Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report.

A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

Neoadjuvant therapy with anlotinib in a locally advanced and pulmonary metastasis PTC patient harboring TERT promoter and BRAFV600E mutations: a case report

SUMMARY A 71-year-old woman with recurrent papillary thyroid carcinoma (PTC) was referred to our hospital. A computed tomography scan revealed extensive recurrence in the neck, invading sternocleidomastoid muscle, internal jugular vein, sternal end of the clavicle, strap muscle and skin; and lateral compartment and subclavian lymph nodes were also involved. Multiple pulmonary micrometastases also noticed. The tumor was considered unresectable; however, the patient was unwilling to accept highly invasive surgery. Therefore, we initiated neoadjuvant therapy with anlotinib, 12mg p.o. daily with a 2-week on/1-week off regimen. The tumor shrunk to resectable state after 4 cycles of treatment, and after 3 weeks of withdrawal, successful surgical resection without gross tumor residual was performed. Pathology confirmed as classic PTC harboring coexistent TERT promoter and BRAFV600E mutations by NGS. After anlotinib therapy, apoptosis induction was observed, and proliferation increased, which was due to three weeks of anlotinib withdraw. Structual recurrence was recorded at 6 months after operation due to no further treatment was taken. Our finding suggests that anlotinib could represent as a good treatment option for patients with locally advanced (with or without distant metastasis) PTC; Anlotinib treatment resulted in sufficient reduction of the tumor mass to enable total thyroidectomy and radioactive iodine treatment, providing long-term control of the disease.

Errate: Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits.

In Figure 1A, the images of CG 24h group and Sham 72h group are duplicated, where the picture of Sham 72h group is correct, now the authors have corrected the picture of CG 24h group. In Figure 2A, the images of CG 72h and CSG 72h groups are duplicated, the images of CG 168h and CSG 168h groups are duplicated，where the pictures of CG 168h and CSG 72h groups are correct, now the authors have corrected the pictures of CG 72h and CSG 168h groups. In Figure 3B, the images of CG 24h group and CSG 72h group are duplicated, where the picture of CSG 72h group is correct, now the authors have corrected the picture of CG 24h group. Reference: Wei-han Cao, Yan-jun Su, Nian-qiu Liu, Ying Peng, Chang Diao, Ruo-chuan Cheng: Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits. Med Sci Monit, 2020; 26: e920546. DOI: 10.12659/MSM.920546.

The role of P62 in the development of human thyroid cancer and its possible mechanism.

BACKGROUND: Thyroid cancer is the most common malignancy in human endocrine system. Increasing evidence has indicated that p62 plays a key role in tumorigenesis. The roles and underlying molecular mechanisms of P62 in thyroid cancer, however, remain to be elucidated. METHODS: The expression levels of P62 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of P62 on thyroid cancer cell proliferation, migration, invasion, cell cycle and apoptosis were measured by CCK-8 assay, transwell assay, flow cytometry and transwell assay, respectively. In terms of the mechanism, P62 could stimulate thyroid cancer progression by the activation of nuclear factor-kappa B (NF-κB) signaling pathway. RESULTS: P62 was highly expressed in thyroid tumor tissues. Furthermore, high expression of p62 was observed in PTC cell lines, and especially in the K1 and TPC-1 cells. In vitro, the up-regulation of p62 promoted cell proliferation, migration, and invasion of thyroid cancer cells, whereas the knockdown of p62 resulted in the opposite effect. Knock-down of P62 increased the number of cells in the G0/G1 phase but reduced it in the S and G2/M phase. Moreover, we confirmed that overexpression of p62 inactivated NF-κB pathway with sequencing analysis and bioinformatics analysis. CONCLUSION: This research work suggested that p62 could promote PTC cell proliferation, migration, and invasion via NF-κB signaling pathway. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis in PTC. Its potential role as a therapeutic target for PTC is worthy of further study.

The Potential Action of Thomsen-Friedenreich Monoclonal Antibody (A78-G/A7) in Thyroid Cancer.

