Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China.

BACKGROUND: Cadonilimab is a bispecific antibody targeting PD-1 and CTLA-4, which has shown substantial clinical benefits in advanced cervical cancer. In the COMPASSION-16 trial, we aimed to evaluate the addition of cadonilimab to first-line standard chemotherapy in persistent, recurrent, or metastatic cervical cancer. METHODS: In this randomised, double-blind, multicentre, placebo-controlled phase 3 trial, women aged 18-75 years across 59 clinical sites in China with previously untreated persistent, recurrent, or metastatic cervical cancer were randomly assigned (1:1) to receive cadonilimab (10 mg/kg) or placebo plus platinum-based chemotherapy with or without bevacizumab every 3 weeks for six cycles, followed by maintenance therapy every 3 weeks for up to 2 years. Randomisation was performed centrally through an interactive web-response system. Stratification factors were the use of bevacizumab (yes or no) and previous concurrent chemoradiotherapy (yes or no). The dual primary outcomes were progression-free survival as assessed by blinded independent central review and overall survival in the full analysis set. This study is registered with ClinicalTrials.gov, NCT04982237; the study has completed enrolment and is ongoing for treatment and follow-up. FINDINGS: 445 eligible women were enrolled between Sept 11, 2021, and June 23, 2022. Median progression-free survival was 12·7 months (95% CI 11·6-16·1) in the cadonilimab group and 8·1 months (7·7-9·6) in the placebo group (hazard ratio 0·62 [95% CI 0·49-0·80], p<0·0001); median overall survival was not reached (27·0 months to not estimable) versus 22·8 months (17·6-29·0), respectively (hazard ratio 0·64 [0·48-0·86], p=0·0011). The most common grade 3 or higher adverse events were decreased neutrophil count, decreased white blood cell count, and anaemia. INTERPRETATION: The addition of cadonilimab to first-line standard chemotherapy significantly improved progression-free survival and overall survival with a manageable safety profile in participants with persistent, recurrent, or metastatic cervical cancer. The data support the use of cadonilimab plus chemotherapy as an efficacious first-line therapy in persistent, recurrent, or metastatic cervical cancer. FUNDING: Akeso Biopharma.

Superspreading Surface with Hierarchical Porous Structure for Highly Efficient Vapor-Liquid Phase Change Heat Dissipation.

Superspreading surfaces with excellent water transport efficiency are highly desirable for addressing thermal failures through the liquid-vapor phase change of water in electronics thermal management applications. However, the trade-off between capillary pressure and viscous resistance in traditional superspreading surfaces with micro/ nanostructures poses a longstanding challenge in the development of superspreading surfaces with high cooling efficiency in confined spaces. Herein, a heat-treated hierarchical porous enhanced superspreading surface (HTHP) for highly efficient electronic cooling is proposed. Compared with the single porous structures in nanograss, nanosheets, and copper foam, HTHP with hierarchical honeycomb pores effectively resolves the trade-off effect by introducing large vertical through-pores to reduce viscous resistance, and connected small pores to provide sufficient capillary pressure synergistically. HTHP exhibits excellent capillary performance in both horizontal spreading and vertical rising. Despite a thickness of only 0.33 mm, the as-prepared ultrathin vapor chamber (UTVC) fabricated to exploit the superior capillary performance of HTHP achieved effective heat dissipation with outstanding thermal conductivity (12 121 Wm-1K-1), and low thermal resistance (0.1 KW-1) at a power of 5 W. This regulation strategy based on hierarchical honeycomb porous structures is expected to promote the development of high-performance superspreading surfaces with a wide range of applications in thermal management.

EN1 promotes lung metastasis of salivary adenoid cystic carcinoma by regulating the PI3K-AKT pathway and epithelial-mesenchymal transition.

