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Biomedical subjects

M Maemura

Publications and source records attributed to M Maemura.

At least 19 recordsLinked to original sources

Recurrence of breast cancer following local excision alone for ductal carcinoma in situ.

OBJECTIVE: To assess recurrence of breast cancer following local excision alone for ductal carcinoma in situ. METHODS: Eighteen patients who received complete resection for noninvasive ductal carcinoma between 1982 and 1997 were investigated in this study. The mean age of the patients was 45 (29-78) years old. The initial presentation was a clinically palpable tumor in 4 patients, nipple discharge in 6, and microcalcification on mammograms in 8. Patients with palpable tumor underwent wide excision with at least a 2-cm free margin. Patients whose mammograms showed microcalcification underwent lumpectomy, and those who showed nipple discharge underwent duct-lobular segmentectomy. Five patients who underwent lymph node dissection up to level I or II had no lymph node metastasis. The mean follow-up period was 86 months. RESULTS: Local recurrence in the conserved breast was seen in five (27.8%) of 18 patients. The actuarial five-year event-free survival was 76.2%. The histological type of the recurrent tumor was ductal carcinoma in situ in three patients and invasive carcinoma in two. There was no difference in age at initial operation or histological subtype between patients with and without recurrent disease, but patients presenting with nipple discharge initially had a significantly shorter ipsilateral disease-free interval than those presenting with tumor or microcalcification on mammograms. All patients with local recurrence in the conserved breast were treated with breast-conserving surgery or subcutaneous mastectomy. CONCLUSION: Local recurrence frequently occurs in patients presenting with nipple discharge treated by duct-lobular segmentectomy for noninvasive ductal carcinoma. Either wide excision with a larger free margin or adjuvant radiation therapy following duct-lobular segmentectomy should be considered for these patients.

Adult↗

Tamoxifen-failed male breast cancer with a high level of circulating estrogen: report of a case.

We report herein the case of a 40-year-old man with grade II invasive ductal carcinoma of the breast (pT1, pN0, M0: stage I) in whom a recurrence developed shortly after completion of a 2-year course of tamoxifen and 5-fluorouracil therapy following a mastectomy. Although the metastatic tumor was estrogen receptor-positive, hormone therapy combined with chemotherapy had no significant effect on tumor growth, and the patient died from disseminated tumors 2 years 6 months after completion of the adjuvant therapy. It is noteworthy that the circulating estradiol level increased from 18.0 to 892.3 pg/ml during the period of tumor progression and dissemination. We interpret these findings as an indication of high aromatase activity in the metastatic tumors. We suggest that extending tamoxifen treatment to 5 years or longer be recommended for the standard adjuvant hormone therapy of male breast cancer to prevent the early recurrence of hormone-responsive disease.

Adult↗

Highest microvessel count as a long-term prognostic factor in Japanese breast cancer patients.

The aim of this study was to determine whether microvessel density (MVD) could add useful information in predicting the prognosis of breast cancer patients. In our study, MVD was calculated by counting microvessels per x200 field in the highest neovascularized area of the tumor (highest microvessel count, HMC). HMC significantly increased according to the increased number of positive nodes. Higher HMC significantly correlated with worse relapse-free survival (RFS) of patients with negative node, one to three positive nodes in the axilla or with stage I and II tumors. HMC, however, was not predictive for RFS of patients with four or more positive nodes or with stage III tumors. Multivariate analysis revealed that HMC was second only to nodal status and tumor size as being predictive for RFS. These results suggest that HMC could be used in selection of patients with early-stage breast cancer who are at high risk for having occult metastasis.

Adult↗

Sudden hemorrhage of the breast caused by breast cancer: a case report and review of the literature.

A rare case of sudden hemorrhage caused by breast cancer is reported. A 71-year-old woman noted bleeding from her left breast. Physical examination of the left breast showed a localized open cavity accompanied by bleeding and coagulation. The patient had no history of breast trauma or anticoagulation therapy. Incisional biopsy followed by histological examination resulted in a diagnosis of granulation tissue with no cancer cells present. Mammography and ultrasonography indicated probable breast cancer. As a result, a second incisional biopsy was performed, which suggested invasive ductal carcinoma without histological skin invasion. A modified radical mastectomy was performed under a diagnosis of stage II breast cancer. Breast cancer with sudden hemorrhage is rare. We review the literature and discuss the cause of this unusual manifestation.

Aged↗

A case report of advanced male breast cancer with an objective response to tamoxifen treatment.

