Three-dimensional quantum imaging of dynamic targets using quantum compressed sensing.

Quantum imaging based on entangled light sources exhibits enhanced background resistance compared to conventional imaging techniques in low-light conditions. However, direct imaging of dynamic targets remains challenging due to the limited count rate of entangled photons. In this paper, we propose a quantum imaging method based on quantum compressed sensing that leverages the strong correlation characteristics of entangled photons and the randomness inherent in photon pair generation and detection. This approach enables the construction of a compressed sensing system capable of directly imaging high-speed dynamic targets. The results demonstrate that our system successfully achieves imaging of a target rotating at a frequency of 10 kHz, while maintaining an impressive data compression rate of 10-6. This proposed method introduces a pioneering approach for the practical implementation of quantum imaging in real-world scenarios.

Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis.

BACKGROUND: MET and AXL dysregulations are implicated in acquired resistance to EGFR-TKIs in NSCLC. But consensus on the optimal definition for MET/AXL dysregulations in EGFR-mutant NSCLC is lacking. Here, we investigated the efficacy and tolerability of ningetinib (a MET/AXL inhibitor) plus gefitinib in EGFR-mutant NSCLC, and evaluated the clinical relevance of MET/AXL dysregulations by different definitions. METHODS: Patients in this phase 1b dose-escalation/dose-expansion trial received ningetinib 30 mg/40 mg/60 mg plus gefitinib 250 mg once daily. Primary endpoints were tolerability (dose-escalation) and objective response rate (dose-expansion). MET/AXL status were analyzed using FISH and IHC. RESULTS: Between March 2017 and January 2021, 108 patients were enrolled. The proportion of MET focal amplification, MET polysomy, MET overexpression, AXL amplification and AXL overexpression is 18.1 %, 5.6 %, 55.8 %, 8.1 % and 45.3 %, respectively. 6.8 % patients have concurrent MET amplification and AXL overexpression. ORR is 30.8 % for tumors with MET amplification, 0 % for MET polysomy, 24.1 % for MET overexpression, 20 % for AXL amplification and 27.6 % for AXL overexpression. For patients with concurrent MET amplification and AXL overexpression, ningetinib plus gefitinib provides an ORR of 80 %, DCR of 100 % and median PFS of 4.7 months. Tumors with higher MET copy number and AXL expression tend to have higher likelihood of response. Biomarker analyses show that MET focal amplification and overexpression are complementary in predicting clinical benefit from MET inhibition, while AXL dysregulations defined by an arbitrary level may dilute the efficacy of AXL blockade. CONCLUSIONS: This study demonstrates that combined blockade of MET, AXL and EGFR is a feasible strategy for a subset of EGFR-mutant NSCLC. TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20160875.

Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer: A Phase 3 Randomized Clinical Trial.

