Proton-Induced Reversible Spin-State Switching in Octanuclear FeIII Spin-Crossover Metal-Organic Cages.

Responsive spin-crossover (SCO) metal-organic cages (MOCs) are emerging dynamic platforms with potential for advanced applications in magnetic sensing and molecular switching. Among these, FeIII-based MOCs are particularly noteworthy for their air stability, yet they remain largely unexplored. Herein, we report the synthesis of two novel FeIII MOCs using a bis-bidentate ligand approach, which exhibit SCO activity above room temperature. These represent the first SCO-active FeIII cages and feature an atypical {FeN6}-type coordination sphere, uncommon for FeIII SCO compounds. Our study reveals that these MOCs are sensitive to acid/base variations, enabling reversible magnetic switching in solution. The presence of multiple active proton sites within these SCO-MOCs facilitates multisite, multilevel proton-induced spin-state modulation. This behavior is observed at room temperature through 1H NMR spectroscopy, capturing the subtle proton-induced spin-state transitions triggered by pH changes. Further insights from extended X-ray absorption fine structure (EXAFS) and theoretical analyses indicate that these magnetic alterations primarily result from the protonation and deprotonation processes at the NH active sites on the ligands. These processes induce changes in the secondary coordination sphere, thereby modulating the magnetic properties of the cages. The capability of these FeIII MOCs to integrate magnetic responses with environmental stimuli underscores their potential as finely tunable magnetic sensors and highlights their versatility as molecular switches. This work paves the way for the development of SCO-active materials with tailored properties for applications in sensing and molecular switching.

Pairwise machine learning-based automatic diagnostic platform utilizing CT images and clinical information for predicting radiotherapy locoregional recurrence in elderly esophageal cancer patients.

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

Integrating spin-dependent emission and dielectric switching in FeII catenated metal-organic frameworks.

Mechanically interlocked molecules (MIMs) including famous catenanes show switchable physical properties and attract continuous research interest due to their potential application in molecular devices. The advantages of using spin crossover (SCO) materials here are enormous, allowing for control through diverse stimuli and highly specific functions, and enabling the transfer of the internal dynamics of MIMs from solution to solid state, leading to macroscopic applications. Herein, we report the efficient self-assembly of catenated metal-organic frameworks (termed catena-MOFs) induced by stacking interactions, through the combination of rationally selected flexible and conjugated naphthalene diimide-based bis-pyridyl ligand (BPND), [MI(CN)2]- (M = Ag or Au) and Fe2+ in a one-step strategy. The obtained bimetallic Hofmann-type SCO-MOFs [FeII(BPND){Ag(CN)2}2]·3CHCl3 (1Ag) and [FeII(BPND{Au(CN)2}2]·2CHCl3·2H2O (1Au) possess a unique three-dimensional (3D) catena-MOF constructed from the polycatenation of two-dimensional (2D) layers with hxl topology. Both complexes undergo thermal- and light-induced SCO. Significantly, abnormal increases in the maximum emission intensity and dielectric constant can be detected simultaneously with the switching of spin states. This research opens up SCO-actuated bistable MIMs that afford dual functionality of coupled fluorescence emission and dielectricity.

Guest water-induced structural transformation and spin-crossover variation of a two-dimensional Hofmann-type compound.

In this paper, we report a two-dimensional (2D) Hofmann-type spin-crossover coordination polymer [FeII(o-NTrz)2PtII(CN)4]·H2O (o-NTrz = 4-(o-nitrobenzyl)imino-1,2,4-triazole). Due to the remarkable configurational flexibility of triazole-based ligand, the porous structure of this compound can be reversibly regulated by the loss of guest water molecules as a consequence of rotation of o-NTrz. The 180° reorientation of the o-nitrobenzyl moiety not only induces a response of gate-closing/opening of the porous framework but also significantly modulates the spin transition temperature. The present investigation highlights the potential of Hofmann-type SCO compounds with flexible ligands in exploring unusual physical and chemical phenomena.

Identification of Dynamic Active Sites Among Cu Species Derived from MOFs@CuPc for Electrocatalytic Nitrate Reduction Reaction to Ammonia.

