Search

Background Controversial findings have been reported in the impact of speckle-type POZ protein (SPOP) on clinicopathological features and prognosis in diverse cancers. We conducted this meta-analysis to confirm whether SPOP was an effective biomarker to predict clinical stage, cancer differentiation and survival. Methods We searched studies published before June 2021 through Medline, Embase, the Cochrane library register of controlled trials and Wanfang databases. The corrections of SPOP expression with expression disparity, tumor differentiation, clinical stage and survival were analyzed. Results Our meta-analysis found that higher expression of SPOP was significantly associated with earlier clinical stage, well differentiation and better overall survival. Subgroup analysis showed that the SPOP expression of adjacent tissue was significantly higher than that in cancer tissues of prostate and liver. However, renal cancer presented improved expression of SPOP in cancer tissue. Conclusions SPOP has the potential function to act as a novel and effective biomarker for cancer diagnosis and prognostic stratification.

Objective To evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT). Methods Based on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff. Results When MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V5, V10, V20 of whole lung, D2%, D1cc, D2cc of the rib, V30 of the rib, D2% and the maximum dose (Dmax) of the skin, and D2% and Dmax of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median Dmax, D2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R50% and D2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively. Conclusions For peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.

BACKGROUND To assess the clinical and survival features of nasopharyngeal carcinoma (NPC) with consistently negative Epstein-Barr virus (EBV) DNA level. METHODS Propensity score matching (PSM) method was used to create well-balanced cohorts. Kaplan-Meier method and Cox proportional hazards models were performed to conduct survival analysis. RESULTS Four hundred and eighty patients were enrolled. Patients with consistently negative plasma EBV DNA level had a greater chance to present a relatively earlier T and N classification compared with those with positive EBV DNA level (p

Cancer has become a leading cause of death and constitutes an enormous burden worldwide. Radiation is a principle treatment modality used alone or in combination with other forms of therapy, with 50%–70% of cancer patients receiving radiotherapy at some point during their illness. It has been suggested that traditional radiotherapy (daily fractions of approximately 1.8–2 Gy over several weeks) might select for radioresistant tumor cell sub-populations, which, if not sterilized, give rise to local treatment failure and distant metastases. Thus, the challenge is to develop treatment strategies and schedules to eradicate the resistant subpopulation of tumorigenic cells rather than the predominant sensitive tumor cell population. With continued technological advances including enhanced conformal treatment technology, radiation oncologists can increasingly maximize the dose to tumors while sparing adjacent normal tissues, to limit toxicity and damage to the latter. Increased dose conformality also facilitates changes in treatment schedules, such as changes in dose per treatment fraction and number of treatment fractions, to enhance the therapeutic ratio. For example, the recently developed large dose per fraction treatment schedules (hypofractionation) have shown clinical advantage over conventional treatment schedules in some tumor types. Experimental studies suggest that following large acute doses of radiation, recurrent tumors, presumably sustained by the most resistant tumor cell populations, may in fact be equally or more radiation sensitive than the primary tumor. In this review, we summarize the related advances in radiotherapy, including the increasing understanding of the molecular mechanisms of radioresistance, and the targeting of these mechanisms with potent small molecule inhibitors, which may selectively sensitize tumor cells to radiation.

Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation, resulting in low ocular bioavailability (< 5%). Worse still, the most convenient and safe route of ocular drug administration, topical administration results in a drug bioavailability of less than 1%. iRGD modified drug delivery strategies have been developed for cancer therapy, however active targeting iRGD platforms for ocular drug delivery have yet to be explored. Herein, an iRGD modified liposomes was developed for ocular drug delivery via topical administration. The results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated manner. These findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.

Background 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-PET/CT) has been widely applied for the imaging of head and neck squamous cell carcinoma (HNSCC). This study examined whether pre- and post-treatment 18F-PET/CT features can help predict the survival of HNSCC patients. Results Three radiomics features were identified as prognostic factors. Radiomics score calculated from these features significantly predicted overall survival (OS) and disease-free disease (DFS). The clinicopathological characteristics combined with pre- or post-treatment nomograms showed better ROC curves and decision curves than the nomogram based only on clinicopathological characteristics. Conclusions Combining clinicopathological characteristics with radiomics features of pre-treatment PET/CT or post-treatment PET/CT assessment of primary tumor sites as positive or negative may substantially improve prediction of OS and DFS of HNSCC patients. Methods 171 patients who received pre-treatment 18F-PET/CT scans and 154 patients who received post-treatment 18F-PET/CT scans with HNSCC in the Cancer Imaging Achieve (TCIA) were included. Nomograms that combined clinicopathological features with either pre-treatment PET/CT radiomics features or post-treatment assessment of primary tumor sites were constructed using data from 154 HNSCC patients. Receiver operating characteristic (ROC) curves and decision curves were used to compare the predictions of these models with those of a model incorporating only clinicopathological features.

Background Induction chemotherapy followed by concurrent chemoradiotherapy is one of the standards of care for patients with nasopharyngeal carcinoma, but the optimal number of induction cycles is unclear. Here we compared survival data from patients treated with 2 to 4 cycles. Methods Patients with nasopharyngeal carcinoma at West China Hospital of Sichuan University between January 2009 and December 2015 were retrospectively analyzed. Results Six hundred and seventy three patients met eligibility criteria. After a median follow-up of 53 months (interquartile range, 38-74), there was no difference between 2 and 3 cycles in overall survival (88.14% vs 91.24%). But four cycles were associated with worse overall survival (79.12%) and higher incidence of treatment-related toxicities. Multivariate analysis showed that the number of induction cycles and lymph node classification were prognostic factors. Conclusions Two and three cycles of induction chemotherapy are associated with similar survival, while four cycles reduce survival and increase treatment-related toxicity in endemic regions.

Nasopharyngeal carcinoma (NPC) is a severe malignancy arising from the nasopharyngeal epithelium and is southern China’s third most common cancer. With the advancement of treatment methods, early-stage NPC patients usually have a better prognosis and more prolonged survival period than those with other malignant tumors. Most treatment failures are due to distant metastasis or a locally advanced stage of NPC in the initial diagnosis. In addition, approximately 10% of patients develop local recurrence, and 10%–20% of patients experience distant metastasis after treatment. These patients have a poor prognosis, with a median survival of only approximately 10–15 months. In the rapid development of treatment options, the efficacy and safety of some treatments have been validated and approved for first-line treatment, while those of other treatments remain unclear. The present study aims to provide a comprehensive overview of recent advances in NPC treatment and explain the various therapeutic possibilities in treating locally advanced, recurrent, and metastatic NPC patients.

