OBJECTIVETo investigate the safety and efficacy of trastuzumab administered concurrently with anthracycline-containing adjuvant regimen for breast cancer.

METHODSIt is a prospective, randomized and controlled trial. Participants were randomized to receive trastuzumab administered concurrently or sequentially with anthracycline-containing adjuvant regimen. The primary endpoint was cardiac safety. The second endpoints were disease-free survival (DFS) and overall survival (OS).

RESULTSOne hundred and nine breast cancer patients were enrolled and randomized in this trial. Fifty-five participants received trastuzumab administered concurrently with anthracycline-containing adjuvant regimen and 54 patients received trastuzumab administered sequentially with anthracycline. The primary cardiac event was asymptomatic decrease in the left ventricular ejection fraction (LVEF). There was no significant difference between concurrent and sequential groups in cardiac event rates (9.1% vs13.0%, P = 0.556), neither of LVEF values at basline or at 3, 6, 9 and 12 months during trastuzumab treatment (P > 0.05). Four patients (7.3%) in the concurrent group suffered local recurrences or distant metastases, and 6 participants (11.1%) in the sequential group had distant metastases. There was no significant difference between the two groups in DFS (P = 0.724). There was no death in both groups.

CONCLUSIONSTrastuzumab administered concurrently with anthracycline is a safe adjuvant regimen for breast cancer and does not increase cardiac events. Further research is needed to determine the efficacy of this treatment regimen.

Adult ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal, Humanized ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Prospective Studies ; Stroke Volume ; Trastuzumab

OBJECTIVETo evaluate the efficacy and prognostic factors of personalized treatment for breast cancer patients who failed chemotherapy.

METHODSSeventy-two patients with breast cancer who failed chemotherapy were treated at the Tumor Hospital of Harbin Medical University from January 2001 to January 2012. Among them, 42 cases received 5.6 cycles (range, 4-8 cycles) of postoperative adjuvant chemotherapy, and 30 cases received 12.2 cycles (range, 6-22 cycles), both postoperative adjuvant and salvage chemotherapy. All of the 72 patients of stage IV were given personalized treatment. Under guidance of the principle that multidisciplinary treatment improves control rate but does not or less damage the normal tissues and host immune function, precise radiotherapy combined with Chinese herbal medicine (CHM), biological agent and others were chosen for the patients.

RESULTSThe median survival time was 20 months. Univariate analysis showed that non-invasive ductal carcinoma, less metastasized organs, without brain, liver and lung metastasis, Karnofsky performance scores ≥ 80, not combined with chemotherapy, and multiple courses of Chinese herbal medicine and biolojical agent treatment had significant impact on survival (P < 0.05). Multivariate analysis showed that no brain metastasis, non-invasive ductal carcinoma, and Chinese herbal medicine and biological agent treatment ≥ 7 courses and not combined with chemotherapy had obvious significance (P < 0.05). The rate of grade 3 and 4 treatment-related hematological toxicity was 8.3% (6/72) and 5.6% (4/72), respectively. All the patients with grade 4 hematological toxicity were the cases of grade 3 at hospital admission. No grade 3 and 4 acute radiation damages of the lung and liver were noticed.

CONCLUSIONChinese herbal medicine combined with biological agents and others prolongs survival time in breast cancer patients who failed chemotherapy, and provides an alternative treatment modality for them.

Adult ; Aged ; Aromatase Inhibitors ; therapeutic use ; Bone Density Conservation Agents ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Brain Neoplasms ; drug therapy ; secondary ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; radiotherapy ; secondary ; surgery ; Chemotherapy, Adjuvant ; Diphosphonates ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Imidazoles ; therapeutic use ; Lung Neoplasms ; drug therapy ; secondary ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasm Staging ; Nitriles ; therapeutic use ; Radiotherapy, Adjuvant ; Radiotherapy, Conformal ; methods ; Remission Induction ; Retrospective Studies ; Survival Rate ; Treatment Failure ; Triazoles ; therapeutic use

OBJECTIVETo evaluate the clinical characteristics and prognosis of adrenal metastasis from breast cancer, and to explore methods to improve prognosis.