Direct electrochemical nitrate reduction reaction (NITRR) is a promising strategy to alleviate the unbalanced nitrogen cycle while achieving the electrosynthesis of ammonia. However, the restructuration of the high-activity Cu-based electrocatalysts in the NITRR process has hindered the identification of dynamical active sites and in-depth investigation of the catalytic mechanism. Herein, Cu species (single-atom, clusters, and nanoparticles) with tunable loading supported on N-doped TiO2/C are successfully manufactured with MOFs@CuPc precursors via the pre-anchor and post-pyrolysis strategy. Restructuration behavior among Cu species is co-dependent on the Cu loading and reaction potential, as evidenced by the advanced operando X-ray absorption spectroscopy, and there exists an incompletely reversible transformation of the restructured structure to the initial state. Notably, restructured CuN4&Cu4 deliver the high NH3 yield of 88.2 mmol h-1 gcata-1 and FE (~ 94.3%) at - 0.75 V, resulting from the optimal adsorption of NO3- as well as the rapid conversion of *NH2OH to *NH2 intermediates originated from the modulation of charge distribution and d-band center for Cu site. This work not only uncovers CuN4&Cu4 have the promising NITRR but also identifies the dynamic Cu species active sites that play a critical role in the efficient electrocatalytic reduction in nitrate to ammonia.

Stress-Induced Inversion of Linear Dichroism by 4,4'-Bipyridine Rotation in a Superelastic Organic Single Crystal.

The molecular crystals that manifest unusual mechanical properties have attracted growing attention. Herein, we prepared an organic single crystal that shows bidirectional superelastic transformation in response to shear stress. Single-crystal X-ray diffractions revealed this crystal-twinning related shape change is owed to a stress-controlled 90° rotation of 4,4'-bipyridine around the hydrogen bonds of a chiral organic trimer. As a consequence of the 90° shift in the aromatic plane, an interconversion of crystallographic a-, b-axes (a→b' and b→a') was detected. The molecular rotations changed the anisotropic absorption of linearly polarized light. Therefore, a stress-induced inversion of linear dichroism spectra was demonstrated for the first time. This study reveals the superior mechanical flexibilities of single crystals can be realized by harnessing the molecular rotations and this superelastic crystal may find applications in optical switching and communications.

Two-Dimensional Coordination Polymer Showing Spin-Crossover Behavior with a 64 K Wide Hysteresis Loop.

A two-dimensional grid-like coordination polymer, [Fe(NCBH3)2(Py2ttz)2]·4CHCl3 (1·4CHCl3, Py2ttz = 2,5-di(pyridin-4-yl)thiazolo[5,4-d]thiazole), showed one-step complete spin crossover with unexpectedly large hysteresis loop of 64 K wide and temperature-induced excited spin-state trapping effect below 91 K.

Synergistic valence tautomerism and fluorescence emission in a two-dimensional coordination polymer.

A tetradentate ligand, 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethene (TPPE), was adopted to construct a two-dimensional coordination polymer that incorporated valence tautomerism and luminescence, and the synergistic effect arising from energy transfer from TPPE to the semiquinone moieties was experimentally and theoretically uncovered.

A spin-crossover framework endowed with pore-adjustable behavior by slow structural dynamics.

Host-guest interactions play critical roles in achieving switchable structures and functionalities in porous materials, but design and control remain challenging. Here, we report a two-dimensional porous magnetic compound, [FeII(prentrz)2PdII(CN)4] (prentrz = (1E,2E)-3-phenyl-N-(4H-1,2,4-triazol-4-yl)prop-2-en-1-imine), which exhibits an atypical pore transformation that directly entangles with a spin state transition in response to water adsorption. In this material, the adsorption-induced, non-uniform pedal motion of the axial prentrz ligands and the crumpling/unfolding of the layer structure actuate a reversible narrow quasi-discrete pore (nqp) to large channel-type pore (lcp) change that leads to a pore rearrangement associated with simultaneous pore opening and closing. The unusual pore transformation results in programmable adsorption in which the lcp structure type must be achieved first by the long-time exposure of the nqp structure type in a steam-saturated atmosphere to accomplish the gate-opening adsorption. The structural transformation is accompanied by a variation in the spin-crossover (SCO) property of FeII, i.e., two-step SCO with a large plateau for the lcp phase and two-step SCO with no plateau for the nqp phase. The unusual adsorption-induced pore rearrangement and the related SCO property offer a way to design and control the pore structure and physical properties of dynamic frameworks.