Purpose To systematically evaluate the effects of Electronic health (eHealth) interventions on fatigue, pain, and sleep disorders in cancer survivors. Design A systematic review and meta-analysis was conducted. Methods Relevant studies were searched from five databases (MEDLINE, Embase, the Cochrane Central Register of Controlled trials, CINAHL, and PsycINFO). The comprehensive literature search was done in December 2020. Only randomized controlled trials (RCTs) that examined the effects of eHealth interventions among cancer survivors were included. Findings Twenty-five RCTs were included. The meta-analysis showed that eHealth interventions had a positive impact on pain interference (SMD = -0.37, 95% CI: -0.54 to -0.20, p = 0.0001) and sleep disorders (SMD = -0.43, 95% CI: -0.77 to -0.08, p = 0.02) but not on pain severity or fatigue in cancer survivors. The sensitivity and subgroup analyses indicated that the pooled results were robust and reliable. Conclusion eHealth interventions are effective in improving pain interference and sleep disorders in cancer survivors. Additional high-quality RCTs are needed to test the effectiveness of eHealth interventions on fatigue, pain, and sleep disorders in cancer survivors. Clinical relevance This systematic review and meta-analysis provides evidence to offer effective and sustainable eHealth care for symptom management among cancer survivors.

Whether regular fish oil supplementation is associated with cancer risk is controversial. We aimed to evaluate the association of fish oil supplementation on cancer risk according to fatty fish consumption patterns. From the UK Biobank cohort, 470 804 participants with fish oil supplementation data were included. A total of 147 316 individuals with fish oil supplementation were in the exposed group; the other 323 488 were in the unexposed group. No association was found between self-report regular fish oil supplementation and overall cancer risk (hazard ratio [HR] = 0.97, 95% confidence intervals [CIs] = 0.95-1). Stratified by fatty fish consumption level, we found the association between fish oil supplementation and lower cancer risk in participants who consumed fatty fish less than two times per week, with association noted for both overall cancer (HR = 0.96, 95% CI = 0.94-0.99) and some specific cancers (colon cancer: HR = 0.84, 95% CI = 0.75-0.94; hepatobiliary cancer: HR = 0.74, 95% CI = 0.58-0.96; lung cancer: HR = 0.87, 95% CI = 0.78-0.98). On the contrary, a higher risk of breast cancer was observed (HR = 1.16, 95% CI = 1.01-1.32) in participants who consumed fatty fish at least two times per week. In conclusion, our findings underscore the need to refine recommendations for nutritional supplements according to inherent diet habits.

To evaluate the value of concurrent chemotherapy after induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT), we performed this retrospective cohort study to compare the efficiency and toxicities of induction chemotherapy plus IMRT alone (IC + RT) versus induction chemotherapy plus IMRT-based concurrent chemoradiotherapy (IC + CCRT). We analyzed data from patients with locoregionally advanced NPC (stage III–IVb) who were treated at the West China hospital between January 2008 and December 2014. Patients received docetaxel, cisplatin, and 5-fluorouracil (TPF) IC followed by IMRT alone (IC + RT group) or IMRT plus cisplatin concurrent chemotherapy (IC + CCRT group). The main endpoint was overall survival (OS), which was evaluated by the Kaplan–Meier method and log-rank test. Multivariate Cox proportional hazard analysis was used to identify potential independent prognostic factors. Treatment-associated toxicities were compared between groups using the Chi squared test. A total of 78 patients treated with IC + RT and 76 with IC + CCRT were analyzed. The median follow-up time was 59 months (range: 7–108 months). There was no difference between patients treated with IC + RT and IC + CCRT in terms of 3-year OS (89.0% versus 88.0%, p = 0.286), progression-free survival (76.8% versus 80.0%, p = 0.142), locoregional recurrence-free survival (87.1% versus 90.5%, p = 0.156), or distant metastasis-free survival (83.6% versus 82.6%, p = 0.567). Treatment (IC + RT versus IC + CCRT) was not an independent prognostic factor for OS (HR 1.425, 95% CI 0.698–2.908; p = 0.331). IC + CCRT was associated with a higher incidence of grade 3–4 neutropenia than IC + RT during radiotherapy (11.8% versus 1.3%, p = 0.020). IC plus IMRT alone achieves similar patient survival outcomes as IC plus IMRT-based concurrent chemoradiotherapy, and has a lower incidence of toxicity.

Aim to analyze the effect of radiotherapy for cervical lymph node metastatic carcinoma with unknown primary (CCUP) and compare the survival benefits between Comprehensive radiotherapy and Involved Field radiotherapy. The patients diagnosed with CCUP between 2009 and 2019 in our institution were analyzed retrospectively. The categorical variables were tested by χ2 test. Kaplan–Meier method was used for survival analysis. Log-rank test and Cox proportional hazards regression were performed with overall survival (OS) and disease-free survival (DFS) as the primary outcome variables. Of 139 patients, 64.7% (90/139) of them received radiotherapy. Of the 90 patients who underwent radiotherapy, 45.6% (41/90) received Involved Field radiotherapy and the rest 49 patients received Comprehensive radiotherapy. The median follow-up of 139 patients is 69 months. The 1-year, 3-year, and 5-year OS rates are 87%, 62%, and 39%, respectively, and the DFS rates are 73%, 45%, and 29%, respectively. Multivariate analysis of 139 patients with CCUP shows that differentiation grade, N stage, radiotherapy, and the length of the largest lymph node (DmaxLN) are the independent prognostic factors for both OS and DFS. Subgroup analysis of 90 patients who received radiotherapy shows that the Comprehensive radiotherapy group has a better OS (P

BACKGROUND: To develop nomograms for predicting recurrence risk and long-term survival in patients with parotid gland cancer (PGC). METHODS: A total of 301 consecutive patients with PGC who underwent surgery were enrolled and randomly divided into a training cohort (n=210) and a validation cohort (n=91). Predictive nomograms were constructed based on the independent indicators of overall survival (OS) and disease-free survival (DFS) as determined by multivariate Cox regression analysis. The discrimination and calibration of nomograms were evaluated using C-indices and calibration curves. RESULTS: Six independent predictors of OS were identified. Incorporating these factors, the nomogram showed good concordance statistics of 0.84 and 0.78 in predicting the 5-year OS in the training and validation cohorts. Five independent predictors of DFS were identified and integrated into the nomogram. The concordance statistics were 0.84 and 0.74 in predicting the 5-year DFS in the training and validation cohorts. The predictive performance of the nomograms outperformed the TNM model. Additionally, the patients were divided into two groups according to the nomogram score, and significant differences in OS and DFS were observed between the high risk and low risk groups. Finally, the role of postoperative treatments was evaluated based on the risk stratification; patients at high risk of disease recurrence showed an improvement in DFS after receiving postoperative treatments. CONCLUSIONS: The nomogram showed good performance in predicting both OS and DFS in patients with PGC. It might be useful for selecting patients for postoperative treatments.