METHODSThirty-four breast cancer patients with adrenal metastasis were diagnosed and treated in our hospital from Jan. 1999 to Dec. 2010. SPSS 17.0 was used for survival analysis.

RESULTSDuring the Jan. 1999 to Dec. 2010 period, 13 595 patients with breast cancer were treated in our hospital. Among them, 34 cases had adrenal metastasis from breast cancer, with an incidence of 0.25%. The median time to progression (TTP) and overall survival of the 34 patients was 6.2 months (95%CI 3.1-9.3 months) and 21.4 months (95%CI 0-44.0 months), respectively. Eleven patients (34.4%) achieved partial response among 32 patients who received chemotherapy, and 10 (31.2%) achieved stable disease. Patients who achieved best response of PR or SD were superior in TTP and OS than patients with disease progression after chemotherapy (TTP: 18.1 months vs. 2.3 months, P < 0.001; OS: 35.2 months vs. 10.3 months, P = 0.003). Patients who received 1st or 2nd line chemotherapy were superior in TTP than patients who received over 2nd line chemotherapy (TTP: 15.7 months vs. 4.2 months, P = 0.005).

CONCLUSIONSThe incidence of adrenal metastasis from breast cancer is low. Chemotherapy-based systemic therapy should be recommended to improve the prognosis for these patients.

Adrenal Gland Neoplasms ; drug therapy ; secondary ; surgery ; Adrenalectomy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; surgery ; Disease Progression ; Female ; Humans ; Middle Aged ; Remission Induction ; Retrospective Studies ; Survival Rate

OBJECTIVETo analyze the clinicopathological features and prognostic factors of breast cancer patients with inguinal lymph node metastases.

METHODSSeventeen breast cancer patients with inguinal lymph node metastases were treated from January 1999 to December 2010 in our cancer center. All of the patients had a history of breast cancer without other primary cancer. Their clinicopathological characteristics and prognostic factors were surveyed.

RESULTSThe frequency of breast cancer cases with inguinal lymph node metastaseis consisted of 0.11% of the total number of breast cancer patients in the same period. Two patients (11.8%) had inguinal lymph node metastasis only, and multi-site metastases were observed in the remaining 15 (88.2%) patients. The number of ER- and/or PR-positive and negative were 10 (58.8%) and 7 (41.2%) cases, respectively, and among the 13 cases who underwent HER-2 test, the number of HER-2-positive was 4 (30.8%). For the 16 patients who underwent surgery, 9 patients were detected with metastatic axillary lymph nodes equal or greater than 4. All of the 17 patients were treated with chemotherapy.The median follow-up time was 156 months. The 5-year overall survival rate was 49.9%. Univariate analysis revealed that metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, disease stage as III/IV at diagnosis and the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis ≤ 36 months were predictors of shorter PFS (P < 0.05). Metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, primary recurrence as multiple distant metastases, the period from diagnosis of breast cancer to the occurrence of inguinal lymph nodes metastasis ≤ 36 months and pleural effusion were predictors of shorter OS (P < 0.05). Multivariate analysis revealed that the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis was an independent prognostic factor concerning PFS (P < 0.05).

CONCLUSIONSThe prognostic factors of breast cancer patients with inguinal lymph node metastases include the number of metastatic axillary lymph nodes, ER and(or) PR status, the cycles of adjuvant chemotherapy, type of primary recurrence, the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis and pleural effusion. Regular and complete physical examination after surgery as well as prompt intensive treatment for high-risk patients may have positive significance in the treatment of such type of patients. However, a type of more reasonable and individualized treatment is warranted in future studies.

Adult ; Aged ; Axilla ; Bone Neoplasms ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Groin ; Humans ; Liver Neoplasms ; secondary ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Recurrence, Local ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Survival Rate

OBJECTIVETo evaluate the efficacy, safety and survival of combination of carboplatin plus paclitaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC.