BACKGROUND: Engrailed homeobox 1 (EN1) is a candidate oncogene that is epigenetically modified in salivary adenoid cystic carcinoma (SACC). We investigated the expression of EN1 in SACC tissues and cells, EN1 promoter methylation, and the role of EN1 in tumour progression in SACC. METHODS: Thirty-five SACC samples were screened for key transcription factors that affect tumour progression. In vitro and in vivo assays were performed to determine the viability, tumorigenicity, and metastatic ability of SACC cells with modulated EN1 expression. Quantitative methylation-specific polymerase chain reaction analysis was performed on SACC samples. RESULTS: EN1 was identified as a transcription factor that was highly overexpressed in SACC tissues, regardless of clinical stage and histology subtype, and its level of expression correlated with distant metastasis. EN1 promoted cell invasion and migration through epithelial-mesenchymal transition in vitro and enhanced SACC metastasis to the lung in vivo. RNA-seq combined with in vitro assays indicated that EN1 might play an oncogenic role in SACC through the PI3K-AKT pathway. EN1 mRNA levels were negatively correlated with promoter hypermethylation, and inhibition of DNA methylation by 5-aza-dC increased EN1 expression. CONCLUSIONS: The transcription factor EN1 is overexpressed in SACC under methylation regulation and plays a pivotal role in SACC progression through the PI3K-AKT pathway. These results suggest that EN1 may be a diagnostic biomarker and a potential therapeutic target for SACC.

An investigator-initiated clinical study in patients with refractory or recurrent solid tumors: 'R-ISV-FOLactis' trial.

Aim: In situ vaccination, a kind of therapeutic cancer vaccine, can be realized by radiotherapy and intratumoral immune injection. This study combines intratumoral injection, radiotherapy and PD-1 blockade for synergistic antitumor effect.Materials & methods: Patients with advanced solid tumors who are unresponsive or intolerant to standard treatment will be treated with hypofractionated radiotherapy, intratumoral injection of FOLactis, PD-1 blockade. The primary end point is to observe the efficacy and safety, with the secondary end point to evaluate abscopal effects and the correlation between the immunological rationale and efficacy.Discussion: The combined regimen will be utilized to trigger antitumor immunity and is expected to be feasible and effective and provide a novel option for the comprehensive treatment of cancer.Clinical Trial Registration: ChiCTR2200060660 (ChiCTR.gov.cn).

[Box: see text].

Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial.

BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450 mg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Notch activation promotes bone metastasis via SPARC inhibition in adenoid cystic carcinoma.

OBJECTIVES: We aimed to investigate bone metastasis induced by Notch signalling pathway dysregulation and to demonstrate that SPARC is a potential therapeutic target in adenoid cystic carcinoma (AdCC) with Notch dysregulation. MATERIALS AND METHODS: This retrospective study enrolled 144 AdCC patients. RNA-sequencing and enrichment analyses were performed using 32 AdCC samples. Osteonectin/SPARC and the Notch activation indicator Notch intracellular domain (NICD) were detected using immunohistochemistry. Cell proliferation and migration assays were conducted using stably NICD over-expressing cells. The effect of SPARC on osteoclast differentiation in NICD cells was investigated using western blotting, quantitative reverse transcription PCR, tartrate-resistant acid phosphatase staining and resorption assays. RESULTS: RNA-sequencing analysis showed that genes down-regulated in Notch-mutant AdCCs, such as SPARC, were enriched in ossification and osteoblast differentiation. Most (75/110, 68.2%) Notch1-wild-type AdCCs showed SPARC over-expression, whereas 30 out of 34 (88.2%) Notch1-mutant tumours showed low SPARC expression. SPARC over-expression was then found negatively to be correlated with NICD expression in 144 AdCCs. NICD over-expression promoted cell growth, migration and osteoclast differentiation, which could be partly reversed by exogenous SPARC. CONCLUSIONS: Notch activation in AdCC contributes to bone metastasis through SPARC inhibition. The study results suggest that SPARC may represent a prognostic biomarker and potential therapeutic target.

Scalable and Versatile Transfer of Sensitive Two-dimensional Materials.

Damage-free transfer of large-area two-dimensional (2D) materials is indispensable to unleash their full potentials in a wide range of electronic, photonic, and biochemical applications. However, the all-surface nature of 2D materials renders many of them vulnerable to surrounding environments, especially etchants and water involved during wet transfer process. Up to now, a scalable and damage-free transfer method for sensitive 2D materials is still lacking. Here, we report a general damage-free transfer method for sensitive 2D materials. The as-transferred 2D materials exhibit well-preserved structural integrity and unaltered physical properties. We further develop a facile TEM sample preparation technique that allows direct recycling of materials on TEM grids with high fidelity. This recycling technique provides an unprecedented opportunity to precisely relate structural characterization with physical/chemical/electrical probing for the same samples. This method can be readily generalized to diverse nanomaterials for large-area damage-free transfer and enables in-depth investigation of structure-property relationship.

Making path selection faster: a routing algorithm for ONoC.

