Gustative Roussy Immune Score is a Predictor for Major Pathological Response in Rectal Cancer: A Result from the Preoperative Intraarterial Chemoembolization Combined with Radiotherapy (PCAR) Study.

Despite the emergence of various treatment strategies for rectal cancer based on neoadjuvant chemoradiotherapy, there is currently a lack of reliable biomarkers to determine which patients will respond well to neoadjuvant chemoradiotherapy. Through collecting hematological and biochemical parameters data of patients prior to receiving neoadjuvant chemoradiotherapy, we evaluated the predictive value of systemic inflammatory indices for pathological response and prognosis in rectal cancer patients. We found that baseline GRIm-Score was an independent predictor for MPR in rectal cancer patients. However, no association was observed between several commonly systemic inflammation indices and long-term outcome.

Kinetically and Thermodynamically Favorable Ni-Al Layered Double Hydroxide/Ni-Doped Zn0.5Cd0.5S S-Scheme Heterojunction Triggering Photocatalytic H2 Evolution.

Layered double hydroxide (LDH)-based photocatalysts have attracted more attention in photocatalysis due to their low cost, wide band gaps, and adjustable photocatalytic active sites; however, their low photogenerated carrier separation efficiency limits their photocatalytic efficiency. Herein, a NiAl-LDH/Ni-doped Zn0.5Cd0.5S (LDH/Ni-ZCS) S-scheme heterojunction is rationally designed and constructed from kinetically and thermodynamically favorable angles. The 15% LDH/1% Ni-ZCS displays comparable photocatalytic hydrogen evolution (PHE) activity with a rate of 6584.0 µmol g-1 h-1, which exceeds by ∼6.14- and ∼1.73-fold those of ZCS and 1% Ni-ZCS, respectively, and outperforms most of the previously reported LDH-based and metal sulfide-based photocatalysts. In addition, the apparent quantum yield of 15% LDH/1% Ni-ZCS reaches 12.1% at 420 nm. In situ X-ray photoelectron spectroscopy, photodeposition, and theoretical calculation reveal the specific transfer path of photogenerated carriers. On this basis, we propose the possible photocatalytic mechanism. The fabrication of the S-scheme heterojunction not only accelerates the separation of photogenerated carriers but also decreases the activation energy of H2 evolution and improves the redox capacity. Moreover, there are huge amounts of hydroxyl groups distributed on the surface of photocatalysts, which is highly polar and easy to combine with H2O with a large dielectric constant to form a hydrogen bond, which can further accelerate PHE.

Relative decline in serum albumin help to predict anastomotic leakage for female patients following sphincter-preserving rectal surgery.

BACKGROUND: Patients with normal preoperative serum albumin still suffer from a significant reduction in serum albumin after major abdominal surgery. The current study aims to explore the predictive value of ∆ALB for AL in patients with normal serum albumin and examine whether there is a gender difference in the prediction of AL. METHODS: Medical reports of consecutive patients undergoing elective sphincter-preserving rectal surgery between July 2010 and June 2016 were reviewed. Receiver operating characteristic (ROC) analysis was adopted to examine the predictive ability of ∆ALB and determine the cut-off value according to the Youden index. The logistic regression model was performed identify independent risk factors for AL. RESULTS: Out of the 499 eligible patients, 40 experienced AL. Results of the ROC analyses showed that ΔALB displayed a significant predictive value for females, and the AUC value was 0.675 (P = 0.024), with a sensitivity of 93%. In male patients, the AUC was 0.575 (P = 0.22), but did not reach a significant level. In the multivariate analysis, ∆ALB ≥ 27.2% and low tumor location prove to be independent risk factors for AL in female patients. CONCLUSIONS: The current study suggested that there may be a gender difference in the prediction of AL and ∆ ALB can serve as a potential predictive biomarker for AL in females. A cut-off value of the relative decline in serum albumin can help predict AL in female patients as early as postoperative day 2. Although our study needs further external validation, our findings may provide an earlier, easier and cheaper biomarker for the detection of AL.