Radiation therapy is regarded as the primary treatment for cancer in clinical, whose target is to apply the accurate dose to the planning target volume (PTV) while protecting the surrounding organs at risk (OARs) from radiation as much as possible. Nevertheless, dose planning is often performed clinically by manual trial and error, which is time consuming and dependent on the subjective experience of physicians. In this paper, we propose an Adaptive Multi-organ Loss (AML) based Generative Adversarial Network (AML-GAN) for automatic dose prediction of cervical cancer, which achieves satisfactory PTV dose coverage and OARs sparing. By considering both the adversarial loss and the loss constraints for each individual organ, we can obtain a more refined dose map. Extensive experiments have been conducted to demonstrate the superiority of our proposed method in almost all PTV and OARs criteria compared with other state-of-the-art methods.

Background To evaluate the role of postoperative treatment in parotid gland carcinoma (PGC) based on risk stratification. Material and methods A total of 301 PGC patients were retrospectively analyzed using risk stratification. The Kaplan-Meier method and Cox analysis were performed to conduct survival analysis. Results In the high-risk group, those treated with postoperative radiotherapy (RT) had a better 5-year disease-free survival (DFS) than those treated with surgery alone. In the low-risk group, both surgery + RT and surgery + chemotherapy (CT) significantly improved DFS when compared with surgery alone. Cox analysis showed that patients who underwent surgery + RT or surgery + CT had a lower risk of disease progression than those who underwent surgery alone in the low-risk group. In the high-risk group, patients who underwent surgery + RT had a lower risk of disease progression. Conclusions Postoperative RT showed considerable benefit in improving disease control in patients with PGC, even in those without high-risk factors.

Background A Bayesian network meta-analysis was performed to compare the efficacy and toxicities among different induction chemotherapy regimens in locally advanced nasopharyngeal carcinoma (LA-NPC). Methods Electronic databases were searched for literature up to September 16, 2019. Two researchers independently selected the articles, evaluated the quality of the literature, and extracted and analyzed the data. Results There were no significant differences in survival outcomes, mucositis, or gastrointestinal adverse events among the four regimens. The probability of GP being the best induction scheme to improve OS was 43.7%. The completion rate of concurrent chemotherapy with the GP regimen was significantly reduced than the other three regimens. Conclusions The survival outcomes of the four regimens in LA-NPC were comparable. Considering only OS, GP showed the highest probability of improving the survival of LA-NPC, while it also affected the completion of concurrent chemotherapy.

Objectives The optimal treatment strategy of combining systemic chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC) is controversial. This study aimed to compare the efficacy and toxicities of induction chemotherapy followed by intensity-modulated radiotherapy (IC-RT) versus concurrent chemoradiotherapy (CCRT) in NPC. Methods Of 448 stage II-IVb NPC patients treated with IC-RT or CCRT were retrospectively analysed. The primary outcome was overall survival, which was analysed by using Kaplan-Meier curves and log-rank (Mantel-Cox) test. Results The median follow-up was 66 months (interquartile range, 46-84 months). There was no statistically significant difference in the estimated 5-year overall survival (OS), progression-free survival (PFS), distance metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) between IC-RT group and CCRT group (OS: 89.5% vs 91.7%, P = .568; PFS: 85.2% vs 87.5%, P = .615; DMFS: 90.9% vs 91.7%, P = .847; LRFS: 92.0% vs 96.9%, P = .104). In the multivariate analysis, the treatment group (IC-RT vs CCRT) was not an independent prognostic factor for OS, PFS, DMFS and LRFS. Less advanced tumour stage and lymph node stage were predictive of higher OS. EBV-DNA level was an independent prognostic factor that was only significantly associated with LRFS. Conclusions IC-RT achieves similar survival outcomes and treatment-related toxicities as CCRT in OS, PFS, DMFS and LRFS for patients with NPC. We need multicentre randomised controlled trials to reconfirm our data.

Background With the advances in immune checkpoint inhibitor therapy, several novel treatment options for metastatic renal cell carcinoma (mRCC) patients have recently emerged. The present study explored the optimal first-line immunotherapy for mRCC through a Bayesian network meta-analysis of the latest research data. Methods PubMed, MEDLINE, EMBASE, American Society of Clinical Oncology (ASCO) meeting abstracts, and the Cochrane Library were searched up to July 2020 to identify any randomized controlled trials related to immunotherapy in the first-line treatment of mRCC. The primary outcome was progressionfree survival, and the secondary outcomes were overall survival and grade 3-4 adverse events. Results The network meta-analysis included 4,049 patients from 5 randomized controlled trials. Avelumab plus axitinib and pembrolizumab plus axitinib were the best treatment options in terms of progression-free survival. For overall survival, pembrolizumab plus axitinib had a 77.89% probability of being the preferred treatment. For adverse events, there was an 89.21% probability that pembrolizumab plus axitinib was the regimen with the worst side effects. Conclusions Through a meta-analysis of the latest available first-line immunotherapy progression-free survival and overall survival data for mRCC, this study found that pembrolizumab plus axitinib might be the best immunotherapy option for first-line treatment. However, attention should be paid to the potential adverse events of this regimen.