Optical network-on-chip (ONoC) is an effective communication architecture to realize high performance and energy efficiency. Diverse routing algorithms are proposed to avoid the congestion, tolerate the faults, and reduce the insertion loss or energy consumption. However, existing algorithms did not consider the characteristic optical circuit-switching of ONoC, which aggravates the network congestion and degrades the associated performance severely. In this paper, by exploiting congestion prediction technique, we propose a new routing algorithm for ONoC, named loophole-routing, to improve the success rate of path-setup and decrease the latency. We use the congestion prediction technique to analyze the latency and predict the port condition caused by the network congestion. Theoretical analysis and experimental results of different synthetic traffic patterns show that the loophole-routing improves network latency over XY routing and OE-turn routing by 15.56%, 25.71%, 18.92%, 66.67% and 42.86% under uniform, hotspot1, hotspot2, transpose2 and transpose3 traffic patterns while improving the saturation throughput by 31.43%, 34.33%, 35.29%, 67.86% and 99.5% under uniform, hotspot1, hotspot2, transpose2 and transpose3 traffic patterns on average than XY routing. In addition, our proposed loophole-routing has the benefits of high path diversity and adaptive degree and low computing complexity and overhead and the potential to make fault-tolerant path selection.

Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis.

BACKGROUND: Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis. METHODS: We searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0. RESULTS: After inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients. CONCLUSIONS: Our meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.

Apatinib treatment is effective for metastatic malignant phyllodes tumors of the breast: a case report.

BACKGROUND: We report a rare case of malignant phyllodes tumors (MPT) with partial response to apatinib. CASE PRESENTATION: A 26-year-old woman had a palpable mass in her right breast for over a year. After resection, pathology indicated malignant phyllodes tumor. Eleven months after surgery, she underwent reoperation for a lung nodule, which demonstrated lung metastasis. She refused chemotherapy and was rehospitalized six months later due to leg pain. Pelvic mass biopsy revealed metastatic malignant phyllodes tumor. After concurrent chemoradiotherapy of the pelvic mass, multiple lung metastases emerged. Subsequent treatment with apatinib 500 mg/day resulted in a reduction in mass size and partial response. She survived for more than 8 months. CONCLUSION: The present case showed the potential therapeutic effects of apatinib in patients with MPT.

Strain elastography as an early predictor of long-term prognosis in patients with locally advanced cervical cancers treated with concurrent chemoradiotherapy.

OBJECTIVE: To explore the value of strain elastography as an early predictor of long-term prognosis in patients with locally advanced cervical cancers treated with concurrent chemoradiotherapy (CCRT). METHODS: Strain elastography examinations were performed on 45 patients with locally advanced cervical cancers at 3 time points: prior to CCRT, and at 1 and 2 weeks after the start of CCRT. The maximum tumor diameter (Dmax), strain ratio (SR), and their percentage changes (ΔDmax and ΔSR) were calculated to predict long-term prognosis. Based on the results of physical examinations, Papanicolaou test, and pelvic magnetic resonance imaging, we classified patients into two groups: responders (complete remission) and non-responders (sustained disease, recurrence, or death). RESULTS: After a median follow-up of 30 months (range, 12-36 months), 36 of 45 (80%) patients were disease free. The Dmax as well as ΔDmax at 2 weeks during CCRT was able to predict the responder outcomes, with an area-under-the-curve (AUC) of 0.733 and 0.731, respectively. Furthermore, significant differences in SR and ΔSR at 1 and 2 weeks during therapy were shown between the responder and non-responder groups (all p < 0.05), and ΔSR at 2 weeks during CCRT presented with the highest AUC (0.91), yielding 88.9% sensitivity and 88.9% specificity with a selected cutoff value. CONCLUSIONS: Strain elastography may be useful as an early predictor of long-term outcomes after CCRT for patients with cervical cancer. KEY POINTS: • The D maxas well as ΔD maxat 2 weeks during CCRT can predict the responder outcomes. • The elastography parameters (SR and ΔSR) exhibited predictive values of favorable response after therapy initiation. • ΔSR at 2 weeks during CCRT held the best predictive value for the responder outcomes.

Mutation of CarO participates in drug resistance in imipenem-resistant Acinetobacter baumannii.

