Radiomic Model for Determining the Value of Elasticity and Grayscale Ultrasound Diagnoses for Predicting BRAFV600E Mutations in Papillary Thyroid Carcinoma.

BRAFV600E is the most common mutated gene in thyroid cancer and is most closely related to papillary thyroid carcinoma(PTC). We investigated the value of elasticity and grayscale ultrasonography for predicting BRAFV600E mutations in PTC. Methods: 138 patients with PTC who underwent preoperative ultrasound between January 2014 and 2021 were retrospectively examined. Patients were divided into BRAFV600E mutation-free group (n=75) and BRAFV600E mutation group (n=63). Patients were randomly divided into training (n=96) and test (n=42) groups. A total of 479 radiomic features were extracted from the grayscale and elasticity ultra-sonograms. Regression analysis was done to select the features that provided the most information. Then, 10-fold cross-validation was used to compare the performance of different classification algorithms. Logistic regression was used to predict BRAFV600E mutations. Results: Eight radiomics features were extracted from the grayscale ultrasonogram, and five radiomics features were extracted from the elasticity ultrasonogram. Three models were developed using these radiomic features. The models were derived from elasticity ultrasound, grayscale ultrasound, and a combination of grayscale and elasticity ultrasound, with areas under the curve (AUC) 0.952 [95% confidence interval (CI), 0.914-0.990], AUC 0.792 [95% CI, 0.703-0.882], and AUC 0.985 [95% CI, 0.965-1.000] in the training dataset, AUC 0.931 [95% CI, 0.841-1.000], AUC 0. 725 [95% CI, 0.569-0.880], and AUC 0.938 [95% CI, 0.851-1.000] in the test dataset, respectively. Conclusion: The radiomic model based on grayscale and elasticity ultrasound had a good predictive value for BRAFV600E gene mutations in patients with PTC.

Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met.

As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer.

[Effect of Fuzheng Peiben therapy on dendritic cell in patients with breast cancer].

OBJECTIVE: To investigate the repairing mechanism of Fuzheng Peiben Therapy on cellular immunofunction in patients with breast cancer on cellar and molecular level. METHODS: The tumor tissue and axillary lymph node samples were evaluated with the flow cytometry for CD83, CD80, CD86 before and after neoadujvant therapy. RESULTS: The levels of CD83, CD80, CD86 were singificantly decreased in group A (treated with surgery only), B (treated with neoadujvant chemotherapy plus surgery) and C (treated with neoadujvant chemotherapy plus surgery with shenqi Fuzheng Injection) compared with that in normal team (P < 0.05 or 0.01); The levels of CD83, CD80, CD86 were significantly decreased in group A, B and C compared between before and after neoadujvant chemotherapy (P < 0.05 or 0.01); They were not significantly decreased between group A and group C (P > 0.05). CONCLUSION: The cellular immunity was inpaired considerably by neoadujvant chemotherapy. Neoadjuvant chemotherapy combined with Shenqi Fuzheng Injection can enhance the cellular immunity considerably.

[Phase I/II clinical trial of weekly administration of docetaxel plus cisplatin for advanced non-small cell lung cancer].

OBJECTIVE: The purpose of this phase I/II study is to investigate the safety/toxicity profile of weekly administration of docetaxel in combination with cisplatin for the chemo-naive patients with advanced non-small cell lung cancer (NSCLC), and to evaluate the efficacy of this regime. METHODS: In phase I trial, 15 patients were included. IV infusion of escalating doses of docetaxel consisting of four levels from 25 to 40 mg/m2 (25, 30, 35, 40 mg/m2) on D1, 8, 15 and cisplatin of 75 mg/m2 on D1 was administered. The regime was repeated every 4 weeks. Blood samples were obtained on D1, 15 in the first cycle to measure the PK. Dose limiting toxicity (DLT) was determined in cycle 1 and defined as any grade 3 non-hematologic toxicity which could not be reverted into grade less than grade 2 within 4 days or any grade 4 hematologic toxicity. Eighty-three patients completed their phase II study with administration of docetaxel at a dose of 35 mg/m2 based on the data of phase I trial. RESULTS: In the phase I trial, grade 3/4 neutropenia was mainly observed in patients who received docetaxel of 40 mg/m2 (level 4) with one patient suffering from an infection signifying dose limiting toxicity (DLT). Non-hematological toxicities including nausea/vomiting, alopecia, fluid retension and asthenia were tolerable. Based on these data, the maximum tolerence dose (MTD) did not reach the level of weekly giving docetaxel at a dose of 40 mg/m2 in combination with cisplatin 75 mg/m2 every 4 weeks. The pharmacokinetic/dynamics results There was no statistically significant difference between clearance value among the 4 dose levels of docetaxel from 25 to 40 mg/m2 when measured by Cmax and AUC. The pharmacokinetics of docetaxel was not influenced by the presence of co-administration of cisplatin when compared D1 with D15 as based on CmaxN, AUCN and CL. In the phase II trial, totally 83 patients received 216 cycles of chemotherapy. One CR (complete response) and 22 PR (partial response) were achieved with an objective response rate of 27.7% in this series and 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3-34 months). Hematologic toxicities were the major side effects, though most were mild; grade III/IV neutropenia developed in 15%. The common non-hematologic toxicities were nausea, vomiting and asthenia. CONCLUSION: Weekly consecutive administration of docetaxel on D1, 8, 15 for 3 weeks plus cisplatin on D1 is tolerable and effective with minimal myelosuppression in chemo-naive patients with advanced NSCLC.

[Effects of neoadjuvant chemotherapy on estrogen and progesterone receptors and HER-2 in breast cancer].

OBJECTIVE: To study the effect of neoadjuvant chemotherapy on estrogen receptor (ER), progesterone receptor (PR), and HER-2 expression in patients with breast cancer. METHODS: From 59 breast cancer patients treated with neoadjuvant chemotherapy and 33 without neoadjuvant therapy (control), core biopsy samples before the chemotherapy or surgery and surgical specimens were obtained for assay of ER, PR, and HER-2 expression. RESULTS: Quantitative alteration of ER expression occurred in 37.29% (22/59) of the patients after neoadjuvant chemotherapy and in 15.15% (5/33) of the control patients, showing statistically significant difference between the two groups (P<0.05), but the changes in ER expression status (conversion between positivity/negativity ratio) exhibited no significant difference. After the surgery, quantitative changes in PR expression was noted in 23.73% (14/59) of patients with neoadjuvant chemotherapy, without significant difference from those in the control group or changes in the expression status. Similarly, the changes in HER-2 expression seen in 13.56% (8/59) of the patients with chemotherapy was also comparable with the control group, without significant changes in the expression status. CONCLUSIONS: Significant changes occur in ER receptor expression after neoadjuvant chemotherapy in patients with breast cancer, but such changes do not affect the ER status. Neoadjuvant chemotherapy has no significant effects on PR and HER-2 expression in breast cancer patients.