Linjun Fan

Inhibition of Glut1 by WZB117 sensitizes radioresistant breast cancer cells to irradiation.

PurposeBreast cancer is the most common type of cancer with high incidence in women. Currently, identifying new therapies that selectively inhibit tumor growth without damaging normal tissue are a major challenge of cancer research. One of the features of cancer cells is that they do not consume more oxygen even under normal oxygen circumstances but prefer to aerobic glycolysis through the enhanced catabolism of glucose and glutamine. In this study, we investigate the mechanisms of the radioresistance in breast cancer cells.MethodsHuman breast cancer cells MDA-MB-231 and MCF-7 were treated with radiation alone, Glut1 inhibitor alone or the combination of both to evaluate cell glucose metabolism and apoptosis. By the establishment of radioresistant cell line, we investigate the mechanisms of the combined treatments of radiation with Glut1 inhibitor in the radioresistant cells.ResultsThe glucose metabolism and the expression of Glut1 are significantly stimulated by radiotherapy. We report the radioresistant breast cancer cells exhibit upregulated Glut1 expression and glucose metabolism. In addition, we observed overexpression of Glut1 renders breast cancer cells resistant to radiation and knocking down of Glut1 sensitizes breast cancer cells to radiation. We treated breast cancer cells with radiation and WZB117 which inhibits Glut1 expression and glucose metabolism and found the combination of WZB117 and radiation exhibits synergistically inhibitory effects on breast cancer cells. Finally, we demonstrate the inhibition of Glut1 re-sensitizes the radioresistant cancer cells to radiation.ConclusionsThis study reveals the roles of Glut1 in the radiosensitivity of human breast cancer. It will provide new mechanisms and strategies for the sensitization of cancer cells to radiotherapy through regulation of glucose metabolism.

Shrink pattern of breast cancer after neoadjuvant chemotherapy and its correlation with clinical pathological factors

BackgroundBreast conservation therapy (BCS) after neoadjuvant chemotherapy (NCT) can improve patients’ quality of life. Currently used intraoperative examination for negative margins may not be sufficient to detect microresidual foci, which are a risk factor for local recurrence. This study was conducted to investigate the shrinking pattern of breast cancer and residual tumors as a risk factor for BCS after NCT.MethodsNinety women with stage II or III invasive ductal carcinoma who achieved partial response after NCT with paclitaxel and epirubicin were enrolled. All patients had undergone modified radical mastectomy. One-half of the surgical specimens were subjected to subserial sectioning. Pathological changes of tumor bed and pericancerous tissues were examined with an optical microscope. The levels of estrogen receptors, progesterone receptors and HER2 were analyzed by immnohistochemical staining.ResultsThe residual tumors were classified into three types according to their microscopic morphology: solitary lesion, multifocal and patchlike lesions, and main residual tumor with satellite lesions. Type I residual tumors were found in 55 patients (61%), type II in 30 patients (33%) and type III in 5 patients (6%). Types II and III were often associated with larger primary tumors. The types of residual tumors were not correlated with the status of hormone receptors or HER2.ConclusionThree types of residual tumors were observed after NCT. The solitary residual tumor is most common, but main residual tumors with satellite lesions are most likely to cause local recurrence after BCS. Subserial sectioning would improve the identification of microfoci and patient survival after BCS.

Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy.

BackgroundBiological molecular markers such as proto-oncogene erbB-2 (HER-2/neu, c-erbB-2), the CXC chemokine receptor 4 (CXCR4), estrogen receptor (ER), Proliferating Cell Nuclear Antigen (PCNA), DNA topoisomerase II (topo II), P-glycoprotein (P-gp) and glutathione S-transferase (GST) were observed for changes after administration of neochemotherapy and whether these protein expression changes were correlated with response to chemotherapy.MethodsSixty-four patients with primary breast cancer who had undergone neo-adjuvant chemotherapy were enrolled in the present study. The expressions of C-erbB-2, CXCR4 and ER-α were measured by immunohistochemistry (IHC) on full tissue sections and on tissue microarrays (TMAs). PCNA, TopoII, P-gp and GST were measured by IHC on TMAs. On the other hand, CXCR4, C-erbB-2 and ER-α expressions were detected using western blot analysis to 16 pairs of fresh preoperative core biopsies. The final surgical specimens were obtained from patients with breast carcinoma who received neo-adjuvant chemotherapy and obtained a partial response (PR).ResultsOur data demonstrated that the levels of C-erbB-2, CXCR4 and ER-α in patients decreased after they received neo-adjuvant chemotherapy on full tissue sections and on TMAs. The PCNA level was down-regulated after receiving neo-adjuvant chemotherapy, and no significant change was observed for TopoII, P-gp and GST. The levels of C-erbB-2, CXCR4 and ER-α were also down-regulated after neo-adjuvant chemotherapy was administered, as detected by western blot. In addition, the change expressions of C-erbB-2 and CXCR4 in specimens tended to be correlated with pathological change to neo-adjuvant chemotherapy on full tissue sections and on TMAs in a Pearson chi-square analysis.ConclusionsAs demonstrated in our study, after breast cancer patients were treated with neo-adjuvant systemic therapy, decreased expressions of C-erbB2, ER-α and CXCR4 were observed. Down-regulated expressions of c-erbB-2 and CXCR4 may be a novel mechanism of chemotherapy; the changes of these objective markers may be useful in evaluating the clinical response of neo-adjuvant chemotherapy in breast cancer.

