The role of intraoperative central lymph node biopsy in the treatment of clinically low-risk PTMC.

PURPOSE: To evaluate the role of intraoperative frozen biopsy of central lymph nodes in central neck dissection and thyroidectomy in patients of unilateral, clinically negative nodes (cN0) papillary thyroid microcarcinoma (PTMC) without extra-glandular invasion. METHODS: The clinical data of 465 patients were collected retrospectively. Part of prelaryngeal, pretracheal and ipsilateral paratracheal lymph nodes were taken for frozen pathological examination during the operation. Then the thyroid lobe on the tumor side and isthmus were excised, and central neck dissection of the affected side was performed in all patients. The number of metastases in entire central lymph nodes of the affected side can be obtained by postoperative paraffin pathology. If the number of positive lymph nodes during surgery is ≥3, contralateral gland resection was performed. RESULTS: In this group of 465 patients, there were 186 cases with central lymph node metastasis. The Kappa coefficient of consistency between frozen pathology and paraffin pathology in central lymph nodes was 0.605. The ROC curve for the number of intraoperative frozen metastases-postoperative pathological metastases over 5 showed that the AUC of the curve was 0.793, while the maximum Youden index was 0.5259, whose corresponding number of positive lymph nodes was 3. CONCLUSION: Intraoperative central lymph nodes biopsy can be used as an important indicator for the status of central lymph node metastasis in unilateral cN0 PTMC patients without extra-glandular invasion and a determinant for central lymph node dissection. While the number of positive lymph nodes intraoperatively is ≥3, total thyroidectomy should be considered.

Neoadjuvant therapy increases the risk of metabolic disorders and osteosarcopenia in patients with early breast cancer.

BACKGROUND: The purpose of this study is to evaluate the effects of neoadjuvant therapy on glucose and lipid metabolism, bone mineral density (BMD) and muscle, and to explore the relationship between metabolic disorders and changes in body composition, so as to provide better health management strategies for breast cancer survivors. METHODS: The clinical data of 43 patients with breast cancer who received neoadjuvant therapy in Xuanwu Hospital from January 2020 to June 2021 were analyzed retrospectively. The biochemical results, including albumin, blood glucose, triglyceride and cholesterol, were collected before neoadjuvant therapy and before surgery. The pectoral muscle area, pectoral muscle density and cancellous bone mineral density of the 12th thoracic vertebra were also measured by chest CT. RESULTS: After neoadjuvant therapy, fasting blood glucose, triglyceride and cholesterol were significantly increased, albumin was decreased. At the same time, pectoral muscle area, pectoral muscle density and T12 BMD were decreased. After treatment, BMD was positively correlated with pectoral muscle area, R2 = 0.319, P = 0.037, and BMD was also positively correlated with pectoral muscle density, R2 = 0.329, P = 0.031. Multivariate analysis showed that BMD and pectoral muscle density were correlated with menstrual status, and pectoral muscle area was correlated with body mass index before treatment, none of which was related to glucose and lipid metabolism. CONCLUSION: Neoadjuvant therapy can cause glucose and lipid metabolism disorder, BMD decrease and muscle reduction. BMD was positively correlated with muscle area and density after treatment, suggesting that patients had an increased chance of developing osteosarcopenia.

Elevated MMP1 Expression in Carcinoma-Associated Fibroblasts of Breast Cancer Contributes to Tumor Progression and Unfavorable Prognosis.

OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer. METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments. RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment. CONCLUSION: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.

Diagnostic value of preoperative examination for evaluating margin status in breast cancer.