BACKGROUND: Thomsen-Friedenreich antibody (TF-Ab) is a specific antibody against the Thomsen-Friedenreich antigen (TF-Ag). At present, studies on a number of other tumors have shown that TF-Ab can effectively inhibit metastasis and induce apoptosis in tumor cells. However, the role of TF-Ab in thyroid cancer (TC) remains unclear. MATERIALS AND METHODS: Normal subjects and patients with primary papillary TC with or without lymph node metastasis were tested for TF-Ab expression by enzyme-linked immunosorbent assays (ELISAs). Immunofluorescence was used to assess the expression of TF-Ag in thyroid papillary carcinoma with or without lymph node metastasis and undifferentiated cancer tissues. To evaluate the role of TF-Ab in TC, the effects of TF monoclonal antibody (mAb A78-G/A7) on cell biological function were investigated by MTT assays, flow cytometry, adhesion assays and transwell experiments. RESULTS: Compared with normal individuals, TF-Ab levels in patients with TC were decreased, but no changes were observed with respect to lymph node metastasis. The expression of TF-Ag in TC tissues was relatively higher than that detected in adjacent tissues, but it was not affected by the presence or absence of lymph node metastasis. Upon treatment mAb A78-G/A7 treating, TC cell cycles were affected, meanwhile the abilities to adhere, invade and migrate were also significantly reduced. CONCLUSION: The results of the present study showed that mAb A78-G/A7 could affect the invasion and migration of all assayed TC cell lines. The effects of mAb A78-G/A7 on the cell cycle, adhesion, invasion and migration of TC cells were more significant than those observed for proliferation and apoptosis.

Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits.

BACKGROUND Hypoparathyroidism is a common complication after thyroidectomy. Calcium supplementation can relieve these symptoms, but it is not clear whether it can protect the parathyroid glands. This study aimed to verify whether Ca²âº inhibits the apoptosis of parathyroid cells following ischemic injury. MATERIAL AND METHODS A rabbit model of parathyroid gland ischemic injury was established. The blood calcium concentrations were measured by colorimetry. The parathyroid hormone (PTH) levels were measured by enzyme-linked immunosorbent assay (ELISA). The parathyroid tissues were observed by hematoxylin and eosin (H&E) staining and the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Western blotting was used to quantify the levels of the following proteins: caspase-3 and p38 MAP Kinase (p38 MAPK). RESULTS This study demonstrates that apoptosis can be a part of the pathological changes associated with parathyroid ischemic injury. Calcium supplementation inhibited the apoptosis of parathyroid cells following ischemic injury. There were no significant differences among the serum calcium levels from the Sham operation (Sham), the Control group (CG), or the Calcium supplementation group (CSG) after 24 h, 72 h, and 168 h of treatment. PTH levels in the CG were significantly higher than in the CSG at 24 h and 72 h after treatments. The apoptosis rate of parathyroid cells from rabbits in the CSG was significantly lower than that of those from rabbits in the CG at 24 h and 72 h after the treatment. Calcium supplementation inhibited p38 MAPK and caspase-3 expression. CONCLUSIONS This study demonstrates that calcium supplementation inhibited the apoptosis of parathyroid cells following ischemic injury.

Validation of the Chinese version of EORTC QLQ-BM22 in patients with bone metastases.

PURPOSE: Our aim is to test the validity, reliability, and acceptability of the Chinese version of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Bone Metastases 22 (EORTC QLQ-BM22) module to assess health-related quality of life (HRQOL) in patients with bone metastases in China. METHODS: Patients with histological confirmation of malignancy and bone metastases from Tianjin Cancer Institution and Hospital from June 2013 to April 2014 were enrolled in this study. All patients self-administered the EORTC QLQ-BM22 and the EORTC QLQ-C30. The Karnofsky Performance Scale (KPS) was performed to evaluate scores. The reliability and validity tests of the questionnaires were based on Cronbach's α coefficients, Pearson correlation test, and Wilcoxon rank sum nonparametric test. RESULTS: Internal consistency reliabilities of all the four scales were acceptable. Scales measuring similar HRQOL aspects were found to correlate with one another between EORTC QLQ-BM22 and EORTC QLQ-C30, but differences still existed. Significant differences were demonstrated in the scores of all four subscales of the QLQ-BM22 between the two KPS subgroups (KPS ≤ 80; KPS > 80). Meanwhile, the compliance for item completion of the QLQ-BM22 was satisfactory. CONCLUSIONS: The Chinese version of EORTC QLQ-BM22 is a reliable and valid instrument, which is appropriate for measuring the HRQOL of patients with bone metastases in China.

