Internal mammary lymph node irradiation (IMLNI) could reduce local recurrence and distant recurrence and improve survival.The NCCN Guidelines have updated the recommends in IMLNI.However, the relative toxicities of IMLNI to the heart and lungs should be carefully considered by clinicians, so individualized indications for IMLNI are needed.Internal mammary sentinel lymph node biopsy (IM-SLNB) could be an accurate technique to guide IMLNI with minimally invasive staging, and provide more survival benefits to patients.This article reviews the benefits of IMLNI, controls of the side effect, and discussion of IMLNI guided by IM-SLNB.

Objective To investigate the changes and significances of peripheral blood CD34,KDR/CD34,CD133/CD34,and CD117/CD34 positive cell levels in patients with hemorrhagic stroke at the acute phase. Methods Thirty patients with acute hemorrhagic stroke admitted to the Department of Neurosurgery, Jiangsu Haimen People’s Hospital from September 2013 to April 2014 were enrolled retrospectively. At the same time,20 healthy subjects were selected as a control group. CD34 +,KDR+ /CD34 +,CD133 + /CD34 +, and CD117 + /CD34 +cell levels in peripheral blood were detected in patients with hemorrhagic stroke at day 1 to day 7 after cerebral hemorrhage and the day of physical examination of the control group using FACSCalibur flow cytometry. The data were obtained and analyzed using CELLQuest software. Results Peripheral blood CD34 + cells and KDR+ /CD34 +, CD133 + /CD34 +, CD117 + /CD34 + cells at day 1 to day 7 after ischemic stroke were all lower than control group (all P<0. 05). CD34 + and CD117 + /CD34 + cells decreased firstly at day 1 and 2, then increased gradually;KDR+ /CD34 + and CD133 + /CD34 + cells increased gradually at day 1 to day 5,they were all reached the peak at day 5,which were (14. 8±3. 5) í105 and (16. 7±3. 3) í105 respectively. Compared with that at day 1,CD34 + cells at day 5 and 6 were (27. 4 ±6. 3) í105 and (25. 4 ±5. 7) í105 respectively;KDR+ /CD34 + and CD133 + /CD34 + cells at day 4,5,and 6 were (10. 2±3. 1) í105,(14. 8±3. 5) í105,(12. 1±3. 4) í105 and (14. 3±3. 6) í105,(16. 7±3. 3) í105,and (13. 1±4. 0) í105,respectively;CD117 + /CD34 + cells at day 5 was (21. 3 ±4. 2) í105,which were all higher than the first day after cerebral hemorrhage (P<0.05). In the CD34 + cells,the proportion of KDR+ /CD34 + cells at day 1 to day 7 all decreased compared with the control group (all P<0. 05);the proportion of CD133 + /CD34 + cells at day 4 was (65±4)%,it was higher than the control group (P<0. 05);the proportion of KDR+ /CD34 + cells at day 5 was (55±6)% compared with day 1;the proportion of CD133 + /CD34 + at day 4 was (65 ±4)%;the proportions of CD117 + /CD34 + cells at day 4 and day 5 were (69 ±6)% and (72 ±6)% respectively,and they all increased (all P <0. 05). Conclusion Peripheral blood CD34 + cells and their cell subsets are change in patients with hemorrhagic stroke in acute phase. Speculating the different cell subsets may have different functions and potential. KDR+ /CD34 + and CD133 + /CD34 + may be the early sensitive indicators of acute hemorrhagic stroke,and CD117 + /CD34 + is largely mobilized in early stage.

Background and purpose:Sentinel lymph node biopsy is regarded as the standard of care in pa-tients without clinical axillary lymph node metastases in early-stage breast cancer. Accurate detection of sentinel lymph node is an important step for staging, prognosis, and treatment. In this study, a new sentinel lymph node tracer was produced by the rituximab to combine with the lfuorescence tracer (indocyanine green, ICG), and to identify the most appropriate combination ratio of the two agents. Its biological property and safety limitation were evaluated.Methods:Rituximab was combined directly with ICG. The new tracer was analyzed for labeled rate by instant thin-layer chroma-tography-silica gel, molecular integrity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and molecular immune activity by ELLAS. The safety limitation was tested according to the Chinese Pharmacopeia. The localization ability of sentinel lymph node was tested in mice.Results:The new tracer was intact and kept the immune activity of rituximab. The ICG labeled rate of rituximab was 100%. The new tracer was bacteria and pyogen free, and was safe to body with location injection. The most appropriate combination ratio of rituximab and ICG was 4∶1 and 6∶1 with the best sentinel lymph node imaging. The location of sentinel lymph node identiifed by the new tracer was accorded with the radiotracer.Conclusion:The preparation method of the new sentinel lymph node tracer is simple and no radioactive injury. The new tracer has no bacteria, no pyogen and no acute toxicity, and can be used in sentinel lymph node visual-ization.