T cell with chimeric antigen receptors (CAR-T) has presented remarkable efficacy for blood cancer as an emerging immunotherapy. However, for solid tumors, the therapeutic efficacy is much impaired due to the lack of infiltration and persistence of CAR-T in tumor tissue. Thus, we constructed an interleukin-7-loaded oncolytic adenovirus and combined the use of oncolytic virus and CAR-T to improve the therapeutic outcome. We constructed an interleukin-7-loaded oncolytic adenovirus (oAD-IL7) and a B7H3-targeted CAR-T and explored the efficacy of the single use of oAD-IL7, B7H3-CAR-T, or the combined therapy for glioblastoma in vitro and in vivo. The improved CAR-T anti-tumor efficacy was evaluated according to the proliferation, survival, persistence, exhaustion of T cells, and tumor regression. Constructed oAD-IL7 and B7H3-CAR-T presented moderate cytotoxicity during in vitro study, but failed to induce a thorough and persistent anti-tumor therapeutic efficacy in vivo. The combination of oAD-IL7 and B7H3-CAR-T in vitro resulted in enhanced T cell proliferation and reduced T cell apoptosis. The joint efficacy was further confirmed using tumor-bearing xenograft mice. During in vivo study, the mice treated with both oAD-IL7 and B7H3-CAR-T showed prolonged survival and reduced tumor burden. According to the ex vivo study, oAD-IL7 improved the proliferation and persistence of tumor-infiltrating B7H3-CAR-T, but failed to reverse the exhaustion. Our results indicated that oAD-IL7 is a promising auxiliary therapy to improve the therapeutic efficacy of B7H3-CAR-T in glioblastoma by providing the activating signals for tumor-infiltrating T cells. Our results also lay the basis for the future clinical trials for the combination of IL7-loaded oncolytic adenovirus and CAR-T therapy for glioblastoma.

Objectives To observe the differences of dosimetric parameters and late toxicities in Nasopharyngeal Carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT), which may provide the selective basis about radiation technology in clinical practices. Methods and materials Dosimetric parameters and late toxicities were collected and retrospectively analyzed from 627 NPC patients (stage as I–IVA/IVB) between January 2010 and December 2015. Results The median D2 of all targets and D50 of PGTVnd (regional lymph nodes) were lower in VAMT than those in IMRT, while the median D95 and D98 of PGTVnx (primary lesions) were higher in VMAT than those in IMRT (p Conclusion For NPC treatment plans, the VMAT might provide not only more favorable dose distributions of targets but also better sparing of normal tissue than observed in IMRT. Furthermore, VMAT possibly provides less treatment-related late toxicities such as ototoxicity, trismus, and temporal lobe injury.

With advances in cancer disease diagnosis and treatment, the trends of cancer survival continue to increase, but cancer survivors usually experience disease- or treatment-related problems (including both physiological and psychological problems) and poorer quality of life. Various types of telehealth interventions have been widespread in the field of medical care and have been shown to be cost-effective, to have high levels of patient satisfaction, and to have high acceptability among health professionals. Currently, there is no definite conclusion about the effectiveness of telehealth interventions on cancer survivors' quality of life.To evaluate the effects of telehealth interventions on cancer survivors' quality of life and compare the effectiveness of different types.A systematic review and meta-analysis.A systematic literature search was conducted in six databases (MEDLINE, Embase, the Cochrane Central Register of Controlled trials, CINAHL, PsycINFO, and Web of Science) to identify relevant studies from inception to 14 April 2021. Two reviewers independently screened studies and extracted the data. The Cochrane risk-of-bias tool was used to evaluate the quality of the included studies. Data synthesis was conducted in Review Manager (Version 5.3), and the quality of life scores were calculated by using the standard mean difference (SMD) and 95% confidence intervals (CIs). Sensitivity analysis and subgroup analysis were also conducted.Twenty-eight randomized controlled trials (RCTs) published from 2002 to 2020 were included. Meta-analysis revealed significant effects of telehealth interventions on cancer survivors' quality of life (SMD = 0.24, 95% CI: 0.14-0.34, P0.00001). Subgroup analysis showed that the most effective method was application-based intervention (SMD = 0.41, 95% CI: 0.17-0.66) and the short-term telehealth intervention was more effective than other durations of intervention (SMD = 0.28, 95% CI: 0.06-0.50). The effects on breast cancer survivors' quality of life were greater than those on the other types of cancer survivors (SMD = 0.30, 95% CI: 0.10-0.51). Sensitivity analysis indicated that the pooled results were robust and reliable.Telehealth interventions are effective and alternative methods for improving quality of life among cancer survivors. The most effective approach was application-based intervention, the most common approach was website-based intervention, and in terms of intervention durations, the short-term telehealth intervention was the most effective. Most telehealth interventions included breast cancer survivors. More large, well-designed RCTs are needed to confirm the effects of telehealth interventions on quality of life in cancer survivors.

// XiaoLin Hu 1, * , Sen Li 2, * , Yan He 3, * , Ping Ai 3, * , Shaoyong Wu 3, * , Yonglin Su 4, * , Xiaolin Li 5 , Lei Cai 6 , Xingchen Peng 3 1 Department of Nursing, West China Hospital, Sichuan University, Chengdu, China 2 Department of Spinal Surgery, Traditional Chinese Medicine Hospital of SouthWest Medical University, Luzhou, China 3 Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China 4 Department of Rehabilitation, West China Hospital, Sichuan University, Chengdu, China 5 Department of Pathophysiology, Basic Medical College, Jilin University, Changchun, China 6 Hepatobiliary Surgery Institute, Southwest Hospital, Third Military Medical University, Chongqing, China * These authors have contributed equally to this work Correspondence to: Xingchen Peng, email: pxx2014@sohu.com Keywords: benzothiazole-2-thiol derivative, breast cancer, proliferation, metastasis, apoptosis Received: November 24, 2016 Accepted: December 21, 2016 Published: January 02, 2017 ABSTRACT The prognosis of metastatic breast cancer is always very poor. Thus, it is urgent to develop novel drugs with less toxicity against metastatic breast cancer. A new drug (XC-591) derived from benzothiazole-2-thiol was designed and synthesized in our lab. In this study, we tried to assess effects of XC-591 treatment on primary breast cancer and pulmonary metastasis in 4T1 mice model. Furthermore, we tried to discover its possible molecular mechanism of action. MTT experiment showed XC-591 had significant anti-cancer activity on diverse cancer cells. Furthermore, XC-591 significantly suppressed the proliferation of 4T1 cells by colony formation assay. The in vivo results displayed that XC-591 could inhibit the growth and metastasis in 4T1 model. Moreover, histological analysis revealed that XC-591 treatment increased apoptosis, inhibited proliferation and angiogenesis in vivo . In addition, XC-591 did not contribute to obvious drug associated toxicity during the whole study. Molecular mechanism showed XC-591 could inhibit RhoGDI, activate caspase-3 and decrease phosphorylated Akt. The present data may be important to further explore this kind of new small-molecule inhibitor.

