A near-infrared fluorescent probe for the detection of Cu2+ in Chinese herbal medicine and imaging in living cells.

Copper is one of the common among the heavy metal pollution in Chinese herbal medicine (CHM). So, it is essential to develop rapid and accurate testing method to quantify the Cu2+ content in CHM. Herein, we prepared a coordination-based near-infrared fluorescent probe (NRh6G-FA) by introducing a hemicyanine dye in rhodamine 6G scaffold. NRh6G-FA had a high sensitivity, anti-interference performance, fast response (within 60 s), visualization (from light yellow to green) for Cu2+ and excellent sensing performance for the detection of Cu2+ at low concentrations (LOD = 0.225 µM). The most likely mechanism was verified on the basis of Job's plot, ESI-HRMS and DFT calculations. NRh6G-FA could be successfully applied for the detection and "naked eye" recognition of Cu2+ in CHM samples. Moreover, NRh6G-FA was used to visualize Cu2+ in living MCF-7 cells by confocal fluorescence imaging.

Novel tetranuclear grid-like Zn(II) complexes derived from dihydrazone pyrimidine derivatives as antitumor agents.

Due to the antitumor properties, Zn(II) complexes have attracted more and more attention. Herein, three novel tetranuclear Zn(II) complexes 1-3 based on dihydrazone pyrimidine derivatives H2L1-H2L3 were synthesized and characterized using IR spectroscopy, 1H NMR spectroscopy, single crystal X-ray diffraction analysis, XRD, TG and elemental analysis. Single crystal X-ray diffraction analysis revealed that 1-3 all displayed a [2 × 2] grid-like topology. The stability in solution, lipophilicity, confocal imaging and antitumor activities were investigated. Complexes 1-3 displayed high structural stability, membrane permeability and different lipophilicities. They can target mitochondria due to the cation charge. The MTT assay indicated that all of them exhibited stronger antiproliferative activity than the corresponding derivatives H2L1-H2L3 and the well-known cisplatin against all the selected tumor cells (BGC-823, BEL-7402, MCF-7 and A549), with IC50 values ranging from 2.83 µM to 7.97 µM. AO/EB double staining, flow cytometry and ROS detection suggested that complexes 1 and 2 could induce BGC-823 apoptosis in a dose-dependent manner. UV-Vis spectra, CD spectra, viscosity analysis and molecular docking revealed that complexes 1 and 2 interact with DNA mainly via partial intercalation and groove binding. Tetranuclear [2 × 2] grid-like Zn(II) complexes have the potential to be promising antitumor agents in the future.

Combining Anti-epidermal Growth Factor Receptor (EGFR) Therapy with Immunotherapy in Metastatic Colorectal Cancer (mCRC).

INTRODUCTION: Monoclonal antibodies binding the EGFR, such as cetuximab and panitumumab, have been extensively used as targeted therapy for the treatment of mCRC. However, in clinical practice, it has been found that these treatment options have some limitations and fail to fully exploit their immunoregulatory activities. Meanwhile, because of the limited effects of current treatments, immunotherapy is being widely studied for patients with mCRC. However, previous immunotherapy trials in mCRC patients have had unsatisfactory outcomes as monotherapy. Thus, combinatorial treatment strategies are being researched. AREAS COVERED: The authors retrieved relevant documents of combination therapy for mCRC from PubMed and Medline. This review elaborates on the knowledge of immunomodulatory effects of anti-EGFR therapy alone and in combination with immunotherapy for mCRC. EXPERT OPINION: Although current treatment options have improved median overall survival (OS) for advanced disease to 30 months, the prognosis remains challenging for those with metastatic disease. More recently, the combination of anti-EGFR therapy with immunotherapy has been shown activity with complementary mechanisms. Hence, anti-EGFR therapy in combination with immunotherapy may hold the key to improving the therapeutic effect of refractory mCRC.

Clinical features and prognostic factors of pulmonary carcinosarcoma: A nomogram development and validation based on surveillance epidemiology and end results database.