IMPORTANCE: This study demonstrates that tislelizumab in combination with chemotherapy is associated with improved progression-free survival (PFS) in patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). OBJECTIVE: To assess the efficacy and safety/tolerability of tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for patients with advanced sq-NSCLC. DESIGN, SETTING, AND PARTICIPANTS: This open-label, randomized phase 3 clinical trial was conducted at 46 sites in China between July 2018 and June 2019 and included patients with treatment-naive, histologically confirmed stage IIIB/IV sq-NSCLC. The data cutoff for these analyses was December 6, 2019; data extraction occurred on January 7, 2020. INTERVENTIONS: Patients were randomized (1:1:1) to receive 1 of the following regimens intravenously on a 21-day cycle: tislelizumab (200 mg, day 1) plus paclitaxel (175 mg/m2, day 1) and carboplatin (area under the concentration of 5, day 1) (arm A); tislelizumab plus nab-paclitaxel (100 mg/m2, days 1, 8, and 15) and carboplatin (arm B); and paclitaxel and carboplatin (arm C). Patients were stratified by disease stage and tumor programmed cell death 1 ligand 1 (PD-L1) expression (<1% vs 1%-49% vs ≥50%). MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS) assessed by an independent review committee (IRC). Secondary end points included overall survival, investigator-assessed (INV) PFS, IRC-assessed objective response rate (ORR), and IRC-assessed duration of response, as well as the incidence and severity of adverse events (AEs). RESULTS: Overall, 355 patients (median [range] age, 62 [34-74] years; 330 men [91.7%]) with sq-NSCLC received treatment. After a median study follow-up of 8.6 months (95% CI, 8.1-9.0 months), IRC-assessed PFS was significantly improved with tislelizumab plus chemotherapy (arm A, 7.6 months; arm B, 7.6 months) vs chemotherapy alone (arm C, 5.5 months; hazard ratios were 0.524 (95% CI, 0.370-0.742; P < .001 [A vs C]) and 0.478 (95% CI, 0.336-0.679; P < .001 [B vs C]). Higher IRC-assessed ORR and longer IRC-assessed duration of response were observed in arms A (72.5%; 8.2 months) and B (74.8%; 8.6 months) vs C (49.6%; 4.2 months). No association was observed between PD-L1 expression and IRC-assessed PFS or ORR. Discontinuation of any treatment because of AEs was reported in 15 (12.5%; arm A), 35 (29.7%; arm B), and 18 (15.4%; arm C) patients. In each arm, the most common grade of 3 or greater AE was decreased neutrophil levels, which aligned with known chemotherapy toxic effects. Six treatment-related AEs leading to death occurred; however, no deaths were solely attributed to tislelizumab. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, adding tislelizumab to chemotherapy was associated with significantly prolonged IRC-assessed PFS, higher IRC-assessed ORRs, and a manageable safety/tolerability profile in patients with advanced sq-NSCLC, regardless of PD-L1 expression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03594747.

The effects of Feshbach resonance on spectral shifts in photoassociation of Cs atoms.

We study the effects of magnetic Feshbach resonance on the shifts in photoassociation (PA) spectra of ultracold Cs atoms. A series of atom loss spectra show a linear variation of the frequency shift with the PA laser intensity at different magnetic fields near the d-wave Feshbach resonance of optically trapped Cs atoms. The magnetic field-dependence of the slope of the shift on the PA laser intensity exhibits a dispersive change near the Feshbach resonance. The theoretical formula derived from a model based on Fano resonance fits well with the experimental data. Using a model rectangular potential with tunable well depth and applying the Franck-Condon principle, we obtain numerical results, which are found to be largely in disagreement with the experimental findings.

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

Fosaprepitant versus aprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: a multicenter, randomized, double-blind, double-simulated, positive-controlled phase III trial.

BACKGROUND: To establish the role of antiemetic therapy with neurokinin-1 (NK-1) receptor antagonists (RAs) in Chinese patients associated with cisplatin-base chemotherapy regimens, this study evaluated the efficacy and safety of single-dose intravenous fosaprepitant-based triple antiemetic regimen to a 3-day orally aprepitant-based antiemetic triplet schedule for the prevention of chemotherapy-induced nausea and vomiting (CINV). METHODS: A randomized, double-blind, positive-control design was used to test the noninferiority of fosaprepitant towards aprepitant. Patients receiving cisplatin-base (≥50 mg/m2) chemotherapy were administrated palonosetron and dexamethasone with a single-dose fosaprepitant (150 mg on day 1) or a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2 and day 3). The primary endpoint was complete response (CR) during overall phase (OP). Secondary endpoints include CR during acute phase (AP) and delayed phase (DP), no vomiting and no significant nausea during OP, AP and DP. Accrual of 324 patients per treatment arm was planned to confirm noninferiority with expected CR of 75% and noninferiority margin of minus 10 percentage points. RESULTS: A total of 648 patients were randomly assigned, and 644 were evaluable for efficacy and safety. Antiemetic efficacy of CR during the OP with fosaprepitant and aprepitant was equivalent (71.96% versus 69.35%, P=0.4894). And a between-group difference of 2.61 percentage points was finally achieved (95% CI, -4.42 to 9.64) within predefined bounds for noninferiority (primary end point achieved). Both regimens were well tolerated and commonly reported adverse events (≥1%) were similar between these two group. CONCLUSIONS: Single-dose intravenous fosaprepitant (150 mg) combined with palonosetron and dexamethasone was well tolerated and demonstrated noninferior control of CINV to aprepitant-based triple regimen in Chinese patients treating with cisplatin-base chemotherapy.

