Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
Sorafenib is one of the options for advanced hepatocellular carcinoma treatment and has been shown to extend median overall survival. However, sorafenib resistance often develops a few months after ...treatment. Hence, developing various strategies to overcome sorafenib resistance and understand the possible mechanisms is urgently needed. We first established sorafenib-resistant hepatocellular carcinoma (HCC) cells. Then, we found that sorafenib-resistant Huh7 cells (Huh7/SR) exhibit higher glucose uptakes and express elevated fatty acid synthesis and glucose metabolism-related proteins than their parental counterparts (Huh7). The current study investigated whether sorafenib resistance could be reversed by suppressing fatty acid synthesis, using a fatty acid synthase (FASN) inhibitor, orlistat, in HCC cells. FASN inhibition-caused changes in protein expressions and cell cycle distribution were analyzed by Western blot and flow cytometry, and changes in glucose uptakes were also evaluated by 18F-FDG uptake. Orlistat remarkably enhanced the cytotoxicity of sorafenib in both Huh7 and Huh7/SR cells, and flow cytometry showed that combination treatment significantly increased the sub-G1 population in both cell lines. Western blot revealed that the combination treatment effectively increased the ratio of Bax/Bcl-2 and decreased expressions of pERK; additionally, the combination treatment also strongly suppressed fatty acid synthesis-related proteins (e.g., FASN and SCD) in both cell lines. Lastly, the 18F-FDG uptake was repressed by the combination treatment in both cell lines. Our results indicated that orlistat-mediated FASN inhibition could overcome sorafenib resistance and enhance cell killing in HCC by changing cell metabolism.
Non-small cell lung cancer (NSCLC) patients harboring a KRAS mutation have unfavorable therapeutic outcomes with chemotherapies, and the mutation also renders tolerance to immunotherapies. There is ...an unmet need for a new strategy for overcoming immunosuppression in KRAS-mutant NSCLC. The recently discovered role of melatonin demonstrates a wide spectrum of anticancer impacts; however, the effect of melatonin on modulating tumor immunity is largely unknown. In the present study, melatonin treatment significantly reduced cell viability accompanied by inducing cell apoptosis in KRAS-mutant NSCLC cell lines including A549, H460, and LLC1 cells. Mechanistically, we found that lung cancer cells harboring the KRAS mutation exhibited a higher level of programmed death ligand 1 (PD-L1). However, treatment with melatonin substantially downregulated PD-L1 expressions in both the presence and absence of interferon (IFN)-γ stimulation. Moreover, KRAS-mutant lung cancer cells exhibited higher Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) levels, and PD-L1 expression was positively correlated with YAP and TAZ in lung cancer cells. Treatment with melatonin effectively suppressed YAP and TAZ, which was accompanied by downregulation of YAP/TAZ downstream gene expressions. The combination of melatonin and an inhibitor of YAP/TAZ robustly decreased YAP and PD-L1 expressions. Clinical analysis using public databases revealed that PD-L1 expression was positively correlated with YAP and TAZ in patients with lung cancer, and PD-L1 overexpression suggested poor survival probability. An animal study further revealed that administration of melatonin significantly inhibited tumor growth and modulated tumor immunity in a syngeneic mouse model. Together, our data revealed a novel antitumor mechanism of melatonin in modulating the immunosuppressive tumor microenvironment by suppressing the YAP/PD-L1 axis and suggest the therapeutic potential of melatonin for treating NSCLC.
Purpose:
Approximately 5%–10% of men who receive prostate cancer radiotherapy will suffer from radiation cystitis. Bladder filling before the administration of radiotherapy results in lower radiation ...exposure to the bladder. BladderScan, an ultrasound-based bladder volume scanner, has the potential to evaluate bladder volume during radiotherapy; thus, a prospective pilot study was initiated.
Methods:
Eleven men receiving tomotherapy for localized prostate cancer were enrolled. The validity of BladderScan was evaluated by comparing the measurements from BladderScan with the calculated volume from megavoltage computed tomography (MVCT). With a crossover design to compare different methods in bladder filling, the radiotherapy was divided into 2 sequences. Conventional method: the patient was asked to drink water after voiding urine. The amount of water and the duration of waiting were the same as in the setting of the simulation. BladderScan feedback method: the bladder filling procedure depended on the BladderScan measurements.
