Does three cycles of neoadjuvant chemotherapy prior to concurrent chemoradiotherapy provide benefits for all childhood patients with locoregionally advanced nasopharyngeal carcinoma?

BACKGROUND: Adding neoadjuvant chemotherapy (NAC) to concurrent chemoradiotherapy (CCRT) is the main strategy in treatment of children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CA-LANPC). Yet, an optimal number of NAC cycles remains unknown. We aimed to optimize the NAC cycle and potentially contribute to clinical decision making for the individual treatment of CA-LANPC. PATIENTS AND METHODS: Utilizing an NPC-specific database through an acknowledged big-data information system at our center, we identified 143 CA-LANPC treated with NAC followed by CCRT between September 2007 through April 2018. Recursive partitioning analysis (RPA) was performed to categorize the patients and predict disease-free survival (DFS). The clinical benefits of NAC cycles (two cycles vs three cycles) were assessed in each risk group. RESULTS: Independent factors derived from multivariable analysis to predict DFS were T stage (T1-3 vs T4) and plasma Epstein-Barr virus (EBV) DNA (< 4000 vs ≥ 4000 copies/mL) for risk stratification. Consequently, 87 (61%) participants were classified as low-risk group (T1-3 with low or high EBV DNA, and T4 with low EBV DNA) and the other 56 patients (39%) were classified as a high-risk group (T4 with high EBV DNA) through RPA, and corresponding 5-year DFS rates of 91.9% and 71.2%, respectively (p = 0.001). Among the high-risk group, patients receiving three cycles of NAC had statistically significant improvement in 5-year DFS over those who received two cycles of NAC (86.7% vs 59.1%; p = 0.020), while the survival benefit of three cycles NAC for low-risk groups were not observed (94.7% vs 89.7%; p = 0.652). CONCLUSIONS: We found three cycles of NAC with CCRT was a positive prognostic indicator for improved DFS for the high-risk group among CA-LANPC. However, whether low-risk patients could benefit from three cycles NAC needs further study.

Self-perceived burden and influencing factors in patients with cervical cancer administered with radiotherapy.

BACKGROUND: Cervical cancer is the fourth commonest malignancy in women around the world. It represents the second most commonly diagnosed cancer in South East Asian women, and an important cancer death cause in women of developing nations. Data collected in 2018 revealed 5690000 cervical cancer cases worldwide, 85% of which occurred in developing countries. AIM: To assess self-perceived burden (SPB) and related influencing factors in cervical cancer patients undergoing radiotherapy. METHODS: Patients were prospectively included by convenient sampling at The Fifth Affiliated Hospital of Sun Yat-Sen University, China between March 2018 and March 2019. The survey was completed using a self-designed general information questionnaire, the SPB scale for cancer patients, and the self-care self-efficacy scale, Strategies Used by People to Promote Health, which were delivered to patients with cervical cancer undergoing radiotherapy. Measurement data are expressed as the mean ± SD. Enumeration data are expressed as frequencies or percentages. Caregivers were the spouse, offspring, and other in 46.4, 40.9, and 12.7%, respectively, and the majority were male (59.1%). As for pathological type, 90 and 20 cases had squamous and adenocarcinoma/adenosquamous carcinomas, respectively. Stage IV disease was found in 12 (10.9%) patients. RESULTS: A total of 115 questionnaires were released, and five patients were excluded for too long evaluation time (n = 2) and the inability to confirm the questionnaire contents (n = 3). Finally, a total of 110 questionnaires were collected. They were aged 31-79 years, with the 40-59 age group being most represented (65.4% of all cases). Most patients were married (91.8%) and an overwhelming number had no religion (92.7%). Total SPB score was 43.13 ± 16.65. SPB was associated with the place of residence, monthly family income, payment method, transfer status, the presence of radiotherapy complications, and the presence of pain (P < 0.05). The SPB and self-care self-efficacy were negatively correlated (P < 0.01). In multivariate analysis, self-care self-efficacy, place of residence, monthly family income, payment method, degree of radiation dermatitis, and radiation proctitis were influencing factors of SPB (P < 0.05). CONCLUSION: Patients with cervical cancer undergoing radiotherapy often have SPB. Self-care self-efficacy scale, place of residence, monthly family income, payment method, and radiation dermatitis and proctitis are factors independently influencing SPB.

Research on the effect of health care integration on patients' negative emotions and satisfaction with lung cancer nursing activities.