The optimal adjuvant treatment of high-risk low-grade glioma (LGG) is controversial. We performed this retrospective cohort study to compare three treatments including observation, radiotherapy (RT) alone, and radiotherapy combined with concomitant and adjuvant temozolomide (TMZ) chemotherapy (STUPP regimen) in patients with high-risk LGG. Patients with high-risk (age > 40 or undergoing subtotal resection or biopsy) LGG treated with observation or radiotherapy alone or STUPP regimen after operation were retrospectively analyzed. Survival rates were evaluated by the Kaplan-Meier method; the log-rank test was applied to compare differences between groups. A total of 250 patients met the inclusion criteria. Median follow-up for living people was 70 months. Overall, patients who received radiotherapy with or without temozolomide had better progression-free survival (PFS) and overall survival (OS) when compared with observation (median PFS: observation, 59 months; RT, 82 months; STUPP, not reached; median OS: observation, 96 months; RT, not reached; STUPP, not reached), whereas STUPP regimen did not further prolong PFS or OS than RT alone (PFS, P = 0.203; OS, P = 0.146). In oligodendroglioma (IDH mutant and 1p/19q codeleted) subtype, only STUPP regimen brought longer PFS when compared with observation (P = 0.008). The incidence of grade 3 or 4 neutropenia (P < 0.001) and nausea or vomiting (P = 0.004) was higher in the STUPP group than the figure for the RT alone group. PFS and OS were similarly improved in patients with high-risk LGG receiving RT alone or STUPP regimen. However, only STUPP regimen was able to bring better PFS for oligodendroglioma (IDH mutant and 1p/19q codeleted) subgroup. Longer follow-up time is needed to determine an association with treatment effect in different histological and molecular subgroups.

Hypertension is an important cardiovascular disease, which need long-term medication. Thus, oral drug delivery system is a preferred route for hypertension patients due to the convenience and compliance. Val-Leu-Pro-Val-Pro (VLPVP, VP5) is an angiotensin converting enzyme inhibitory peptide with antihypertensive effects. However, the oral peptide delivery is faced with obstacles, such as gastric acid, enzyme degradation and intestine barriers. Herein, we developed a controlled release system consisting of a PLGA core encapsulated with VP5 and a folate-decorated lipid shell (FA-VP5-LNPs) for the oral delivery of antihypertensive peptide. The results found that FA-VP5-LNPs exhibited high stability and possessed a controlled release behavior. Besides, FA-VP5-LNPs improved the cellular uptake both in Caco-2 and HT29 cells and enhanced in situ intestinal absorption in SD rats. The in vivo bioavailability study showed a superior oral absorption of FA-VP5-LNPs, and the AUC0-72 h of FA-VP5-LNPs was 30.71-fold higher than that of free VP5. The pharmacodynamics study exhibited that FA-VP5-LNPs maintained strong antihypertensive effect for six days compared with free VP5, which may reduce the frequency of administration and improve patient compliance. In addition, the nano-formulations showed no toxicity to cells and tissues. These promising results suggested that FA-VP5-LNPs could overcome the intestinal barrier and provide a potential strategy for enhancing peptide delivery and improve the antihypertensive effects.

Background It has been reported that radiation therapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy could improve progression-free survival (PFS) and overall survival (OS) in patients with high-risk World Health Organization (WHO) grade 2 gliomas after surgery. However, procarbazine is not available in China. In clinical practice, Chinese doctors often use radiotherapy combined with temozolomide (TMZ) to treat these patients, although large-scale prospective studies are lacking. This trial aims to confirm whether RT combined with temozolomide can improve PFS and OS in high-risk patients with low-grade gliomas (LGGs). Methods/design This is a two-group, randomized controlled trial (RCT) enrolling patients who have LGGs (WHO grade 2) and are aged 40 years or older without regard to the extent of resection or are aged younger than 40 years old with subtotal resection or biopsy. An estimated 250 patients will be enrolled. Eligible participants will be randomly assigned to receive RT alone or RT plus TMZ chemotherapy in a 1:1 ratio. The same RT will be given to all eligible participants regardless of whether they are randomly assigned to the RT group or the chemoradiotherapy (CRT) group. While in the CRT group, patients will receive adjuvant TMZ with or without concurrent radiochemotherapy. The primary outcome of this trial is PFS, and it will be analyzed by the intention-to-treat approach. Secondary outcomes include OS, adverse events, and cognitive function. Discussion The objective of our research is to assess the effect of radiotherapy coupled with TMZ in high-risk patients with LGGs after surgery, compared with RT alone. Different histological types and molecular subtypes will be examined, and a corresponding subgroup analysis will be conducted. Our data can provide evidence for postoperative adjuvant therapy in patients with high-risk LGGs in China. Trial registration Chinese Clinical Trial Registry, ChiCTR1800015199. Registered on 13 March 2018.

Background: Which induction chemotherapy (IC) regimen followed by cisplatin-based concurrent chemoradiotherapy (CCRT) is the best choice among PF (cisplatin and 5-fluorouracil), TP (docetaxel and cisplatin) and TPF (docetaxel, cisplatin, and 5-fluorouracil) remains controversial in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This Bayesian network meta-analysis investigated the efficacy and toxicity of these three common IC regimens and attempted to find the optimal chemotherapy regimen. Methods: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) up to December, 2017. Then, we screened studies for eligibility, extracted data, assessed their quality, tested consistency, and used Bayesian network meta-analysis to combine direct and indirect evidence. Results: Ten records were identified involving 7 eligible RCTs with 1,570 patients. Results of the Bayesian network meta-analysis shows that TPF [hazard ratios (HRs) 0.68; 95% credibility interval (CrI), 0.42–1.1], TP (HRs 0.70; 95% CrI, 0.22–2.2) and PF (HRs 1.0; 95% CrI, 0.71–1.5) have the probability of 49.61%, 47.45% and 1.57% respectively to be the optimal induction regimen. Docetaxel-based regimens, including TP [risk ratios (RRs) 5.9; 95% CrI, 1.4–26.0) and TPF (RRs 4.5; 95% CrI, 1.1–18.0), significantly increase the incidence of hematological toxicity. As for ≥ grade 3 mucositis, 5-fluorouracil-based regimens, including PF (RRs 2.1; 95% CrI, 0.91–5.8) and TPF (RRs 1.4; 95% CrI, 0.48–4. 6), are higher than TP (RRs 1.1; 95% CrI, 0.30–4.6). Conclusions: Only considering overall survival (OS), TPF has the highest probability to be the optimal choice in LA-NPC and TP also shows encouraging anti-tumor effects. However, we also noticed that TPF induced worse adverse events, especially in ≥ grade 3 hematological toxicity and oral mucositis.

