Spontaneous and cyclophosphamide-enhanced metastasis inhibited by traditional Chinese medicine (TCM) herbal mixture LQ.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22209-e22209
Author(s):  
Lei Zhang ◽  
Chengyu Wu ◽  
Yong Zhang ◽  
Robert M. Hoffman

e22209 Background: Cyclophosphamide pretreatment of mice enhances metastatsis of HT1080 human fibrosarsoma cells (Cancer Res. 68, 516-520, 2008). Methods: HT1080 human fibrosarsoma cells were injected into the footpad or were injected into the epigastric cranialis vein of mice pre-treated with cyclophosphamide (CYC) or a combination of CYC and the herbal mixture LQ. The efficacy was monitored through dynamic subcellular imaging of trafficking of cancer cells in lymph nodes and blood vessels in live mice. Results: LQ significantly inhibited HT1080 spontaneous metastases to local lymph nodes in the foot-pad-injection model. In the control group, 100% of mice had lymph node metastasis, compared to 12.5% of the mice in the LQ treatment group. LQ also significantly inhibited CYC-enhanced experimental metastasis in the epigastric cranialis vein injection model. LQ prolonged the overall survival of mice in the spontaneous-lymph-node metastatic footpad-injection model. Conclusions: The TCM herbal mixture LQ shows promis to inhibit metastasis and will be further tested in other metastatic models.

Author(s):  
Toru Odate ◽  
Naoki Oishi ◽  
Masataka Kawai ◽  
Ippei Tahara ◽  
Kunio Mochizuki ◽  
...  

AbstractMost anaplastic thyroid carcinomas (ATCs) arise from papillary thyroid carcinoma (PTC). This process is also called anaplastic transformation, and the morphological harbingers of this phenomenon in nodal recurrence have not been assessed systematically. For this reason, the current study focused on features of 10 PTCs with regional lymph node recurrence that was accompanied with disease progression due to anaplastic transformation in at least one of the nodal recurrences. The findings of additional 19 PTCs which recurred without anaplastic transformation after ≥ 10 years of follow-up served as the control group. There were no clinicopathological differences between the two groups at initial surgery including age, gender, tumor size, lymph node metastasis, distant metastasis, extrathyroidal extension, histologic subtype, and treatment. The median time from the initial thyroid surgery to anaplastic transformation in the nodal recurrence was 106 months (range 6 to 437 months). Mutational analyses showed recurrent PTCs with anaplastic transformation had a high prevalence of BRAFV600E mutation (8/9) and TERT promoter mutation (9/9), both of which were detected in primary tumors. PIK3CAH1047R mutation was detected in one case. No case had RAS mutation. Nineteen recurrent PTCs without anaplastic transformation harbored BRAFV600E mutation and seventeen of these had TERT promoter mutation. Unlike primary tumors with subsequent nodal anaplastic transformation, TERT promoter mutation was only present in the metastatic nodal recurrence from 4 patients without transformation. No patients had neither high-grade features (necrosis and increased mitotic activity) nor solid/insular growth or hobnail cell features in their primary tumors. In the group of patients with transformation, 3 had solid/insular growth in the lymph node metastasis at the time of primary tumor resection (one displaying nuclear features of PTC and solid growth with increased mitotic activity, one with insular component consistent with poorly differentiated carcinoma component, and one displaying nuclear features of PTC and solid growth), and additional 2 patients had solid/insular growth with no high-grade features or poorly differentiated carcinoma component at the time of subsequent nodal recurrence prior to anaplastic transformation. Hobnail cell features were exclusively seen in subsequent metastatic lymph nodes prior to anaplastic transformation. The control group lacked solid/insular growth and hobnail cell features in the metastatic nodal disease. Aberrant p53 expression and loss of TTF-1 featured tumor components with anaplastic transformation. This series identified a subset of recurrent PTCs with TERT promoter mutation was prone to undergo anaplastic transformation, and that solid/insular growth and hobnail cell features were morphological predictors of anaplastic transformation in the nodal recurrence.


Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 757
Author(s):  
Sanaz Samiei ◽  
Renée W. Y. Granzier ◽  
Abdalla Ibrahim ◽  
Sergey Primakov ◽  
Marc B. I. Lobbes ◽  
...  

Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51–68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41–0.74 and 0.48–0.89 in the training cohorts, respectively, and between 0.30–0.98 and 0.37–0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.