METHODSPatients with core needle biopsy confirmed pathological diagnosis of IIA ∼ IIIC invasive breast cancer, negative for estrogen and progesterone receptors and HER2 by immunohistochemistry, and with indication for NACT were eligible in this study. The biopsy tumor tissues were tested for CK5/6, CK14, EGFR and Ki67. The patients received paclitaxel 175 mg/m(2) on day 1, carboplatin at an area under the curve 5 mg×min/ml on day 2 of every 21 days. The clinical response was evaluated every 2 cycles according to Standard RECIST 1.0 criteria and surgery was done after four to six cycles. Pathological complete remission (pCR) was defined if absence of invasive tumor in the breast and axillary lymph nodes samples or residual carcinoma in situ only.

RESULTSOverall, thirty-one patients were enrolled from January 2008 to November 2010. The median age was 51 years and 83.9% of the patients were diagnosed as stage IIB to IIIC diseases. 30 Patients completed chemotherapy as planed while one patient changed regimen due to paclitaxel allergy. Twenty-eight patients could be evaluated for clinical efficacy, of which CR, PR, SD, PD were achieved in 4, 20, 3 and 1 women, respectively. The objective response rate was 85.7%. The expression rate of CK5/6, CK14 and EGFR were 88.9% (24/27), 59.3% (16/27) and 63% (17/27), respectively. Among 27 patients who received modified radical mastectomy or breast-conserving surgery, 11 patients obtained pCR, with a pCR rate of 40.7% (95%CI 22.2% - 59.3%). Five of six CK5/6- and CK14-positive patients achieved pCR. All the 31 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (93.5%), vomiting (45.2%) and ALT/AST increase (32.3%), and grade 3-4 toxicities accounted for 74.2%, 3.2%, 0, respectively. Until December 2011, at a median follow-up of 28.9 months (range 5 - 47.9), eight patients developed recurrence including 5 patients died. Among 11 patients with pCR, one suffered from lung metastasis at 45 months after diagnosis and survived with tumor until now. The other ten were alive and disease free. The 3-year DFS and OS were 62% and 74.7%, respectively.

CONCLUSIONSAs a neoadjuvant treatment for triple-negative breast cancer, carboplatin plus paclitaxel regimen achieves notable higher objective response rate and pCR rate compared with the anthracycline plus paclitaxel regimen reported in the literature, and is well tolerable. It is an optimized regimen for TNBC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Biopsy, Large-Core Needle ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Carboplatin ; administration & dosage ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neutropenia ; chemically induced ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Survival Rate ; Young Adult

OBJECTIVEEndobronchial metastases (EBM) secondary to extrapulmonary solid malignant tumors are rare but may occur. The most common extrathoracic malignancies associated with EBM are colorectal, renal and breast cancer. This study aimed to evaluate the clinicopathological aspects of EBM from breast cancer and the prognosis of the patients.

METHODSClinicopathological data of 11 cases diagnosed as EBM from breast cancer treated in our hospital from 2003 to 2010 were re-evaluated. Their symptoms, recurrence interval, radiological features, histopathological properties, and prognosis were assessed.

RESULTSEleven cases were diagnosed by bronchoscopic bronchial biopsy. The median interval from diagnosis of breast cancer was 57 months (range: 11 - 189 mo). All patients had other proven metastases when the EBM was diagnosed. The most frequently observed symptoms were cough (8 cases). Interestingly, two patients were asymptomatic. Hilar mass (5 cases) was a common radiological finding. No disaccordance between the hormone receptor status in the primary and metastatic lesions in these patients was found. The median survival after EBM diagnosis was 21 months (range: 6 - 36) with four patients still alive and one of these four patients was surviving more than 7 years.

CONCLUSIONSOn average, EBM is diagnosed about 5 years after the diagnosis of breast cancer, which is a relatively long lead time, but the median survival time is short, as 21 months in our group. The treatment plan must be individualized, because in some cases, long-term survival can be expected.

