Teiri Sagawa

Enzyme-linked immunosorbent assay (ELISA) for human epidermal growth factor (hEGF)

An enzyme-linked immunosorbent assay for human epidermal growth factor (hEGF) by the sandwich method with the use of orthophenylene diamine (OPDA) for the substrate of the enzyme reaction was developed. This assay showed high sensitivity, and there was no problem with the recovery rates even without any pretreatment of samples. The changes of hEGF levels in plasma and serum depend on the condition of blood storage from sampling until separation of the cell content. The levels of hEGF markedly increased with time in serum, especially when stored at room temperature but less so in plasma. Changes of hEGF levels in plasma were negligible for up to 3 h if the blood was stored at 4 degrees C until separation.

Enzyme-linked immunosorbent assay (ELISA) for human tumor necrosis factor (hTNF)

Tumor necrosis factor (TNF), a monokine released mainly by macrophages, has the ability to kill cells, especially tumor cells [l]. Since the first report by Carswell et al in 1975 [2], many researchers have given a great deal of attention to this factor because of its potential for use in cancer therapy. Assays for TNF have mainly been by bioassay using L929 cells [3,4], but this approach is not suited to human sera because of assay imprecision. In order to overcome this problem, we developed an ELISA for hTNF.

Urine human epidermal growth factor (hEGF) levels following surgery

In order to investigate the contribution of growth factors in conditions of postoperative stress, we measured the blood and urine hEGF levels in patients with various surgical disorders. While the levels of serum and plasma hEGF did not change significantly after surgery, urine hEGF (u-hEGF) stayed at the base-level followed by a single peak within a postoperative period of two weeks. The peak day of u-hEGF in patients with more than 1000 ml of intraoperative bleeding was later than that in patients with bleeding of less than 1000 ml. In patients with postoperative renal failure or dysfunction, u-hEGF levels dropped and did not rise until the recovery of renal function. The changing pattern of u-hEGF levels was an indicator of operative bleeding volume and renal function.

Safety and efficacy of gemcitabine and trastuzumab in HER2-directed therapy pretreated patients with HER2-positive metastatic breast cancer: SBP-01 study.

142 Background: Prognosis of HER2-positive metastatic breast cancer (MBC) has been dramatically improved by trastuzumab (Tmab). More recently, newer anti-HER2 agents such as lapatinib, pertuzumab and T-DM1 have prolonged survival. Despite the efficacy of these drugs, most patients develop progressive disease during or after treatment, and alternative anti-HER2 agents plus chemotherapies are required in subsequent lines of treatment. However, there are few evidence on efficacy of Tmab-containing regimens after disease progression. Gemcitabine (GEM) is non-cross resistant to anthracycline and taxane. Preclinical studies have shown that the combination of Tmab and GEM has synergistic effect against HER2-positive breast cancer cell lines. SBP-01 study assessed the efficacy and safety of the combination of Tamb and GEM in patients with HER2-positive MBC previously treated with anti-HER2 therapy. METHODS SBP-01 study included patients treated with one or more anti-HER2 directed regimens for MBC. Patients were administered with GEM 1250 mg/m2 on days 1 and 8 of each 21-day cycle and Tmab 4mg/kg loading dose and then 2mg/kg weekly. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival, and safety. RESULTS Between June 2011 and June 2014, 35 patients were enrolled. Patients had ER positive tumor (37.1%), a median of 2 metastatic organ sites, visceral metastasis (80.0%), prior (neo) adjuvant Tmab (22.9%) and a median of 2 prior chemotherapy regimens for MBC. Previous HER2-directed drugs included Tmab (94.3%), lapatinib (37.1%), T-DM1 (8.6%) and pertuzumab (2.9%). ORR was 22.9% (95% CI, 8.6%-36.8%). Median PFS was 146 days. Patients with stable disease response received a median of 7 cycles (6-28 cycles) of treatment. Grade3/4 leukopenia (20.0%) and neutropenia (48.6%) were observed. All non-hematological toxicities were less than grade3. CONCLUSIONS The Combination Tmab and GEM is effective and well-tolerated regimen for patients previously treated with HER2-directed therapy, and appears to make disease stable for long time period. CLINICAL TRIAL INFORMATION UMIN000005881.

HER2-Positive Metaplastic Spindle Cell Carcinoma Associated with Synchronous Bilateral Apocrine Carcinoma of the Breast

Apocrine carcinoma, which is strictly defined as over 90% of tumor cells showing apocrine differentiation, is a rare variant of breast cancer. Here we report an uncommon case in which apocrine carcinomas developed concurrently in both breasts; in addition, a sarcomatoid spindle cell lesion was coincident in the right breast. Both apocrine carcinomas were immunohistochemically negative for estrogen receptor (ER) and progesterone receptor (PgR), but diffusely positive for androgen receptor (AR), GCDFP-15, and HER2. The presence of intraductal components in bilateral carcinomas and the absence of lymph node metastasis suggested that they were more likely to be individual primary lesions rather than metastatic disease. The spindle cell lesion showed a relatively well-circumscribed nodule contiguous with the apocrine carcinoma. HER2 oncoprotein overexpression was observed not only in the apocrine carcinoma, but also in the spindle cell lesion. Since the spindle cell component was intimately admixed with apocrine carcinoma and had focal cytokeratin expression, we diagnosed it as metaplastic spindle cell carcinoma, which was originated from the apocrine carcinoma. To our knowledge, this is the first case report of a patient with synchronous bilateral apocrine carcinomas coinciding with metaplastic carcinoma.

A case of matrix-producing breast carcinoma.

背景:metaplastic carcinomaの一亜型であるrnatrix-producing carcinomaを経験したので報告する.症例:77歳, 女性, 平成12年2月右乳房腫瘤を自覚し近医受診. 腫瘤が増大傾向のため当院外科に紹介された. 穿刺吸引細胞診では, 粘液様背景に小集塊, 一列状配列を示す2相性の欠如した細胞塊が散見され粘液癌を疑った. 組織診では, 粘液様基質内に小型の腫瘍細胞が索状ないしは小胞巣を形成する比較的細胞成分の豊富な部分と, 間質が軟骨で細胞成分の乏しい部分を認め, matrix-producing carcinomaと診断した.結語:細胞診で粘液と考えていた背景の一部に軟骨様細胞を認めた. 軟骨様細胞を認めた場合は本疾患も念頭に置く必要があると思われる.