Recent advances in immunotherapy for hepatocellular carcinoma.

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions. Conventional systemic chemotherapy has failed in HCC, and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory. DATA SOURCES: Literature search was conducted in PubMed for relevant articles published before January 2021. The search aimed to identify recent developments in immune-based treatment approaches for HCC. Information of clinical trials was obtained from https://clinicaltrials.gov/. RESULTS: Two immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab were approved as monotherapies, which has revolutionized HCC treatment. Besides, combination ICIs have also got accelerated FDA approval recently. Immune-based therapies have challenged targeted drugs owing to their safety, tolerability, and survival benefits. In addition to the significant success in ICIs, other immunotherapeutic strategies such as cancer vaccine, chimeric antigen receptor T-cells, natural killer cells, cytokines, and combination therapy, have also shown promising outcomes in clinical trials. Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs. CONCLUSIONS: Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years. However, challenges such as low response rate and acquired resistance in previously respondent patients still exist. Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.

Spin-crossover iron(ii) long-chain complex with slow spin equilibrium at low temperatures.

A mononuclear complex with long alkyl chains, [FeII(H2Bpz2)2(C9bpy)] (1; H2Bpz2 = dihydrobis(1-pyrazolyl)borate, C9bpy = 4,4'-dinonyl-2,2'-bipyridine), was synthesized. Single-crystal X-ray crystallographic studies revealed that the Δ- and Λ-forms of the complex co-crystallized in the lattice asymmetric unit, while magnetic measurements unveiled that this complex underwent incomplete one-step spin crossover (SCO) with the transition completeness and temperature depending on the measurement velocity because of slow spin equilibrium. Multivariable approaches such as varying scan rate, annealing the sample, light irradiation and pressure have been adopted to effectively overcome the slow spin equilibrium and thus improve the SCO completeness.

Halogen-Substituted Spin-Crossover Fe(III) Compounds with Photoresponsive Properties.

Halogen-substituted Fe(III) compounds, [Fe(HphsalpmX)2]PTFB (HphsalpmX = 5-X-(R,S)-((phenyl(2-pyridyl)methylimino)methyl)phenol, PTFB = phenyltrifluoroborate; X = F for 1, Cl for 2, Br for 3) and [Fe(HphsalpmX)2]PTFB·MeOH (X = I for 4·MeOH), were synthesized. Compounds 1, 4·MeOH, and its desolvated form 4 exhibited an invariant high-spin state in the whole temperature range, while 2 and 3 underwent gradual, nonhysteretic, and incomplete spin crossover (SCO) with transition temperatures (TC) of 153 and 220 K, respectively. Interestingly, the SCO-active compounds 2 and 3 showed light-induced excited spin-state trapping (LIESST) effects at 10 K, and light-induced reversible ON/OFF switching behaviors were realized by alternately using 880 and 1064 nm light, while the thermally inert compound 4·MeOH unexpectedly showed a reverse-LIESST effect. These results may help to design and synthesize new photoresponsive SCO Fe(III) compounds for the development of switchable materials.

Application of machine learning models for predicting acute kidney injury following donation after cardiac death liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. METHODS: A total of 493 patients with donation after cardiac death LT (DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes (KDIGO). The clinical data of patients with AKI (AKI group) and without AKI (non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of AKI was 35.7% (176/493) during the follow-up period. Compared with the non-AKI group, the AKI group showed a remarkably lower survival rate (P < 0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval (CI): 0.794-0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models (P < 0.001). CONCLUSIONS: The random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.

Influence of VEGFR2 gene polymorphism on the clinical outcomes of apatinib for patients with chemotherapy-refractory extensive-stage SCLC: a real-world retrospective study.