Cosmc Disruption-Mediated Aberrant O-glycosylation Suppresses Breast Cancer Cell Growth via Impairment of CD44.

BACKGROUND: Breast cancer remains the most lethal malignancy in women worldwide. Aberrant O-glycosylation is closely related to many human diseases, including breast carcinoma; however, its precise role in cancer development is insufficiently understood. Cosmc is an endoplasmic reticulum-localized chaperone that regulates the O-glycosylation of proteins. Cosmc dysfunction results in inactive T-synthase and expression of truncated O-glycans such as Tn antigen. Here we investigated the impact of Cosmc disruption-mediated aberrant O-glycosylation on breast cancer cell development through in vitro and in vivo experiments. MATERIALS AND METHODS: We deleted the Cosmc gene in two breast cancer cell lines (MCF7, T47D) using the CRISPR/Cas-9 system and then measured the expression levels of Tn antigen. The proliferation of Tn-positive cells was examined by RTCA, colony formation and in vivo experiments. The effects of Cosmc deficiency on glycoprotein CD44 and MAPK pathway were also determined. RESULTS: Both in vitro and in vivo studies showed that Cosmc deficiency markedly suppressed breast cancer cell growth compared with the corresponding controls. Mechanistically, Cosmc disruption impaired the protein expression of CD44 and the associated MAPK signaling pathway; the latter plays a crucial role in cell proliferation. Reconstitution of CD44 substantially reversed the observed alterations, confirming that CD44 requires normal O-glycosylation for its proper expression and activation of the related signaling pathway. CONCLUSION: This study showed that Cosmc deficiency-mediated aberrant O-glycosylation suppressed breast cancer cell growth, which was likely mediated by the impairment of CD44 expression.

The relationship of plasma fibrinogen with clinicopathological stages and tumor markers in patients with non-small cell lung cancer.

Numerous studies have shown that the blood of cancer patients are generally in hypercoagulable statement. The aim of the present research is to study the relationships of plasma fibrinogen (Fbg) levels with clinicopathological stages (CS) and tumor markers of non-small cell lung cancer (NSCLC).Baseline information, plasma Fbg levels, CS, and expression level of tumor markers were collected from medical records retrospectively. Unitary linear regression was used to analyze the relationships between continuous variables and Fbg, and multiple linear regression was used to analyze the relationships between categorical variables and Fbg. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 4) for NSCLC were adopted to evaluate CS.A total of 652 NSCLC patients were included. Compared with the females, male patients had higher mean plasma Fbg levels (P < .001). The later the N stages (P = .002), M stages (P = .002), and CS (P = .001) were, the higher the average plasma Fbg levels were. The levels of squamous cell carcinoma antigen (P = .001), carbohydrate antigen 125 (P = .041), and neuron-specific enolase (P < .001) were positively correlated with plasma Fbg concentration. The plasma level of Fbg in lung adenocarcinoma patients (P < .001) was the lowest, while that of lung squamous cell carcinoma patients (P < .001) was the highest in NSCLC patients.The plasma Fbg concentration is related to gender, CS, and tumor markers in patients with NSCLC.

Tn antigen promotes human colorectal cancer metastasis via H-Ras mediated epithelial-mesenchymal transition activation.