[A prospective randomized and controlled study on no drainage after surgery for benign thyroid disorders].

OBJECTIVE: To evaluate the necessity of drainage after thyroidectomy for benign thyroid disorders. METHODS: A total of 272 patients who underwent thyroidectomy for benign thyroid disorders were randomly divided into drainage group or non-drainage group. Operating time, postoperative stay time in hospital, comfort of neck assessed by visual analogue scale (VAS) on postoperative day (POD) 0 and POD1 were and the incidence of complications, including post-thyroidectomy bleeding, hematoma, seroma, wound infection, hoarseness, and hypoparathyroidism, were assessed and compared between two groups. RESULTS: Both groups were similar in the mean age, the sex ratio and the underwent procedure types. There was no significant difference in the mean operating time between two groups (87.5 ± 32.0) min and (93.8 ± 30.1) min (t = 0.12, P = 0.45). The mean postoperative hospital stay time of non-drainage group (1.9 ± 0.3) d was significantly shorter than that of drainage group (2.6 ± 0.6) d (t = 1.45, P = 0.02). The mean VAS scores of neck comfort on POD0 and POD1 in non-drainage group were significantly high than those in non-drainage group(t = 2.67, P = 0.03 and t = 0.33, P = 0.006). There were no significant difference in postoperative complications, including permanent hoarseness and hypoparathyroidism, between two groups. CONCLUSIONS: No drainage after thyroidectomy for benign thyroid disorders does not increase postoperative complications, with the increase in postoperative neck comfort, the decrease in hospital stay time and potential wound infections. The routine drainage is not necessary after thyroid surgery for benign disorders.

Role of adjuvant chemotherapy after pneumonectomy for non-small cell lung cancer.

Adjuvant chemotherapy is used as an alternative treatment for non-small cell lung cancer (NSCLC); however, the efficiency of post-pneumonectomy adjuvant chemotherapy in NSCLC has not been clarified. In the present study, patients who benefited from adjuvant chemotherapy with TP/NP/GP were identified. A total of 217 patients who underwent pneumonectomy were identified in this study. Of these, 87 underwent pneumonectomy combined with adjuvant chemotherapy (TP/NP/GP regimen) and 130 underwent pneumonectomy only in the initial management. The primary endpoint of the present study was overall survival. Actuarial survival analysis was conducted using the Kaplan-Meier method. Postoperative adjuvant chemotherapy significantly improved the survival rate of patients who underwent left pneumonectomy and in patients with a preoperative forced expiratory volume in 1 sec (FEV1) greater than or equal to 21. Age had no effect on the survival rate of patients with or without postoperative adjuvant therapy. Post-pneumonectomy adjuvant chemotherapy is an efficient therapy in NSCLC for patients with preoperative FEV1 greater than or equal to 21 or who received left pneumonectomy.

[Treatment and prognostic analysis of 1638 patients with non-small cell lung cancer].

OBJECTIVE: To study the prognosis and prognostic factors of non-small-cell lung carcinoma (NSCLC) according the new TNM stage system. METHODS: Clinic data of 1638 inpatient cases admitted from January 2001 to January 2005 were retrospectively reviewed. There were 1083 male and 555 female patients in the study and the average age was 59.5 years. All the patients received surgical procedures. RESULTS: The overall 1, 3, 5-year survival rate was 80.0%, 52.3%, 39.0%. The main prognostic factors were bronchial stump, operation type, T stage, N stage, the number of lymph nodes (LNs) in lymph nodes dissection (1 - 10, 11 - 20, and > 20), overall N stations (< 4 and ≥ 4) and postoperative radiotherapy (all P < 0.05). Cox regression suggested that T stage (P = 0.000), N stage (P = 0.000), operation type (P = 0.001) and LNs (P = 0.013) were independent factors affecting the prognosis. CONCLUSIONS: The overall survival rate of NSCLC is poor. T stage, N stage, operation type and LNs are independent factors affecting the prognosis.

Up-regulation of the expression of S100A8 and S100A9 in lung adenocarcinoma and its correlation with inflammation and other clinical features.