Post-traumatic growth in cancer patients refers to perceived positive changes following cancer diagnosis and treatment. Little is known about the status and factors related to posttraumatic growth among Chinese patients with lung cancer. To investigate the status and factors of posttraumatic growth among Chinese patients with lung cancer. A cross-sectional design was adopted in this study. Patients (N = 173) from the oncology unit at one teaching hospital in Sichuan were recruited. Posttraumatic growth, depression, anxiety, and coping style were self-reported by the patients. Multiple linear regression analysis was to examine factors related to posttraumatic growth. Posttraumatic growth was a common exit in Chinese lung cancer patients. Time since cancer diagnosis, patient depression, and coping strategies are factors that affect the experience of posttraumatic growth. Reducing depression, providing available support, and improving active coping strategies are areas to facilitate posttraumatic growth.

Objective This study aims to conduct a systematic review and meta-analysis of the performance of PET-CT, CT, and MRI in diagnosing mandible invasion induced by head and neck cancer (HNC). Materials and methods The MEDLINE, Embase, Science Direct, CNKI and CQVIP databases were searched from inception until August 1, 2020. Then, a meta-analysis was conducted to calculate the combined diagnostic values with the corresponding 95% CIs. Two independent researchers completed the full text screening, data abstraction, and risk assessment. Results This meta-analysis included 53 studies (N = 2 946 participants). For the pooled sensitivity (SEN), MRI (SEN: 0.88, 95% CI: 0.81–0.93) was found to have a significantly higher SEN (P = 0.0045), when compared to CT (SEN: 0.77, 95% CI: 0.71–0.82), while compared with PET-CT (SEN: 0.88, 95% CI: 0.64–0.97), the SEN was approximately equal (P > 0.05). The analysis revealed that the combined specificity (SPE) of MRI (SPE: 0.83, 95% CI: 0.74–0.89) and PET-CT (SPE: 0.81, 95% CI: 0.57–0.93) was lower than that of CT (SPE: 0.87, 95% CI: 0.83–0.90), but there was no statistical significance among these (P > 0.05). The comparison of the area under curve (AUC) reflected that PET-CT, CT and MRI have approximately equal summary diagnostic power in detecting mandibular invasion (P > 0.05). Conclusion The findings suggest that compared with CT, MRI is significantly superior for higher SEN in diagnosing mandibular invasion. The SEN of MRI and PET-CT were approximately equal. For the summary of diagnostic power, more prospective clinical trials that directly compare these three methods are needed in the future.

To evaluate the effectiveness of psychosocial interventions for posttraumatic growth in patients with cancer.A systematic literature search was performed, and relevant studies published prior to January 8, 2020, were retrieved from MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trails, CINAHL, and PsycINFO. Two reviewers independently assessed the eligibility of each study and extracted the data. The Cochrane risk-of-bias tool was utilized to assess the quality of the studies. Review Manager (Version 5.3) was used to analyse the data. The posttraumatic growth scores were calculated using the standard mean difference (SMD) and 95% confidence intervals (CIs).Fifteen randomized controlled trials published between 2000 and 2019 were included. Most of the studies had a moderate risk of bias due to low methodological quality. The meta-analysis indicated that the PTG scores in the experimental groups were higher than those in the control groups (SMD = 0.42, 95% CI: 0.26-0.57, P 0.00001). The most effective and commonly used method was mindfulness-based interventions (SMD = 0.55, 95% CI: 0.15-0.95, P = 0.007). Subgroup analysis showed that the effects of psychosocial interventions on breast cancer patients are greater than the effects on other types of cancer patients (SMD = 0.72, 95% CI: 0.44-0.99, P 0.00001).Psychosocial interventions for cancer patients are effective in facilitating posttraumatic growth. The most commonly used and effective methods are mindfulness-based interventions. More large well-designed randomized controlled trials are needed to identify the effectiveness of psychosocial interventions for posttraumatic growth in patients with cancer.

Supplemental Digital Content is available in the text, Background: Glioma-associated oncogene homolog 1(GLI1) expression correlates with the clinical significance and prognosis of several cancers. However, the evaluation of the role GLI1 expression plays in pancreatic ductal adenocarcinoma (PDAC) clinicopathological features and outcomes still lacks. Objective: The present study systemic reviewed the association of GLI1 expression and clinical significance as well as patients survival in PDAC. Methods: We systematically searched the database of The Cochrane Library, PubMed, Embase, CNKI, Weipu data, and Wanfang data according to the inclusion and exclusion criteria. (The search ended on January 1, 2019; no language restrictions). The Newcastle-Ottawa Scale (NOS) scale was implemented to assess the quality of the literature and the Review Manager 5.3 Software was used to conduct a meta-analysis. Finally, 9 studies, a total of 1058 patients, have been included. Results: GLI1 is more likely expressed in PDAC tissue rather than para-carcinoma tissue (OR = 2.86, 95%CI = 1.87–4.36, P

Sorafenib provides survival benefits in patients with advanced renal cell carcinoma (RCC), but its use is hampered by acquired drug resistance. It is important to fully clarify the molecular mechanisms of sorafenib resistance, which can help to avoid, delay or reverse drug resistance. Extracellular vesicles (EVs) can mediate intercellular communication by delivering effector molecules between cells. Here, we studied whether EVs are involved in sorafenib resistance of RCC and its possible molecular mechanisms. Using differential centrifugation, EVs were isolated from established sorafenib-resistant RCC cells (786-0 and ACHN), and EVs derived from sorafenib-resistant cells were uptaken by sensitive parental RCC cells and thus promoted drug resistance. Elevated exogenous miR-31-5p within EVs effectively downregulated MutL homolog 1 (MLH1) expression and thus promoted sorafenib resistance in vitro. Mice experiments also confirmed that miR-31-5p could mediate drug sensitivity in vivo. In addition, low expression of MLH1 was observed in sorafenib-resistant RCC cells and upregulation of MLH1 expression restored the sensitivity of resistant cell lines to sorafenib. Finally, miR-31-5p level in circulating EVs of RCC patients with progressive disease (PD) during sorafenib therapy was higher when compared to that in the pretherapy status. In conclusion, EVs shuttled miR-31-5p can transfer resistance information from sorafenib-resistant cells to sensitive cells by directly targeting MLH1, and thus magnify the drug resistance information to the whole tumor. Furthermore, miR-31-5p and MLH1 could be promising predictive biomarkers and therapeutic targets to prevent sorafenib resistance.