Robotic versus laparoscopic left colectomy with complete mesocolic excision for left-sided colon cancer: a multicentre study with propensity score matching analysis.

PURPOSE: Robotic surgery for right-sided colon and rectal cancer has rapidly increased; however, there is limited evidence in the literature of advantages of robotic left colectomy (RLC) for left-sided colon cancer. The purpose of this study was to compare the outcomes of RLC versus laparoscopic left colectomy (LLC) with complete mesocolic excision (CME) for left-sided colon cancer. METHODS: Patients who had RLC or LLC with CME for left-sided colon cancer at five hospitals in China between January 2014 and April 2022 were included. A one-to-one propensity score matched analysis was performed to decrease confounding. The primary outcome was postoperative complications occurring within 30 days of surgery. Secondary outcomes were disease-free survival, overall survival and the number of harvested lymph nodes. RESULTS: A total of 292 patients (187 male; median age 61.0 [20.0-85.0] years) were eligible for this study, and propensity score matching yielded 102 patients in each group. The clinicopathological characteristics were well-matched between groups. The two groups did not differ in estimated blood loss, conversion to open rate, time to first flatus, reoperation rate, or postoperative length of hospital stay (p > 0.05). RLC was associated with a longer operation time (192.9 ± 53.2 vs. 168.9 ± 52.8 min, p = 0.001). The incidence of postoperative complications did not differ between the RLC and LLC groups (18.6% vs. 17.6%, p = 0.856). The total number of lymph nodes harvested in the RLC group was higher than that in the LLC group (15.7 ± 8.3 vs. 12.1 ± 5.9, p < 0.001). There were no significant differences in 3-year and 5-year overall survival or 3-year and 5-year disease-free survival. CONCLUSION: Compared to laparoscopic surgery, RLC with CME for left-sided colon cancer was found to be associated with higher numbers of lymph nodes harvested and similar postoperative complications and long-term survival outcomes.

Analysis of variation characteristics, transport paths, and influencing factors of atmospheric NO2 pollution in Western Europe.

Climate change and air pollution are one of the global environmental problems. It is significant to grasp the air pollution situation of Western Europe in recent 10 years for its or the global pollution control. Based on the OMI tropospheric nitrogen dioxide (NO2) column density data, the spatial and temporal distribution characteristics, variation trend, transmission path, and influencing factors of NO2 in 15 countries in Western Europe from 2011 to 2022 are discussed in this paper. Meanwhile, the annual average spatial and temporal distribution in 2023 is predicted by the random forest (RF) model. The results showed that (1) the 12-year spatial distribution map showed an increasing trend from southwest to northeast, with the border area of the Netherlands and Germany and Milan as two high-value areas, and the overall trend over time was that the high-concentration area gradually shrank, the low-concentration area gradually expanded, and the annual average concentration gradually decreased. (2) The inter-month trend presents a "U" shape, with the mean NO2 pollution ranking in winter > autumn > spring > summer. (3) Natural factors are one of the reasons affecting NO2; for instance, NO2 pollution has a strong positive correlation with the lifted index, relative humidity, and wind speed and a moderately strong negative correlation with precipitable water and air temperature. (4) Exogenous atmospheric transport is another important factor affecting the change of NO2 pollution in Western Europe. The HYSPLIT model is used to analyze the backward trajectory of Milan, Italy, and Nijmegen, Netherlands, in the four seasons of 2022. Both are mainly influenced by westerly airflows, and therefore, the transport effect in the atmosphere brings air pollutants from westerly regions in the atmosphere.

[Microwave sensor for recognition of abnormal nodule tissue on body surface].