Tn antigen is a truncated O-glycan, frequently detected in colorectal cancer (CRC), but its precise role in CRC metastasis is not well addressed. Here we investigated the effects of Core 1 ß3Gal-T specific molecular chaperone (Cosmc) deletion-mediated Tn antigen exposure on CRC metastasis and its underlying mechanism. We first used CRISPR/Cas9 technology to knockout Cosmc, which is required for normal O-glycosylation, and thereby obtained Tn-positive CRC cells. We then investigated the biological consequences of Tn antigen expression in CRC. The results showed that Tn-positive cells exhibited an enhanced metastatic capability both in vitro and in vivo. A further analysis indicated that Tn antigen expression induced typical activation of epithelial-mesenchymal transition (EMT). Mechanistically, we found that H-Ras, which is known to drive EMT, was markedly up-regulated in Tn-positive cells, whereas knockdown of H-Ras suppressed Tn antigen induced activation of EMT. Furthermore, we confirmed that LS174T cells (Tn-positive) transfected with wild-type Cosmc, thus expressing no Tn antigen, had down-regulation of H-Ras expression and subsequent inhibition of EMT process. In addition, analysis of 438 samples in TCGA cohort demonstrated that Cosmc expression was reversely correlated with H-Ras, underscoring the significance of Tn antigen-H-Ras signalling in CRC patients. These data demonstrated that Cosmc deletion-mediated Tn antigen exposure promotes CRC metastasis, which is possibly mediated by H-Ras-induced EMT activation.

Biosimilar candidate IBI305 plus paclitaxel/carboplatin for the treatment of non-squamous non-small cell lung cancer.

BACKGROUND: Bevacizumab is a monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF) and used for treatments of various cancers. Due to the high costs of bevacizumab treatments, a biosimilar provides an affordable alternative therapy for cancer patients. METHODS: In this randomized, double-blind, multicenter, phase 3 study, locally advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor were enrolled and randomized (1:1) into IBI305 or bevacizumab groups. Patients received 6 cycles of paclitaxel/carboplatin plus IBI305 or bevacizumab 15 mg/kg intravenously followed by IBI305 or bevacizumab 7.5 mg/kg maintenance until disease progression, unacceptable toxicity or death. The primary endpoint was confirmed objective response rate (ORR) by an independent radiological review committee (IRRC) and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. RESULTS: A total of 450 NSCLC patients were enrolled (224 in IBI305 group and 226 in bevacizumab group). ORRs were 44.3% for IBI305 and 46.4% for bevacizumab, and the ORR ratio was 0.95 (90% CI: 0.803 to 1.135), within the predefined equivalence margin of 0.75 to 1.33. No significant difference in PFS (7.64 vs. 7.77 m, P=0.9987) was observed between the 2 groups. Serious adverse events (AEs) occurred in 33.5% (75/224) of patients in the IBI305 group and 37.6% (85/226) in the bevacizumab group. AEs ≥ grade 3 were similar in the IBI305 and bevacizumab groups [84.4% (189/224) vs. 89.8% (203/226), P=0.085]. CONCLUSIONS: IBI305 is similar to bevacizumab in terms of efficacy and safety. TRIAL REGISTRATION: Clinicaltrials.org Identifier: NCT02954172. Registered on 3 November 2016. Https://clinicaltrials.gov/.

Factors associated with gene aberration test status and treatment decision in patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer: A multicenter survey in China (CTONG 1506).

OBJECTIVES: This study investigated factors associated with (i) the likelihood of receiving a gene aberration test and (ii) the choice of treatment between chemotherapy and targeted therapy in patients with non-small cell lung cancer (NSCLC) in China. MATERIALS AND METHODS: This cross-sectional study analyzed data previously extracted from the medical charts of patients with unresectable Stage IIIB/IV nonsquamous NSCLC discharged from one of 12 tertiary hospitals in China between August 2015 and March 2016. Logistic regressions were applied to investigate factors associated with receiving a gene aberration test and the treatment decision. RESULTS: Data from 932 patients were analyzed. Patients were less likely to have a gene aberration test if they had a histologic subtype other than adenocarcinoma or a hospital waiting time for test results of >5 days. Patients were more likely to receive tyrosine kinase inhibitor (TKI) treatment than chemotherapy if they had a positive result for epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase gene aberration testing. EGFR positive patients were more likely to receive TKI treatment than chemotherapy if they did not have insurance for TKI or pemetrexed treatment, and more likely to receive chemotherapy than TKI treatment if they had a waiting time for test results of >5 days. EGFR wild-type/unknown patients receiving chemotherapy were more likely to receive pemetrexed if they attended a hospital in a developed area or had insurance for pemetrexed. CONCLUSION: In this real-world setting in China, the choice of first-line treatment for advanced NSCLC was appropriately guided by gene aberration testing for most patients. However, gene aberration testing and the treatment decision were influenced by practical factors such as hospital location, the waiting time for test results, and insurance coverage, which should be addressed to ensure optimal patient care.

