RESUMO
Multidrug resistance (MDR) remains a major obstacle to effective chemotherapy treatment in ovarian cancer. In our study, paclitaxel-resistant ovarian cancer patients and cell lines had decreased miR-145 levels and expressed high levels of Sp1 and Cdk6. Introducing miR-145 into SKOV3/PTX and A2780/PTX cells led to a reduction in Cdk6 and Sp1 along with downregulation of P-gp and pRb. These changes resulted in increased accumulation of antineoplastic drugs and G1 cell cycle arrest, which rendered the cells more sensitive to paclitaxel in vitro and in vivo. These effects could be reversed by reintroducing Sp1 or Cdk6 into cells expressing high levels of miR-145, resulting in restoration of P-gp and pRb levels. Furthermore, we confirmed that both Cdk6 and Sp1 are targets of miR-145. Intriguingly, demethylation with 5-aza-dC led to reactivation of miR-145 expression in drug-resistant ovarian cancer cell lines, which also resulted in increased sensitivity to paclitaxel. Collectively, these findings begin to elucidate the role of miR-145 as an important regulator of chemoresistance in ovarian cancer by controlling both Cdk6 and Sp1.
Assuntos
Quinase 6 Dependente de Ciclina/metabolismo , MicroRNAs/administração & dosagem , MicroRNAs/metabolismo , Neoplasias Ovarianas/terapia , Paclitaxel/farmacologia , Fator de Transcrição Sp1/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Quinase 6 Dependente de Ciclina/biossíntese , Quinase 6 Dependente de Ciclina/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacocinética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Proteína do Retinoblastoma/biossíntese , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Fator de Transcrição Sp1/biossíntese , Fator de Transcrição Sp1/genética , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Recent studies have shown that microRNA-106a (miR-106a) is overexpressed in gastric cancer and contributes to tumor growth. In this study, we investigated whether miR-106a mediated resistance of the gastric cancer cell line SGC7901 to the chemotherapeutic agent cisplatin (DDP). MiR-106a expression was up-regulated in the DDP resistant cell line SGC7901/DDP compared with its parental line SGC7901. Transfection of miR-106a induced DDP resistance in SGC7901, while suppression of miR-106a in SGC7901/DDP led to enhanced DDP cytotoxicity. Further study indicated that the mechanism of miR-106a-induced DDP resistance involved the expression of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) protein and its downstream phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway. This study provides a novel mechanism of DDP resistance in gastric cancer.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , MicroRNAs/fisiologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Sequência de Bases , Western Blotting , Linhagem Celular Tumoral , Primers do DNA , Humanos , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Regulação para CimaRESUMO
Objective: The aim of this study was to perform across-cultural adaptation of the English version of the personalized psychological flexibility index (PPFI) into Chinese, and to evaluate its psychometric properties in patients with cancer. Methods: This study was conducted in two phases. In phase 1, we followed Beaton's guidelines for cross-cultural adaptation of PPFI. In phase 2, we conducted a cross-sectional study to assess the validity and reliability of the PPFI among a total of 455 patients with cancer in Hunan Province of China. Item analysis was used to evaluate and screen items, while content validity, construct validity, convergent validity, and concurrent validity were used to evaluate the validity. Reliability was assessed using Cronbach's É coefficient, retest reliability, and composite reliability. Results: The item-level content validity index of the modified Chinese version of PPFI (PPFI-C) ranged from 0.89 to 1.00, the scale-level CVI/universal agreement was 0.87, and the S-CVI/average was 0.99. Exploratory factor analysis identified a 14-item, three-factor structure of PPFI (item 11 deleted). Confirmatory factor analysis showed χ2/df â= â2.42, RMSEA â= â0.07, GFI â= â0.92, NFI â= â0.91, TLI â= â0.93, CFI â= â0.95, and IFI â= â0.95. PPFI-C demonstrated positive correlations with the 8-item Commitment Action Questionnaire, and negative correlations with Acceptance and Action Questionnaire-II, Hospital Anxiety and Depression Scale, and Short Form Quality Life Scale. The Cronbach's É coefficient of modified PPFI-C stood at 0.84. Conclusions: The results suggest that the 14-item PPFI-C is a reliable and valid tool for measuring PF in Chinese patients with cancer. However, additional studies are needed to validate the psychometric properties of PPFI-C in other populations.