Author(s):  
Yoonhyeong Byun ◽  
Kyoung‐Bun Lee ◽  
Jin‐Young Jang ◽  
Youngmin Han ◽  
Yoo Jin Choi ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Lixia Zhang ◽  
Qiang Chen ◽  
Jing Hu ◽  
Yue Chen ◽  
Chenglong Liu ◽  
...  

CSCC is a systemic disease involving polygenic alteration and multiple steps, and HIF and VEGF are closely associated with tumorigenesis. Specimens surgically resected from 64 cases of CSCC and 22 cases of normal cervical tissue were selected randomly to detect the expression of HIF-2αand VEGF in CSCC for exploring their clinical significance; information regarding the age, lymph node metastasis, and FIGO staging were collected as well; expression of HIF-2αand VEGF was detected by qPCR and immunohistochemistry. We found that the expression of HIF-2αand VEGF mRNA in CSCC was significantly higher than that of normal cervical tissues and showed a positive correlation between them. The positive rates of HIF-2αand VEGF protein expression in CSCC and normal cervical tissues were 93.8% and 18.2%, respectively, with correlation between them. The expression of both HIF-2αand VEGF mRNA did not relate closely to age but the FIGO staging and lymph node metastasis. Compared with the counterpart control group, CSCC tissues with high FIGO staging and lymph node metastasis had a higher level of HIF-2αand VEGF mRNA expression. So, HIF-2αand VEGF were overexpressed in CSCC, which has a great clinical significance for its diagnosis.


2020 ◽  
Author(s):  
Xindi Su ◽  
Fang Chai ◽  
Benrui Lin ◽  
Lu Qu ◽  
Keyi Liu ◽  
...  

Abstract Objective. To investigate the application of carbon nanoparticles in lymph node dissection and parathyroid gland protection during thyroid cancer surgery. Subjects and Methods. Retrospective analysis was performed on 282 cases of thyroid cancer surgery in our hospital from 2018 to 2019. All patients underwent total thyroidectomy and cervical central lymph node dissection. Nanocarbon was not used in the control group, but was used in the experimental group. The general situation of the patients, the number of postoperative lymph nodes and the number of metastasis were collected, and the differences between serum parathyroid hormone and blood calcium were compared before and on the 3rd and 30th day after surgery. Results. There was no difference in age, sex and TNM stage between the two groups (P > 0.05). The number of metastatic lymph nodes in the experimental group (9.80 ± 4.80) was different from that in the control group (6.95 ± 3.86) (P < 0.05), and the number of metastatic lymph nodes in the experimental group was different from that in the control group (χ2 = 14.968, P < 0.05). There was no difference in blood calcium and PTH between the two groups before and at 3 and 30 days after surgery (P > 0. 05). Conclusion. The application of carbon nanoparticles in thyroid cancer surgery can significantly increase the number of lymph nodes seized and the positive rate of metastatic lymph node removal, but the protection of parathyroid gland is not obvious.


2021 ◽  
Author(s):  
Xiaoxiao Wang ◽  
Cong Li ◽  
Mengjie Fang ◽  
Liwen Zhang ◽  
Lianzhen Zhong ◽  
...  

Abstract Background:This study aimed to evaluate the value of radiomic nomogram in predicting lymph node metastasis in T1-2 gastric cancer according to the No. 3 station lymph nodes.Methods:A total of 159 T1-2 gastric cancer (GC) patients who had undergone surgery with lymphadenectomy between March 2012 and November 2017 were retrospectively collected and divided into a primary cohort (n = 80) and a validation cohort (n = 79). Radiomic features were extracted from both tumor region and No. 3 station lymph nodes (LN) based on computed tomography (CT) images per patient. Then, key features were selected using minimum redundancy maximum relevance algorithm and fed into two radiomic signatures, respectively. Meanwhile, the predictive performance of clinical risk factors was studied. Finally, a nomogram was built by merging radiomic signatures and clinical risk factors and evaluated by the area under the receiver operator characteristic curve (AUC) as well as decision curve.Results: Two radiomic signatures, reflecting phenotypes of the tumor and LN respectively, were significantly associated with LN metastasis. A nomogram incorporating two radiomic signatures and CT-reported LN metastasis status showed good discrimination of LN metastasis in both the primary cohort (AUC: 0.915; 95% confidence interval [CI]: 0.832-0.998) and validation cohort (AUC: 0.908; 95%CI: 0.814-1.000). The decision curve also indicated its potential clinical usefulness.Conclusions:The nomogram received favorable predictive accuracy in predicting No.3 station LN metastasis in T1-2 GC, and could assist the choice of therapy.