A 70-year-old man presented with a firm tumor in his right breast first noticed eight years ago. The tumor had enlarged gradually and had produced an ulcer with bleeding. On physical examination, a huge tumor entirely occupied the right breast and extensively had infiltrated the chest wall. Chest X-ray and CT showed massive pleural effusion and multiple small nodular lesions in the lung. Invasive ductal carcinoma of the breast was diagnosed by incisional biopsy,confirming advanced breast cancer with lung metastases and bilateral pleural effusion(T4cN2M1, Stage IV). Because ER and PgR levels were 110 fmol/mg and 190 fmol/mg, respectively, and because his general condition was poor, we selected medical treatment with tamoxifen(TAM). Thirty-two weeks later, the tumor had showed pronounced reduction with scarring. The patient underwent local excision of the scar tissue. The quality of life of the patient was favorably improved and no severe adverse events were observed. The tumor in the chest wall recurred two months after the end of TAM treatment, possibly because the patient did not accept continuous TAM therapy. The patient died from complications of brain metastasis 32 months after the start of TAM treatment. We report a rare case of advanced male breast cancer and on the effectiveness of continuous TAM treatment.

Aged↗

Primary squamous cell carcinoma of the breast during lactation: a case report.

A case of primary squamous cell carcinoma of the breast during lactation is reported. The patient was a 32-year-old woman, in post-partum lactating 18 months after delivery, who was referred to our hospital following detection of a lump in her left breast during physical examination in mass screening for breast cancer. The tumor, palpated in the upper outer quadrant of the left breast, was firm, well-defined and 2.8 x 2.6 cm in size. Ultrasonograms identified an irregular-shaped hypoechoic lesion and mammograms revealed a well-defined, circumscribed tumor. Based on these findings, breast cancer was suspected and an excisional biopsy was performed. The resected specimen was a firm, solid and circumscribed tumor with central hemorrhage. Microscopic findings demonstrated that the tumor consisted of an invasive ductal carcinoma with marked squamous metaplasia, such as keratinization and squamo-columnar junction. Breast-conserving surgery was performed and no lymph node involvement was noted. Both estrogen and progesterone receptors of the tumor were negative. Generally, the size of both squamous cell carcinoma and carcinoma during the lactation period tends to be larger than ordinary carcinomas. In this case, the cancerous lesion was detected at a relatively early stage. Although the cancerous lesion was detected at a relatively early stage and no lymph node involvement was noted, lung metastases occurred within 12 months of the surgery. Malignant potential is generally considered to be high in cases of squamous cell carcinoma of the breast with lactation and thus intensive treatment potentially resulting in severe side effects was considered to be necessary for this patient.

Adult↗

Activation of protein kinase C by phorbol esters modulates alpha2beta1 integrin on MCF-7 breast cancer cells.

Cellular adhesions to other cells and to the extracellular matrix play crucial roles in the malignant progression of cancer. In this study, we investigated the role of protein kinase C (PKC) in the regulation of cell-substratum adhesion by the breast adenocarcinoma cell line MCF-7. A PKC activator, 12-O-tetradecanoylphorbol-l, 3-acetate (TPA), stimulated cell adhesion to laminin and collagen I in a dose-dependent manner over a 1- to 4-h interval. This enhanced adhesion was mediated by alpha2beta1 integrin, since both anti-alpha2 and anti-beta1 blocking antibodies each completely abrogated the TPA-induced adhesion. FACS analysis determined that TPA treatment does not change the cell surface expression of alpha2beta1 integrin over a 4-h time interval. However, alpha2beta1 levels were increased after 24 h of TPA treatment. Thus, the enhanced avidity of alpha2beta1-dependent cellular adhesion preceded the induction of alpha2beta1 cell surface expression. Northern blot analysis revealed that mRNA levels of both alpha2 and beta1 subunits were increased after exposure to TPA for 4 h, indicating that the induction of alpha2beta1 mRNA preceded that of its cell surface expression. This further suggested that the TPA-induced avidity of alpha2beta1 was independent of increased expression of alpha2beta1. Pretreatment of cells with the PKC inhibitor calphostin C partially antagonized the TPA-induced increase in expression of alpha2beta1 integrin expression and of alpha2beta1-mediated cellular adhesion. To identify a possible mechanism by which TPA could be acting to promote the rapid induction of alpha2beta1 adhesion, we treated the cells with the Rho-GTPase inhibitor Clostridium botulinumexotoxin C3. C3 inhibited TPA-induced adhesion to laminin and collagen I in a dose-dependant manner, suggesting a likely role for Rho in TPA-induced adhesion. Together, these results suggest that PKC can modulate the alpha2beta1-dependent adhesion of MCF-7 cells by two distinct mechanisms: altering the gene expression of integrins alpha2 and beta1 and altering the avidity of the alpha2beta1 integrin by a Rho-dependant mechanism.