Implantation is a common clinical therapeutic intervention for the management and treatment of sclerous tissue–related diseases. However, the antibacterial activity and osteogenicity of implant materials, two main factors for the long-term success of implantations, remain a challenging area of implant development. Here, we developed a general coating on the implant material surface using two bioinspired polypeptides, G4-(DOPA)4–modified DDDEEK and WRWRWR, separately. DDDEEK, which is bioinspired from salivary acquired pellicles in the dental plaque biofilm, is a benefit for bone cell adhesion and proliferation owing to its excellent capacity of inducing the formation of biominerals. Cationic WRWRWR is a well-known antibacterial peptide, which can sterilize multidrug-resistant bacteria through blocking respiration and destroying the integrity of the cell wall. After being modified with G4-(DOPA)4 segments, these functional polypeptides can form a stable coating on virtually any type of material surface. When these polypeptides are mixed at equal molar ratios, the resulting coating exhibits improved bioactivities, including antibacterial activity, biomineralization capacity, and cell adhesion capacity. In animal experiments, mixed polypeptide–coated Ti6Al4V screws exhibited better antibacterial, osteogenic, and osseointegration performance (2.3-fold bone-implant contact) than untreated screws. As a result, this bioinspired coating has the potential for application in the treatment of hard tissue–related diseases.

Yan He,1,* Tao Guo,2,* Hui Guan,1 Jingjing Wang,1 Yu Sun,1 Xingchen Peng1 1Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 2Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China *These authors contributed equally to this work Purpose: In this study, we attempted to compare the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with radiotherapy alone (RT) for locoregionally advanced nasopharyngeal carcinoma (LANPC) in the era of intensity-modulated radiotherapy (IMRT) by meta-analysis. Materials and methods: We searched databases, and all randomized controlled trials meeting the inclusion criteria were utilized for a meta-analysis with RevMan 5.3 based on the Cochrane methodology. Results: Fifteen studies were found suitable based on the inclusion criteria. CCRT not only significantly improved the overall response rate (risk ratio [RR]=0.53, 95% CI 0.43–0.66) and the complete response rate (RR=0.60, 95% CI 0.51–0.71) but also contributed to longer overall survival. The incidence of grade 3–4 adverse eventsfrom CCRT group increased in hematologic toxicity (RR 2.25, 95% CI 1.54–3.29), radiation-induced oral mucositis (RR 1.64, 95% CI 1.14–2.35), and radiodermatitis (RR 1.80, 95% CI 1.13–2.88). Conclusion: Compared with IMRT alone, CCRT provided survival benefit with acceptable toxicity in patients with LANPC. However, we need multicenter randomized controlled trials and long-term follow-up to evaluate the eventual efficacy and toxicity of concurrent chemotherapy plus IMRT. Keywords: locoregionally advanced nasopharyngeal carcinoma, intensity-modulated radiotherapy, concurrent chemoradiotherapy, meta-analysis

PURPOSE To investigate the status of caregiver burden and to identify the factors related to caregiver burden among Chinese family caregivers of patients with lung cancer. METHODS A cross-sectional design with convenience sampling was used in this study. Participants (N = 116) from the oncology inpatient ward at one teaching hospital in Chengdu were recruited from June 2015 to June 2016. The following measurement tools were used: a demographic questionnaire, the Social Support Rating Scale, the General Self-efficacy Scale, and the Zarit Burden Interview. Multiple linear regression analysis was used to identify factors associated with caregiver burden. RESULTS The average ZBI score was 38.8 (SD = 13.4). Patient age (p

Brain drug delivery is still facing significant challenges due to the low permeability of the blood–brain barrier (BBB). To overcome such an insurmountable obstacle, we developed gemini quaternary ammonium (GQA) as a cell penetrating molecule incorporated into biodegradable multiblock poly(e-caprolactone urethanes)s (BMPUs) drug nanocarriers for improvement of drug accumulation in brain parenchyma. The zeta potential of Dox-loaded GQA-BMPUs micelles was around 26 mV with a mean particle size near 100 nm. It was found that GQA-BMPUs micelles achieved steadily time-dependent and concentration-dependent Dox accumulation in human brain microvascular endothelial cells (HBMECs) much higher than GQA-free BMPUs micelles and free Dox, as confirmed by flow cytometry and confocal laser scanning microscopy (CLSM) experiments. Meanwhile, no pronounced cytotoxicity was noticed in GQA-BMPUs micelles and GQA-free BMPUs micelles, and Dox associated cytotoxicity might be reduced once encapsulated into micelles. More importantly, CLSM of brain sections showed higher accumulation of Dox-loaded GQA-BMPUs micelles in the subcortical area after administrated intravenously, while no Dox accumulation was observed in either Dox-BMPUs micelles or free Dox formulation. Coupling with in vivo pharmacokinetics, biodistribution and histological toxicity studies, the results show that GQA introduced into drug nanocarriers is a promising avenue to transport therapeutic agents across BBB and improve brain drug accumulation.

Background and purpose SKLB-163 is a novel benzothiazole-2-thiol derivative with antitumor activities. This study investigated the effects of SKLB-163 on nasopharyngeal carcinoma (NPC) and its mechanisms. Materials and methods Rho GDP-dissociation inhibitor (RhoGDI) expression was examined in NPC cell lines by western blot. Effects of SKLB-163 on proliferation, migration and radiosensitivity were assessed by MTT, wound healing and colony formation assays in vitro. Anti-tumor and anti-metastatic effects, and radiosensitizing effects of SKLB-163 were evaluated in a NPC lung metastatic nude mouse model and a subcutaneous xenograft mouse model. Effects of SKLB-163 on proliferation and apoptosis were assessed by PCNA immunohistochemistry and TUNEL assay in vivo. Key molecules in RhoGDI/c-Jun N-terminal kinases-1 (JNK-1) pathway were examined by western blot. Results RhoGDI was up-regulated in NPC cell lines. SKLB-163 inhibited proliferation and migration, and increased radiosensitivity of NPC cells. SKLB-163 inhibited tumor growth and metastases, and sensitized tumor to irradiation. The radiosensitizing effects were correlated with induction of apoptosis and suppression of proliferation. The molecular mechanism was the down-regulation of RhoGDI and activation of JNK-1 signaling, and the subsequent activation of caspase-3 and the decrease in phosphorylated AKT. Conclusions SKLB-163 shows strong anti-tumor activities against NPC and sensitizes NPC to irradiation by affecting the RhoGDI/JNK-1 pathway.