Adult ; Antineoplastic Agents ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Bronchial Neoplasms ; drug therapy ; secondary ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; radiotherapy ; secondary ; surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Nitriles ; therapeutic use ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Analysis ; Triazoles ; therapeutic use

OBJECTIVETo characterize the sites of distant recurrence and clinical outcomes in a cohort of Chinese patients with metastatic triple-negative breast cancer (TNBC).

METHODSOne hundred and thirty-four patients with metastatic TNBC treated at Cancer Hospital of CAMS from January 1999 to December 2007 were included in this study. The clinicopathological features and long-term survival of the patients were retrospectively analyzed.

RESULTSThe median age of the patients was 45 years. Most patients (72.7%) had a higher predilection for visceral metastasis and early recurrence within the first two years of follow-up. Six patients (4.5%) presented with stage IV disease, 14 patients were diagnosed with locoregional recurrence after mastectomy, 75 patients with distant metastases, and 45 patients with both locoregional recurrence and distant metastasis. The most common site of first recurrence was the lung, and 62(51.7%)of the patients had more than two sites of metastasis. By July 30, 2009, 75 patients died of breast cancer (56.0%). The median overall survival (OS) was 26.5 months [95% confidence interval (CI), 20.5 - 32.6 months]. The 1-, 3- and 5-year overall survivals (OS) were 80.9%,37.1% and 30.1%, respectively. The median overall survival time of 58 patients with single site of metastasis was 28.5 months, longer than that of patients with more than two sites of metastases. Patients whose initial distant recurrence was bone metastasis only (7 patients) had better prognosis, with a median OS of 84.2 months. The median OS (28.5 vs. 12.6 months, P = 0.0001) differed significantly between patients who received first-line chemotherapy and those who did not. Forty-five of the 96 patients with measurable disease achieved complete/partial response (CR/PR), 39 patients had stable disease (SD), and 12 patients had disease progression (PD). The median OS was 36.1 months in patients with CR/PR, 20.8 months with SD, and 14 months with PD, respectively. The median OS of patients with CR/PR was significantly longer than that of patients with SD/PD (P = 0.0108). Distant metastasis, first-line chemotherapy and clinical response were significantly related with OS by univariate analysis. Furthermore, first-line chemotherapy and the clinical response were demonstrated to be an independent prognostic factor by multivariate analysis.

CONCLUSIONSRecurrence risk and mortality are considerably higher in TNBC patients within the early years of follow-up. TNBC patients have a higher risk of multiple and visceral metastases, and poorer survival, which might attribute to its aggressive clinical behavior and lack of effective regimens. Our findings also suggest that chemotherapy can effectively improve the clinical outcome of those patients.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; secondary ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Remission Induction ; Retrospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo investigate the clinicopathological characteristics and prognosis in young patients with estrogen receptor (ER)-negative, progesterone receptor(PR)-negative, and Her-2-negative (triple-negative) breast cancer (TNBC).

METHODS94 young patients (< or = 35 years old) with TNBC at the Cancer Hospital of CAMS between January 1999 and December 2007 were included in this study. The clinicopathological features and prognosis of those 94 patients were retrospectively evaluated.

RESULTSAmong 786 young patients with breast cancer, 94 patients (12.0%) were triple-negative. The median age of the 94 young TNBC patients was 31 years.81 patients (86.2%) were diagnosed with invasive ductal carcinoma. 82.0% of the patients were classified as T1 or T2. The TNM stages included: 17 patients in stage I (18.1%), 48 in stage II (51.1%), 28 in stage III (29.8%) and 1 in stage IV (1.1%). 14 patients (14.9%) were diagnosed with lymphovascular invasion. The 1-, 3-, 5- and 7-year disease-free survival (DFS) was 88.3%, 66.9%, 59.7% and 59.7%, respectively. The corresponding overall survival (OS) rate was 98.9%, 85.6%, 72.9% and 69.6%, respectively. The univariate analysis showed that T stage, lymph node metastasis, clinical stage and lymphovascular invasion were correlated with the overall survival. However, only vascular invasion was showed to be an independent prognostic factor assessed by multivariate analysis. 33 patients developed recurrence or metastatic TNBC during the follow-up period. Among those 33 cases, 29 had recurrent or metastatic diseases within 3 years postoperatively and the other 4 cases after 3 years following surgery.