Results:
There were 314 sets of data from 11 patients. The correlation coefficient between VBS and VCT was 0.87, where VBS is the mean volume of 3 measurements by BladderScan and VCT is the bladder volume derived from MVCT. The BladderScan feedback method resulted in a significant larger bladder volume than the conventional method, with a mean difference of 36.9 mL. When the failure was defined as VCT <80% of planned volume, the BladderScan feedback method brought about a relative reduction in the failure rate with an odds ratio of 0.44 and an absolute reduction of 9.1%.
Conclusion:
The accuracy of BladderScan was validated by MVCT in our study. The BladderScan feedback method can help patients fill the bladder adequately, with a larger bladder volume and a lower failure rate.
Background: For advanced breast cancer with lymph node involvement, adjuvant radiotherapy (RT) with regional nodal irradiation (RNI) has been indicated to reduce cancer recurrence and mortality. ...However, an extensive RT volume is associated with normal organ exposure, which increases the toxicity and affects patient outcomes. Modern arc RT techniques can improve normal organ sparing compared with conventional techniques. The aim of this study was to explore the optimal technique for left-breast RT with RNI. Methods: We retrospectively reviewed patients receiving RT with RNI for left-breast cancer. We used modern arc RT techniques with either volumetric-modulated arc therapy (VMAT) or helical tomotherapy (HT) with a novel block technique, and compared differences in dosimetry parameters between the two groups. Subgroup analysis of RNI with or without internal mammary node (IMN) volume was also performed. Results: A total of 108 eligible patients were enrolled between 2017 and 2020, of whom 70 received VMAT and 38 received HT. The median RT dose was 55 Gy. No significant differences were found regarding the surgery, RT dose, number of fractions, target volume, and RNI volume between the VMAT and HT groups. VMAT reduced the heart mean dose more than HT (3.82 vs. 5.13 Gy, p < 0.001), as well as the cardiac parameters of V5–V20, whole-lung mean dose, lung parameters of V5–V20, and contralateral-breast and esophagus mean dose. In the subgroup analysis of RNI with IMNs, the advantage of VMAT persisted in protecting the heart, lung, contralateral breast, and esophagus. HT was beneficial for lowering the thyroid mean dose. For RNI without IMN, VMAT improved the low-dose exposure of the heart and lung, but HT was similar to VMAT in terms of heart, whole-lung, and contralateral-breast mean dose. Conclusions: For patients with left-breast cancer receiving adjuvant RT with RNI, VMAT reduced the exposure dose to the heart, lung, contralateral breast, and esophagus compared with HT. VMAT was superior to HT in terms of normal organ sparing in the patients who underwent RNI with IMN irradiation. Considering the reduction in normal organ exposure and potential toxicity, VMAT is the optimal technique for patients receiving RNI when deep inspiration breath-hold is not available.
Background: The target volume for post-mastectomy radiation therapy (PMRT) in breast cancer patients with reconstruction has been a subject of debate. Traditionally, the RT chest wall (CW) volume ...encompasses the entire implant. For patients with retropectoral implants, the deep lymphatic plexus dorsal part of the implant is no longer considered high risk and can be omitted. This study aimed to assess the radiation dose distribution and treatment outcomes associated with different CW delineation according to ESTRO ACROP guideline for patients who have undergone implant-based reconstruction. Methods: We conducted a retrospective review of breast cancer patients who underwent a mastectomy followed by two-stage implant-based breast reconstruction and adjuvant radiation therapy (RT) between 2007 and 2022. The expanders/implants were positioned retropectorally. The chest wall target volumes were categorized into two groups: the prepectoral group, which excluded the deep lymphatic plexus, and the whole expander group. Results: The study included 26 patients, with 15 in the prepectoral group and 11 in the whole expander group. No significant differences were observed in normal organ exposure between the two groups. There was a trend toward a lower ipsilateral lung mean dose in the prepectoral group (10.2 vs. 11.1 Gy, p = 0.06). Both groups exhibited limited instances of reconstruction failure and local recurrence. Conclusions: For patients undergoing two-stage expander/implant retropectoral breast reconstruction and PMRT, our data provided comparable outcomes and normal organ exposure for those omitting the deep lymphatic plexus.