BACKGROUND: S100A8 and S100A9 are two members of the S100 protein family characterized by the presence of two Ca2+-binding sites of the EF-hand type. Previous studies suggested that the whole S100 family displays significant functions in tumor growth, progression and invasion. This study aimed to determine the expression of the two indices of the family, S100A8 and S100A9, in lung cancer tissues and normal lung tissues and its correlation with clinical features. METHODS: A total of 60 cases with a variety of clinical data that were diagnosed with different histological subtypes of lung cancer were investigated. Semi-quantitative reverse transcriptase-PCR (Sq-Rt-PCR) and immunohistochemical staining of cancer, adjacent and peripheral lung tissues were executed to distinguish the expression patterns of S100A8 and S100A9 and to further clarify their correlation with clinical features. RESULTS: Immunohistochemical staining of both proteins showed a significant up-regulation in lung cancer tissue (S100A8, S100A9, P<0.0001), and PCR revealed that the levels of S100A8 and S100A9 expression were significantly higher in lung cancer tissues (S100A8 P=0.002/0.004; S100A9 P=0.022/0.026). The higher expression was found to be correlated with the clinical characteristics of adenocarcinoma, inflammation and stage IV lesion. CONCLUSIONS: S100A8, S100A9 up-regulation was found in the lung adenocarcinoma and end stage lung cancer tissue, the correlation of which with their higher expression in inflammatory lung tissues may indicate the collaborative effect of inflammation on the progression of cancer.

Do tumor cavitation and sex in resected stage I non-small-cell lung cancer correlate with prognosis?

BACKGROUND: Multiple factors have been reported as affecting the prognosis, and they affect the therapeutic outcomes of stage I non-small-cell lung cancer (NSCLC) patients. Most studies focus on patients receiving combined-modality therapy, whereas there are few studies that focus on patients undergoing surgery alone. The aim of this study was to identify risk factors for disease relapse and unfavorable prognosis in stage I NSCLC patients treated with surgery alone. METHODS: A total of 315 stage I NSCLC patients who were treated with surgery alone as the definitive therapy were identified. Risk factors for disease relapse and unfavorable prognosis were estimated by univariate and multivariate analyses. RESULTS: Sex, tumor pathologic stage, and cavitating lung cancer were identified as independent risk factors for relapse and overall survival using the multivariate analysis. Sex, tumor pathologic stage, and cavitating lung cancer were identified as independent risk factors for early relapse, and sex and cavitating lung cancer were independent risk factors for late relapse. CONCLUSION: Tumor cavitation, pathologic stage IB, and being male are predictors of poor outcome for patients with stage I NSCLC who undergo resection.

[Clinical observation of XELOX (Capecitabine puls Oxaliplatin): an adjuvant chemotherapy regimen used in stage III colorectal cancer].

OBJECTIVE: To evaluate the efficacy and safety of an adjuvant chemotherapy regimen: XELOX (Capecitabine puls Oxaliplatin) used after curative resection for stage III colorectal cancer. METHODS: From Jan. 1998 to Jan. 2004, 256 cases with stage III colorectal cancer randomized received de Gramont, modified FOLFOX4 (mFOLFOX4) and XELOX regimens. The 3-year disease-free survival (DFS) and overall survival (OS) were compared within the three groups and relative prognosis factors within mFOLFOX4 and XELOX groups. Therapeutic adverse events were recorded and analyzed with Kaplan-Meier test. RESULTS: 98, 87 and 71 cases were respectively enrolled in the de Gramont, mFOLFOX4 and XELOX groups, mFOLFOX4 and XELOX had superior efficacy compared with de Gramont regimen. The two former could significantly improve 3-year DFS (79.7% vs. 66.2%, P = 0.015; 81.5% vs. 66.2%, P = 0.004) and medium survival time (40.2 mon vs. 37.8 mon, P = 0.024; 41.4 mon vs. 37.8 mon, P = 0.014). Meanwhile they could respectively decrease the ratio of recurrence risk by 18.0% (P = 0.024) and 21.0% (P = 0.003). The relative benefit of mFOLFOX4 versus XELOX didn't differ for 3-year DFS [hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.79-1.12, P = 0.13] and OS (HR: 0.87, 95% CI: 0.84-1.06, P = 0.54). In the analysis of DFS in relative prognosis factors, XELOX had a better trend of survival advantage. mFOLFOX4 had higher adverse events within these regimens, especially in grade 3 or 4 neutropenia and peripheral neurologic adverse events. CONCLUSION: XELOX maintains its efficacy and safety ratio in advanced colorectal cancer. Patients have good tolerance and compliance. The regiment is deserves to be applied in clinical treatment. Oxaliplatin;