OBJECTIVE: Acinetobacter baumannii has become an important problem because of the high drug resistance rate. The aim of this study was to assess the antimicrobial resistance profile and explore the role of membrane porin in imipenem resistance of A baumannii. METHODS: A total of 63 isolates of imipenem-resistant A baumannii (IRAB) and 21 of imipenem-sensitive A baumannii (ISAB) were collected. Susceptibility testing to 16 kinds of antimicrobial agents was conducted by K-B method. PCR technique was used to detect carO and oprD genes, and sequencing was performed to compare the sequence between IRAB and ISAB. Three-dimensional structure model of CarO protein was established. RESULTS: While ISAB isolates presented sensitive to most classes of antibiotics, isolates of IRAB displayed much higher resistance rate except tigecycline (3.2%), cefoperazone/sulbactam (28.6%), and minocycline (30.2%). All 84 isolates were observed carrying both carO and oprD genes. Further sequencing revealed important mutations of carO gene existed in IRAB in comparison with ISAB. Meanwhile, significant differences in three-dimensional structure of carO protein molecule were also found between IRAB and ISAB. CONCLUSIONS: The drug resistance profile of IRAB is increasingly severe in clinical settings. Mutation of CarO was identified as one of the molecular mechanisms involved in imipenem resistance in A baumannii.

Strain elastography imaging for early detection and prediction of tumor response to concurrent chemo-radiotherapy in locally advanced cervical cancer: feasibility study.

BACKGROUND: To investigate the feasibility of strain elastography imaging in early detecting and predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for locally advanced cervical cancer. METHODS: Between January 2015 and June 2016, 47 patients with locally advanced cervical cancer were enrolled in a feasibility study approved by the institutional review board. All patients underwent CCRT and received strain elastography examinations at 4 time points: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Treatment response was evaluated by MRI at the time of diagnosis and immediately after CCRT. Based on the MRI findings, the treatment outcome was characterized as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Strain ratio of the normal parametrial tissue vs. cervical tumor was calculated and compared with the clinical outcome. RESULTS: Out of the 47 patients, 36 patients who completed all 4 examinations were included in the analyses: 25 were classified as CR, 11 as PR, and 0 in the SD/PD groups. Strain ratios were significantly different among the time points in both the CR group (F = 87.004, p < 0.001) and PR group (F = 38.317, p < 0.001). Strain ratios were significantly difference between the CR and PR groups (F = 7.203 p = 0.011). Strain ratios between the CR group and PR group were significantly different at 1 week after treatment initiation (p < 0.05). Compared to the baseline, a significant decrease in the CR group was observed at week 1, week 2 and post treatment (all p < 0.001), while a significant decrease in the PR group was shown in week 2 and post treatment (both p < 0.05), but not at week 1 during CCRT (p = 0.084). CONCLUSIONS: We have conducted a prospective longitudinal study to evaluate tumor response in women receiving CCRT for cervical cancers. This study has demonstrated the potential of strain elastography imaging in monitoring and early predicting tumor response induced by CCRT.

Predicting and Early Monitoring Treatment Efficiency of Cervical Cancer Under Concurrent Chemoradiotherapy by Intravoxel Incoherent Motion Magnetic Resonance Imaging.

OBJECTIVE: The aim of this study was to explore the potential of intravoxel incoherent motion magnetic resonance (MR) imaging in predicting and measuring responses to concurrent chemoradiotherapy (CCRT) in advanced cervical cancers. METHODS: Thirty-seven patients with advanced cervical cancers scheduled for CCRT underwent MR examinations including intravoxel incoherent motion sequence with 9 b values (0-800 s/mm) before CCRT, 2 and 4 weeks after the initiation of CCRT, and immediately after CCRT. Apparent diffusion coefficient, f, D, and D* values were obtained during the course. The maximum diameter of the tumor was measured to determine the treatment efficiency. RESULTS: At the end of CCRT, 25 patients were classified as complete response and 12 as partial response. The pretreatment f of cervical cancer showed its efficiency in predicting partial response and complete response with an area under receiver operating characteristic curve of 0.768. During CCRT, the apparent diffusion coefficient, D, and D* values kept on rising, whereas f increased first and then decreased after 4 weeks of CCRT. CONCLUSIONS: Intravoxel incoherent motion MR imaging held great potential in both predicting and early monitoring treatment efficiency of advanced cervical cancer under CCRT.

Early Changes of Irradiated Parotid Glands Evaluated by T1rho-Weighted Imaging: A Pilot Study.