Breast Cancer and Poland’s Syndrome: A Case Report and Literature Review

Abstract:  Poland’s syndrome is a rare congenital development malformation characterized by unilateral chest wall hypoplasia and ipsilateral hand abnormalities. It is also known to be associated with some malignant diseases. We herein report a case of Poland’s syndrome associated with invasive ductal carcinoma of breast, and review the literatures to investigate the clinical characteristics of breast cancer with Poland’s syndrome.

Association between the spread of circulating tumor cells and breast cancer subtypes.

We read with great interest the recent publication by Fehm and coworkers [1] about the association between the spread of circulating tumor cells (CTCs) and breast cancer subtypes. Th e authors observed that the highest CTC positivity rate was obtained in triple-negative patients followed by those with estrogen receptor (ER)positive and/or progesterone receptor (PR)-positive tumors, while no CTCs could be detected in the human epidermal growth factor receptor 2 (HER2)-positive subtype group. However, another study [2] showed contradictory results, indicating that HER2 was the only primary tumor characteristic that correlated with the presence of CTCs, while ER and PR status were not association with their presence. To clarify the correlation between CTCs and breast cancer subtypes, a total of 156 operable breast cancer patients admitted to our hospital were enrolled. Th is study was approved by the regional ethics committee. Written informed consent was obtained from all participating patients. Mononuclear cell enrichment and CTC detection were done as previously described [3]. Th e expression of ER, PR and HER2 in primary tumors was routinely detected. Results showed that the overall positive rate of CTCs in operable breast cancer patients was 32.1% (50 out of 156). Th ere existed signifi cant diff erences in the positive rate of CTCs between patients at diff erent pTNM stages (P = 0.0219) and between those with diff erent immunohisto chemical subtypes (P = 0.0003). Further analysis revealed that the positive rate of CTCs in the HER2positive and triple-negative subtypes was signifi cantly higher than that of the luminal subtype ( P= 0.0034 and 0.0003, respectively). In subgroup analysis by pTNM stage, signifi cant diff erences in the positive rate of CTCs between patients with diff erent breast cancer subtypes were identifi ed at stages I (P = 0.0207), II (P = 0.0478) and III (P = 0.0324) (Table 1), further supporting that the presence of CTCs was associated with the HER2-positive and triple-negative subtypes.

Endoscopic excision of branchial cleft cyst in the neck using mammary areolae and axilla approach: a case report.

Branchial cleft cysts are prone to recurrence and secondary infections, and hence, surgical resection is necessary. These masses are traditionally removed through an overlying incision; however, the resulting scar can be considered aesthetically displeasing. We accomplished a case of endoscopic resection of branchial cleft cyst in the right side of the neck of an 18-year-old female patient. Incisions were made in the bilateral mammary areolae and right axilla of the patient. We completely resected the mass using an ultrasonic scalpel and electrocoagulation hook within 45 minutes. All of the procedures were finished on the deep face of platysma muscle, which was not severed. There was no significant bleeding during the operation and the postoperative recovery was smooth, without recurrence for 6 months. The endoscopic resection of the neck mass through bilateral areolae and axillary incisions is simple, safe, and feasible, because there were covert incisions and fewer complications.

Endoscopic nipple sparing mastectomy with immediate implant-based reconstruction versus breast conserving surgery: a long-term study

To evaluate the differences between endoscopic nipple sparing mastectomy (ENSM) with immediate implant-based reconstruction and breast conserving surgery(BCS) applied to early-stage breast cancer in postoperative outcomes, function, and cosmesis. we made a prospective, non-randomized study reviewed a total of 346 cases of breast cancer from January 2007 to December 2011, including 189 cases of BCS and 157 cases of ENSM. All the patients were followed up to April 2016, with a median follow-up time of 74 months. The operative time, blood loss and drainage, postoperative complications, postoperative cosmesis, local recurrence rate, disease-free survival rate and overall survival rate of the two groups were compared. we found out that the operative time of ENSM was longer than that of BCS. There was no difference in blood loss and drainage, the postoperative complications, the disease-free survival rate and overall survival rate between the two groups. In regarding to cosmesis, patients in the ENSM group were more likely to get a satisfactory postoperative breast appearance. we reached a conclusion that ENSM is a safe and effective operative method retainingadvantages of TSSM to further improve the postoperative cosmetic effect, without increasing other risks. The surgery provides a new choice for patients with early-stage breast cancer.