A novel N staging system for NPC based on IMRT and RTOG guidelines for lymph node levels: Results of a prospective multicentric clinical study.

The present study aimed to investigate the cervical lymph node metastasis of nasopharyngeal carcinoma (NPC) and to establish a novel N staging standard for NPC, based on intensity modulated radiation therapy (IMRT) via a prospective multicenter clinical trial. Between January 2006 and December 2009, a total of 492 patients with NPC without distant metastasis were included in the present study. All patients were treated with IMRT. According to Radiation Therapy Oncology Group division standards, the present study proposed a novel N staging system following the review of magnetic resonance images in comparison with the 7th edition of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system. Retropharyngeal lymph nodes, cervical lymph node level and cervical lymph node laterality were independent prognostic factors used in multivariate analyses. According to the results of the risk variety, the present study suggested that the novel N staging system included: N0 (no lymph node metastasis), N1 [retropharyngeal or/and unilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis], N2 [bilateral upper cervical (I, II, III, Va, VIIb, VIII, IX and X regions) lymph node metastasis] and N3 (lymph node metastasis in IVa and Vb regions and their lower regions). The novel N staging system proposed in the present study performs better in risk difference and distribution balance. Furthermore, the differences of 5-year curves of distant metastasis-free survival and overall survival had greater statistically significant differences compared with the 7th edition of the UICC/AJCC staging system. The present study suggested a novel N staging system for cervical lymph node metastasis of NPC, which may predict the prognosis of patients with NPC in a more objective and accurate way.

Colon cancers carrying BRAF V600E and ß-catenin T41A activating mutations are resistant to numerous common anticancer drugs.

Colorectal cancer is a common malignancy with a high prevalence and associated mortality rate. However, the preclinical tools currently used for drug development are insufficient. The aim of the present study was to establish and characterize a specific patient-derived colon cancer xenograft (PDCCX) mouse model for drug testing. Primary colon tumors were obtained from 10 patients by surgical resection, and tumor tissues were subsequently grafted into nude mice followed by consecutive passages. Primary tumors and xenograft tumors were collected and processed for DNA sequencing, histological evaluation and immunohistochemical staining. The responses of fifth-generation PDCCX mice to 5-fluorouracil, oxaliplatin, and cetuximab were assessed. Two PDCCX cell lines were successfully established. The histology and protein expression levels of SMAD family member 3, epidermal growth factor receptor, c-MET, caudal type homeobox 2, E-cadherin and ß-catenin in the xenograft tumors were consistently maintained from the primary cancer tissues. BRAF V600E and ß-catenin T41A double mutations were identified in one cell line, and were associated with a lack of response to 5-fluorouracil, oxaliplatin and cetuximab treatment. This PDCCX cell line may provide a reliable tool for preclinical evaluation of the efficacy of novel therapies that may target the BRAF V600E and ß-catenin mutations.

A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy (IMRT).