To explore the clinical utility of the systemic inflammation response index (SIRI) in the prediction of patients with poor treatment response to concurrent chemoradiotherapy (CCRT) in locally ...advanced nasopharyngeal cancer (NPC).
A total of 167 stage III-IVB (AJCC 7th edition) nasopharyngeal cancer patients who received CCRT were retrospectively collected. The SIRI was calculated using the following formula: SIRI = neutrophil count × monocyte count/lymphocyte count (109/L). The optimal cutoff values of the SIRI for noncomplete response were determined by receiver operating characteristic curve analysis. Logistic regression analyses were performed to identify factors predictive of treatment response. We used Cox proportional hazards models to identify predictors of survival.
Multivariate logistic regression showed that only the posttreatment SIRI was independently associated with treatment response in locally advanced NPC. A posttreatment SIRI≥1.15 was a risk factor for developing an incomplete response after CCRT (odds ratio 3.10, 95% confidence interval (CI): 1.22-9.08, p=0.025). A posttreatment SIRI≥1.15 was also an independent negative predictor of progression-free survival (hazard ratio 2.38, 95% CI: 1.35-4.20, p=0.003) and overall survival (hazard ratio 2.13, 95% CI: 1.15-3.96, p=0.017).
The posttreatment SIRI could be used to predict the treatment response and prognosis of locally advanced NPC.
Background
The purpose of this study was to review the risks and benefits of concurrent chemoradiation therapy (CCRT) with esophageal self‐expandable metal stents (SEMS) for the treatment of locally ...advanced esophageal cancer.
Materials and Methods
Between January 2014 and December 2016, the data from 46 locally advanced esophageal cancer patients who received CCRT at our institution were retrospectively reviewed. Eight patients who received CCRT concomitant with SEMS placement (SEMS plus CCRT group) and thirty‐eight patients who received CCRT without SEMS placement (CCRT group) were identified. The risk of developing esophageal fistula and the overall survival of the two groups were analyzed.
Results
The rate of esophageal fistula formation during or after CCRT was 87.5% in the SEMS plus CCRT group and 2.6% in the CCRT group. The median doses of radiotherapy in the SEMS plus CCRT group and the CCRT group were 47.5 Gy and 50 Gy, respectively. SEMS combined with CCRT was associated with a greater risk of esophageal fistula formation than CCRT alone (hazard ratio HR, 72.30; 95% confidence interval CI, 8.62–606.12; p < .001). The median overall survival times in the SEMS plus CCRT and CCRT groups were 6 months and 16 months, respectively. Overall survival was significantly worse in the SEMS plus CCRT group than in the CCRT group (HR, 5.72; 95% CI, 2.15–15.21; p < .001).
Conclusion
CCRT concomitant with SEMS for locally advanced esophageal cancer results in earlier life‐threatening morbidity and a higher mortality rate than treatment with CCRT alone. Further prospective and randomized studies are warranted to confirm these observations.
Implications for Practice
Patients treated with SEMS placement followed by CCRT had higher risk of esophageal fistula formation and inferior overall survival rate compared with patients treated with CCRT alone. SEMS placement should be performed cautiously in patients who are scheduled to receive CCRT with curative intent.