For the detection and identification of abnormal nodular tissues on the body surface, a microwave sensor structure loaded with a spiral resonator is proposed in this paper, a sensor simulation model is established using HFSS software, the structural parameters are optimized, and the actual sensor is fabricated. The S21 parameters of the tissue were obtained when nodules appeared by simulation, and the characteristic relationship between the difference of S21 parameters with position was analyzed and tested experimentally. The results showed that when nodules were present in normal tissues, the curve of S21 parameter difference with position change had obvious inverted bimodal characteristics, and the extreme value of S21 parameter difference appeared when the sensor was directly above the nodules, which was easy to identify the position of nodules. It provides an objective detection tool for the identification of abnormal nodular tissues on the body surface.

Interior and Surface Synergistic Modifications Modulate the SnNb2O6/Ni-Doped ZnIn2S4 S-Scheme Heterojunction for Efficient Photocatalytic H2 Evolution.

Interior and surface synergistic modifications can endow the photocatalytic reaction with tuned photogenerated carrier flow at the atomic level. Herein, a new class of 2D/2D SnNb2O6/Ni-doped ZnIn2S4 (SNO/Ni-ZIS) S-scheme heterojunctions is synthesized by a simple hydrothermal strategy, which was used to evaluate the synergy between interior and surface modifications. Theoretical calculations show that the S-scheme heterojunction boosts the desorption of H atoms for rapid H2 evolution. As a result, 25% SNO/Ni0.4-ZIS exhibits significantly improved PHE activity under visible light, roughly 4.49 and 2.00 times stronger than that of single ZIS and Ni0.4-ZIS, respectively. In addition, 25% SNO/Ni0.4-ZIS also shows superior structural stability. This work provides advanced insight for developing high-performance S-scheme systems from photocatalyst design to mechanistic insight.

The impact of postoperative complications severity on stoma reversal following sphincter-preserving surgery for rectal cancer.

BACKGROUND: Currently, the relationship between temporary stoma reversal and the severity of postoperative complications (POCs) after the index surgery based on the Clavien-Dindo classification has not yet been explored. METHODS: From July 2010 to June 2016, 380 patients undergoing sphincter-preserving surgery for rectal cancer with a temporary stoma in our hospital were included. Temporary stoma nonclosure rates, disease-free survival rates, and overall survival rates were estimated utilizing the Kaplan-Meier method. RESULTS: Of all the 380 patients, primary stomas were created in 335 patients and secondary stomas in 45 patients. After the index surgery, 36.6% (139/380) of patients developed at least one postoperative complication. In the first analysis, which included all the patients, 24.7% of temporary stomas remained unclosed. In the second analysis for 335 patients with a primary stoma, 23.3% were left with unclosed stomas. After the COX regression analysis, both major POCs and minor POCs were found to be independent risk factors for the permanent stoma, and there was an increasing tendency toward the risk of permanent stoma with the increase in POC severity. CONCLUSION: POCs are independent predictors of permanent stoma after rectal cancer surgery. Even minor POCs may affect the outcome, while there is a clear direct relationship between POC severity and permanent stoma rates.

Boosting H2 Production over C60 -Mediated NH2 -MIL-125(Ti)/Zn0.5 Cd0.5 S S-Scheme Heterojunction via Enhanced Interfacial Carrier Separation.

Improving greatly the separation efficiency of interfacial charge carrier is a major challenge in photocatalysis. Herein, a new class of C60 -mediated NH2 -MIL-125(Ti)/Zn0.5 Cd0.5 S S-scheme heterojunction with enhanced interfacial charge carrier separation is designed and synthesized. The constructed S-scheme heterojunction thermodynamically favors photocatalytic H2 evolution because of the large driving force resulting from its strong redox abilities. As a consequence, the optimum proportion of C60 -mediated NH2 -MIL-125(Ti)/Zn0.5 Cd0.5 S S-scheme heterojunction displays comparable H2 evolution activity with a rate of 7825.20 µmol h-1 g-1 under visible light irradiation, which is about 93.05 times, 6.38 times and 2.65 times higher than that of 2% C60 /NH2 -MIL-125(Ti), Zn0.5 Cd0.5 S and 45% NH2 -MIL-125(Ti)/Zn0.5 Cd0.5 S, and outperforms the majority of the previously reported MOFs-based photocatalysts. Spectroscopic characterizations and theory calculations indicate that the S-scheme heterojunction can powerfully promote the separation of photogenerated carriers. This work offers a new insight for future design and development of highly active MOFs-based photocatalysts.