BACKGROUND: A positive resection margin is a major risk factor for local breast cancer recurrence after breast-conserving surgery (BCS). Preoperative imaging examinations are frequently employed to assess the surgical margin. AIM: To investigate the role and value of preoperative imaging examinations [magnetic resonance imaging (MRI), molybdenum target, and ultrasound] in evaluating margins for BCS. METHODS: A retrospective study was conducted on 323 breast cancer patients who met the criteria for BCS and consented to the procedure from January 2014 to July 2021. The study gathered preoperative imaging data (MRI, ultrasound, and molybdenum target examination) and intraoperative and postoperative pathological information. Based on their BCS outcomes, patients were categorized into positive and negative margin groups. Subsequently, the patients were randomly split into a training set (226 patients, approximately 70%) and a validation set (97 patients, approximately 30%). The imaging and pathological information was analyzed and summarized using R software. Non-conditional logistic regression and LASSO regression were conducted in the validation set to identify factors that might influence the failure of BCS. A column chart was generated and applied to the validation set to examine the relationship between pathological margin range and prognosis. This study aims to identify the risk factors associated with failure in BCS. RESULTS: The multivariate non-conditional logistic regression analysis demonstrated that various factors raise the risk of positive margins following BCS. These factors comprise non-mass enhancement (NME) on dynamic contrast-enhanced MRI, multiple focal vascular signs around the lesion on MRI, tumor size exceeding 2 cm, type III time-signal intensity curve, indistinct margins on molybdenum target examination, unclear margins on ultrasound examination, and estrogen receptor (ER) positivity in immunohistochemistry. LASSO regression was additionally employed in this study to identify four predictive factors for the model: ER, molybdenum target tumor type (MT Xmd Shape), maximum intensity projection imaging feature, and lesion type on MRI. The model constructed with these predictive factors exhibited strong consistency with the real-world scenario in both the training set and validation set. Particularly, the outcomes of the column chart model accurately predicted the likelihood of positive margins in BCS. CONCLUSION: The proposed column chart model effectively predicts the success of BCS for breast cancer. The model utilizes preoperative ultrasound, molybdenum target, MRI, and core needle biopsy pathology evaluation results, all of which align with the real-world scenario. Hence, our model can offer dependable guidance for clinical decision-making concerning BCS.

A nomogram for intraoperatively predicting non-sentinel lymph node metastases in early breast cancer patients with positive sentinel lymph nodes.

Background: Individualized decisions are required in early-stage breast cancer patients. We aimed to establish a novel model for predicting non-sentinel lymph node (SLN) metastases in patients with positive SLNs, using preoperative and intraoperative characteristics and inflammatory indicators. Methods: The data of 489 patients with invasive breast cancer were retrospectively collected from Xuanwu Hospital between 2014 and 2021. Among them, 96 patients with at least one positive SLN were used to build the predictive model. Univariate and multivariate analyses were performed to identify the risk factors of non-SLN metastases. A nomogram was developed using these risk factors and was validated by calibration curves. The area under the receiver operating characteristics curve (AUC) and decision curve analyses (DCA) were used to compare our novel nomogram with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Cross-validation was performed for further internal validation of the predictive model. External validation was conducted using another treatment group (n=46 patients) in Xuanwu Hospital. Results: Non-SLN metastases occurred in 42 of the 83 patients with positive SLNs (50.6%). Multivariate stepwise logistic regression indicated that the risk factors were age (P=0.032), number of positive SLNs (P=0.020), number of negative SLNs (P=0.011), resected tumor size (P=0.038), and monocyte count (P=0.012). A predictive model was developed and virtualized by nomogram using these five risk factors. The AUC of our nomogram was 0.867, which was significantly higher than that of the MSKCC model. DCA also showed a superior clinical value for our novel nomogram. After 10-fold cross-validation with 400 times repetitions, the AUC of our model was still 0.830. External validation of our model showed an AUC of 0.727. The model was well-calibrated in the internal and external validation series. Conclusions: A five-factor nomogram was developed for predicting non-SLN metastases in early-stage breast cancer patients. This novel tool exhibited good accuracy and could assist clinicians with intraoperative decisions in breast cancer patients with positive SLNs.

Changes of Tumor Markers in Patients with Breast Cancer during Postoperative Adjuvant Chemotherapy.