OBJECTIVE: This study is to establish a new staging system for nasopharyngeal carcinoma (NPC) based on the magnetic resonance imaging (MRI) and intensity-modulated radiation therapy (IMRT). METHODS: Totally 492 patients with nasopharyngeal carcinoma were included in this study. These patients were diagnosed by pathological detection (without distant metastasis) and underwent the initial treatment of IMRT. These patients were subjected to the staging with the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system. Survival rates were calculated by the Kaplan-Meier method. Log-rank test was used to calculate the single factor prognosis, and the COX risk model was used to analyze the multivariate prognosis. RESULTS: In these 492 patients, according to our recommended new T and N staging criteria, there were 290 cases of T1 and 202 cases of T2; there were 64 cases of N0, 159 cases of N1, 226 cases of N2, and 43 cases of N3. Univariate and multivariate analyses showed that the T and N staging combination parameters were independent prognostic factors, which affected the overall survival rates and tumor-free survival rates. According to risk difference and survival curve distribution, the following new clinical staging criteria were established: stage I (T1N0M0), stage II (T1N1M0 and T2N0M0), stage III (T1N2M0 and T2N1-2M0), stage IVa (T1-2N3M0), and stage IVb (TxNxM1). CONCLUSION: A new staging system for NPC based on MRI and IMRT has been recommended, which provides valuable evidence for disease treatment and prognosis prediction.

Manipulation of photoassociation of ultracold Cs atoms with tunable scattering length by external magnetic fields.

We demonstrate that for ultracold, optically trapped Cs atoms the photoassociation (PA) can be manipulated by using external uniform magnetic fields due to the alteration of the scattering wavefunction in the region of the free-bound optical transition. We present PA-induced atom loss measurements with the same intensity for PA laser but different external magnetic fields, and analyze main contributions of the PA to the variation of the number of atoms in the trap. The PA rate exhibits a strong dependence on the changing uniform magnetic field. The experimental data are simulated within the model of a single-channel one-well rectangular potential, whose depth is adjusted so as to assure the predicted variation of the scattering length with the magnetic field. The computational and experimental results are in a reasonable agreement to each other. The same model is used to illustrate some general properties of the two-body quantum system in the near-threshold state.

Validation of the 8th edition of the UICC/AJCC staging system for nasopharyngeal carcinoma treated with intensity-modulated radiotherapy.

An accurate TNM staging system is crucial for treatment guidance and prognosis prediction in nasopharyngeal carcinoma (NPC) patients. In this retrospective study, we evaluated the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for NPC treated with intensity-modulated radiotherapy (IMRT). A total of 608 patients with biopsy-proven, non-metastatic NPC, treated with IMRT between January 2008 and March 2010, were enrolled. The 5-year overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 81.5%, 80.1%, 86.0%, and 81.1%, respectively. The LRFS rates of patients with stages T1 vs. T2, T2 vs. T3, and T1 vs. T3 did not differ between the 7th and 8th editions. By contrast, the DMFS rates of patients with N0 vs. N1, N1 vs. N2, and N2 vs. N3 differed between the 8th and the 7th editions, though no difference was observed between N3a and N3b, according to the 7th edition. The difference in OS between stages II and III, and between stages III and IVa, was larger according to the 8th edition than the 7th edition. There was no difference in the OS between stages I and II. These data indicate that in the IMRT era, the 8th edition staging system can predict the prognosis of NPC patients more accurately than the 7th edition.

A multicenter survey of first-line treatment patterns and gene aberration test status of patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer in China (CTONG 1506).

BACKGROUND: In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. METHODS: Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis. RESULTS: Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs. CONCLUSIONS: Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results.

A new T staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results from a prospective multicentric clinical study.

PURPOSE: This prospective multicentric study aimed to establish a new clinical T staging standard for nasopharyngeal carcinoma (NPC) based on intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between January 2006 and December 2009, four hundred and ninety-two NPC patients undergoing IMRT were staged according to the seventh edition of the UICC/AJCC staging system. The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to compare survival differences. RESULTS: The 5-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and distant metastasis-free survival (DMSF) rates were 80.5%, 78.6%, 94.1%, and 84.3%, respectively. Univariate and multivariate analyses showed that the invasion of the nasal cavity, parapharyngeal space, oropharynx, skull base, internal pterygoid muscle, external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus, and intracalvarium were independent prognostic factors (P<0.05). According to the results of risk variety and survival curves, we suggest that the new T staging system for NPC based on magnetic resonance imaging and intensity modulated radiation therapy can be classified as T1 (nasopharynx, nasal cavity, parapharyngeal space, oropharynx, skull base and internal pterygoid muscle) and T2 (external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus and intracalvarium). Compared to the seventh edition of UICC/AJCC staging system, our new recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences between the substages of 5-year curves of LRFS, DMFS and OS were all statistically significant in our new recommended staging system. CONCLUSIONS: Our new recommended staging system is more adaptable to IMRT and can predict the prognosis of NPC patient in a more objective and accurate manner.