Impact of preoperative transcatheter rectal arterial chemoembolization with concurrent chemoradiotherapy on surgery and prognosis of patients with locally advanced rectal cancer.

BACKGROUND AND OBJECTIVES: To analyze and evaluate the impact of preoperative transcatheter rectal arterial chemoembolization (TRACE) with concurrent chemoradiotherapy on surgery and prognosis of locally advanced rectal cancer (LARC). METHODS: A total of 118 patients with LARC were enrolled in this nonrandomized prospective study. They were assigned into the experimental group receiving preoperative TRACE with concurrent chemoradiotherapy (TRACE-CRT group, N = 60) and the control group receiving only neoadjuvant chemoradiotherapy (CRT group, N = 58). All patients underwent surgery after their preoperative treatments. RESULTS: All patients successfully completed the surgical operation. No significant differences were found in sphincter preservation rate and R0 resection rate between TRACE-CRT group and CRT group (p > 0.05). No significant differences were found between the two groups in terms of the perioperative indicators and postoperative complications except mean operation time (165.8 vs. 196.6 min, p < 0.001). Local recurrence occurred in 8 and 5 patients, respectively (p > 0.05). Distant metastasis occurred in 5 and 11 patients, respectively (p < 0.05). CONCLUSIONS: Adding TRACE in the preoperative standard treatment for LARC did not increase perioperative complications. In addition, it has the potential advantage of preventing distant metastasis. It is worthy of further application and promotion in clinical practice.

Resveratrol Inhibits Hepatic Stellate Cell Activation via the Hippo Pathway.

Liver fibrosis, which results from chronic liver injury due to factors such as chronic alcohol consumption, hepatitis virus infections, and immune attacks, is marked by excessive deposition of extracellular matrix (ECM). Resveratrol (Res), a polyphenol phytoalexin, has been demonstrated to show anti-inflammatory, antioxidative, antiproliferative, and chemopreventive activities. In recent years, Res has been found to inhibit liver fibrosis. Enhanced Hippo pathway activation has also been reported to inhibit tumor progression and liver fibrosis. In the present study, the role of the Hippo pathway in mediating the effects of Res on hepatic stellate cells (HSCs) was examined. We found that Res significantly suppresses HSC proliferation, reducing the cell index. Res induced HSC inactivation, reducing collagen deposition and α-smooth muscle actin (α-SMA) expression. In addition, Res contributed to HSC apoptosis, upregulating Bax and downregulating Bcl-2 expression. Notably, the Hippo pathway was involved in the Res-mediated suppression of HSC activation. Res enhanced the activation of the Hippo pathway and reduced yes-associated protein (YAP) and transcriptional coactivator with the PDZ-binding motif (TAZ) expression. Interestingly, the YAP overexpression inhibited Res-induced HSC inactivation and apoptosis. In conclusion, these results demonstrate that Res inhibits HSC activation, at least in part, via the Hippo pathway. The present study indicates a new antifibrotic mechanism of Res and provides novel insights into Hippo-mediated HSC apoptosis and HSC activation in liver fibrosis.

Thymoquinone alleviates liver fibrosis via miR-30a-mediated epithelial-mesenchymal transition.