Background and purpose:Sentinel lymph node biopsy has replaced axillary lymph node dissec-tion as the standard staging procedure in early breast cancer patients with clinically negative axillary lymph nodes. It is a critical step for staging and treatment. This study investigated the localization effect of a novel tracer for breast cancer sentinel lymph node biopsy [indocyanine green (ICG)-rituximab (R)], using the hind limb drainage in mice as an animal model.Methods:For exploring the optimal dose and imaging time, different doses of ICG-R were injected subcutane-ously to the dorsum of the foot in the BALB/c mice. Then the lfuorescence vasculature imaging instrument was used continuously to observe the popliteal fossa lymph node (as sentinel lymph node) from the injection to 3 h after injection. For exploring the sustained localization effect, the optimal dose of ICG-R was injected and the imaging instrument was used from imaging to 24 h after injection.Results:The time from injection to imaging and the time from injection to the optimal imaging were shortened with the increased doses, and the imaging rate of the second or third level node increased accordingly. The best dosage of the novel tracer was 0.12 μg (dosage of indocyanine green) and the time from injection to the optimal imaging was about 34 min. After the observation for 24 h, the imaging rate of sentinel lymphnode was maintained at 100%, and the imaging rate of the second and the third level lymph node increased from 0% to 20% and 10%, respectively.Conclusion:ICG-R could clearly locate the sentinel lymph node. There is no imaging of the second level lymph node within 6 h. The novel tracer has high value in the clinical application.

Objective:This study was conducted to evaluate the roles of internal mammary sentinel lymph node biopsy (IM-SL-NB) in the treatment of breast cancer patients with clinically positive axillary lymph nodes. Methods:This study is a one-armed clini-cal research conducted from June 2013 to October 2014. A total of 64 breast cancer patients from Shandong Cancer Hospital with clini-cally positive axillary lymph nodes were enrolled in the study. All patients underwent axillary lymph node dissection. Meanwhile, IM-SLNB was performed in all patients using the new injection method of radiotracer. Results:Among the 64 enrolled patients, the visual-ization rate of internal mammary lymph node was 59.4%(38/64). For the 38 patients who were subjected to visualization of the internal mammary node, the detection rate was 100%(38/38), and the incidence of complications was 7.9%(3/38). The metastasis rate of inter-nal mammary lymph node was 21.1%(8/38). Patients with upper inner quadrant tumors and metastasis of more axillary lymph nodes had a significantly higher chance of developing sentinel lymph node metastasis (P<0.001 and P=0.017, respectively) than the other pa-tients. The clinical benefit rate of the above mentioned treatment was 59.4%. Among the patients, 12.5%(8/64) received extra internal mammary radiotherapy, whereas 46.9%(30/64) patients avoided the unnecessary internal mammary radiotherapy. Conclusion:IM-SL-NB should be performed in breast cancer patients with clinically positive axillary lymph nodes because IM-SLNB could provide the ac-curate indication of radiation to the internal mammary area, especially for the patients with upper inner quadrant tumors and those with a suspiciously high level of axillary lymph node metastasis.