Objective: Serum tumor marker (STM) elevation can detect metastasis earlier than imaging diagnosis and, although not recommended by guidelines, is still widely used in clinical practice for postoperative follow-up of breast cancer patients. The purpose of this study was to investigate the change rules of CEA and CA153 in patients with HER2-negative breast cancer during postoperative adjuvant chemotherapy and their influencing factors. Materials and Methods: The medical records of patients with HER2-negative early breast cancer who visited Xuanwu Hospital from September 2018 to June 2021 were retrospectively analyzed. Demographic characteristics and baseline data of CEA and CA153 at initial diagnosis were collected. Data of CEA, CA153, biochemistry (including ALT, AST, rGT, triglycerides, cholesterol, and blood glucose) and blood routine (including white blood cells, neutrophils, monocytes, lymphocytes, and platelets) were also collected before chemotherapy, at the end of chemotherapy and more than 3 months after the end of chemotherapy. LY/MONO, NEUT/LY, PLT/LY, and systemic immune inflammation index (SII) were calculated and statistically analyzed using SPSSAU software. Results: A total of 90 patients were enrolled, all of whom were female, with a mean age of 55.11 ± 10.60 y. The value of CEA at initial diagnosis was 2.10 ± 1.11 ng/mL, and high expression was mostly correlated with past history of chronic diseases and tumor lymph node metastasis; the value of CA153 was 11.80 ± 6.60 U/mL, and high expression was correlated with high SII at initial diagnosis. Surgery did not affect the values of serum CEA and CA153. At the end of chemotherapy, CEA and CA153 were 2.68 ± 1.34 ng/mL and 18.51 ± 8.50 U/mL, respectively, which were significantly increased compared with those before chemotherapy, and were linearly correlated with the values before chemotherapy. They decreased (CEA 2.45 ± 1.19 ng/mL, CA153 10.87 ± 5.96 U/mL) again three months after the end of chemotherapy, manifested as "spiking" phenomenon, which was associated with lymph node metastasis at diagnosis, body metabolic disorders, and chronic inflammatory status. Conclusion: CEA and CA153 were increased presenting as "spiking" phenomena in patients with early HER2-negative breast cancer during postoperative adjuvant chemotherapy, and the peak of increase was linearly correlated with the indicators before chemotherapy. Clinical attention should be paid to this change to avoid excessive diagnosis and treatment leading to medical resource consumption.

A Nomogram Based on Clinicopathological and Ultrasound Imaging Characteristics for Predicting Cervical Lymph Node Metastasis in cN0 Unilateral Papillary Thyroid Microcarcinoma.

Objective: The aim of this study was to establish a practical nomogram for preoperatively predicting the possibility of cervical lymph node metastasis (CLNM) based on clinicopathological and ultrasound (US) imaging characteristics in patients with clinically node-negative (cN0) unilateral papillary thyroid microcarcinoma (PTMC) in order to determine a personal surgical volume and therapeutic strategy. Methods: A total of 269 consecutive patients diagnosed with cN0 unilateral PTMC by postoperative pathological examination from January 2018 to December 2020 were retrospectively analyzed. All the patients underwent lobectomy or thyroidectomy with routine prophylactic central lymph node dissection (CLND) and were divided into a CLNM group and a non-CLNM group. Using logistic regression, the least absolute shrinkage and selection operator (LASSO) regression analysis was applied to determine the risk factors for CLNM in patients with unilateral cN0 PTMC. A nomogram including risk-factor screening using LASSO regression for predicting the CLNM in patients with cN0 unilateral PTMC was further developed and validated. Results: Risk factors identified by LASSO regression, including age, sex, tumor size, presence of extrathyroidal extension (ETE), tumor diameter/lobe thickness (D/T), tumor location, and coexistent benign lesions, were potential predictors for CLNM in patients with cN0 unilateral PTMC. Meanwhile, age (odds ratio [OR] = 0.261, 95% CI.104-0.605; P = 0.003), sex (men: OR = 3.866; 95% CI 1.758-8.880; P < 0.001), ETE (OR = 3.821; 95% CI 1.168-13.861; P = 0.032), D/T (OR = 72.411; 95% CI 5.483-1212.497; P < 0.001), and coexistent benign lesions (OR = 3.112 95% CI 1.407-7.303; P = 0.007) were shown to be significantly related to CLNM by multivariant logistic regression. A nomogram for predicting CLNM in patients with cN0 unilateral PTMC was established based on the risk factors identified by the LASSO regression analysis. The receiver operating characteristic (ROC) curve for predicting CLNM by nomogram showed that the area under the curve (AUC) was 0.777 and exhibited an excellent consistency. Conclusions: A nomogram based on clinical and US imaging characteristics for predicting the probability of CLNM in patients with cN0 unilateral PTMC was developed, which showed a favorable predictive value and consistency. Further prospective research to observe the oncological outcomes is necessary to determine whether the nomogram could potentially guide a personalized surgical volume and surgical approach.