RESUMO
BACKGROUND: Cancer-related chronic pain is reported by many patients during treatment. There are very few Chinese tools for measuring psychological inflexibility caused by cancer pain, particularly with regard to psychological processes that might influence pain severity and function disorder during cancer treatment. OBJECTIVE: To culturally adapt the Psychological Inflexibility in Pain Scale (PIPS) to Chinese cancer patients experiencing chronic pain, including the determination of psychometric properties of the translated PIPS. METHODS: This cross-sectional study included 2 phases: (1) translation and cultural adaptation and (2) determination of psychometric properties of the translated PIPS. In total, 389 cancer patients with several types of cancer experiencing chronic pain enrolled from May to September 2018 at a tertiary cancer hospital in Yuelu District of Hunan Province, China. RESULTS: The Chinese PIPS version was semantically equivalent to the original. It had a 2-factor structure with satisfactory content validity (content validity index = 0.78-1.00), convergent and discriminant validity (composite reliability and average variance extracted at 0.41-0.89, P < .001), criterion-related validity (r = 0.54 and 0.41, P < .001), Cronbach's α coefficients (α = .87), and test-retest reliability (0.9 ≤ r ≤ 0.98). CONCLUSIONS: The Chinese PIPS version has been culturally adapted and has strong psychometric properties. The scale is a psychometrically sound assessment of psychological inflexibility that can be used for future studies of pain and pain management for cancer patients. IMPLICATIONS FOR PRACTICE: The study provides a vital tool for the psychological management of cancer patients with chronic pain.
Assuntos
Dor Crônica/psicologia , Neoplasias/psicologia , Medição da Dor/psicologia , Inquéritos e Questionários/normas , Adaptação Fisiológica , Adulto , China , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/normas , Psicometria , Reprodutibilidade dos Testes , Tradução , TraduçõesRESUMO
PURPOSE: To assess the quality of life, functional status, and their predictors in tongue cancer patients up to three months after anterolateral thigh free flap (ALTFF) reconstruction. PATIENTS AND METHODS: Tongue cancer patients were examined before and one and three months after ALTFF reconstruction using three validated questionnaires: the MD Anderson Dysphagia Inventory (MDADI), Eating Assessment Tool (EAT-10), and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N). Mean scores were compared using the Friedman test. Forward selection and backward elimination methods of multiple linear regression analysis were used to identify the predictors of quality of life and functional status using SPSS at a 95% significance level. RESULTS: The present study included 265 participants (88.68% males, mean age 46.7 ± 11.05 years). The mean MDADI and EAT-10 scores were highest at one month after the surgery and lowest at three months after the surgery (p < 0.05). The mean FACT-H&N score was lowest at one month after the surgery (p < 0.05); however, post hoc analysis revealed that the difference in the scores before and three months after the surgery was non significant (p > 0.05). Denture use, occupation, age, tumor site, illness duration, drinking habit, and diet predicted the patients' quality of life, while denture use, betel nut consumption, age, marital status, and diet predicted their functional status. CONCLUSION: Although tongue cancer patients have a poor quality of life and functional status in the first month after ALTFF reconstruction, their quality of life and functional status improve thereafter. We recommend the implementation of swallowing training programs and case-oriented psychological interventions to assist patients in coping with temporary deterioration during the first month after the surgery.
RESUMO
BACKGROUND: Pain acceptance is associated with disability, pain interference, depression, and anxiety. Few studies have been conducted on the acceptance of cancer pain and its correlates. OBJECTIVES: The aim of this study was to examine the level and correlates of pain acceptance in cancer patients from mainland China. SETTING AND PARTICIPANTS: The study comprised 156 cancer patients in a tertiary cancer hospital in Hunan Province of China. DESIGN: The study is based on a cross-sectional survey design. SUBJECTS AND METHODS: The 8-item Chronic Pain Acceptance Questionnaire (CPAQ-8) was completed by 156 cancer patients with chronic pain from a tertiary cancer hospital. Demographics, pain, and negative mood assessed by the Hospital Anxiety and Depression Scale (HADS) were explored in relation to the CPAQ-8 scores using descriptive univariate analysis. RESULTS: For the 156 patients, the mean CPAQ-8 score was 25.99 (SD = 8.56; range: 9 to 44). The scores were associated with age, gender, marital status, pain duration, number of pain sites, and duration of taking analgesics. The total scores on the CPAQ-8 and its two subscales (activity engagement and pain willingness) were negatively correlated with the HADS scores. CONCLUSIONS: The findings suggest that the prevalence of pain acceptance is relatively low for Chinese cancer patients. The cancer pain acceptance is affected by age, gender, pain duration, number of pain sites, and duration of taking analgesics. The acceptance of cancer pain is negatively correlated with depression and anxiety. Therefore, patients with risk factors for low pain acceptance should receive more attention in Chinese medical settings.
Assuntos
Dor do Câncer/psicologia , Neoplasias/complicações , Neoplasias/psicologia , Adulto , Idoso , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The purpose of this qualitative study was to describe the experiences of pain acceptance in Chinese cancer patients with chronic pain. METHODS: Twelve hospitalized cancer patients with chronic pain participated in this qualitative descriptive study from August to November 2017. In-person semi-structured interviews were conducted, recorded, transcribed, and analyzed using Colaizzi's seven-step method. RESULTS: The following four main themes and 15 subthemes emerged. Theme 1 (adaptation): pain is overwhelming and pain relief is a top priority, avoidance of pain-inducing factors, and resignation; theme 2 (emotional reactions to pain): feeling misunderstood, hopelessness, frustration, irritability, and concern for loved ones; theme 3 (functional limitations): daily life activities, social communication, and work; theme 4 (coping strategies): pharmacological therapies, behavioral strategies, social support strategies, and spiritual strategies. CONCLUSIONS: This study provides a description of cancer patients' experiences related to the need for pain acceptance. These findings provide insight into the essential role of pain acceptance and underline the need to apply acceptance-based cognitive behavioral interventions as adjunctive non-pharmacological alternatives for chronic cancer pain.