PURPOSE: Great individual differences were observed regarding the efficacy of apatinib clinically. The aim of present study was to investigate the influence of vascular endothelial growth factor receptor2 (VEGFR2) gene polymorphism on the clinical outcomes of apatinib for patients with chemotherapy-refractory extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 128 patients with chemotherapy-refractory ES-SCLC who were treated with apatinib at an initial dosage of 250 or 500 mg were included in this study. The change of target lesions was assessed. Overall response rate (ORR) was evaluated. Prognosis was carried out and safety profile was documented. Additionally, peripheral blood and biopsy cancer tissue specimens of the patients with SCLC were collected for the analysis of polymorphism and VEGFR2 gene mRNA expression, respectively. The association between genotype status and baseline characteristics was performed. Univariate analysis of genotype status and prognosis was carried out using Kaplan-Meier survival analysis and multivariate analysis were adjusted by Cox regression analysis. RESULTS: Efficacy of apatinib included partial response (PR) in 15 patients, stable disease (SD) in 86 patients, progressive disease (PD) in 27 patients. Therefore, ORR of the 128 patients with ES-SCLC was 11.7%, and disease control rate (DCR) was 78.9%. Prognosis suggested that the median progression-free survival (PFS) and overall survival (OS) of the 128 patients with ES-SCLC was 4.2 months and 8.2 months, respectively. The polymorphism analysis focusing on VEGFR2 gene indicated that one single nucleotide polymorphism 889C>T was of clinical significance. Prevalence of 889C>T among the 128 patients with SCLC were as follows: CC genotype 87 cases (68.0%), CT genotype 38 cases (29.7%) and TT genotype 3 cases (2.3%), the minor allele frequency of 889C>T was 0.17, which was in accordance with Hardy-Weinberg Equilibrium (P = 0.628). Patients with CT and TT genotypes were merged in the subsequent analysis. Prognosis analysis exhibited that the median PFS of patients with CT/TT genotype and CC genotype was 3.3 and 5.0 months, respectively (P = 0.02). Furthermore, the median OS of patients was 5.5 and 9.0 months, respectively (P = 0.008). Additionally, multivariate Cox regression analysis of OS demonstrated that CT/TT genotype was an independent factor for OS [Hazard ratio (HR) = 0.64, P = 0.019]. However, the safety profile according to genotype status of 889C>T failed to show significant difference. Interestingly, mRNA expression analysis suggested that the mRNA expression of VEGFR2 in cancer tissues were significantly different according to CC and CT/TT genotypes (P < 0.001). CONCLUSION: The administration with apatinib for patients with chemotherapy-refractory ES-SCLC was of potential clinical significance. The clinical outcomes of patients with ES-SCLC who were treated with apatinib could be impacted by VEGFR2 889C>T polymorphism through mediating the VEGFR2 mRNA expression.

Dosimetric Predictors of Radiation Gastritis Due to Postoperative Intensity Modulated Irradiation Therapy in Patients with Esophageal Squamous Cell Carcinoma After Radical Esophagectomy.

Objective: To explore the association between the incidence of acute radiation gastritis attributed to postoperative intensity modulated irradiation therapy (IMRT) and the dose volume of intrathoracic stomach of patients with esophageal squamous cell carcinoma (ESCC) after radical esophagectomy. Methods: The authors retrospectively collected the data of 49 ESCC patients who participated in postoperative IMRT treatment after radical esophagectomy, and analyzed the incidence of acute radiation gastritis during the treatment. Results: Among all the 49 patients, acute grade ≥2 radiation gastritis was observed in 19 patients (39%). Receiver operating characteristic (ROC) curve analysis showed that the physical variables, such as stomach Dmax, Dmean, length of the whole stomach received 5-40 Gy (LSTT5-LSTT40), and V10-V50, were associated with acute radiation gastritis. Patients were grouped according to cutoff values in physical indicators obtained from the ROC curve. Other than V5, the incidence of acute grade ≥2 radiation gastritis was significantly higher in the group with indicators above cutoff values than that below cutoff values, and the between-group difference was statistically significant in terms of physical indicators. Multivariate analysis suggested that LSTT5 and V40 could be acted as indicators to predict the incidence of acute grade ≥2 radiation gastritis. Conclusions: In the postoperative IMRT treatment for ESCC patients, protection of intrathoracic stomach is strongly recommended. Dose-volume histogram is a preferable predictive indicator for the occurrence of acute radiation gastritis, especially for the stomach LSTT5 and V40. Nevertheless, a larger sample size is needed to provide insight into the relevant study.