Background and purpose:Whether axillary sentinel lymph node biopsy (ASLNB) could replace axillary lymph node dissection (ALND) in patients who converted after neoadjuvant chemotherapy (NAC) from cN+ to ycN0 is still contentious, and the previous study only evaluated the pathological status of ALN without internal mammary lymph node (IMLN) condition. This study is to evaluate roles of ASLNB and internal mammary sentinel lymph node biopsy (IM-SLNB) in breast cancer patients after NAC.Methods:From Jan. 2012 to Dec. 2014, 60 breast cancer cT1-4N0-3M0patients who were scheduled for neoadjuvant chemotherapy (NAC) and agreed to accept surgery after NAC from our department were enrolled into the retrospective study. Patients with cN0 before NAC and ycN0 after NAC underwent ASLNB (group A). Patients with cN+ received NAC and ycN0 after NAC (group B) were treated with ASLNB and ALND. Only patients whose clinical nodal status remained positive (ycN+) after NAC underwent ALND without ASLNB (group C). All the patients received radiotracer injection and patients in group A and group B received blue dye injection additionally. Meanwhile, IM-SLNB would be performed for all patients with IM-SLN visualization.Results:The number of patients enrolled in group A, group B and group C was 6, 45 and 9 cases respectively. The accuracy rate of ASLNB in group A was 100% (6/6). Only one patient was axillary sentinel lymph node (ASLN) positive performed ALND. With combination of blue dye and radiolabeled colloid, the accuracy rate of ASLNB in group B was 100% (48/48) and the false negative rate (FNR) was 17.9% (5/28). The FNR in patients with 1, 2 and>2 SLNs examined was 27.3% (3/11), 20.0% (2/10) and 0% (0/7). All of the ALNs were positive in group C. The visualization rate of IM-SLN was 63.3% (38/60). The detection rate of IM-SLNB was 97.4% (37/38) and the metastasis rate was 8.1% (3/37). The incidence of complications was 5.3% (2/38).Conclusion:ASLNB can be performed either before or after preoperative chemotherapy for patients with cN0 disease. Among women with cN+ converted to ycN0 who had 3 or more SLNs examined, the FNR could return to be less than 10%. Those patients whose nodes are still ycN+ should perform ALND. IM-SLNB should be performed routinely in all breast cancer patients after NAC, for it might help to make clear of the nodal staging and the pathological status of IM-SLN and provide the accurate indication of radiation to the internal mammary area in case of under-stage and under-/over-treatment, expecting to develop the deifnition of pathological complete response (pCR).

OBJECTIVETo ascertain whether proanthocyanidins inhibit cell growth and migration by increasing let-7a expression in pancreatic cancer AsPC-1 cells.

METHODSThe proliferation rate, cell apoptosis rate and cell migration ability of AsPC-1 cells treated with proanthocyanidins were measured by MTT assay, Annexin V-FITC/PI staining, and Transwell migration assay, respectively. The expression of let-7a AsPC cells was detected by miRNA real-time RT-PCR after proanthocyanidins treatment. The changes in the biological behaviors of AsPC-1 cells were evaluated after transfection with let-7a mimics.

RESULTSCompared with the control group, proanthocyanidins treatment caused dose-dependent decrements of the proliferation rate and migration ability and increased the apoptosis rate in AsPC-1 cells. AsPC-1 cells with proanthocyanidins treatment showed increased expression of let-7a. Transfection with let-7a mimics resulted in obvious decreases in the cell growth rate and migration ability, and proanthocyanidins treatment significantly enhanced the inhibitory effect of let-7a mimics.

CONCLUSIONProanthocyanidins-induced cell growth and migration inhibition are partially mediated by up-regulation of let-7a expression in AsPC-1 cells.

Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; MicroRNAs ; metabolism ; Pancreatic Neoplasms ; pathology ; Proanthocyanidins ; chemistry ; Transfection ; Up-Regulation

Objective To verify the accuracy of the modified technique for internal mammary sentinel lymph node biopsy ( IM-SLNB) in breast cancer .Methods In the validation study , the radiotracer was injected with the modified technique , and fluorescence tracer was injected into the peritumoral breast tissue .The radioac-tive IM-SLN was identified by preoperative lymphoscintigraphy and γprobe.The radioactive IM-SLN received bi-opsy during operation .The status of the fluorescence tracer was identified by the fluorescence imaging system . Results A total of 162 patients were enrolled from Sep .2013 to Dec.2014.IM-SLNB was performed in 110 pa-tients.The radiotracer and the fluorescence tracer were identified in the same IM-SLN in 94 cases, and the con-cordance rate was 85.5%(Case-base, Spearman coefficient correlation 0.823, P<0.001).Conclusion Dif-ferent tracers injected into the different sites of the intra-parenchyma can reach the same IM-SLN, proving the ac-curacy of the modified technique and the hypothesis of IM-SLN lymphatic drainage pattern ( IM-SLN receives not only the lymphatic drainage from the primary tumor area but the entire breast parenchyma ) .