OBJECTIVE: The aim of the study was to confirm the feasibility of T1rho-weighted imaging to evaluate the dynamic changes of parotid glands in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy. METHODS: Twenty-six NPC patients (19 men; 7 women; mean [SD] age, 48.9 [13.4] years) underwent the following 3 serial T1rho-weighted imaging: within 2 weeks before radiotherapy (RT, pre-RT), 5 weeks after the beginning of RT (mid-RT), and 4 weeks after RT (post-RT). Parotid volumes, T1rho values, mean radiation doses, and xerostomia degrees were recorded. Change rates of parotid T1rho values were correlated with parotid atrophy rates, mean radiation doses, and xerostomia degrees. RESULTS: During RT, parotid volume decreased (atrophy rate, 32.7 [8.1%] at mid-RT and 27.9 [10.0%] at post-RT compared with pre-RT; both P < 0.001) and parotid T1rho values increased (change rate, 25.0 [15.8%] at mid-RT and 30.1 [18.0%] at post-RT compared with pre-RT, both P < 0.001) significantly. The change rate of parotid T1rho value correlated with the atrophy rate significantly at post-RT (r = 0.301, P = 0.047). Intraobserver and interobserver reproducibility of parotid T1rho measurements were excellent (intraclass correlation coefficient, 0.974 and 0.956, respectively). CONCLUSIONS: Dynamic changes of radiation-induced parotid damage in NPC patients who underwent intensity-modulated radiation therapy could be noninvasively evaluated by T1rho-weighted imaging.

Three-dimensional power Doppler ultrasound in the early assessment of response to concurrent chemo-radiotherapy for advanced cervical cancer.

Background Three-dimensional power Doppler ultrasound (3D-PDU) imaging has been widely applied to the differentiation of benign and malignant cervical lesions; however, its potential value for predicting response to chemo-radiotherapy has not been fully explored. Purpose To investigate the feasibility of 3D-PDU imaging in predicting treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancer. Material and Methods Fifty-two patients with advanced cervical cancer who received CCRT underwent 3D-PDU examinations at four timepoints: pre-therapy (baseline), 1 week and 2 weeks during, as well as immediately post CCRT. Final tumor response was determined by change in tumor size using magnetic resonance imaging (MRI). Cervical tumor volumes and vascular indices were calculated and compared with the clinical outcome. Results Of the 52 patients, 32 patients who completed all four examinations were included in the analyses: 21 were classified as complete response (CR) and 11 as partial response (PR). During the treatment, the CR group showed that 3D vascular indices (VI and VFI) significantly increased at 1 week ( P = 0.028, P = 0.017, respectively) then decreased at 2 weeks and obviously decreased at therapy completion (both P < 0.001), whereas tumors significantly decreased in volume at 2 weeks after therapy initiation ( P < 0.05). However, no significant differences in 3D vascular indices values were seen in the PR group during the treatment course (all P > 0.05). Conclusion Prospective longitudinal 3D-PDU imaging may have potentials in monitoring early therapeutic response to CCRT in patients with cervical cancer.

Histogram analysis of apparent diffusion coefficient for monitoring early response in patients with advanced cervical cancers undergoing concurrent chemo-radiotherapy.

Background Apparent diffusion coefficient (ADC) histogram analysis has been widely used in determining tumor prognosis. Purpose To investigate the dynamic changes of ADC histogram parameters during concurrent chemo-radiotherapy (CCRT) in patients with advanced cervical cancers. Material and Methods This prospective study enrolled 32 patients with advanced cervical cancers undergoing CCRT who received diffusion-weighted (DW) magnetic resonance imaging (MRI) before CCRT, at the end of the second and fourth week during CCRT and one month after CCRT completion. The ADC histogram for the entire tumor volume was generated, and a series of histogram parameters was obtained. Dynamic changes of those parameters in cervical cancers were investigated as early biomarkers for treatment response. Results All histogram parameters except AUClow showed significant changes during CCRT (all P < 0.05). There were three variable trends involving different parameters. The mode, 5th, 10th, and 25th percentiles showed similar early increase rates (33.33%, 33.99%, 34.12%, and 30.49%, respectively) at the end of the second week of CCRT. The pre-CCRT 5th and 25th percentiles of the complete response (CR) group were significantly lower than those of the partial response (PR) group. Conclusion A series of ADC histogram parameters of cervical cancers changed significantly at the early stage of CCRT, indicating their potential in monitoring early tumor response to therapy.