Thymoquinone (TQ), the main active constituent of Nigella sativa seeds, has been shown to play a role in antioxidation, anti-inflammation, and antitumor. Recent studies have demonstrated that TQ contributes to the suppression of liver fibrosis. Abnormal activated epithelial-mesenchymal transition (EMT) promotes the activation of hepatic stellate cells (HSCs). However, whether the antifibrotic effects of TQ occur through inhibiting EMT is largely unknown. In this study, it was found that TQ ameliorated liver fibrosis and collagen accumulation in carbon tetrachloride (CCl4) mice. In vitro, TQ inhibited HSC activation including reduced proliferation, α-smooth muscle actin, and collagen. In addition, TQ markedly suppressed the EMT process, with enhanced E-cadherin and reduced desmin. Notably, snail family transcriptional repressor 1 (Snai1), the EMT master transcription factor, was obviously inhibited by TQ in vivo and in vitro. Further studies demonstrated that Snai1 was a target of microRNA-30a (miR-30a), which was upregulated by TQ. Interestingly, the effects of TQ on HSC activation and EMT were almost inhibited by miR-30a inhibitor. Collectively, we demonstrate that TQ inhibits HSC activation, at least in part, via regulation of miR-30a and Snai1. TQ upregulates miR-30a expression, resulting in a reduced Snai1 level as well as EMT process inactivation, which contributes to the inhibition of HSC activation. TQ may be a potential therapeutic agent for liver fibrosis.

The impact of sedation on quality metrics of colonoscopy: a single-center experience of 48,838 procedures.

PURPOSE: Investigation of the role of sedation during colonoscopy is meaningful as the advantages of colonoscopy performing with sedation are still controversial. METHODS: Medical records of patients who underwent colonoscopy in our institution were retrospectively analyzed. The sedation rate, adenoma detection rate (ADR), polyp detection rate (PDR), cecal intubation rate (CIR), iatrogenic colonic perforation rate (ICP) were calculated. RESULTS: A total of 48,838 colonoscopies (24,498 in males) dated from July 2007 to February 2017 were analyzed. The median age was 50 years (range 16-85 years). An overall sedation rate was 80.38%. The PDR was 26.77%, and was not statistically different between colonoscopy with or without sedation (26.67% vs 27.22, p = 0.474). ADR was 12.9% regardless of applying sedation or not (13.0% vs 12.44%, p = 0.337). The CIR was 87.42% in all examinations with an adjusted CIR of 90.34%, and was higher when performed with sedation than without sedation (88.92% vs 80.64%, p < 0.0001). Five cases (0.01%) of ICP were reported, all of which occurred in patients under sedation. CONCLUSIONS: The use of sedation is associated with increased CIR, but ADR and PDR remain unchanged with or without sedation. However, perforation rate, albeit very low, is significantly higher in sedated patients.

The molecular landscape of synchronous colorectal cancer reveals genetic heterogeneity.

Synchronous colorectal cancers (syCRCs), which present two or more lesions at diagnosis, are rare and pose a great challenge for clinical management. Although some predisposing factors associated with syCRCs have been studied with limited accession, the full repertoire of genomic events among the lesions within an individual and the causes of syCRCs remain unclear. We performed whole-exome sequencing of 40 surgical tumour samples of paired lesions from 20 patients to characterize the genetic alterations. Lesions from same patient showed distinct landscapes of somatic aberrations and shared few mutations, which suggests that they originate and develop independently, although they shared the similar genetic background. Canonical genes, such as APC, KRAS, TP53 and PIK3CA, were frequently mutated in the syCRCs, and most of them show different mutation profile compared with solitary colorectal cancer. We identified a recurrent somatic alteration (K15fs) in RPL22 in 25% of the syCRCs. Functional analysis indicated that mutated RPL22 may suppress cell apoptosis and promote the epithelial-mesenchymal transition (EMT). Potential drug targets were identified in several signalling pathways, and they present great discrepancy between lesions from the same patient. Our data show that the syCRCs within the same patient present great genetic heterogeneity, and they may be driven by distinct molecular events and develop independently. The discrepancy of potential drug targets and mutation burden in lesions from one patient provides valuable information in clinical management for patients with syCRCs.

The influence of neoadjuvant therapy for the prognosis in patients with rectal carcinoma: a retrospective study.