Mammotome-assisted endoscopic breast-conserving surgery: a novel technique for early-stage breast cancer

BackgroundBecause of its minimally invasive and highly accurate nature, the use of Mammotome, a vacuum-assisted breast biopsy device has proven beneficial to the treatment of benign breast lesions. Taking advantage of endoscopic and Mammotome techniques together, we utilized the Mammotome device for therapeutic excision of malignant lesions in breast-conserving surgery (BCS).MethodsBetween December 2009 and January 2010, two patients with early breast cancer received Mammotome-assisted endoscopic BCSs. Under ultrasound monitoring, the Mammotome system dissected the surrounding tissue and freed the tumor en bloc leaving negative margins; endoscopic axillary lymph node dissection then followed.ResultsThe operation time was less than 180 minutes and the mean blood loss was 60 ml. The post-operative pathology report confirmed two patients to have invasive ductal carcinoma, one without axillary lymph nodes metastasis (0/11) and the other with one lymph node metastasis (1/21). No adverse events were noted. During a mean follow-up of 26.5 months, no evidence of recurrence or metastasis was found. The patients were satisfied with the cosmetic results.ConclusionsMammotome-assisted endoscopic surgery appears to be a valuable option for early breast cancer. The long-term therapeutic effect remains to be confirmed.

Robot-assisted internal mammary lymph chain excision for breast cancer: A case report

Rationale: Understanding the status of internal mammary lymph nodes of breast cancer is critical in the accurate staging of breast cancer and the development of accurate therapeutic regimen for selected patients. Current techniques for dissection of internal mammary lymph node biopsy involve endoscopic or Traditional thoracic surgery, An important drawback of the current techniques is the great trauma caused by them. Patient concerns: Da Vinci robotic surgery system (Intuitive Surgical Inc. Sunnyvale, CA) was used to perform the internal mammary lymph chain excision for a breast cancer patient with left internal mammary lymph node metastasis. Diagnoses: Positron emission tomography-computed tomography examination and Ultrasonography examination. Interventions: In this paper, we introduce a Robot-assisted technique for dissection of internal mammary lymph node biopsy with only 3 small trocar ports. This technique reduces the incision size and considerably reduce the trauma. Outcomes: The operation lasted a duration of 1.5 hours. The operation was carried out smoothly with removal of 9 internal mammary lymph nodes in total. The amount of intra operative bleeding was less than 10 ml. The patients postoperative recovery was fast. 11-month postoperative follow-up showed that the patient recovered well after surgery, no local recurrence or distant metastasis was found, and no obvious discomfort was reported. Lessons: Robot-assisted excision of internal mammary lymph chain in breast cancer is a safe, effective and simple operation with minimal invasion.

First report of in-situ preservation of a subcapsular parathyroid gland through super-meticulous capsular dissection during robotic radical thyroidectomy

PURPOSE Meticulous capsular dissection can preserve the function of the parathyroid gland in most patients, but it is difficult to identify and preserve the subcapsular parathyroid gland. We performed in-situ preservation of the subcapsular parathyroid gland during robotic radical thyroidectomy using super-meticulous capsular dissection, and evaluated its effect on postoperative parathyroid function. METHODS A 45-year-old woman was admitted with bilateral thyroid nodules. Color Doppler ultrasound demonstrated a 7 × 7 × 6 mm hypoechoic area in the middle and inferior part of the right lobe and 3 × 3 × 3 mm hypoechoic nodule in the middle part of the left lobe. She was diagnosed with right thyroid papillary cancer by fine-needle aspiration. Robotic bilateral thyroidectomy plus right central lymph node dissection was performed. During the left thyroidectomy, we found that the left inferior parathyroid gland was just under the true capsule. Subsequently, the super-meticulous capsular dissection was performed for in-situ preservation of the parathyroid gland. RESULTS The patients serum parathyroid hormone concentration was 43.77 pg/ml before and 37.98 pg/ml after surgery (normal: 15-65 pg/ml). Her blood calcium level was 2.21 mmol/l before and 2.18 mol/l after surgery (normal: 2.10-2.65 mmol/l). CONCLUSIONS The super-meticulous capsular dissection, which could cut through the true capsule to identify subcapsular parathyroid and protect its anatomic structure as well as blood supply, is recommend for in-situ preservation of subcapsular parathyroid gland during robotic radical thyroidectomy.