Background: Pulmonary carcinosarcoma (PCS) is a rare but aggressive malignant disease in the lung. It is characterized by coexisting histologic elements of carcinomatous and sarcomatous components. This study aimed to comprehensively understand the clinical features of PCS and develop a nomogram for prognostic prediction of PCS patients. Methods: Data were collected from the Surveillance Epidemiology and End Results (SEER) database between 1975 and 2018. Propensity-score matching (PSM) was used to match the demographic characteristic of the PCS vs. pulmonary sarcoma (PS). Cancer-specific survival (CSS) and overall survival (OS) were the main endpoints of the survival of patients and were evaluated using the Kaplan Meier curves and Cox proportional hazards regression. We further randomly split enrolled PCS patients from SEER into the training and validation sets. All independent predictors for OS of the training set were integrated to create a predictive nomogram. The performance of the nomogram was determined by discrimination, calibration ability, clinical usefulness, and risk stratification ability both in the training and validation cohorts. In addition, the clinical data of PCS patients from the West China Hospital were also retrospectively analyzed by this model. Results: A total of 428 PCS patients and 249 PS patients were enrolled from SEER. Compared to pure PS, PCS was associated with significantly better survival in the unmatched cohorts, whereas non-significantly better survival after PSM. In subgroup analysis, PCS showed significantly worse survival than pure PS in subgroups among the race, marital status, and radiation treatment. A nomogram was constructed for PCS patients' survival prediction by combining the independent risk factors, including gender, stage, surgery, radiation, and chemotherapy. The nomogram showed good discrimination, calibration, and predictive power in the training and validation sets. Risk stratification analysis indicated that the nomogram scores efficiently divided PCS patients into low and high-risk groups. Conclusion: PCS is a rare malignant disease of the lung with distinct clinical features. It had a comparable survival compared with pure PS in the matched cohorts. In addition, a nomogram was developed and validated for predicting the OS in PCS patients.

Clinical characteristics and prognostic factors of anal adenocarcinoma: a nomogram development based on SEER database and validation in the WCH database.

PURPOSE: The purpose of this study was to comprehensively understand anal canal adenocarcinomas (AA) and develop a nomogram for prognostic prediction of AA. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (the year 2004-2015). An external validation set was collected from West China Hospital (WCH) databases. Propensity-score matching (PSM) was performed to balance the demographic characteristic. A novel nomogram was developed to estimate individual survival probability and its performance was validated using the concordance index (C-index), calibration curves, and decision curve analyses (DCA). RESULTS: A total of 7901 patients were enrolled including 749 AA patients and 7152 squamous cell carcinomas of the anal canal (ASCC) patients. Before PSM, patients with AA had shorter cancer-specific survival (CSS) and OS than those with ASCC. However, after PSM, patients with AA were related to a favorable OS (p < 0.001), but a comparable CSS (p = 0.140) to those with ASCC. Age, sex, grade, surgery, and M stage were the independent prognostic factors of CSS for AA and were included in the establishment of a novel nomogram. Patients from the WCH database (n = 112) were used as an external validation cohort. The C-index of the nomogram was 0.78 and 0.735 in internal and external validation, respectively, which suggested the good discrimination power of the model. Furthermore, calibration curves and DCA suggested good agreement between the predicted and actual survival. Lastly, a risk classification system based on a nomogram revealed the reliability of the novel model. CONCLUSION: AA and ASCC had distinct clinical features. AA was associated with a better prognosis than ASCC after PSM. The model of nomogram showed an accurate predictive ability for prognostic factors of AA patients.

[Application of pedicle fat flap for defect repair in breast-conserving surgery of breast cancer].

OBJECTIVE: To evaluate the cosmetic outcomes of applying pedicle fat flap below breast fold for repairing inferior quadrant defect in breast-conserving surgery. METHODS: From May 2009 to July 2011, 18 cases of breast cancer at our hospital were recruited. All cases underwent breast-conserving procedures and achieved negative margin by frozen section examination. Then pedicle fat flap below breast fold was applied to reshape breast defect. All of them were of females with a median age of 43 years (range: 33 - 59). The median tumor size was 2.5 cm (range: 2.0 - 3.0). All tumors were located at the inferior quadrant of breast. All of them received whole breast radiotherapy and adjuvant chemotherapy. And 10 cases with positive estrogen receptor had adjuvant endocrine therapy. They were followed up at one-month postoperatively. Upon the completion of chemotherapy and radiotherapy, then follow-up was once every 4 months. The cosmetic outcomes and disease relapse were observed. RESULTS: All pedicle fat flaps survived without necrosis. After a median follow-up period of 15 months, all survived disease-free. Fat liquefaction was observed in 2 cases. The whole breast radiotherapy had no significant effect on pedicle fat flap. The rate of good cosmetics was 88.9%. And their subjective satisfactory rate was 100.0%. CONCLUSION: Both satisfactory aesthetic outcome and good efficacy are obtained with pedicle fat flap below breast fold for tumors located at the inferior quadrant of breast.