摘要
背景。本次研究的目的是回顾分析同步放化疗(CCRT) 伴随食管自膨式金属支架 (SEMS)用于治疗局部晚期食管癌的风险和益处
材料和方法。2014年1月至2016年12月,回顾性分析了在我院接受CCRT的46名局部晚期食管癌患者的数据。共选择8名接受CCRT 伴随SEMS植入的患者(SEMS+CCRT组)和38名仅接受CCRT、未植入SEMS的患者(CCRT组)。分析了两组患者的食管瘘发生风险和总生存期
结果。在CCRT期间或之后,SEMS+CCRT组和CCRT组的食管瘘发生率分别为87.5%和2.6%。SEMS+CCRT组和CCRT组的中位放疗剂量分别为47.5 Gy 和50 Gy。与单纯CCRT治疗相比,SEMS联合CCRT会导致食管瘘形成风险升高风险比 (HR), 72.30; 95% 置信区间(CI), 8.62–606.12; p<0.001。SEMS+CCRT组和 CCRT组的中位总生存期分别为6个月和16个月。SEMS+CCRT组的总生存期显著低于CCRT组(HR, 5.72; 95% CI, 2.15–15.21; p<0.001)
结论。与单独采用CCRT治疗相比,CCRT伴随SEMS用于治疗局部晚期食管癌可导致更早发生危及生命的疾病和更高的死亡率。未来需要展开进一步前瞻性随机研究,以证实这些观察结果。
实践意义:与单独接受CCRT治疗的患者相比,接受SEMS植入伴随CCRT治疗的患者食管瘘形成的风险更高,总生存率也较低。对计划接受CCRT治疗以实现根治目的的患者,应慎用SEMS植入
This article reports on the effects of esophageal self‐expandable metal stents placement on the risk of esophageal fistula formation and clinical outcomes in patients undergoing concurrent chemoradiation therapy.
Head and neck cancer (HNC) shares some risk factors with cardiovascular disease. Neck radiotherapy (RT) causes carotid artery injury and stenosis. In HNC patients treated with RT, the prevalence rate ...of severe (>70%) carotid artery stenosis is >10%, and the cumulative incidence continuously increases over time. There is at least a two-fold risk of cerebrovascular events in these patients compared with the normal population. Carotid artery stenosis is mainly assessed and diagnosed via duplex ultrasonography. Angioplasty and stenting may be recommended to patients who developed severe post-irradiation carotid artery stenosis. This review assessed Taiwanese data that provided some recommendations for HNC patients treated with RT. With consideration of the high prevalence rate of carotid artery stenosis after neck irradiation, duplex ultrasonography should be included in the follow-up workup.
To evaluate the practicality of NS-21 cream with regard to its skin-related toxicity in patients with head and neck cancer (HNC) who are undergoing concurrent chemoradiation therapy (CCRT) or ...radiotherapy (RT).
Between July 2015 and November 2017, 30 HNC patients who underwent RT or CCRT were randomly allocated to receive either NS-21 or control treatment on their irradiated skin three times per day, starting at the initiation of RT or CCRT and ending 2 weeks after the completion of RT or until the appearance of grade 3 acute radiation dermatitis (ARD). Dermatitis was recorded weekly according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Skin humidity was monitored by a digital moisture meter. The generalized estimating equation (GEE) and logit link function method were used for statistical analysis.
No serious adverse events were observed in either group. Itching dermatitis occurred on the right lower neck in one patient of the NS-21 group during the 3rd week of CCRT, but the severity was mild. The median skin moisture value at the time of the final treatment was significantly different between the study and control groups (30.6 vs. 27.3, p = 0.013). Additionally, there was an inverse relationship between skin moisture and ARD grade (B = -0.04, p = 0.005). The incidence of ARD at the time of the last treatment was not significantly different between the study and control groups (6.7% vs 26.7%, p = 0.165). The risk of grade 3 ARD for skin that had received an irradiation dose of 47-70 Gy was higher than that of skin that had received an irradiation dose ≤46 Gy (OR = 31.06, 95% CI =5.95-162.21, p < 0.001). Nevertheless, the risk of ARD was not significantly different between the groups (OR = 0.38, 95% CI = 0.08-1.74, p = 0.212).
NS-21 was well tolerated and effective for the maintenance of skin moisture; however, there was no statistically significant reduction in the risk of ARD in HNC patients undergoing RT or CCRT when compared with HNC patients in the control group.
The study was approved by the Institutional Review Board of Far Eastern Memorial Hospital ( FEMH-IRB , 104048-F), Registered 1st June 2015.
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