Development and validation of a novel 14-gene signature for predicting lymph node metastasis in papillary thyroid carcinoma.

BACKGROUND: There is still no reasonably accurate method of preoperatively predicting central lymph node metastasis (LNM), and it is essential to develop an effective evaluation model for predicting LNM in papillary thyroid carcinoma (PTC) patients. METHODS: PTC samples were collected from The Cancer Genome Atlas database. Candidate genes were identified as continuously upregulated or downregulated genes in the process of N0 to N1a and N1a to N1b. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct the predictive model for LNM. Multivariate logistic regression analysis was performed to screen the potential factors related to LNM, and a nomogram was established. The risk score of the gene signature model for predicting disease-free survival (DFS) was evaluated by Kaplan-Meier analysis. RESULTS: A 14-gene signature was developed by LASSO regression for predicting LNM based on 69 differential expression genes (DEGs) that were continuously upregulated or downregulated in the progress of PTC. The receiver operating characteristic (ROC) curves of the 14-gene signature predicting LNM, central LNM and lateral LNM were generated. The area under the ROC (AUC) values were 0.806 [95% confidence interval (CI): 0.7608-0.8815], 0.755 (95% CI: 0.6839-0.8263) and 0.821 (95% CI: 0.7608-0.8815). The nomogram's C-index value, including the 14-gene signature and other potential risk factors, was 0.786 (95% CI: 0.7296-0.8425), and the calibration exhibited fairly good consistency with the perfect prediction. Based on the 14-gene risk score, high-risk PTC patients had a worse DFS. CONCLUSIONS: A novel 14-gene signature was developed for predicting LNM in PTC patients. The risk score also correlated with DFS in PTC patients.

Carbon nanoparticle-guided intraoperative lymph node biopsy predicts the status of lymph nodes posterior to right recurrent laryngeal nerve in cN0 papillary thyroid carcinoma.

BACKGROUND: The lymph nodes in the right central compartment can be divided into 2 parts by the right recurrent laryngeal nerve (RLN), and there is a lack of an accurate and convenient method for assessing metastases in the lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) in cN0 thyroid papillary carcinoma patients. METHODS: Patients diagnosed with cN0 thyroid papillary carcinoma and underwent intraoperative carbon nanoparticle-guided lymph node biopsy from January 2017 to November 2020 at the Center for Thyroid and Breast Surgery of Xuanwu Hospital were retrospectively analyzed. The intraoperative frozen section examination and postoperative LN-prRLN status should have been comprehensively recorded. The participants were divided into the LN-prRLN positive group and LN-prRLN negative group according to their recorded LN-prRLN status. RESULTS: In total, 189 cases (LN-prRLN positive group, n=30; LN-prRLN negative group, n=159) were included in the analysis. The univariate and multivariate regression analyses revealed that the number of metastatic lymph nodes during intraoperative lymph node biopsy was the potential predictor for LN-prRLN metastasis [odds ratio (OR): 1.320, 95% confidence interval (CI): 1.057 to 1.649, P=0.014]. The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) reached 0.7 upon a combined analysis of multiple lymph node statuses located at pre-laryngeal (Delphian), pre-tracheal, and para-tracheal lymph nodes ipsilateral to the tumor in predicting the metastasis of LN-prRLN, and the cut-off value was 0.5. CONCLUSIONS: Number of metastatic lymph nodes in intraoperative biopsy was an indicator of LN-prRLN metastasis in cN0 thyroid carcinoma patients. Patients staging in cN0 with negative intraoperative lymph node status might be considered not to require LN-prRLN dissection during central lymph nodes dissection.