[Efficacy of adjuvant chemotherapy after left pneumonectomy on non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Presently, whether non-small cell lung cancer (NSCLC) patients may benefit from adjuvant chemotherapy after left pneumonectomy is controversial. This study was to evaluate the efficacy of adjuvant chemotherapy after left pneumonectomy on NSCLC, and explore candidate patient selection for adjuvant chemotherapy. METHODS: Clinical data of 51 NSCLC patients received radical left pneumonectomy and adjuvant chemotherapy of TP/NP regimen and 102 patients received left pneumonectomy alone between Jan. 1997 and Jan. 2002 were compared. RESULTS: The 1-, 3-, and 5-year survival rates were 88.2%, 54.9%, and 36.1% in adjuvant chemotherapy group, and 76.5%, 37.3%, and 23.9% in control group (P>0.05). For the patients at stage N2 or IIIA, the 1-, 3-, and 5-year survival rates were significantly higher in adjuvant chemotherapy group than in control group (P<0.05). For the patients with preoperative forced expiratory volume at the first second (FEV1) of >2 L, the 1-, 3-, and 5-year survival rates were significantly higher in adjuvant chemotherapy group than in control group (P<0.05). For the patients aged of >65 or < o r =65, there was no significant difference in survival between the two groups (P>0.05). CONCLUSIONS: For the NSCLC patients at stage IIIA, N2 or with preoperative FEV1 of >2 L, adjuvant chemotherapy after left pneumonectomy may improve survival rate. For the patients with good pulmonary function, even aged patients, adjuvant chemotherapy is needed.

[Clinical significance of CD4+ CD25+ regulatory T-cells detection in tumor-draining lymph nodes of nonsmall cell lung cancer patients].

OBJECTIVE: To evaluate the distribution of CD4+ CD25+ regulatory T-cells (T-regs) in tumor-draining lymph nodes (TDLN) in patients with non-small cell lung caner (NSCLC), and to investigate the effect of CD4+ CD25+ T regulatory cells on the immune status of TDLN and the progression of NSCLC. METHODS: Regional tumor-draining lymph nodes of 53 NSCLC patients were resected during the operation. The percentage of CD4+ CD25+ T-regs as a subset of CD4+ T cells and CD8+ T cells were detected by immunofluorescence and regular immunohistochemistry, respectively. The level of cytokines TGF-beta1 and IL-10 was detected by real time quantitative RT-PCR. RESULTS: CD4+ CD25+ T-regs in tumor-infiltrating lymph nodes from the patients with NSCLC accounted for 28.80% +/- 8.06% of total CD4+ T cells, and were significantly increased comparing with that (15.48% +/- 4.66%) in the tumor-free lymph nodes (P < 0.01). The percentage of CD4+ CD25+ T-regs in TDLN of NSCLC patients was negatively correlated with the amount of CD8+ T cells within the lymph nodes (r = -0. 756, P < 0.001), but positively correlated with the level of TGF-beta1 (r = 0.645, P < 0.001) and IL-10 (r = 0.769, P < 0.001). It also increased as NSCLC getting progressed, which was 30.42% +/- 7.47% in stage III versus 16.22% +/- 4.88% in stage I and III; 32.58% +/- 7.52% in N2 versus 22.76% +/- 4.67% in N1, with a significant difference between the two groups, respectively (P < 0.01). CONCLUSION: The population of CD4+ CD25+ T regulatory cells in tumor-draining lymph nodes in patients with non-small cell lung caner is positively correlated with the progression and infiltration of lung cancer, which might provide new immunologic method to evaluate the progression and prognosis of non-small cell lung caner. The outcomes of biotherapy for NSCLC may be improved in the future through regulating the CD4+ CD25+ T regulatory cells.