Rectal cancer, defined as a cancerous lesion of the colon distal to the rectosigmoid junction, is the fourth most common cancer cause of death globally. There were 474 patients with rectal cancer who underwent surgery between October 2007 and May 2013 enrolled in our center. Patients were respectively categorized by neoadjuvant therapy. This study aimed to explore the predictive factors that affected the Progression-free survival and overall survival of the patients with rectal cancer. Clinical characteristics of patients were compared with the groups and potential prognostic factors were analyzed by SPSS 19.0. In our study, neoadjuvant therapy increased the anus-retained rate (64.4 vs 53.4 % P = 0.016) and remission rate in the treatment group, compared to the non-treatment group (62.6 vs 34.8 %; P = 0.000). The neoadjuvant concurrent chemoradiotherapy, more operative duration, anus retained and micturition damaged are positive prognostic factors of PFS to patients. Poor differentiation, the tumor of ulcer, invasive, and pT4 stage, contributed the poor factors for PFS of patients (P < 0.05). Additionally, the patients with neoadjuvant concurrent chemoradiotherapy and adjuvant chemotherapy underwent the better prognosis of OS. Adjuvant chemotherapy cannot increase PFS of the patients who accepted neoadjuvant therapy after surgery get pCR, but can improve OS. The anus-retained and neoadjuvant radiotherapy, duration of surgery in rectal cancer have the positive correlation. Micturition damaged and neoadjuvant radiotherapy were positively correlated as well. In conclusion, adjuvant chemotherapy does not improve the PFS of patients with pCR to neoadjuvant therapy, but is good for OS. Further prospective and large population-based clinical studies are needed to establish clinical guidelines for the use of neoadjuvant therapy and adjuvant chemotherapy in patients with rectal cancer.

[Content determination of twelve major components in Tibetan medicine Zuozhu Daxi by UPLC].

A quantitative analytical method of ultra-high performance liquid chromatography (UPLC) was developed for simultaneously determining twelve components in Tibetan medicine Zuozhu Daxi. SIMPCA 12.0 software was used a principal component analysis PCA) and partial small squares analysis (PLSD-DA) on the twelve components in 10 batches from four pharmaceutical factories. Acquity UPLC BEH C15 column (2.1 mm x 100 mm, 1.7 µm) was adopted at the column temperature of 35 °C and eluted with acetonitrile (A) -0.05% phosphate acid solution (B) as the mobile phase with a flow rate of 0. 3 mL · min(-1). The injection volume was 1 µL. The detection wavelengths were set at 210 nm for alantolactone, isoalantolactone and oleanolic; 260 nm for trychnine and brucine; 288 nm for protopine; 306 nm for protopine, resveratrol and piperine; 370 nm for quercetin and isorhamnetin. The results showed a good separation among index components, with a good linearity relationship (R2 = 0.999 6) within the selected concentration range. The average sample recovery rates ranged between 99.44%-101.8%, with RSD between 0.37%-1.7%, indicating the method is rapid and accurate with a good repeatability and stability. The PCA and PLSD-DA analysis on the sample determination results revealed a great difference among samples from different pharmaceutical factories. The twelve components included in this study contributed significantly to the quantitative determination of intrinsic quality of Zuozhu Daxi. The UPLC established for to the quantitative determination of the twelve components can provide scientific basis for the comprehensive quality evaluation of Zuozhu Daxi.

Effect of different surgical options on curative effect, nutrition, and health status of patients with slow transit constipation.

OBJECTIVE: This study aims to investigate the influence of total colectomy with ileorectal anastomosis (IRA) and subtotal colectomy with cecorectal anastomosis (CRA) on curative effects, nutritional status, and health of patients with slow transit constipation (STC). METHODS: The purpose of the present study is to compare the hemoglobin, the total protein level, the albumin, and the percentage of lymphocytes before and after operations. The 36-item short-form health survey questionnaire (SF-36), the mininutritional assessment (MNA), the postoperative general condition questionnaire, and the social activities questionnaire were used. The questionnaires were modified. The patients with higher scores were shown to recover better postoperatively. RESULTS: More than 87.5 % of patients in both groups were satisfied with the surgery. Increased stool frequency was improved 6 months after surgery. Antidiarrheal agent use, abdominal pain, and distention in the IRA group were more frequent than in the CRA group (p < 0.05). Postoperative levels of hemoglobin, total protein level, albumin, and percentage of lymphocytes in the IRA group were higher than in the CRA group (p < 0.05). There was no difference in MNA for both groups (p > 0.05). There was no difference in the postoperative general condition questionnaire for both groups (p > 0.05). But the scores for health condition, emotion, and feeling for life were low, only 68.8 to 82.4 % at their highest. CONCLUSIONS: Symptoms can be relieved by IRA and CRA surgeries. The postoperative nutritional conditions are fine. Health conditions and social life are affected. Both IRA and CRA surgeries are compliant for the treatment of STC.