// Jinlan He 1, * , Jianghong Xiao 1, * , Xingchen Peng 1, * , Baofeng Duan 1 , Yan Li 1 , Ping Ai 1 , Min Yao 2 and Nianyong Chen 1 1 Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China 2 Department of Radiation Oncology, Case Comprehensive Cancer Center, University Hospitals and Case Western Reserve University School of Medicine, Cleveland, OH 44106, United States * These authors contributed equally to this work Correspondence to: Nianyong Chen, email: nchenyy@yahoo.com Keywords: dose escalation, image-guided radiotherapy, intensity-modulated radiation therapy, pain relief, spinal metastasis Received: December 15, 2016 Accepted: June 18, 2017 Published: July 04, 2017 ABSTRACT Purpose: Under the existing condition that the optimum radiotherapy regimen for spinal metastases is controversial, this study investigates the benefits of dose escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60–66 Gy in 20–30 fractions for spinal metastases. Results : In the dose-escalation group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The median biological effective dose (BED) of Dmax of spinal cord was lower in the dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16 Gy, p < 0.001). After one month and three months of the radiotherapy, pain responses were better in the dose-escalation group than those in the 30-Gy group ( p = 0.005 and p = 0.024), and the complete pain relief rates were respectively 73.69% and 34.29% ( p = 0.006), 73.69% and 41.38% ( p = 0.028) in two compared groups. In the dose-escalation group, there is a trend of a longer duration of pain relief, a longer overall survival and a lower incidence of acute radiation toxicities. No late radiation toxicities were observed in both groups. Materials and Methods : Dosimetric parameters and clinical outcomes, including pain response, duration of pain relief, radiation toxicities and overall survival, were compared among twenty-five metastatic spinal lesions irradiated with the dose-escalation regimen and among forty-four lesions treated with the 30-Gy regimen. Conclusions: Conventionally-fractionated IG-IMRT for spinal metastases could escalate dose to the vertebral lesions while sparing the spinal cord, achieving a better pain relief without increasing radiation complications.

Radiotherapy is the main treatment strategy for nasopharyngeal carcinoma. A major factor affecting radiotherapy outcome is the accuracy of target delineation. Target delineation is time-consuming, and the results can vary depending on the experience of the oncologist. Using deep learning methods to automate target delineation may increase its efficiency. We used a modified deep learning model called U-Net to automatically segment and delineate tumor targets in patients with nasopharyngeal carcinoma. Patients were randomly divided into a training set (302 patients), validation set (100 patients), and test set (100 patients). The U-Net model was trained using labeled computed tomography images from the training set. The U-Net was able to delineate nasopharyngeal carcinoma tumors with an overall dice similarity coefficient of 65.86% for lymph nodes and 74.00% for primary tumor, with respective Hausdorff distances of 32.10 and 12.85 mm. Delineation accuracy decreased with increasing cancer stage. Automatic delineation took approximately 2.6 hours, compared to 3 hours, using an entirely manual procedure. Deep learning models can therefore improve accuracy, consistency, and efficiency of target delineation in T stage, but additional physician input may be required for lymph nodes.

Summary Objectives Ikappa B kinase alpha ( IKKα ) plays an inhibitory role in the development of epithelial-derived tumors. However, its specific function in the development of nasopharyngeal carcinoma (NPC) remains unknown. In this study we identify the role and mechanism of IKKα in IKKα -mediated NPC development. Material and methods The effect of IKKα on migration, invasion and tumorigenesis of NPC cell lines was determined using in vitro and in vivo studies. SUNE-1-5-8F cells transfected to overexpress IKKα , SUNE-1-6-10B cells with shRNA-mediated knockdown of IKKα , and three NPC cell lines were studied using Western blotting techniques to compare the major molecules in NF-κB pathways. Additionally, the extracellular signal-regulated kinase (ERK) pathway and matrix metalloproteinases (MMPs) in IKKα -regulated NPC and the effect of Epstein-Barr Nuclear Antigen 1 (EBNA1) on IKKα were examined. Results IKKα was underexpressed in highly invasive SUNE-1-5-8F cells compared with non-invasive cells (SUNE-1 and SUNE-6-10B). Overexpression of IKKα in SUNE-1-5-8F cells was achieved through transfection and resulted in inhibited migration and invasion in vitro . Furthermore, IKKα inhibited tumorigenesis in mice inoculated with IKKα -transfected NPC cells in vivo . These processes were independent of the conventional effect of IKKα on Nuclear factor κB (NF-κB) pathways. The ERK pathway was involved in IKKα -related NPC inhibition. Phosphorylation of ERK1/2 and subsequent secretion of MMP-9 were inhibited by the ERK inhibitor U0126 and not regulated by overexpressed IKKα . EBNA1 knockdown using small interfering RNA (siRNA) did not alter the expression of IKKα . Conclusion Increase in IKKα expression suppresses the progression of NPC through a NF-κB-independent and ERK-dependent pathway.

Docetaxel-based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel-resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel-resistance-associated proteins between human NPC CNE-2 cells and docetaxel-resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, α-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that α-enolase was upregulated in docetaxel-resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance.

Cytokines play important roles in regulating immune responses. Interleukin-2 (IL-2) has usually been used as an adjuvant to enhance antitumour immune responses. However, its crucial role in activation-induced cell death, inhibition of homeostatic proliferation of CD8+ memory T cells and its notable biological side effects impair its prospect of application. IL-15 has several similar functions to IL-2 and shows potential advantages over IL-2, and is being investigated to enhance antitumour dendritic cell (DC) vaccine strategies in our ongoing studies. In this preliminary study, we evaluated the ability of IL-15, compared with IL-2, to act as an adjuvant to enhance T-cell responses activated by DCs in vitro. Bone marrow-derived DCs (BMDCs) were pulsed with tumour antigens and used to stimulate lymphocyte responses in the presence of IL-15 or IL-2. The activated T lymphocytes were examined by flow cytometric analysis, and interferon-γ (IFN-γ) enzyme-linked immunospot and cytotoxicity assays. IL-15 was observed to activate lymphocytes with comparable phenotype characteristics of activated/memory CD8+ lymphocytes, compared with IL-2. Both in primary and secondary stimulation with DCs, when using IL-15 as an adjuvant, activated lymphocytes showed higher proportions of IFN-γ-secreting subsets. In secondary stimulation with BMDCs in the presence of IL-15, the activated lymphocytes showed a stronger cytotoxicity to antigen-specific tumour target cells. Our study suggested that IL-15 might be a prospective adjuvant for a DC vaccine strategy against cancers. The further observation that IL-15 acts as an adjuvant for an antitumour DC vaccine strategy is worth investigating.