BACKGROUND: Lung cancer is a clinical disease with multiple malignant tumors. Currently, it is difficult for patients to benefit from routine clinical nursing due to the lack of a pertinent and systematic approach. AIM: To investigate the effect of integrated nursing care on the negative emotions and satisfaction of lung cancer patients. METHODS: From January 2018 to December 2019, 92 patients with lung cancer were selected and divided into the study group and the control group; there were 46 patients in each group. The control group received routine nursing, and the study group received integrated medical care in addition to the care received by the control group. Negative emotions before and after the intervention, the self-management ability score after the intervention, family care burden after the intervention and nursing satisfaction after the intervention were measured in the two groups. RESULTS: After the intervention, the self-rating anxiety scale and self-rating depression scale scores in the study group were lower than those in the control group (P < 0.05); the scores for health knowledge, self-concept, self-responsibility and self-care skills in the study group were higher than those in the control group (P < 0.05); the scores for individual burden and responsibility burden in the study group were lower than those before the intervention (P < 0.05); and the nursing satisfaction in the study group (93.48%) was higher than that in the control group (78.26%, P < 0.05). CONCLUSION: An integrated nursing care approach for lung cancer patients can effectively relieve the patient's negative feelings, improve their self-management ability, help to reduce the burden of family care and improve patient satisfaction with nursing activities.

Downregulated LRRK2 gene expression inhibits proliferation and migration while promoting the apoptosis of thyroid cancer cells by inhibiting activation of the JNK signaling pathway.

Emerging studies have indicated that leucine­rich repeat kinase 2 (LRRK2) is associated with thyroid cancer (TC). The present study investigated the effect of LRRK2 on the cell cycle and apoptosis in TC, and examined the underlying mechanisms in vitro. To screen TC­associated differentially expressed genes, gene expression microarray analysis was conducted. Retrieval of pathways associated with TC from the Kyoto Encyclopedia of Genes and Genomes database indicated that the c­Jun N­terminal kinase (JNK) signaling pathway serves an essential role in TC. SW579, IHH­4, TFC­133, TPC­1 and Nthy­ori3­1 cell lines were used to screen cell lines with the highest and lowest LRRK2 expression for subsequent experiments. The two selected cell lines were transfected with pcDNA­LRRK2, or small interfering RNA against LRRK2 or SP600125 (a JNK inhibitor). Subsequently, flow cytometry, terminal deoxynucleotidyl transferase­mediated dUTP­biotin nick end labeling, a 5­ethynyl­2'­deoxyuridine assay and a scratch test was conducted to detect the cell cycle distribution, apoptosis, proliferation and migration, respectively, in each group. The LRRK2 gene was determined to be elevated in TC based on the microarray data of the GSE3678 dataset. The SW579 cell line was identified to exhibit the highest LRRK2 expression, while IHH­4 cells exhibited the lowest LRRK2 expression. LRRK2 silencing, through inhibiting the activation of the JNK signaling pathway, increased the expression levels of genes and proteins associated with cell cycle arrest and apoptosis in TC cells, promoted cell cycle arrest and apoptosis, and inhibited cell migration and proliferation in TC cells, indicating that LRRK2 repression could exert beneficial effects through the JNK signaling pathway on TC cells. These observations demonstrate that LRRK2 silencing promotes TC cell growth inhibition, and facilitates apoptosis and cell cycle arrest. The JNK signaling pathway may serve a crucial role in mediating the anti­carcinogenic activities of downregulated LRRK2 in TC.

SDC4 Gene Silencing Favors Human Papillary Thyroid Carcinoma Cell Apoptosis and Inhibits Epithelial Mesenchymal Transition via Wnt/ß-Catenin Pathway.