CONCLUSIONYoung patients with TNBC represent distinctive clinicopathological and prognostic characteristics. Progression on tailored treatment for such population is still crucial. Further studies on rational individualized treatment regimen are warranted.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Brain Neoplasms ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Carcinoma, Medullary ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Mastectomy ; methods ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate ; Young Adult

A malignant tumor is generally believed to be very unlikely to metastasize to the thymus. Only three cases of thymic metastases have been reported so far in the medical literature. We report here a rare case of metastatic breast cancer to the thymus, which was detected by CT and PET scanning, and the metastasis was also confirmed by video-assisted thoracic surgery biopsy. Recognition of an unusual breast cancer metastasis, such as to the thymus, as well as the usual patterns of breast cancer metastasis will facilitate an accurate, prompt diagnosis and its appropriate treatment.
Adult ; Antineoplastic Agents, Phytogenic/therapeutic use ; Breast Neoplasms/drug therapy/*pathology ; Carcinoma, Ductal, Breast/drug therapy/*pathology/secondary ; Female ; Humans ; Paclitaxel/therapeutic use ; Thymus Neoplasms/drug therapy/*secondary

OBJECTIVETo study the changes in circulating VEGF and endostatin (ES) levels during chemotherapy for patients with breast cancer, and their correlation with efficacy of chemotherapy.

METHODS40 breast cancer patients with metastases were included in this study. They received TAC/TEC, CAF/CEF, NP, CAP, CMF, TFP, TA or TC regime chemotherapy, respectively. Totally 120 serum samples were collected from the patients at three time points: before chemotherapy, the end of 1 and 5-6 chemotherapy cycles, and analyzed for VEGF and ES levels using ELISA. Tumor agiogenesis activity was evaluated by serum soluble vascular cell adhesion molecule (VCAM - 1) measured by ELISA as a surrogate marker.

RESULTS(1) Before chemotherapy, the median level of VEGF in patients with breast cancer was 496.6 pg/ml, 4.7 times higher than that of healthy controls (P <0.001). The median level of ES was 95.5 ng/ml, 18.3% lower than that of healthy controls (P = 0.183). VCAM-1 was 1077.1 ng/ml and higher than that of controls (P <0.001). The serum VEGF levels correlated with VCAM-1 levels, tumor staging and metastatic sites (P <0.05). (2) At the end of 1 cycle of chemotherapy, the serum VEGF level (median 524.8 pg/ml) was higher than the pretreatment values (P = 0.047), whereas the levels of ES and VCAM-1 were not significantly altered (110.5 ng/ml, P = 0.055; and 975.6 ng/ml, P = 0.27). (3) At the end of 5-6 cycles, the changes in VEGF correlated with the response to chemotherapy. Serum VEGF levels in 27 patients with chemotherapy-responsive and stable disease showed a significant decrease (median 287.4 pg/ml) , but not observed in 13 patients with progressive disease. VCAM-1 also showed a treatment-related change like VEGF. However, chemotherapy might only have a minor effect on ES, because there was no significant difference in the ES levels among 5-6 cycle patients, 1 cycle patients and healthy controls, and neither between therapy-responsive patients.

CONCLUSIONIntensive chemotherapy for breast cancer results in a significant decrease of serum VEGF level, which might be an indicator of the controlled disease status, and following the treatment-induced response or stabilization, the tumor angiogenesis seems to change into an anti-angiogenesis direction.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; blood ; drug therapy ; secondary ; Breast Neoplasms ; blood ; drug therapy ; pathology ; Carcinoma, Ductal, Breast ; blood ; drug therapy ; secondary ; Endostatins ; blood ; Female ; Humans ; Liver Neoplasms ; blood ; drug therapy ; secondary ; Lung Neoplasms ; blood ; drug therapy ; secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Remission Induction ; Vascular Cell Adhesion Molecule-1 ; blood ; Vascular Endothelial Growth Factor A ; blood