[A case of breast adenocarcinoma changed to squamous cell carcinoma after neoadjuvant chemotherapy].

Squamous cell carcinoma(SCC)of the breast is a rare pathological-type cancer with an unclear origin. It has been suggested that breast SCC may originate from squamous metaplasia of the ductal epithelium. We report a case of SCC of the breast which histological carcinoma type changed after neoadjuvant chemotherapy. A 66-year-old woman visited our hospital for a tumor of the left breast. Mammography indicated breast cancer. On CT scan the tumor was 40mm in diameter, and was located in the upper lateral quadrant of the left breast. Because she requested breast-conserving surgery, core needle biopsy(CNB)was performed. The histological findings showed solid-tubular adenocarcinoma, PgR(-), ER(-), HER2(-), cT2cN1cM0, cStage II B. She received neoadjuvant chemotherapy consisting of 4 courses of CEF(cyclophosphamide, epirubicin, 5-fluorouracil)and 3 courses of paclitaxel. After chemotherapy, she was considered to have progressive disease, and a modified radical mastectomy was performed. The resected tumor was cystic and 60mm in diameter, containing muddy fluid. Histopathological examination showed pure squamous cell carcinoma, PgR(-), ER(-), HER2(-), pT3pN0pM0, pStage II B. The cancer metastasized with the light axillary lymph nodes at the 6th month after the operation, and she underwent chemo-radiation therapy. She died 6 years after the operation from brain metastasis.

Targeted drug delivery to tumor vasculature by a carbohydrate mimetic peptide.

Although numerous carbohydrates play significant roles in mammalian cells, carbohydrate-based drug discovery has not been explored due to the technical difficulty of chemically synthesizing complex carbohydrate structures. Previously, we identified a series of carbohydrate mimetic peptides and found that a 7-mer peptide, designated I-peptide, inhibits hematogenous carbohydrate-dependent cancer cell colonization. During analysis of the endothelial surface receptor for I-peptide, we found that I-peptide bound to annexin 1 (Anxa1). Because Anxa1 is a highly specific tumor vasculature surface marker, we hypothesized that an I-peptide-like peptide could target anticancer drugs to the tumor vasculature. This study identifies IFLLWQR peptide, designated IF7, as homing to tumors. When synthetic IF7 peptide was conjugated to fluorescent Alexa 488 (A488) and injected intravenously into tumor-bearing mice, IF7-A488 targeted tumors within minutes. IF7 conjugated to the potent anticancer drug SN-38 and injected intravenously into nude mice carrying human colon HCT116 tumors efficiently suppressed tumor growth at low dosages with no apparent side effects. These results suggest that IF7 serves as an efficient drug delivery vehicle by targeting Anxa1 expressed on the surface of tumor vasculature. Given its extremely specific tumor-targeting activity, IF7 may represent a clinically relevant vehicle for anticancer drugs.

[Efficacy of FEC and trastuzumab/docetaxel combination therapy for metastatic breast cancer].

A 56-year-old female visited our department due to bleeding from a mass in her left breast in November 2007. There was a tumor (diameter, 5 cm) accompanied by ulcer formation and fixation to the pectoral muscle, centering on the left breast Carea. CT examination showed multiple lung metastasis and liver metastasis. Core needle biopsy demonstrated scirrhous carcinoma. The tumor was positive for ER and strongly positive for HER2. After 4 courses of FEC100, 10 courses of trastuzumab / docetaxel combination therapy were performed for a total of 30 weeks. After the therapy, the breast tumor decreased in size, and the lung and liver metastatic lesions disappeared, showing a partial response (PR). FDG-PET examination revealed no abnormal accumulation. In February 2009, left mastectomy was performed. Pathological examination revealed Grade 2b and only a slight residue of cancer cells. This patient with advanced breast cancer accompanied by distant metastasis responded to trastuzumab/docetaxel combination therapy.

Chemoenzymatic synthesis of a MUC1 glycopeptide carrying non-natural sialyl TF-beta O-glycan.

A MUC1 type of glycopeptide was synthesized by the 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS) protocol using benzyl and benzylidene-protected beta-D-Gal-(1-->3)-beta-D-GalNAc-Ser/Thr (TF-beta: a stereoisomer of the Thomsen-Friedenreich antigen). The synthetic glycopeptide was released from the resin with reagent K, and the resulting benzylated glycopeptide was deprotected under conditions of low-acidity trifluoromethanesulfonic acid (TfOH). The glycopeptide carrying duplicate non-natural O-glycans was dominant in the products, but was accompanied by a considerable amount of the glycopeptide missing one of the O-glycans. In contrast, the native alpha-glycoside was relatively stable under the acidic debenzylation conditions as shown by a parallel experiment with the glycopeptide involving alpha-D-GalNAc-Ser/Thr linkage. Enzymatic glycosylation with CMP-NeuAc was successful with both natural and non-natural O-glycans of the synthetic glycopeptide.

Synthesis of a mimic for the heterogeneous surface of core 2 sialoglycan-linked glycoprotein.

[structure: see text] An O-glycosylated peptide carrying two core 2 sialopentasaccharides of different glycoform was synthesized as a model of the heterogeneous surface of mucin glycoprotein. Solid-phase synthesis and the subsequent enzymatic sialylation gave two segments, which were coupled by selective thioester activation to produce the title compound.