Middle hepatic vein reconstruction in adult right lobe living donor liver transplantation improves recipient survival.

BACKGROUND: The efficacy and necessity of middle hepatic vein (MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation (LDLT) remain controversial. The present study aimed to evaluate the survival beneficiary of MHV reconstructions in LDLT. METHODS: We compared the clinical outcomes of liver recipients with MHV reconstruction (n = 101) and without MHV reconstruction (n = 43) who underwent LDLT using right lobe grafts at our institution from January 2006 to May 2017. RESULTS: The overall survival (OS) rate of recipients with MHV reconstruction was significantly higher than that of those without MHV reconstruction in liver transplantation (P = 0.022; 5-yr OS: 76.2% vs 58.1%). The survival of two segments (segments 5 and 8) hepatic vein reconstruction was better than that of the only one segment (segment 5 or segment 8) hepatic vein reconstruction (P = 0.034; 5-yr OS: 83.6% vs 67.4%). The survival of using two straight vascular reconstructions was better than that using Y-shaped vascular reconstruction in liver transplantation with two segments hepatic vein reconstruction (P = 0.020; 5-yr OS: 100% vs 75.0%). The multivariate analysis demonstrated that MHV tributary reconstructions were an independent beneficiary prognostic factor for OS (hazard ratio=0.519, 95% CI: 0.282-0.954, P = 0.035). Biliary complications were significantly increased in recipients with MHV reconstruction (28.7% vs 11.6%, P = 0.027). CONCLUSIONS: MHV reconstruction ensured excellent outflow drainage and favored recipient outcome. The MHV tributaries (segments 5 and 8) should be reconstructed as much as possible to enlarge the hepatic vein anastomosis and reduce congestion.

17-beta-hydroxysteroid dehydrogenase 13 inhibits the progression and recurrence of hepatocellular carcinoma.

BACKGROUND: Our previous study showed that 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) is down-regulated in hepatocellular carcinoma (HCC). But its function in HCC remains unknown. This study aimed to reveal the function of HSD17B13 and its clinical significance in HCC. METHODS: mRNA levels of HSD17B13 were analyzed in cohort 1 (30 normal, 30 HBV cirrhosis, 60 HBV-related HCC and 60 peritumoral tissue) by real-time PCR. HSD17B13 protein was evaluated in cohort 2 (15 normal, 33 HBV-cirrhosis, 12 dysplastic nodules, 34 HBV-related HCC, and 9 metastatic HCC) using immunohistochemistry. The association between HSD17B13 and the survival of HCC patients was analyzed in cohort 3 (n = 88). The inhibitory mechanism of HSD17B13 on HCC was explored . RESULTS: The mRNA of HSD17B13 and its protein expression were significantly down-regulated in HCC compared to non-tumor specimens (P < 0.001). The sensitivity, specificity and area under curve (AUC) values of HSD17B13 expression levels for HCC detection were 81.7%, 83.7% and 0.856, respectively (P < 0.001). Lower HSD17B13 in peritumoral tissue was an independent risk factor of worse recurrence free survival of HCC patients (HR: 0.41; 95% CI: 0.20-0.83; P = 0.014). The study in Huh 7 and SK-HEP-1 cells showed that HSD17B13 induced an accumulation of cells in G1 phase and reduction of cells in S and G2 phases via up-regulating the expression of P21, P27 and MMP2. CONCLUSIONS: Lower HSD17B13 in peritumoral tissues was associated with worse recurrence free survival and overall survival of HCC patients. HSD17B13 delayed G1/S progression of HCC cells. HSD17B13 may be a therapeutic target for the treatment of HCC.