A 10-Gene Signature for Predicting the Response to Neoadjuvant Trastuzumab Therapy in HER2-Positive Breast Cancer.

BACKGROUND AND PURPOSE: Dual-target therapy may increase the incidence of adverse events and cause economic burden to patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. It is necessary to identify the patients who could benefit greatly from a single-target neoadjuvant therapy in order to avoid overtreatment of patients. PATIENTS AND METHODS: The baseline transcriptome data and clinical characteristics of patients with HER2-positive breast cancer who received neoadjuvant trastuzumab therapy were obtained from the Gene Expression Omnibus database. Least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the predictive model for pathologic complete response (pCR). RESULTS: A 10-gene signature model for predicting pCR rate after neoadjuvant trastuzumab therapy was constructed by LASSO regression. The areas under the receiver operating characteristics (ROC) curves in the training set and validation set were 0.896 (95% confidence interval [CI], 0.8165-0.9758) and 0.775 (95% CI, 0.5402-1), respectively. The result of logistic regression analysis showed that the risk score calculated by the 10-gene signature model was a potential predictor for pCR. Among the 10-gene signature, TFAP2B, SUSD2, AQP3, MUCL1, and ANKRD30A were found to be predictors for worse relapse-free survival (RFS) in patients with HER2-positive breast cancer, whereas MGP, YIF1B, ANKRD36BP2, and FBXO6 were found to be predictors for favorable RFS. CONCLUSION: A novel 10-gene signature that could predict the response of neoadjuvant anti-HER2 therapy in patients with HER2-positive breast cancer was developed, and the risk score of the 10-gene signature could be calculated to guide the selection of anti-HER2 therapy regimens.

Profilin 2 (PFN2) promotes the proliferation, migration, invasion and epithelial-to-mesenchymal transition of triple negative breast cancer cells.

BACKGROUND: Triple negative breast cancer (TNBC) is the most aggressive subtype with the worst prognosis. The role of profilin 2 (PFN2) in TNBC is very controversial. The current study is to explore the role of PFN2 in TNBC. METHODS: PFN2 expression in TNBC and normal breast tissues were evaluated by immunohistochemical analysis. The association between PFN2 expression and prognosis in TNBC patients was analyzed from the TCGA database. A cell counting kit-8 (CCK8) assay was employed to investigate the effects of PFN2 in TNBC cell proliferations. The migration and invasion capability of TNBC cells was evaluated by transwell assays. Western blot was performed to assess the related protein expression of TGF-ß/Smad signaling and epithelial to mesenchymal transition. Finally, TNBC xenografts were established to determine the tumorigenicity in vivo using female Nod/Scid mice. RESULTS: PFN2 is upregulated in TNBC and the higher expression was associated with worse survival. CCK8 assays and Transwell assays demonstrated that PFN2 promoted the proliferation, migration and invasion of TNBC cells. Smad2 and Smad3 were upregulated in PFN2 overexpressing TNBC cells, which further induced the process of epithelial­to­mesenchymal transition. Similarly, the overexpressing PFN2 TNBC cells exhibited stronger tumorigenicity in vivo. CONCLUSIONS: Higher PFN2 expression is associated with a worse 10-year overall survival and relapse-free survival in breast cancer patients, as well as worse 10-year relapse-free survival in TNBC patients. PFN2 promotes the proliferation, migration and invasion of TNBC cells by regulating epithelial-to-mesenchymal transition.