ADP Ribose Transferases↗

Granular Cell Tumor of the Breast Diagnosed by Core Needle Biopsy: A Case Report.

Granular cell tumor rarely occurs in the breast. We report a 69-year-old woman with a right breast mass that simulated carcinoma on palpation, mammography, and ultrasonography. Aspiration biopsy cytology showed no malignant atypical cells. Core needle biopsy was performed to obtain an accurate diagnosis. The lesion was histologically confirmed to be a granular cell tumor. Immunostaining was positive for S-100 protein and vimentin, and negative for keratin, carcinoembryonicantigen, estrogen receptor and gross cystic disease fluid protein-15. The tumorwas treated by wide local excision. Surgeons should be aware that granular cell tumor can resemble breast cancer in order to avoid performing a needless radical mastectomy.

Journal Article↗

Treatment for accidental occlusion of the hepatic artery after hepatic resection: report of two cases.

Two patients in whom accidental hepatic artery occlusion (HAO) occurred after hepatic resection (Hx) were reported. A 59-year-old female who underwent Hx for hepatocellular carcinoma with underlying liver cirrhosis developed HAO on postoperative day (POD) 14 and died of hepatic failure on POD 23. The autopsy findings showed multiple necrosis in the remnant liver and an extraluminal hematoma of the hepatic artery, suggesting an injury caused by Pringle's maneuver. The second case was a 53-year-old male who underwent Hx for cholangiocarcinoma without any underlying liver disease. He developed HAO on POD 6, and radiological studies indicated a pseudoaneurysma formation and severe stenosis of the hepatic artery. It was speculated that the cause of the HAO was intraluminal injury of the hepatic artery during an angiographic study conducted prior to Hx. Partial arterialization of the portal vein was performed, following which his liver function test results improved. In both cases, measuring the serum hepatocyte growth factor level and the hepatic vein oxygen saturation proved useful, not only for determining the degree of liver injury, but also for predicting the outcome after treatments for HAO. Furthermore, the partial arterialization of the portal vein for HAO after Hx may rescue the normal remnant liver.

Aneurysm, False↗

The efficacy of technetium-99m-MIBI scan and intraoperative methylene blue staining for the localization of abnormal parathyroid glands.

The efficacy of the technetium-99m-2-methoxyisobutylisonitrile (Tc-MIBI) scan and intraoperative methylene blue staining was analyzed in a consecutive series of 15 patients with primary hyperparathyroidism who underwent neck surgical exploration. A total of 17 abnormal parathyroid glands were removed, 7 of which were confirmed histologically as adenomas and 10 as hyperplasias. The Tc-MIBI scan and the thallium-201-technetium-99m subtraction (Tl/Tc) scan preoperatively localized 11 (69%) of 16, and 6 (40%) of 15 abnormal parathyroid glands, respectively. The Tc-MIBI scan correctly localized two ectopic abnormal parathyroid glands which were not localized by the Tl/Tc scan or ultrasonography (US). However, it also demonstrated false-positive accumulations caused by thyroid diseases in two patients. There were 4 abnormal parathyroid glands not detected by the preoperative imaging techniques, whereas all 17 abnormal parathyroid glands were stained with methylene blue, the infusion of which caused no adverse effects or toxicity. In conclusion, Tc-MIBI scanning and intraoperative methylene blue staining are effective techniques for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism.

Adenoma↗

Natural history of fibroadenomas based on the correlation between size and patient age.