[Change of hepatic drug metabolism enzymes in rat depression model with kidney-yang deficiency].

This study was designed to explore the impact of depression on kidney-yang deficiency in rats. Rats were repeatedly injected with hydrocortisone for 21 days to establish the depression model with kidneyyang deficiency. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were used as substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1, and CYP2D2 to test the depression impact on drug metabolism. Plasma concentrations of six CYP450 were determined by LC-MS/MS and used as pharmacokinetic parameters. Consequently, metabolism of theophylline, chlorzoxazone and tolbutamide were accelerated significantly in the model relative to the control (P < 0.01), but dextromethorphan, omeprazole and midazolam did not exhibit a significant difference. The present study suggests that depression with kidneyyang deficiency had a strong induction of CYP2E1 and moderate induction of CYP1A2, CYP2C6 in the rat model.

Evaluating early response of cervical cancer under concurrent chemo-radiotherapy by intravoxel incoherent motion MR imaging.

BACKGROUND: Intravoxel incoherent motion (IVIM) MR imaging has been applied in researches of various diseases, however its potential in cervical cancer patients has not been fully explored. The purpose of this study was to investigate the feasibility of IVIM MR imaging to monitor early treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancers. METHODS: Twenty-one patients receiving CCRT for advanced cervical cancer were prospectively enrolled. MR examinations including IVIM imaging (with 14 b values, 0 ~ 1000 s/mm(2)) were performed at 4 time points: 1-week prior to, 2-week and 4-week during, as well as immediately post CCRT (within 1 week). The apparent diffusion coefficient (ADC) maps were derived from the mono-exponential model, while the diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) maps were calculated from the bi-exponential model. Dynamic changes of ADC, D, f and D* in cervical cancers were investigated as early surrogate markers for treatment response. RESULTS: ADC and D values increased throughout the CCRT course. Both f and D* increased in the first 2 to 3 weeks of CCRT and started to decrease around 4 weeks of CCRT. Significant increase of f value was observed from prior to CCRT (f 1 = 0.12 ± 0.52) to two-week during CCRT (f2 = 0.20 ± 0.90, p = 0.002). CONCLUSIONS: IVIM MR imaging has the potential in monitoring early tumor response induced by CCRT in patients with cervical cancers.

Early evaluation of irradiated parotid glands with intravoxel incoherent motion MR imaging: correlation with dynamic contrast-enhanced MR imaging.

BACKGROUND: Radiation-induced parotid damage is one of the most common complications in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy (RT). Intravoxel incoherent motion (IVIM) magnetic resonance (MR) imaging has been reported for evaluating irradiated parotid damage. However, the changes of IVIM perfusion-related parameters in irradiated parotid glands have not been confirmed by conventional perfusion measurements obtained from dynamic contrast-enhanced (DCE) MR imaging. The purposes of this study were to monitor radiation-induced parotid damage using IVIM and DCE MR imaging and to investigate the correlations between changes of these MR parameters. METHODS: Eighteen NPC patients underwent bilateral parotid T1-weighted, IVIM and DCE MR imaging pre-RT (2 weeks before RT) and post-RT (4 weeks after RT). Parotid volume; IVIM MR parameters, including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f); and DCE MR parameters, including maximum relative enhancement (MRE), time to peak (TTP), Wash in Rate, and the degree of xerostomia were recorded. Correlations of parotid MR parameters with mean radiation dose, atrophy rate and xerostomia degree, as well as the relationships between IVIM and DCE MR parameters, were investigated. RESULTS: From pre-RT to post-RT, all of the IVIM and DCE MR parameters increased significantly (p < 0.001 for ADC, D, f, MRE, Wash in Rate; p = 0.024 for D*; p = 0.037 for TTP). Change rates of ADC, f and MRE were negatively correlated with atrophy rate significantly (all p < 0.05). Significant correlations were observed between the change rates of D* and MRE (r = 0.371, p = 0.026) and between the change rates of D* and TTP (r = 0.396, p = 0.017). The intra- and interobserver reproducibility of IVIM and DCE MR parameters was good to excellent (intraclass correlation coefficient, 0.633-0.983). CONCLUSIONS: Early radiation-induced changes of parotid glands could be evaluated by IVIM and DCE MR imaging. Certain IVIM and DCE MR parameters were correlated significantly.