Role of intraoperative neuromonitoring of recurrent laryngeal nerve in thyroid and parathyroid surgery.

OBJECTIVE: To investigate whether intraoperative neuromonitoring (IONM) has a significant advantage in reducing the incidence of recurrent laryngeal nerve (RLN) injury. METHODS: Patients who underwent thyroid and parathyroid surgery from October 2012 to December 2017 at the Center for Thyroid and Breast Surgery of Xuanwu Hospital were retrospectively analyzed. They were divided into the IONM group and visualization alone group (VA group) according to whether IONM was used. RESULTS: In total, 1696 nerves at risk of injury (IONM group, n = 1104; VA group, n = 592) were included in the analysis. Among the high-risk nerves, permanent damage occurred in no cases in the IONM group but in one case in the VA group. Because the higher proportion of central lymph node metastasis caused difficulties in central cervical lymph node dissection and identification of the RLN, the patients undergoing lateral cervical lymph node dissection in the VA group had a significantly higher risk of postoperative RLN injury (11.76% vs. 0.00%). CONCLUSION: IONM technology has advantages in protection of the RLN, especially in high-risk nerves and patients with a high proportion of central lymph node metastasis who require central and lateral cervical lymph node dissection.

Cell swelling, softening and invasion in a three-dimensional breast cancer model.

Sculpting of structure and function of three-dimensional multicellular tissues depend critically on the spatial and temporal coordination of cellular physical properties, yet the organizational principles that govern these events, and their disruption in disease, remain poorly understood. Using a multicellular mammary cancer organoid model, here we map in three dimensions the spatial and temporal evolution of positions, motions, and physical characteristics of individual cells. Compared with cells in the organoid core, cells at the organoid periphery and the invasive front are found to be systematically softer, larger and more dynamic. These mechanical changes are shown to arise from supracellular fluid flow through gap junctions, suppression of which delays transition to an invasive phenotype. Together, these findings highlight the role of spatiotemporal coordination of cellular physical properties in tissue organization and disease progression.

Influence of Infiltration Pressure on the Microstructure and Properties of 2D-CFRP Prepared by the Vacuum Infiltration Hot Pressing Molding Process.

The critical infiltration pressures of the matrix in a two-dimensional (2D) carbon fiber preform were calculated theoretically, and the calculated values of the static and dynamic models were 0.115 and 0.478 MPa, respectively. Compared with the dynamic model, there is no viscous resistance or infiltration front gas pressure in the static model, so the static value is obviously lower than the dynamic value. To verify the rationality of theoretical calculation, 2D carbon fiber reinforced plastics (2D-CFRP) with infiltration pressures of 0.5, 0.6, 0.7, 0.8, and 0.9 MPa were prepared by the vacuum infiltration hot pressing molding process. The microstructure of the composite was observed and the bending strength was tested by three-point bending test. The results show that the infiltration pressure has an important influence on the infiltration effect and the bending fracture morphology. When the infiltration pressure is 0.7 MPa, the composite has an excellent infiltration effect. The fibers distribute reasonable in the fracture. Stress can be effectively transferred when the composite material is loaded. And the bending strength of the composite material reaches 627 MPa at this time.

Upregulating MMP-1 in carcinoma-associated fibroblasts reduces the efficacy of Taxotere on breast cancer synergized by Collagen IV.

