[A case of bisphosphonate-associated osteonecrosis of the jaw in a patient with bone metastasis of breast cancer].

A 5 6-year-old woman underwent modified radical mastectomy for left breast cancer in 2002. Bone metastases developed in November 2005, and she received pamidronate from February 2006. Pamidronate was changed to zoledronate in November 2006. In November 2007, she was referred to a dentist for pain and swelling of the right lower gum. Conservative therapy with local irrigation and antibiotics was performed, but the lesion progressed and showed ulceration with exposed bone. She was diagnosed as bisphosphonate-associated osteonecrosis of the jaws, and zoledronate was withdrawn in January 2008. Conservative therapy was continued but the necrotic lesion caused pathological fracture and fistula. In February 2009, surgical intervention was performed for the improvement of her QOL.

[A case of premenopausal stage IV breast cancer responding to neoadjuvant endocrine therapy after chemotherapy with FEC].

A 33-year-old woman was referred to our hospital with a complaint of left breast tumor. After examinations, she was diagnosed as invasive ductal carcinoma with sternum metastasis (T2N0M1(OSS), Stage IV). The tumor was hormone receptor- positive and HER2-negative. Primary systemic chemotherapy with FEC was performed. After four courses, the efficacy was judged as a partial response (PR). After chemotherapy, endocrine therapy with goserelin and tamoxifen was performed. The efficacy of endocrine therapy was as good as that of chemotherapy. After endocrine therapy for 13 months, breast conserving-surgery was performed. After surgery, radiotherapy for left breast and sternum was performed. She continues to undergo outpatient endocrine therapy with no detectable tumor. It is suggested that neoadjuvant endocrine therapy may be useful with consideration for treatment effectiveness and the patient's quality of life.

[Two cases of breast cancer responding to primary systemic chemotherapy containing trastuzumab without surgery].

The first case was a 40-year-old woman who was referred to our hospital with a complaint of left breast tumor. She was diagnosed as invasive ductal carcinoma (T2N0M0, Stage IIA). The tumor was ER-negative, PR-negative and HER2-positive. After primary systemic chemotherapy with 6 courses of 5-fluorouracil+epirubicin+cyclophosphamide(FEC)and 3 courses of weekly paclitaxel (PTX)+trastuzumab, the efficacy of chemotherapy was judged as a complete response (CR). After chemotherapy, radiotherapy for her left breast was performed without surgery. At 21 months after CR, local efficacy was judged as CR, but liver and bone metastases appeared, and were treated by capecitabine and trastuzumab. The efficacy of chemotherapy was judged as a partial response (PR). The second case was a 26-year-old woman referred to our hospital with a complaint of right breast tumor. She was diagnosed as invasive lobular carcinoma (T2N0M0, Stage IIA). The tumor was ER-positive, PR-negative and HER2-positive. After primary systemic chemotherapy with 4 courses of FEC and 6 courses of docetaxel+trastuzumab, the efficacy of chemotherapy was judged as CR. Then, 4 courses of weekly PTX+trastuzumab were performed. After chemotherapy, radiotherapy for her right breast was performed without surgery. The efficacy of treatment was judged as CR for 15 months.

[A case of stage IV breast cancer with large cancer ulcer responding to combination therapy of capecitabine and medroxyprogesterone acetate and cyclophosphamide].

A 53-year-old woman suffering from nausea and vomiting was admitted to our hospital. There was a large ulcer from her left anterior chest to her right side chest. After pathological examination from the ulcer, she was diagnosed as breast cancer, scirrhous carcinoma. The estrogen and progesterone receptors were positive in the tumor. HER2 score was 1+ in the tumor. The stage was T4bNxM1(OTH). Uterine metastases of the breast cancer caused obstructive nephropathy. Ureteral obstruction was treated by urinary tract catheter. After improvement of renal failure, chemotherapy with 5-FU+epirubicin+cyclophosphamide (FEC) and docetaxel was performed. The efficacy was judged as stable disease (SD). For third-line chemotherapy, she was then treated with oral combination chemoendocrine therapy with capecitabine and medroxyprogesterone acetate. After the combination chemoendocrine therapy, the local tumor was remarkably reduced. With added cyclophosphamide, the partial response (PR) continued for 19 months. She died of peritonitis carcinomatosa and pleuritis carcinomatosa. No adverse reactions occurred with the combination chemoendocrine therapy. It is suggested that this oral combination chemoendocrine therapy may be useful with consideration for treatment effectiveness and the quality of life of the patient.

[A case of bilateral T4 breast cancer with different responses to chemotherapy].

It is recognized that hormone receptors and HER2 are important as prognostic factors in breast cancer. Moreover, it seems likely that hormone receptors and HER2 are important predictive factors for response to chemotherapy in breast cancer. We report a case of bilateral T4 breast cancer with different expression for hormone receptors and HER2. The patient was a 67-year-old woman. The Stage was T4bN2aM0, respectively. The right tumor was negative for hormone receptors and positive for HER2, while the left tumor was positive for hormone receptors and negative for HER2. After primary chemotherapy with FEC, paclitaxel and docetaxel, the efficacy for the right local tumor was judged as cCR. However, brain metastases appeared and were treated by resection and radiation. The efficacy for the left tumor was judged as PR. Modified radical mastectomy with axillary lymph node dissection was performed. The patient has survived with no recurrence.

[A case of recurrent breast cancer with multiple liver metastases responding to combination therapy of capecitabine and MPA].