RESUMO
OBJECTIVE: To translate the English work-related acceptance and action questionnaire (WAAQ), make cross-cultural adaptations, and examine its psychometric properties when used by Chinese oncology nurses. METHODS: After translation, the psychometric properties of the Chinese WAAQ were analyzed among 417 nurses, and content validity was determined by six experts. RESULTS: Item-level content validity index (CVI) values were between 0.83 and 1.00; scale-level CVI/universal agreement (S-CVI/UA) and S-CVI/average were 0.86 and 0.98, respectively, which implicated a good content validity. The correlation of the Chinese WAAQ with AAQ-II (rs = -0.247, P < 0.001) suggested criterion validity, and those with General Health Questionnaire-12 (-0.250, <0.001) and general self-efficacy scale (0.491, <0.001) and Utrecht work engagement scale (UWES) (0.439, <0.001) suggested convergent validity. Exploratory factor analysis identified a seven-item, one-factor structure of WAAQ. The Chinese version of WAAQ had high internal consistency (Cronbach's α = 0.920), with an item-total correlation coefficient of 0.702-0.828 (P < 0.05), split-half reliability of 0.933, and test-retest reliability of 0.772. CONCLUSIONS: The Chinese WAAQ is a reliable and valid tool for assessing psychological flexibility in Chinese oncology nurses.
RESUMO
OBJECTIVE: To detect the levels of miR-21a-5p, miR-155-5p, miR-218-5p, miR-222-3p, miR-494-3p in ovarian cancer tissues and the number of myeloid-derived suppressor cells (MDSCs) in peripheral blood and spleen in ovarian cancer-bearing mice, and explore their clinical significance and correlations. METHODS: The mRNA expressions of miR-21a-5p, miR-155a-5p, miR-218-5p, miR-222-3p, miR-494-3p were detected by real-time quantitative PCR (qRT-PCR) in tumor tissues and tumor-adjacent normal tissues from 12 ovarian cancer-bearing mice. The frequency of MDSCs in the peripheral blood and spleen from the 12 tumor-bearing mice was measured by flow cytometry. Spearman correlation analysis was used to find out the correlations between MDSCs and miRNAs. RESULTS: Compared with the normal mice, the number of MDSCs in the peripheral blood and spleen of the tumor-bearing mice significantly increased. The levels of miR-21a-5p, miR-218-5p and miR-222-3p in tumor tissues were significantly higher than those in tumor-adjacent normal tissues; conversely, miR-155a-5p and miR-494-3p levels in the former were significantly lower than those in the latter. There was no correlation between miR-222-3p and MDSCs, but miR-494-3p had a negative correlation with MDSCs. The expression differences of miR-21a-5p, miR-155a-5p, miR-218-5p between tumor tissues and tumor-adjacent normal tissues had positive correlations with the number of MDSCs. CONCLUSION: The levels of miR-21a-5p, miR-155a-5p, miR-218-5p, miR-494-3p in tumor tissues had correlations with the number of MDSCs in the peripheral blood and spleen of ovarian cancer-bearing mice.
Assuntos
MicroRNAs/genética , Células Mieloides/citologia , Neoplasias Ovarianas/genética , Baço/citologia , Animais , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/metabolismo , Neoplasias Ovarianas/metabolismoRESUMO
OBJECTIVE: To explore the effect of the supernatant of 4T1 murine breast cancer cell culture on arginase 1 (Arg-1) in ANA-1 macrophages in vitro by simulating the microenvironment of breast cancer. METHODS: The experimental ANA-1 macrophages were treated with the supernatant of 4T1 culture, and meanwhile, the control cells were cultured in the absence of the supernatant. Morphological changes of the ANA-1 macrophages were observed with a light microscope at 6, 8, 10, 24 hours, respectively. Real-time quantitative PCR (qRT-PCR) was performed to detect the levels of inducible nitric oxide synthase (iNOS) and Arg-1 mRNAs. Immunofluorescence and Western blotting were used to determine the levels of iNOS and Arg-1 proteins. RESULTS: The qRT-PCR indicated that the level of iNOS mRNA decreased in the experiment group compared with the control group, while Arg-1 mRNA level significantly increased compared with the control group and it reached a peak at the 8th hour. The immunofluorescence and Western blotting also demonstrated that Arg-1 protein expression was enhanced in the experimental group compared with the control group. However, iNOS protein expression was no significantly different between the experiment group and the control group. CONCLUSION: The supernatant of 4T1 cell culture increases Arg-1 production in ANA-1 macrophages.