Mutant Allele Frequency-Based Intra-Tumoral Genetic Heterogeneity Related to the Tumor Shrinkage Mode After Neoadjuvant Chemotherapy in Breast Cancer Patients.

The shrinkage mode of tumor extent after neoadjuvant chemotherapy (NAC) is an important index to evaluate the odds of breast-conserving surgery. However, there is no sufficient measurement to predict the shrinkage mode after NAC. In this study, we analyzed 24 patients' formalin-fixed, paraffin-embedded samples before and after treatment and analyzed 456 cancer-related genes panel by using target next-generation sequencing. Meanwhile, the pathological shrinkage mode was reconstructed in three dimensions after surgery, and the genetic heterogeneity level was estimated by mutant-allele tumor heterogeneity (MATH). We measured the genetic intra-tumor heterogeneity and explored its correlation with the shrinkage mode after NAC. A total of 17 matched pair samples of primary tumor tissue and residual tumor tissue were successfully accessed. It was found that the most common mutated genes were TP53 and PIK3CA in both samples before and after NAC, and no recurrent mutations were significantly associated with the shrinkage mode. Besides, the MATH value of formalin-fixed, paraffin-embedded samples before and after NAC was analyzed by the area under the curve of the receiver operating characteristic, and it is feasible to classify patients into concentric shrinkage mode and non-concentric shrinkage mode in NAC based on the MATH threshold of 58. Our findings indicate that the MATH value was associated with the shrinkage mode of breast cancer in a non-linear model. Patients with the MATH value below the threshold of 58 before and after NAC displayed a concentric shrinkage mode. The area under the curve was 0.89, with a sensitivity of 0.69 and specificity of 1. Our study might provide a promising application of intra-tumor heterogeneity that is measured by MATH to make a choice of surgery.

Meta-Analysis of Shrinkage Mode After Neoadjuvant Chemotherapy for Breast Cancers: Association With Hormonal Receptor.

Background: Patients with concentric shrinkage mode after neoadjuvant chemotherapy (NAC) is considered to be ideal candidates for breast conserving treatment (BCT). While, what proportion of patients would represent CSM have not been well defined. This study was conducted to pool the rates of concentric shrinkage mode (CSM) in patients undergoing NAC, determine the impact of hormonal receptor on the shrinkage mode after NAC and estimate the rates of the CSM in various subgroups. Methods: We conducted a systematic review following the guidelines for Meta-Analyses and Systematic reviews for the PRISMA guidelines. We systematically searched the literature about shrinkage mode after NAC from PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang database published from January 2002 to June 2020 on breast cancer shrinkage mode after NAC and carefully screened the literature by using eligibility criteria: (1) patients with primary breast cancer treated with NAC; (2) publications with available data of shrinkage mode measured by magnetic resonance imaging (MRI), or data of pathology and hormonal receptor. The association between shrinkage mode and hormonal receptor was estimated using Stata 15.1 software. Results: This analysis included a total of 2434 tumors from 23 papers. The included studies were heterogeneous (I2 = 89.4%, P<0.01). Random effects model was used to estimate the overall rates of CSM: 56.6% [95%CI (50.5%, 62.7%)]. According to the analysis of hormonal receptor, 10 of the paper was included for HR+ (hormone receptor positive) type analysis and the rate of CSM for HR+ type was 45.7% [95%CI (36.4%, 55.0%)]; 9 of the paper was used for HR- type (hormone receptor negative) analysis and the incidence of HR-CSM is 63.1% [95%CI (50.0%, 76.1%)]; with HR+ type as the control, the OR of the HR- CSM rate is 2.32 (1.32, 4.08) folds of HR+ type. From subgroup analyses, the CSM% of luminal A, luminal B, Her2+, and triple negative were 29.7% (16.5%, 42.8%); 47.2% (19.1%, 75.3%); 59.0% (39.7%, 78.3%); 66.2% (52.8%, 79.6%), respectively. Conclusions: Breast cancer patients undergoing NAC did not get an ideal odds ratio of CSM. The incidence of CSM in breast cancer after NAC is associated with hormonal receptor. Patients with triple-negative breast cancers have the highest rates of CSM after NAC. More care should be taken to select patients with the luminal subtypes for BCT throughout NAC.

Is Pathologic Complete Response the Surrogate in Primary Gastric Angiosarcoma Undergoing Doxorubicin-Based Neoadjuvant Chemotherapy? A Case Report.

