The evaluation of Cannabidiol's effect on the immunotherapy of Burkitt lymphoma.

AIM: AF1q has a precise oncogenic function. The purpose of this study is to investigate whether CBD has an effect on the AF1q/ICAM-1 regulatory axis in Burkitt's lymphoma (BL), and thus has potential to enhance immunotherapy and reduce side effects. METHODS: We established BL cell lines with altered AF1q expression using lentivirus. After confirmation of gene expression by RT-PCR, cells were treated with CBD followed by co-culture of killing assay. RESULTS: AF1q increased oncogenic growth and colony formation, and induced resistance against cell-mediated cytotoxic chemotherapy through attenuation of ICAM-1 expression in BL. CBD was able to reverse the acquired resistance mediated by AF1q/ICAM-1 regulatory axis. CONCLUSION: CBD holds potential to enhance the efficacy of immunotherapy for BL with hyperactive AF1q/ICAM-1 regulatory axis, and warrants further study.

A comparison of indocyanine green fluorescence imaging plus blue dye and blue dye alone for sentinel node navigation surgery in breast cancer patients.

PURPOSE: To evaluate two methods of sentinel node navigation surgery (SNNS) using blue dye with and without indocyanine green (ICG) fluorescence imaging (FI) to determine the usefulness of combined ICG and blue dye. METHODS: Between 2005 and 2010, a total of 501 patients underwent SNNS in our hospital. Detection of sentinel lymph node (SLN) was performed with sulfan blue (SB) alone until 2008 and with a combination of SB and ICG-FI since 2009. ICG 5 mg and SB 15 mg were injected in the subareolar region, and FI was obtained by a fluorescence imaging device. RESULTS: We attempted to identify SLNs in 393 patients by SB alone and in 108 patients by a combination of SB and FI. The mean number of SLNs detected was 1.6 (0-5) for SB alone and 2.2 (1-6) for the combination method. The SLN identification rate was 95.7 % for SB alone and 100 % for the combination method so that the combination was significantly superior to SB in terms of the identification rate (p = 0.0037). In patients who received the combination method, detection of SLN was made through only SB in 1 patient, only ICG in 8 patients, and both in 99 patients. Lymph node metastasis was found in 56 patients with SB alone and in 16 patients with the combination method. Recurrence of an axillary node was observed in 3 patients (0.8 %) with SB alone and in no patients with the combination method. CONCLUSIONS: ICG-FI is a useful method and is especially recommended in cases where no radiotracers are available.

[Responses to primary systemic therapy for breast cancer as assessed by hormone receptor and HER2 status].

The aim of this study was to investigate responses to primary systemic therapy (PST) for breast cancer, by hormone receptor (HR) and HER2 status. This study included 107 women with T>3 cm and/or node-positive breast cancer who received PST at this department between March 2004 and January 2009. Treatment with epirubicin and cyclophosphamide (EC) followed by docetaxel (DTX) therapy was undertaken up to December 2005. From January 2006, EC followed by weekly paclitaxel (PTX) with or without trastuzumab (T) therapy was performed. From February 2008 and thereafter, the EC-PTX-T therapy was continued in HER2-positive patients, whereas the preceding EC-DTX therapy was administered in HER2-negative patients. Clinical responses of the 107 patients (56 were treated with EC-DTX, 37 with EC-PTX, and 14 with EC-PTX-T) were as follows: CR was achieved in 18 patients, PR in 74 patients, SD in 12 patients, and PD in 3 patients, with a response rate of 86. 0%. Histologically, 14 patients(13. 2%)had pathological CR(pCR)in a limited sense. When these patients were further divided according to HR status, those positive for both estrogen receptor (ER) and progesterone receptor (PgR) accounted for 1. 8%, those positive for ER and negative for PgR accounted for 5. 3%, and those negative for both ER and PgR accounted for a significantly higher percentage of 40. 0% (p<0. 0001) . By HER2 status, pCR was achieved at a significantly higher rate (47. 8%) of HER2-positive patients, compared to 3. 6% of HER2-negative patients (p<0. 0001). Common adverse events included Grade 3/4 leukopenia (57. 9%), neutropenia (67. 3%), and Grade 3 febrile neutropenia (11. 2%). The results show that a higher pCR rate can be expected after PST in HR-negative patients and HER2-positive patients. HER2-positive patients would particularly benefit from preoperative anthracycline chemotherapy followed by a taxane combined with trastuzumab.

A phase II study of epirubicin and cyclophosphamide followed by weekly paclitaxel with or without trastuzumab as primary systemic therapy in locally advanced breast cancer.

BACKGROUND: The aim of this study was to evaluate the activity and toxicity of epirubicin and cyclophosphamide followed by weekly paclitaxel with or without trastuzumab as primary systemic therapy in locally advanced breast cancer. PATIENTS AND METHODS: Patients with T2-4 (>3 cm) or N1-3 breast cancer received epirubicin (100 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every three weeks for four cycles followed by paclitaxel (80 mg/m(2)) every week for twelve cycles. Trastuzumab (initially 4 mg/kg, then 2 mg/kg) was added to paclitaxel in HER2-positive patients. The primary endpoint was the pathological complete response (pCR) rate in the breast and axilla, and secondary endpoints were the breast-conserving rate and toxicity. RESULTS: Forty-three patients were enrolled into this study and 3 patients withdrew. The pCR rate was 20.0% (95% confidence interval, 10.5-34.8%). Patients with HER2-positive tumours had a significantly higher pCR rate than the others (62.5% vs. 9.4%; p=0.0008). Twenty-four patients (60.0%) underwent breast-conserving surgery. Grade 4 neutropenia was recorded in 30.0% of the patients, and febrile neutropenia occurred in 7 patients (17.5%). CONCLUSION: Epirubicin and cyclophosphamide followed by weekly paclitaxel, either with or without trastuzumab, was an active and well-tolerated treatment for locally advanced breast cancer.

Successful neoadjuvant therapy with trastuzumab, paclitaxel and epirubicin for an elderly patient with inflammatory breast cancer.

A 75-year old woman presented with diffuse left breast enlargement, redness, edema, and a firm palpable lymph node with skin fixation in the left axilla. The tumor was diagnosed as invasive ductal carcinoma with a strongly positive human epidermal growth factor receptor 2 (HER2) score (3+). She was diagnosed as having inflammatory breast cancer (IBC) (T4d N2M0, stage IIIb). The patient received primary systemic chemotherapy with 4 courses of epirubicin 75 mg/m(2) and cyclophosphamide 500 mg/m(2) every three weeks, then 12 courses of paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (initially 4 mg/kg) weekly. Six months after the start of chemotherapy, a left modified radical mastectomy with axillary dissection was performed. No cancer cells in the breast specimen and no metastases to the axillary nodes were observed, so the therapeutic effect was determined as a pathological complete response (pCR). This report suggests that combination therapy with epirubicin and cyclophosphamide followed by trastuzumab and paclitaxel was useful for HER2-positive IBC.

Hammett studies of enantiocontrol by PHOX ligands in Pd-catalyzed allylic substitution reactions.

Electronically modified PHOX ligands 3a-e were synthesized to probe the mechanism of the enantioselective palladium-catalyzed allylic alkylation and amination reactions. Alkylation with dimethyl sodiomalonate produced only a small variation in the ee (89.3% to 93.4%), but amination with benzylamine gave a much wider variation in the ee (16.4% to 66.6%). Hammett analysis suggests that the substituents interact more significantly with phosphorus and supports a combined electronic and steric basis for enantioselection. [reaction: see text]