The patient was a 68-year-old woman who underwent left partial mastectomy on February 1999. The stage was T2N1. There were positive for estrogen and progesterone receptors in the tumor. After operation, adjuvant therapy consisting of oral administration of tamoxifen and radiation was performed. On February 2005, she felt dyspnea and right femoral pain. After examinations, she was diagnosed as recurrent breast cancer with pleuritis carcinomatosa and bone metastasis. The patient was treated with oral administration of anastrozole and pamidronate disodium 90 mg intravenously every 4 weeks, radiation of her right femur, and OK-432 injection into the intrapleural cavity. On November 2005, she felt general fatigue and anorexia. CT examination revealed multiple liver metastases. She was treated with oral combination chemoendocrine therapy with capecitabine (2,400 mg/day) and MPA (600 mg/day). After the four courses, multiple liver metastases were remarkably reduced in the CT findings. After twelve courses, the partial response continued. No adverse reactions occurred except for gain in weight of grade 1. It is suggested that this oral combination chemoendocrine therapy may be useful for recurrent breast cancer with consideration for treatment effectiveness and the quality of life of the patient.

[A case of rectal cancer with multiple liver metastases responding to TS-1].

A 63-year-old woman was referred to our hospital with complaints of anal pain, constipation and abdominal distention caused by a rectal tumor. After examinations, she was diagnosed as rectal cancer with multiple liver metastases. The CEA level was 70.0 ng/ml and the CA19-9 level was more than 5,000 U/ml at admission. To prevent bowel obstruction, low anterior resection of the rectum was performed. At 34 days after operation, TS-1 chemotherapy was started as outpatient treatment (each course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the CEA level was reduced to 3.3 ng/ml and the CA19-9 level to 15 U/ml, both under the normal value. After the second course, administration was discontinued due to diarrhea, and restarted as a daily oral administration of 80 mg TS-1. After the five courses, the CEA level was 4.0 ng/ml and the CA19-9 level was 4 U/ml, both under the normal value. Multiple liver metastases had remarkably reduced in the CT findings. The patient continues to undergo outpatient treatment with good QOL.

[A case of Giant GIST of the stomach successfully treated with imatinib mesylate neoadjuvant therapy and followed postoperatively].

Since the advent of imatinib mesylate (IM), its clinical efficacy against gastrointestinal stromal tumor (GIST) has been widely acknowledged, and therapeutic strategies for this disease have undergone great changes. We recently experienced a case of giant GIST of the stomach that was successfully treated with IM neoadjuvant therapy prior to surgical resection, but liver metastasis recurred 1 year and 7 months after the operation. The patient was a 65-year-old male who presented at our department with the chief complaints of dizziness, malaise, and fever in April 2002. An abdominal CT revealed a mass with a maximum diameter of 17 cm, as well as a cystic septate mass, 12 cm in diameter, with a thick capsule in the left lobe of the liver. The patient was diagnosed with GIST of the stomach and liver metastasis. Since radical operation was considered difficult at that point, IM (400 mg/day) was started on May 9. The result of treatment was determined to be PR, and radical operation was considered feasible. On March 18, 2003, total gastrectomy and left hepatic lobectomy/S 6 partial lobectomy were performed in the surgery department of our hospital. The postoperative course was favorable and oral administration of IM was resumed soon after the operation. However, the drug was discontinued for financial reasons and a decreased white blood cell count (grade 3) 2 months after the operation. Recurrence in the liver and abdominal wall was found in October 2004, and oral administration of IM was resumed again. Currently, treatment with IM is ongoing. Case reports on the efficacy of IM neoadjuvant therapy are occasionally found in the literature, but there are few reports on its long-term prognosis. We report this case with a discussion of future therapeutic options.

Simple and rapid chromatographic purification of type V collagen from a pepsin digest of porcine intestinal connective tissue, an unmanageable starting material for conventional column chromatography.

A chromatographic method is described for purification of type V collagen, a minor constituent in extracellular matrix, from a pepsin digest of porcine intestinal connective tissue. The starting material was a viscous and turbid solution even after centrifugation. Direct application of the sample to a commercially available DEAE-cellulose column resulted in clogging. On the other hand, type V collagen, [alpha1(V)](2)alpha2(V) form, was successfully captured by a filter paper-based DEAE-cellulose column chromatography and purified by a subsequent commercially available cation-exchange medium without clogging. This is a vast improvement over previously described salt fractionation methods.

Isolation and identification of indigestible pyroglutamyl peptides in an enzymatic hydrolysate of wheat gluten prepared on an industrial scale.

An enzymatic hydrolysate of wheat gluten was further digested in vitro with porcine pepsin and pancreatin to obtain an indigestible peptide. Indigestible pyroglutamyl peptide was isolated from the digest by strong cation-exchange, size-exclusion, and reversed-phase chromatographies. The pyroglutamyl peptide was digested with pyroglutamate aminopeptidase, and the digest was reacted with phenyl isothiocyanate. The resultant phenylthiocarbamyl (PTC) peptides were purified by reversed-phase HPLC by using binary gradient elution with ammonium acetate buffer, pH 6.0, and acetonitrile. The PTC peptides were analyzed with an automatic peptide sequencer on the basis of the Edman degradation method with a modified program. Some pyroglutamyl peptides were also analyzed by fast-atom bombardment ionization mass spectrometry without the pyroglutamate amino peptidase digestion. Consequently, pyroGlu-Asn-Pro-Gln, pyroGlu-Gln-Gln-Pro-Gln, pyroGlu-Gln-Pro-Gln, pyroGlu-Gln-Pro-Gly-Gln-Gly-Gln, pyroGlu-Gln, pyroGlu-Gln-Pro, pyroGlu-Ile-Pro-Gln, pyroGlu-Ile-Pro, pyroGlu-Gln-Pro-Leu, pyroGlu-Gln-Phe-Pro-Gln, pyroGlu-Ser-Phe-Pro-Gln, pyroGlu-Phe-Pro-Gln, and pyroGlu-Gln-Pro-Pro-Phe-Ser were identified.