INTRODUCTION: Angiosarcoma is a malignant tumor with low incidence. Especially in the advanced tumors, there is still a lack of knowledge of evidence-based medicine. CASE PRESENTATION: We report a case of a 55-year-old woman with abdominal pain of 2 months of duration, which had increased in severity for 2 weeks prior to the presentation. The diagnosis is primary gastric angiosarcoma. We performed multiple disciplinary team (MDT), and doxorubicin-based neoadjuvant chemotherapy (NAC) was proposed. After two cycles of NAC, a computed tomography (CT) scan showed complete regression compared with the previous scan. An open surgery was done, and surgical specimens were confirmed as a pathological complete response (PCR) by pathological and immunohistochemical examination, but unfortunately, the patient suffered a relapse after the surgery in 3 months. CONCLUSION: Repeated endoscopic biopsy and biopsy specimen examinations can improve accuracy in diagnosis. It seems that NAC could be a candidate for advanced primary gastric angiosarcomas. But after the rapid relapse, we are wondering whether pathologic complete response is the surrogate in primary gastric angiosarcoma undergoing NAC.

Biotransformation of 5-hydroxymethylfurfural into 2,5-dihydroxymethylfuran by Ganoderma sessile and toxicological assessment of both compounds.

Biotransformation has the advantages of low cost and environmental protection and is a preferred method for production of compounds. At present, most 2,5-dihydroxymethylfuran (DHMF) is synthesized by chemical methods. In this study, 12.008 µg/mL DHMF was produced from 9.045 µg/mL 5-hydroxymethylfurfural (5-HMF) with a yield of 1.33 g/g using the crude enzymes from fungus Ganoderma sessile. To elucidate the toxic potential for both compounds, cytotoxicity tests and acute toxicity were evaluated respectively. 5-HMF induced weak cytotoxicity in HCT-8, A549 and SGC-7901 cells and DHMF exerted no cytotoxicity on HCT-8 while induced inhibition proliferation of A549 and SGC-7901 cells. The acute toxicity study showed no mortality happened in any group even at the single dose of 2000 mg/kg body weight. These results suggest it is feasible to convert 5-HMF to DHMF via crude enzymes from fungus G. sessile under mild condition, and that DHMF displays a potential effect of antitumor in vitro with little acute toxicity.

Inhibition of CXCR4 regulates epithelial mesenchymal transition of NSCLC via the Hippo-YAP signaling pathway.

CXCR4 has been shown to play a key role in the metastasis of non-small cell lung cancer (NSCLC). And CXCR may be associated with the Hippo-Yes kinase-associated protein (YAP) pathway, thus involving in the occurrence and progression of NSCLC. This study aims to investigate the effect of CXCR4 inhibition on epithelial-mesenchymal transition (EMT), invasion and migration of NSCLC cells via the Hippo-YAP pathway. QRT-PCR and Western blot were employed to detect CXCR4 expression in NSCLC cell lines. A549 and H1299 cells were treated with WZ811 (0, 10, 30, and 50 µM), and A549 cells were also divided into the Control, WZ811, YAP siRNA, and WZ811 + YAP groups. Wound-healing, Transwell assay, immunofluorescent staining, and a luciferase reporter gene assay were performed in this experiment. Compared with human bronchial epithelial (HBE) cells, CXCR4 expression was up-regulated in NSCLC cell lines. WZ811 increased E-cadherin; decreased expression of Twist, vimentin, Snail, p-YAP, CTGF, and BIRC5; blocked GTIIC reporter activity; and reduced migration and invasion of A549 cells, all in a dose-dependent manner. YAP siRNA had a similar effect to WZ811 by inhibiting EMT, invasion and migration of A549 cells. However, compared with A549 cells in the YAP siRNA and WZ811 groups, cells in the WZ811 + YAP group showed a dramatically enhanced EMT phenotype as well as invasion and migration abilities. Inhibition of CXCR4 may reduce EMT, invasion and migration of NSCLC cells, thereby providing a new therapeutic target for NSCLC.

[High-risk factors for quality of general movements in infants].

OBJECTIVE: To investigate the high-risk factors for the quality of general movements (GMs), which has a predictive value for brain dysfunction in infants. METHODS: A total of 618 infants in the stage of writhing movements and 539 infants in the stage of fidgety movements were selected separately for the evaluation of GMs. The high-risk factors for the quality of GMs in infants were analyzed by ANOVA, chi-square test, and multivariate logistic regression. RESULTS: Multivariate logistic regression analysis showed that the factors significantly associated with the quality of GMs in the stage of writhing movements were gestational age (OR=0.762, P<0.001), birth weight (OR=0.264, P<0.001), severe asphyxia (OR=2.445, P=0.012), and intrauterine distress (OR=4.865, P<0.001); the factors significantly associated with the quality of GMs in the stage of fidget movements were gestational age (OR=0.786, P=0.003), birth weight (OR=0.217, P<0.001), severe asphyxia (OR=3.765, P=0.001), and hyperbilirubinemia (OR=2.640, P=0.028). CONCLUSIONS: Low gestational age, low birth weight, severe asphyxia, hyperbilirubinemia and intrauterine distress are high-risk factors for abnormal GMs in infants, and early screening and intervention should be performed to reduce the incidence of abnormal nervous system sequelae.