Chemotherapy is an important comprehensive treatment for breast cancer, which targets micro-environment of tumors as well as their characterisitcs. A previous microarray analysis revealed that matrix metalloproteinase (MMP)-1 was highly upregulated in carcinoma-associated fibroblasts (CAFs) prior to and following treatment with Taxotere under co-culture conditions. However, whether the chemotherapeutic effects of Taxotere were influenced by the changes in MMP-1 remained unclear. The purpose of the present study was to investigate the impact and mechanism of CAFs in regulating the efficacy of Taxotere on breast cancer cells. CAFs isolated from primary invasive ductal human breast tumors following surgical resection, were used in co-culture with MDA-MB-231 cells to simulate the tumor micro-environment. Following the addition of Taxotere, changes in MMP-1 gene and protein expression were assessed by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Proliferation, invasion and apoptosis assays revealed that when MMP-1 was upregulated in CAFs, the therapeutic efficacy of Taxotere was reduced in breast cancer cells. Chemosensitivity was significantly increased when MMP-1 expression was inhibited by GM6001. In addition, Collagen IV was upregulated in CAFs following chemotherapy and protected breast cancer cells against chemotherapeutic side effects. Collagen IV expression significantly decreased, as well as MMP-1 expression when GM6001 was added. Proliferation and invasion assays demonstrated that the exogenous addition of Collagen IV weakend the chemotherapeutic effect of Taxotere on breast tumor cells. Overall, the results revealed that in CAFs, MMP-1 synergized with Collagen IV as a key gene in regulating the chemotherapeutic effect of Taxotere on breast tumor cells and served an important role in reducing the efficacy of Taxotere on breast cancer, potentially via the transforming growth factor-ß signaling pathway. These fidings provide a theoretical basis for the mechanism of CAFs in reducing the chemotherapeutic effect of Taxotere on breast cancer cells and a novel approach for enhancing the chemosensitivity of tumors.

Extraction of biomedical compounds from the wood of Pterocarpus macarocarpus Kurz heartwood.

Some wood can be used as traditional Chinese medicine. The medicinal value of wood is associated with its extractives. Pterocarpus macarocarpus Kurz heartwood is a kind of top valuable reddish hardwood in making furniture and handicrafts, but the research about medicine value of this wood is not enough. In order to investigate the high value biomedical compounds in Pterocarpus macarocarpus Kurz heartwood, the woody extractives were obtained by Soxhlet extraction and ultrasonic extraction with benzene-ethanol (1:2, v/v) solvent simultaneously and were analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). Combining with the results of the two extraction methods, 44 compounds can be identified in total. Amony these identified compounds, there were 5 flavonoids, 15 terpenes and 3 steroidal compounds. The representative biomedical compositions were homopterocarpin, medicarpin, (-)-pterocarpin, formononetin, ß-eudesmol, stigmasterol, linoleic acid and so on, which indicated that the extractives from Pterocarpus macarocarpus Kurz heartwood have huge potential in biomedicine. This research provides scientific basis for further comprehensive utilization of Pterocarpus macarocarpus Kurz heartwood as Chinese medicine.

Development of ipsilateral chest wall spindle cell carcinoma in a patient with invasive ductal breast carcinoma during postoperative adjuvant therapy: A case report.

RATIONALE: Metaplastic breast carcinoma (MBC) is rare subtype of breast carcinoma and is regarded as ductal carcinoma that undergoes metaplasia into a glandular growth pattern. Spindle cell carcinoma (SPC) is a subtype of MBC with a predominant spindle cell component. PATIENT CONCERNS: The patient was a 52-year-old female with invasive ductal breast carcinoma who underwent a modified radical mastectomy and an axillary node dissection. A new lump was observed underneath the surgical site between the pectoralis major and pectoralis minor muscles 45 days after the patient underwent sequential postoperative chemotherapy and radiotherapy. DIAGNOSES: It was speculated that the new lesion had developed during postoperative adjuvant therapy. And the new lesion was regarded as a recurrence. INTERVENTIONS: We performed a wide dissection of the tumor with negative margins. The pathology of the tumor indicated SPC. Then, the patient received chemotherapy and demonstrated a poor response. OUTCOMES: Local recurrence and pulmonary metastasis developed shortly afterwards, and the patient succumbed to the disease within 5 months. LESSONS: Local recurrence with metaplastic SPC transformed from invasive ductal breast carcinoma during postoperative chemotherapy and radiotherapy is rare. The failure of subsequent chemotherapy and the progression of disease indicate the aggressive nature of SPC and its decreased sensitivity to chemotherapy and radiotherapy. Further studies must be performed to improve the prognosis of these patients.