2020 ◽  
Author(s):  
Yuhua Zhao ◽  
Gong Li ◽  
Lei Gao

Abstract Background: This study aimed to evaluate the therapeutic efficacy of extended-field intensity-modulated radiotherapy (EF-IMRT) and dosage boost for positive lymph nodes, prognostic factors, treatment failure, and toxicity for Federation of Gynecology and Obstetrics (FIGO) stage IIICr and IVA cervical cancer patients with positive regional lymph nodes.Methods: We retrospectively evaluated 34 patients with stage IIICr and IVA who had received treatment in our institute between 2013 and 2016. Patients with stage IVA cervical cancer who had been enrolled in the analysis all had positive regional lymph nodes (pelvic or/and para-aortic). All 34 patients were treated with EF-IMRT and simultaneously integrated boost-IMRT (SIB-IMRT) for lymph node metastasis with concurrent chemotherapy and brachytherapy. Positive regional lymph nodes (short-axis diameter ≥5 mm in computed tomography [CT] or magnetic resonance imaging [MRI]) remaining after SIB-IMRT were then treated with sequential boost-IMRT (SeB-IMRT). The prognostic factors for overall survival (OS); disease-free survival (DFS); local control rate (LCR); regional control rate (RCR); distant metastasis-free survival (DMFS), including age, FIGO stage, pretreatment hemoglobin (HB) level, tumor size, para-aortic lymph node (PALN) metastasis, point A equivalent dose in 2-Gy fractions (EQD2 dose), concurrent chemotherapy, and adjuvant chemotherapy cycles, were analyzed.Results: Complete response (CR) was achieved in 31 (91.2%) patients with acceptable adverse effects. Notably, the three-year OS, DFS, LCR, RCR, DMFS for these patients were 73.5%, 70.6%, 88.1%, 87.9%, and 81.6%, respectively. In particular, the three-year OS, DFS, LCR, RCR, and DMFS of patients with positive PALNs was 41.7%, 33.3%, 65.6%, 72.2%, and 60.2%, respectively. The corresponding values in patients without positive PALNs were 90.9%, 90.9%, 100%, 95.5%, and 90.9%, respectively.Conclusions: Our study suggested that the EF-IMRT and nodal dosage boost decreased regional node failure and that patients with stage IIIC1r and IVA cervical cancer without PALN metastasis who received EF-IMRT and SIB-IMRT with or without SeB-IMRT had a significant survival advantage in terms of the DFS and OS.


2021 ◽  
Vol 11 ◽  
Author(s):  
Qingke Duan ◽  
Chao Tang ◽  
Zhao Ma ◽  
Chuangui Chen ◽  
Xiaobin Shang ◽  
...  

Gastroesophageal junction (GEJ) cancer is a tumor that occurs at the junction of stomach and esophagus anatomically. GEJ cancer frequently metastasizes to lymph nodes, however the heterogeneity and clonal evolution process are unclear. This study is the first of this kind to use single cell DNA sequencing to determine genomic variations and clonal evolution related to lymph node metastasis. Multiple Annealing and Looping Based Amplification Cycles (MALBAC) and bulk exome sequencing were performed to detect single cell copy number variations (CNVs) and single nucleotide variations (SNVs) respectively. Four GEJ cancer patients were enrolled with two (Pt.3, Pt.4) having metastatic lymph nodes. The most common mutation we found happened in the TTN gene, which was reported to be related with the tumor mutation burden in cancers. Significant intra-patient heterogeneity in SNVs and CNVs were found. We identified the SNV subclonal architecture in each tumor. To study the heterogeneity of CNVs, the single cells were sequenced. The number of subclones in the primary tumor was larger than that in lymph nodes, indicating the heterogeneity of primary site was higher. We observed two patterns of multi-station lymph node metastasis: one was skip metastasis and the other was to follow the lymphatic drainage. Taken together, our single cell genomic analysis has revealed the heterogeneity and clonal evolution in GEJ cancer.


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