-340-5p on radiosensitivity were evaluated by qPCR, western blot IHC, flow cytometry, TUNEL assay, etc. Tumour xenografts and clinical samples were used for evaluating radiosensitivity and dissecting underlying mechanisms. Results: Hypoxic exosomes can alleviate radiation induced apoptosis and accelerate DNA damage repair. miR-340-5p is highly expressed in hypoxic exosomes and causes radioresistance. Knockdown miR-340-5p in hypoxic EVs reversed whose radioresistant effect, indicating miR-340-5p is critical for hypoxic EV-induced radioresistance. KLF10 is the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance radiosensitivity of OSCC. And higher levels of miR-340-5p in the plasma exosomes of OSCC patients are related to poor radiotherapy response and prognosis. Conclusions: Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Combined use of metformin and radiotherapy might benefit OSCC patients.

scholarly journals Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10

2021 ◽  
Author(s):  
Fangyu Chen ◽  
Bing Xu ◽  
Jie Li ◽  
Xi Yang ◽  
Junjie Gu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Cell ◽  
Therapeutic Option ◽  
In Vitro Assays ◽  
Luciferase Reporter ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Potential Biomarker ◽  
Hypoxic Tumour Cell

Abstract Background: Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear. Methods: Exo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter.Results: Hypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis. Conclusions: Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.

scholarly journals Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Fangyu Chen ◽  
Bing Xu ◽  
Jie Li ◽  
Xi Yang ◽  
Junjie Gu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Cell ◽  
Therapeutic Option ◽  
In Vitro Assays ◽  
Luciferase Reporter ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Potential Biomarker ◽  
Hypoxic Tumour Cell

Abstract Background Radiotherapy resistance is a major obstacle in the treatment of oesophageal squamous cell carcinoma (OSCC). Hypoxia is a critical cause of radioresistance. However, the communication between hypoxic cells and aerobic cells via exosomes during the transfer of radiation resistance remains unclear. Methods Exo-miR-340-5p levels were analysed by RNA-seq and qRT-PCR. We co-cultured OSCC cells with isolated normoxic and hypoxic exosomes to study their impact on radiosensitivity. We used a specific exo-miR-340-5p mimic and knock-down retrovirus to explore the role of this miRNA in the transfer of radioresistance from hypoxic to normoxic cells. Dual-luciferase reporter and RIP assays were used to verify KLF10 as a putative target of miR-340-5p. Several in vitro assays were conducted and xenograft models were established to investigate the effect of exo-miR-340-5p on OSCC radiosensitivity. The plasma exo-miR-340-5p levels in OSCC patients were analysed to study the clinical value of this parameter. Results Hypoxic exosomes alleviated radiation-induced apoptosis and accelerated DNA damage repair. miR-340-5p was highly expressed in hypoxic exosomes and was transferred into normoxic cells, where it induced radioresistance. Overexpression of miR-340-5p in normoxic OSCC cells mimicked the radioresistance of cells co-cultured with hypoxic exosomes. Knockdown of miR-340-5p in hypoxic exosomes reversed the radioresistance effect, indicating that exo-miR-340-5p is critical for hypoxic EV-transferred radioresistance. KLF10 was identified as the direct target of miR-340-5p. Moreover, metformin was found to increase the expression of KLF10 and enhance the radiosensitivity of OSCC. Higher levels of miR-340-5p in the plasma exosomes from OSCC patients are related to a poorer radiotherapy response and prognosis. Conclusions Hypoxic tumour cell-derived exosomal miR-340-5p confers radioresistance in OSCC by targeting KLF10/UVRAG, suggesting that miR-340-5p could be a potential biomarker and therapeutic target for the enhancement of radiosensitivity in OSCC. Metformin can increase KLF10 expression, which ameliorates the radioresistance induced by exo-miR-340-5p transfer. Therefore, metformin could be further investigated as a therapeutic option for the treatment of OSCC.

A Clinical Study of Twenty-seven Children Exhibiting Functional Hearing Loss

1981 ◽  
Vol 12 (1) ◽  
pp. 26-35 ◽  
Author(s):  
Donald L. McCanna ◽  
Giacinto DeLapa
Keyword(s):  
Hearing Loss ◽  
Clinical Study ◽  
Early Identification ◽  
Behavioral Responses ◽  
Upper Elementary ◽  
Elementary Grades ◽  
Ability Level ◽  
Hearing Problem

This report reviews 27 cases of children exhibiting functional hearing loss. The study reveals that most students were in the upper elementary grades and were predominantly females. These subjects were functioning below their ability level in school and were usually in conflict with school, home, or peers. Tests used were selected on the basis of their helping to provide early identification. The subjects' oral and behavioral responses are presented, as well as ways of resolving the hearing problem. Some helpful counseling techniques are also presented.

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