BACKGROUND: Several recent studies have reported that most fibroadenomas remain static or regress when they are managed conservatively; however, no such studies have evaluated the breast disorder in Japanese women. To understand the natural history of fibroadenomas in Japanese women, we examined the correlation between the sizes of the fibroadenomas and the women's age. METHODS: Fifty-eight consecutive patients (age range, 17-51 years; mean, 33.9 years) with histologically confirmed fibroadenoma were enrolled in this study. The sizes of the excised fibroadenomas were analyzed in relation to the women's ages. RESULTS: The fibroadenomas decreased significantly in size (Y, mm) with patient age (X, years) (P = 0.0012) according the equation Y = -0.340X + 27.0 (95% confidence limits for the slope, -0.139 to -0.540). From this equation, the mean sizes of the fibroadenoma in women aged 20, 30 and 40 years were expected to be 20.2 mm (95% confidence interval, 16.2-24.2 mm), 16.8 mm (95% confidence interval, 10.8-22.8 mm) and 13.4 mm (95% confidence interval, 5.4-21.4 mm), respectively. The mean annual decrease in the size of the fibroadenomas was 0.340 mm. CONCLUSIONS: Our results indicate that in Japanese women fibroadenomas increase in size more frequently in younger than in older women. Moreover, it is speculated that most fibroadenomas might stop growing when they reach an approximate maximum diameter of 20 mm, after which time they might remain static or regress.

Adolescent↗

Mitogen-activated protein kinase cascade in breast cancer.

The mitogen-activated protein (MAP) kinase is considered to play a central role in diverse cellular events including carcinogenesis and tumor progression. Indeed, expression of MAP kinase, tyrosine-phosphorylated MAP kinase, and Raf-1 protein was greater in cancerous human tissues than in the surrounding noncancerous glands. In a 7,12-dimethylbenz[a]anthracene-induced rat mammary carcinoma model, estrogen promoted and ovariectomy and antiestrogen, tamoxifen (TAM) inhibited the tumor growth. Ovariectomy suppressed expression of MAP kinase, tyrosine-phosphorylated MAP kinase and Raf-1, whereas estrogen as well as TAM induced expression of MAP kinase and Raf-1 under castrated conditions. Since it was reported that MAP kinase was activated during the progression of breast carcinoma cells, such estrogenic actions of TAM toward the MAP kinase cascade might be responsible for malignant progression.

Animals↗

The mechanisms of antitumor effects of luteinizing hormone-releasing hormone agonist (buserelin) in 7, 12-dimethylbenz(a)anthracene-induced rat mammary cancer.

We evaluated the mechanism of antitumor effects of buserelin, which is one of LH-RH agonists, on a hormone dependent breast cancer model, using 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary cancer. Rats developing solid mammary tumors within 5-7 weeks following the DMBA administration were divided into groups weekly, and treated without delay. The tumor bearing rats were randomized into five groups with regard to tumor size or average weight (15 rats per group). Each group received one of the following treatments during 4 weeks: a) no treatment (NT); b) ovariectomy (Ovx); c) buserelin; d) Ovx and 17beta-estradiol (E2) (Ovx+E2); e) Ovx+E2+buserelin. Tumor regression immediately began at one week after both buserelin treatment and ovariectomy. A significant reduction of tumor size was observed in both buserelin-treated rats and Ovx rats compared with NT rats (p<0.01). No significant difference of tumor size was observed between buserelin-treated rats and ovariectomized rats. No reduction of tumor size was observed in Ovx+E2 rats and Ovx+E2+buserelin rats. Although the mean uterine wet weight of the buserelin group was significantly higher than that of the Ovx group, it was significantly lower than that of the NT group. The mean uterine wet weight of the NT group, the Ovx+E2 group and the Ovx+E2+buserelin group was similar and was significantly higher than that of the Ovx group. Buserelin did not inhibit exogenous estrogen-dependent tumor growth in DMBA-induced rat mammary cancers. These results suggest that buserelin has no direct effects on DMBA-induced rat mammary cancers, and the main mechanism of action of buserelin for tumor-reduction is due to ovarian estrogen deficiency.

9,10-Dimethyl-1,2-benzanthracene↗

Serum concentration of hepatocyte growth factor in patients with metastatic breast cancer.

The serum concentration of hepatocyte growth factor (HGF) was examined in 34 patients with metastatic breast cancer. Although no significant difference was observed between HGF concentration and the site of metastasis, serum HGF levels were slightly higher in patients with liver metastasis and in patients with multiple metastatic sites than in patients with other lesions. Significantly higher levels of serum HGF were observed in patients with progressive metastasis of breast cancer compared with those with stable metastasis. The patients with high HGF levels exhibited a significantly shorter survival rate than those with low HGF levels. Circulating HGF levels may be a useful indicator for the progression of metastatic lesions and the prognosis of patients with metastatic breast cancer.

Adult↗

A combination chemoendocrine therapy of mitoxantrone, doxifluridine, and medroxyprogesterone acetate for anthracycline-resistant advanced breast cancer.