Upregulated NNT-AS1, a long noncoding RNA, contributes to proliferation and migration of colorectal cancer cells in vitro and in vivo.

The expression patterns of the long non-coding RNA Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) have not been investigated in the context of cancer. In this study, we aim to investigate the NNT-AS1 expression level in colorectal cancer (CRC) patients and its potential roles in tumor biology. We measured the expression of NNT-AS1 in 70 paired tumor tissues and adjacent normal tissues. NNT-AS1 was expressed higher in tumor tissues than that in adjacent noncancer tissues, and higher expression of NNT-AS1 was significantly correlated with lymph node metastasis (Yes vs. No, P=0.004), TNM stage (I/II vs. III/IV, P=0.004), vessel invasion (Yes vs. No, P=0.002) and differentiation (well and moderate vs. poor, P=0.008). Multivariate analyses revealed that NNT-AS1 expression was an independent predictor of overall survival (P=0.0174) and progression free survival (P=0.0132) for CRC. Knockdown of NNT-AS1 using small interfering RNA (siRNA) significantly impaired CRC cell proliferation, migration and invasion in vitro and silencing NNT-AS1 also suppressed tumor growth and metastasis in nude mice. The western blot experiments revealed that silencing NNT-AS1 inhibited epithelial-mesenchymal transition (EMT) and inactivated MAPK/Erk signaling pathway in CRC cell lines. In conclusion, our studies implied that NNT-AS1 may involve in the development and progression of CRC via its regulation of cell proliferation, migration, and invasion by NNT-AS1-mediated activating of MAPK/Erk signaling pathway and EMT. NNT-AS1 may be a useful diagnostic and prognostic biomarker and a potential therapeutic target in CRC patients.

Cinnamaldehyde Ameliorates Cadmium-Inhibited Root Elongation in Tobacco Seedlings via Decreasing Endogenous Hydrogen Sulfide Production.

Cinnamaldehyde (CA) is natural plant-derived compound that has been highly appreciated for its medicinal properties. However, little information is known about the regulation of plant intrinsic physiology by CA. To address these gaps, physiological, histochemical, and biochemical approaches were applied to investigate CA-facilitated cadmium (Cd) tolerance in the roots of tobacco (Nicotiana tabacum) seedlings. Treatment with CdCl2 at 20 µM for 72 h resulted in the significant decrease in root elongation by 40.39% as compared to control. CA alleviated Cd-inhibited root elongation in dose- and time-dependent manners. The addition of CA at 20 µM induced significant increase in root elongation by 42.58% as compared to Cd treatment alone. CA abolished Cd-induced ROS (reactive oxygen species) accumulation, lipid peroxidation, loss of membrane integrity, cell death, and free Cd2+ accumulation in roots. CA blocked the Cd-induced increase in the endogenous H2S level through the down-regulation of d-cysteine desulfhydrase (DCD) expression. H2S scavenger hypotaurine (HT) or potent H2S-biosynthetic inhibitor dl-propargylglicine (PAG) were able mimic the action of CA on the blockade of Cd-induced H2S accumulation, cell death, and growth inhibition. Enhancement of the endogenous H2S level with NaHS (H2S donor) abrogated all the beneficial capabilities of CA, HT, and PAG. Collectively, these results suggest that CA has great potential to confer plant tolerance against Cd stress, which is closely associated with its capability to inhibit Cd-induced H2S production. This study not only provides evidences for the regulation of plant physiology by CA but also sheds new light on the cross-talk between CA and H2S in physiological modulations.