As the most common type of endocrine malignancy, papillary thyroid cancer (PTC) accounts for 85-90% of all thyroid cancers. In this study, we presented the hypothesis that SDC4 gene silencing could effectively attenuate epithelial mesenchymal transition (EMT), and promote cell apoptosis via the Wnt/ß-catenin signaling pathway in human PTC cells. Bioinformatics methods were employed to screen the determined differential expression levels of SDC4 in PTC and adjacent normal samples. PTC tissues and adjacent normal tissues were prepared and their respective levels of SDC4 protein positive expression, in addition to the mRNA and protein levels of SDC4, Wnt/ß-catenin signaling pathway, EMT and apoptosis related genes were all detected accordingly. Flow cytometry was applied in order to detect cell cycle entry and apoptosis. Finally, analyses of PTC migration and invasion abilities were assessed by using a Transwell assay and scratch test. In PTC tissues, activated Wnt/ß-catenin signaling pathway, increased EMT and repressed cell apoptosis were determined. Moreover, the PTC K1 and TPC-1 cell lines exhibiting the highest SDC4 expression were selected for further experiments. In vitro experiments revealed that SDC4 gene silencing could suppress cell migration, invasion and EMT, while acting to promote the apoptosis of PTC cells by inhibiting the activation of the Wnt/ß-catenin signaling pathway. Besides, si-ß-catenin was observed to inhibit the promotion of PTC cell migration and invasion caused by SDC4 overexpression. Our study revealed that SDC4 gene silencing represses EMT, and enhances cell apoptosis by suppressing the activation of the Wnt/ß-catenin signaling pathway in human PTC.

RNASET2 tag SNP but not CCR6 polymorphisms is associated with autoimmune thyroid diseases in the Chinese Han population.

BACKGROUND: Polymorphisms of the CC chemokine receptor 6 (CCR6) and RNASET2 tag SNP have been shown to be associated with the susceptibility to several immune-related diseases. This study was conducted to identify the association of CCR6 and RNASET2 tag SNP with autoimmune thyroid diseases (AITDs) in the Chinese Han population. METHODS: We enrolled 1061 patients with AITDs, including 701 patients with Graves' disease (GD) and 360 patients with Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control genetic association study. Three CCR6 single nucleotides polymorphisms (SNPs) (rs3093023/rs3093024/rs6902119) and one tagging SNP (rs9355610) within RNASET2 gene were selected for genotyping by multiplex polymerase chain reaction (PCR) and ligase detection reaction (LDR). RESULTS: The frequency of rs9355610 genotypes in the patients with GD differed significantly from that in the controls (p = 0.017). The frequency of the minor G allele of rs9355610 was significantly higher in the GD patients than in the healthy controls (p = 0.005, OR = 1.225, 95% CI:1.063-1.412). However, we could not find significant differences in the genotype or allele frequencies of HT patients compared with healthy controls. After gender stratification, the frequency of the minor G allele in both male and female GD patients was significantly higher than that in the healthy controls (p = 0.036, OR = 1.308, 95% CI:1.017-1.684 ; p = 0.048, OR = 1.19, 95% CI:1.001-1.413; respectively);. Furthermore, the frequency of haplotype AT in GD patients was significantly lower than that in their control groups (p = 0.003) and showed a protective effect against GD (OR = 0.806, 95% CI: 0.699-0.929). The frequency of haplotype GT in GD patients was significantly higher than that in their control groups (p = 0.048), indicating that GT was the risk haplotype to GD (OR = 1.267, 95% CI: 1.001-1.603). There were no significant differences in the allele or genotype frequencies of three SNPs of CCR6 (rs3093023/rs3093024/ rs6902119) gene between GD patients, HT patients and controls. CONCLUSIONS: Our results suggest that the rs9355610 tag SNP of RNASET2 gene is positively associated with susceptibility to GD in the Chinese Han population. No association was found for the tested CCR6 SNPs.

An ER membrane protein, Sop4, facilitates ER export of the yeast plasma membrane [H+]ATPase, Pma1.

We have analyzed the mechanism by which Sop4, a novel ER membrane protein, regulates quality control and intracellular transport of Pma1-7, a mutant plasma membrane ATPase. At the restrictive temperature, newly synthesized Pma1-7 is targeted for vacuolar degradation instead of being correctly delivered to the cell surface. Loss of Sop4 at least partially corrects vacuolar mislocalization, allowing Pma1-7 routing to the plasma membrane. Ste2-3 is a mutant pheromone receptor which, like Pma1-7, is defective in targeting to the cell surface, resulting in a mating defect. sop4delta suppresses the mating defect of ste2-3 cells as well as the growth defect of pma1-7. Visualization of newly synthesized Pma1-7 in sop4delta cells by indirect immunofluorescence reveals delayed export from the ER. Similarly, ER export of wild-type Pma1 is delayed in the absence of Sop4 although intracellular transport of Gas1 and CPY is unaffected. These observations suggest a model in which a selective increase in ER residence time for Pma1-7 may allow it to achieve a more favorable conformation for subsequent delivery to the plasma membrane. In support of this model, newly synthesized Pma1-7 is also routed to the plasma membrane upon release from a general block of ER-to-Golgi transport in sec13-1 cells.