PURPOSE: Sentinel lymph node biopsy (SLNB), a critical staging and treatment step, has replaced axillary lymph node (LN) dissection as the standard staging procedure for early stage breast cancer patients with clinically negative axillary LNs. Hence, using a murine sentinel lymph node (SLN) model, we investigated the localization effect of the new receptor-targeted tracer, indocyanine green (ICG)-rituximab, on breast cancer SLNB. METHODS: After establishing the murine SLN model, different doses of ICG-rituximab were subcutaneously injected into the hind insteps of BALB/c mice to determine the optimal dose and imaging time using continuous (> 3 hours) MDM-I fluorescence vasculature imaging. To explore the capacity of ICG-rituximab for sustained SLN localization with the optimal dose, MDM-I imaging was monitored at 6, 12, and 24 hours. RESULTS: The popliteal LN was defined as the SLN for hindlimb lymphatic drainage, the iliac LN as the secondary, and the para-aortic or renal LN as the tertiary LNs. The SLN initial imaging and optimal imaging times were shortened with increased ICG-rituximab doses, and the imaging rates of the secondary and tertiary LNs increased accordingly. The optimal ICG dose was 0.12 μg, and its optimal imaging time was 34 minutes. After 24 hours, the SLN imaging rate remained 100%, while those of the secondary and the tertiary LNs increased from 0% (6 hours) and 0% (6 hours) to 10% (12 hours) and 10% (12 hours) to 20% (24 hours) and 10% (24 hours), respectively. CONCLUSION: ICG-rituximab localized to the SLN without imaging from the secondary or tertiary LNs within 6 hours. The optimal ICG dose was 0.12 μg, and the optimal interval for SLN detection was 34 minutes to 6 hours post-injection. This novel receptor-targeted tracer is of great value to clinical research and application.
Animals ; Breast Neoplasms ; Breast ; Drainage ; Fluorescence ; Hindlimb ; Humans ; Indocyanine Green ; Lymph Nodes ; Mice ; Models, Animal ; Rituximab ; Sentinel Lymph Node Biopsy

OBJECTIVE: To explore the eff ect of grape seed proanthocyanidins extract (GSPE) on the growth of pancreatic cancer cells and the underlying mechanisms. METHODS: The pancreatic cancer AsPC-1 cells were cultured in vitro. The effects of GSPE on cell proliferation, apoptosis and migration were analyzed by MTT, Annexin V-FITC/PI and Transwell migration assay, respectively. The expression of miR-27a and FOXO1 in AsPC-1 cells was determined by real-time RT-PCR and Western blot, respectively. The miR-27a inhibitors were applied to verify the role of miR-27a in mediation of GSPE effects. RESULTS: GSPE inhibited cell growth in a dose-dependent manner. This inhibitory effect was significant when the dosage of GSPE was more than 50 μg/mL (P<0.05 vs control). GSPE also could induce apoptosis and inhibit cell migration. MiR-27a expression was notably down-regulated when the dosage of GSPE was 75 μg/mL (P<0.01 vs control). Compared with the control group, cell proliferation inhibition was significantly increased in the miR-27a inhibitor group, the GSPE group and the miR-27a inhibitor plus GSPE group (P<0.01), while cell migration was significantly decreased (P<0.01). Compared with the GSPE or the miR-27a inhibitor group, the growth and migration inhibitory effects in the miR-27a inhibitor plus GSPE group were more obviously (P<0.01). Both GSPE and miR-27a inhibitor alone could up-regulate FOXO1 expression. But these effects were more apparent when they are applied in combination. CONCLUSION GSPE inhibites AsPC-1 cells' growth and migration partly through down-regulation of miR-27a expression.
Apoptosis ; Cell Line, Tumor ; drug effects ; Cell Movement ; Cell Proliferation ; Down-Regulation ; Grape Seed Extract ; pharmacology ; Humans ; MicroRNAs ; genetics ; metabolism ; Pancreatic Neoplasms ; pathology ; Proanthocyanidins ; pharmacology ; Up-Regulation