BMI-1 suppression increases the radiosensitivity of oesophageal carcinoma via the PI3K/Akt signaling pathway.

B-cell­specific Moloney murine leukaemia virus integration site-1 (BMI-1) contributes to the growth of tumour cells post-irradiation (IR). The aim of the present study was to characterize the effects of BMI-1 on cell viability, radiosensitivity and its mechanisms of action in oesophageal squamous cell cancer (ESCC). Western blotting and immunohistochemistry were employed to evaluate the protein expression of BMI-1 in ESCC cells and specimens, respectively. Additionally, the protein expression levels of BMI-1, H2AK119ub and γH2AX in ESCC cells were detected following different doses of IR and at different times after IR. The protein expression levels of MDC1 and 53BP1 were also measured. Flow cytometry and MTT assays were used to determine cell cycle progression, apoptosis and cell viability. The phosphatidylinositol 3-kinase inhibitor LY294002 and the agonist IGF-1 were employed to suppress or induce the phosphorylation of Akt to determine whether BMI-1 induces radioresistance in ESCC cells via activation of the PI3K/Akt pathway. The expression of BMI-1 was higher in ESCC tissues and cells compared with that in normal oesophageal tissues and cells. In addition, BMI-1 was positively related to tumour size and lymph node metastases and negatively to the overall survival of ESCC patients. IR induced the expression of BMI-1, H2AK119ub and γH2AX in a dose- and time-dependent manner. BMI-1 knockdown lowered the expression of γH2AX, MDC1 and 53BP1, suppressed cell viability and increased radiosensitivity. G2/M phase arrest was eliminated; this was followed by an increased proportion of cells entering the G0/G1 phase after IR and BMI-1 knockdown via the upregulation of P16 and downregulation of cyclin D2 and cyclin-dependent kinase-4. Moreover, BMI-1 knockdown increased cell apoptosis, downregulated MCL-1 and p-Akt and upregulated Bax. Additionally, the inhibitory effect of the downregulation of p-Akt by LY294002 on tumour cell viability was identical to that of BMI-1 knockdown, while the kinase agonist IGF-1 reversed the effects of BMI-1 knockdown on cell viability and radiosensitivity. Taken together, BMI-1 knockdown induces radiosensitivity in ESCC and significantly inhibits cell viability, which may contribute to an increased proportion of cells in the G0/G1 phase and cell apoptosis via suppression of the PI3K/Akt signalling pathway.

Analysis of failure patterns in patients with resectable esophageal squamous cell carcinoma receiving chemoradiotherapy.

PURPOSE: This study investigates the failure pattern after chemoradiotherapy of patients with resectable esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: We retrospectively analyzed 92 patients with T1-2, N0-1, and M0 ESCC. These patients were inoperable because of poor performance, comorbidities, poor tumor region, or refusal of operation. RESULTS: Among the 92 patients, 29 cases displayed simple locoregional recurrence, 12 cases displayed simple distant metastasis, and 6 cases displayed distant metastasis with locoregional recurrence. Univariate analysis shows that the incidence of recurrence in the middle thoracic region was significantly higher than other regions (χ2 = 14.415, P = 0.001). For the 18 patients with distant metastasis, incidence of distant metastasis in the lower thoracic region was significantly higher than the other regions (= 39.359, P < 0.001). Among 35 cases with regional recurrence, 7 cases reached complete remission (14.6%) and 28 cases reached partial remission (PR; 63.6%) (χ2= 23.435, P < 0.001). Multivariate analysis shows that the patient age, tumor node metastasis (TNM) stage, and short-term efficacy were independent factors for locoregional recurrence. Patient age, TNM stage, X-ray length of the lesions, and short-term efficacy were the independent factors for distant metastases. CONCLUSION: The incidence of locoregional recurrence and distant metastasis in patients with upper thoracic esophageal cancer was lower than those who had middle thoracic and lower thoracic esophageal cancer. The incidence of locoregional recurrence and distant metastasis in patients who achieved complete response after treatment was low.