Between January 1993 and October 1995, 34 patients with anthracycline-resistant advanced breast cancer were treated with a combination chemoendocrine therapy of mitoxantrone (MIT), doxifluridine (5'-DFUR) and medroxyprogesterone acetate (MPA). Of 34 patients, 28 were evaluable for efficacy of this combination therapy, and 30 including 2 for whom data were incomplete were assessed for adverse drug reactions. Adriamycin (ADM) was used for pretreatment in 12 patients, 4'-epi-ADM in 6, and THP-ADM in 12. In the eligible patients, 8.0 mg/m2 MIT was administered intravenously every 4 weeks, and 600 mg MPA and 600 mg 5'-DFUR were given orally every day. The median follow-up period was 25 weeks (range 2-90 weeks). The median cumulative dose of mitoxantrone was 66 mg (range 12-121 mg). Of the 28 patients, 11 (39.3%) responded to this combination therapy. As for response in relation to predominant site of lesion, 1 of 5 soft tissue lesions (20%) and 8 of 12 bone metastases (66.7%) showed a partial response, and one complete response and one partial response (25.0%) were seen in eight lung lesions. None of three pleural lesions responded to this therapy. The median duration of response was 31 +/- weeks (range 12-82 weeks). Adverse drug reactions were controllable or tolerable. Combined chemoendocrine therapy with a low dose of MIT is a well-tolerated and moderately effective regimen for the treatment of anthracycline-resistant advanced breast cancer.

Adult↗

c-erbB-2 status is an independent predictor of survival after first recurrence.

We studied retrospectively the interaction between c-erbB-2 overexpression and the prognosis in 239 invasive breast cancer patients who underwent radical operations between January 1984 and April 1991. The c-erbB-2 protein was overexpressed in 42 (17.6%) of 239 patients. There was no correlation between c-erbB-2 overexpression and age at operation, tumor size, lymph node involvement, or clinical stage. Only an inverse correlation was found between c-erbB-2 overexpression and hormone receptor levels. Patients with c-erbB-2 overexpression had a significantly worse overall survival than those without c-erbB-2 overexpression. In relation to lymph node involvement or estrogen receptor status, a significant difference in overall survival between the c-erbB-2-positive and -negative groups was found in patients with lymph node metastasis or in those with estrogen receptor-negative tumors. Out of 237 patients (two were lost to follow-up), 42 recurred and 25 died of breast cancer. The c-erbB-2-negative patients survived significantly longer after the time of first recurrence than the c-erbB-2-positive patients. In a multivariate analysis using Cox proportional-hazard regression model, c-erbB-2 status and disease-free interval were independent predictors of survival after first recurrence. In conclusion, c-erbB-2 status is an independent prognostic indicator of survival after first recurrence.

Biomarkers, Tumor↗

Angiogenesis and stromal fibronectin expression in invasive breast carcinoma.

Angiogenesis and stromal fibronectin (SFN) expression were immunohistochemically analyzed in 83 breast cancer specimens. Microvessel count (MVC), which correlated with lymph node metastasis, TNM stage, recurrence, and mortality, was relatively low in SFN-positive tumors. SFN expression did not correlate with lymph node metastases or tumor size. However, SFN positivity was less likely in patients with recurrent disease than in those without recurrence, and relapse-free survival was significantly better in patients with SFN-positive tumors than in those with SFN-negative tumors. MVC and SFN positivity were significant independent predictors of relapse-free survival as well as tumor size and axillary nodal status (Cox's proportional hazards regression analysis). Angiogenesis and SFN expression, both of which are inversely related, can be used prognostically in patients with breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Inhibitory effects of an antiestrogen, toremifene, on the phorbol ester-induced adhesive capacity of breast carcinoma cells.

Previous studies have revealed that protein kinase C (PKC) is responsible for malignant progression. In the present study, we investigated the potent inhibitory effects of an antiestrogen, toremifene, on PKC-mediated cellular adhesion. A phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly enhanced alpha2beta1 integrin-dependent adhesion of MCF-7 breast carcinoma cells. This PMA-induced adhesion was partially inhibited by incubating cells with toremifene prior to PMA exposure in a time- and dose-dependent manner. FACS analysis demonstrated that the PMA-induced alpha2beta1-dependent cellular adhesion was accompanied with elevated expression of alpha2beta1+integrin subunit on the cell surface. However, toremifene did not affect the elevated expression levels of these integrins but rather the avidity of alpha2beta1 integrin. We concluded that toremifene inhibited cellular adhesion activated by PMA, probably through mechanism which inhibits PKC.

Breast Neoplasms↗