Correction: Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis.

Correction for 'Critical role of hydrogen bonding between microcrystalline cellulose and g-C3N4 enables highly efficient photocatalysis' by Zhaoqiang Wang et al., Chem. Commun., 2024, 60, 204-207, https://doi.org/10.1039/D3CC04800D.

Activate the endogenous Cu2+ switch for Zn(DDC)2 liposomes conversion: Providing a safer and less toxic alternative in cancer therapy.

The ancient anti-alcohol drug disulfiram (DSF) has gained widespread attention for its highly effective anti-tumor effects in cancer treatment. Our previous studies have developed liposome of Cu (DDC)2 to overcome the limitations, like the poor water solubility. However, Cu (DDC)2 liposomes still have shown difficulties in severe hemolytic reactions at high doses and systemic toxicity, which have limited their clinical use. Therefore, this study aims to exploratively investigate the feasibility of using DSF or DDC in combination also can chelate Zn2+ to form zinc diethyldithiocarbamate (Zn (DDC)2). Furthermore, this study prepared stable and homogeneous Zn (DDC)2 liposomes, which were able to be released in the tumor microenvironment (TME). The released Zn (DDC)2 was converted to Cu (DDC)2 with the help of endogenous Cu2+-switch enriched in the TME, which has a higher stability constant compared with Zn (DDC)2. In other words, the Cu2+-switch is activated at the tumor site, completing the conversion of the less cytotoxic Zn (DDC)2 to the more cytotoxic Cu (DDC)2 for effective tumor therapy so that the Zn (DDC)2 liposomes in vivo achieved the comparable therapeutic efficacy and provided a safer alternative to Cu (DDC)2 liposomes in cancer therapy.

Negative prognostic impact of Co-mutations in TGFß and TP53 pathways in surgically resected rectal tumors following neoadjuvant chemoradiotherapy.

BACKGROUND: Preoperative neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is a common approach for treating patients with locally advanced rectal cancer. Nevertheless, the mutational profile and its prognostic impact in surgically resected tumor specimens after nCRT remains to be clarified. METHODS: The comprehensive analysis of mutational landscape was retrospectively conducted by target regions sequencing approach that covered 150 tumor-related genes. Univariate and multivariate logistic regression and Cox regression was used to examine the association of mutation status in genes and pathways with pathological response and prognosis. Data from Memorial Sloan Kettering Cancer Center (MSK) cohort was used for comparison with our results. RESULTS: The top five commonly mutated genes in resected rectal tumor tissue samples following nCRT were TP53 (42%), APC (31%), KRAS (27%), PIK3CA (14%) and FBXW7 (11%). Mutations in the WNT pathway, which was mainly represented by APC mutation, were found to be significantly associated with tumor regression grade (TRG) 3. In our cohort, co-mutations in the receptor tyrosine kinase (RTK)/RAS and WNT pathways were found to be independently associated with reduced risk of recurrent and significantly associated with longer disease-free survival (DFS). In both our cohort and the MSK cohort, co-mutations in the TGF-ß and TP53 pathways were significantly associated with worse DFS. CONCLUSIONS: Resected rectal tumor samples from patients without complete pathological response can be appropriately used to detect mutations. Co-mutations in the TGF-ß and TP53 pathways may provide more prognostic information beyond commonly used clinical factors.