Letrozole-induced functional changes in carcinoma-associated fibroblasts and their influence on breast cancer cell biology.

Accumulating evidence suggests that carcinoma-associated fibroblasts (CAFs) influence the efficacy of endocrine therapy. Aromatase inhibitors inhibit the growth of breast tumors by inhibiting the synthesis of estrogen. However, it remains unknown whether the aromatase inhibitor letrozole has an additional impact on CAFs, which further influence the efficacy of endocrine therapy. Primary CAFs were isolated from primary estrogen receptor-positive human breast tumors. Estrogen-deprived culture medium was used to exclude the influence of steroids. In co-culture, primary cultured CAFs increased MCF7 cell adhesion, invasion, migration and proliferation, and letrozole treatment inhibited these increases, except for the increase in proliferation. In total, 258 up-regulated genes and 47 down-regulated genes with an absolute fold change >2 were identified in CAFs co-cultured with MCF7 cell after letrozole treatment. One up-regulated genes (POSTN) and seven down-regulated genes (CCL2, CCL5, CXCL1, IL-8, CXCL5, LEP and NGF) were further validated by real-time PCR. The changes in CCL2 and CXCL1 expression were further confirmed using an automated microscopic imaging-based, high content analysis platform. Although the results need further functional validation, this study is the first to describe the differential tumor-promoting phenotype of CAFs induced by letrozole and the associated gene expression alterations. Most importantly, our data revealed that down-regulation of several secreted factors (CCL2, CCL5, CXCL1 etc.) in CAFs might be partially responsible for the efficacy of letrozole.

Biomimetic soy protein nanocomposites with calcium carbonate crystalline arrays for use as wood adhesive.

Despite the biodegradability, non-toxicity, and renewability, commercially available soy protein-based adhesives still have not been widely adopted by industry, partially due to their disappointing performances, i.e., low glue strength in the dry state and no glue strength in the wet state. In this study, biomimetic soy protein/CaCO(3) hybrid wood glue was devised and an attempt made to improve the adhesion strength. The structure and morphology of the adhesive and its fracture bonding interface and adhesion strength were investigated. Results showed that the compact rivets or interlocking links, and ion crosslinking of calcium, carbonate, hydroxyl ions in the adhesive greatly improving the water-resistance and bonding strength of soy protein adhesives. Glue strength of soy protein hybrid adhesive was higher than 6 MPa even after three water-immersion cycles. This green and sustainable proteinous hybrid adhesive, with high glue strength and good water-resistance, is a good substitute for formaldehyde wood glues.

Starch composites reinforced by bamboo cellulosic crystals.

Using a method of combined HNO(3)-KClO(3) treatment and sulfuric acid hydrolysis, bamboo cellulose crystals (BCCs) were prepared and used to reinforce glycerol plasticized starch. The structure and morphology of BCCs were investigated using X-ray diffraction, electron microscopy, and solid-state (13)C NMR. Results showed that BCCs were of typical cellulose I structure, and the morphology was dependent on its concentration in the suspension. BCC of 50-100 nm were assembled into leaf nervations at low concentration (i.e. 0.1 wt.% of solids), but congregated into a micro-sized "flower" geometry at high concentration (i.e. 10.0 wt.% of solids). Tensile strength and Young's modulus of the starch/BCC composite films (SBC) were enhanced by the incorporation of the crystals due to reinforcement of BCCs and reduction of water uptake. BCCs at the optimal 8% loading level exhibited a higher reinforcing efficiency for plasticized starch plastic than any other loading level.