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Biomedical subjects

K Hisamatsu

Publications and source records attributed to K Hisamatsu.

At least 55 records · Page 3Linked to original sources

[Report of two cases presenting with myelodysplastic syndrome during treatment of recurrent breast cancer].

Two women with recurrent breast cancer presenting with myelodysplastic syndrome (refractory anemia) during chemotherapy were reported. At diagnosis of myelodysplastic syndrome, white blood cell count, hemoglobin and platelet count were 3,300/mm3, 4600/mm3, 5.5 g/dl, 6.3 g/dl, 1.1 x 10(4)/mm3 and 6.8 x 10(4)/mm3, respectively, in case 1 and 2. Bone marrow taps showed hypercellular marrows with dysplastic changes of erythrocytes, granulocytes and megakaryocytes in both cases. Before the occurrence of the myelodysplastic syndrome, both patients received various cytotoxic agents (mitomycin C: 77 mg, 108 mg; cyclophosphamide: 34,400 mg, 40,000 mg; doxorubicin: 340 mg, 460 mg; methotrexate: 410 mg, 700 mg; and vincristine: 9.5 mg, 14 mg, in case 1 and 2, respectively). One patient died 2 months after the onset of the myelodysplastic syndrome, and the other died 3 months after due to progression of metastatic breast cancer. Risk-benefits analysis of chemotherapy, especially adjuvant chemotherapy, should be performed in cases of breast cancer.

Adult↗

[Significance of normal oral flora, particularly group oral streptococci as defense mechanism against infection in healthy individuals (normal defense mechanism by oral Streptococcus group)].

The alpha-streptococci, consisted of normal oral flora mainly, with inhibitory activity against pathogenic microbes in healthy individuals was investigated by group A Streptococcus (indicator strain 6-22 nonmucoid T-12). Rate of alpha-streptococci with inhibitory activity against group A Streptococcus was increased as aging, and the rate in pre-school children was higher than that in school children. These results suggested that more than 90% of the tested alpha-streptococci with strong inhibitory activities (S. salivarius) against indicator strain had inhibitory activities against group A Streptococcus (mucoid T-6), H. influenzae, S. pneumoniae, group C Streptococcus, and from 40% to 70% of the tested strains had also inhibitory activities against other pathogens. As there were many strains of alpha-streptococci with inhibitory activities against pathogens, that usually detected in the upper respiratory infection, the problem on the strains in the future will explain significance of the defense mechanism against upper respiratory infection and this can be applied clinically.

Adolescent↗

[Aminoglutethimide and aminoglutethimide+tamoxifen treatment for advanced breast cancer].

Twenty-eight and 24 patients with advanced breast cancer were treated with Aminoglutethimide (AG) or AG + Tamoxifen (AG + TAM) from June 1984 to June 1989, respectively. Evaluated cases were 25 and 21 treated with AG or AG+TAM, respectively. Objective response was seen in 5/25 (20.0%) for AG treatment with 9, 13, 16, 20 and 31 months remission and 4/21 (19.1%) for AG + TAM treatment with 6, 7, 12 and 26 months remission. Response rate according to dominant site of metastases were 1/10 in soft tissue, 2/7 in bone, 2/7 in lung and pleura treated with AG, 1/9 in soft tissue, and 3/5 in lung treated with AG + TAM treatment. Two of the 5 responding patients in AG treatment group had prior tamoxifen treatment and 3 out of 4 responding patients in AG + TAM treatment group had prior chemoendocrine therapy with tamoxifen and FAC chemotherapy. Main toxic side effects were lethargy and/or rash, and drug discontinuation was required in 3 cases of AG treatment group and 2 cases of AG + TAM treatment group. Serial determination of serum hormone levels during AG or AG + TAM treatment revealed a decrease in estrone and an increase in androstenedione in many cases of both treatment groups. This data suggested that AG treatment may be favorable for endocrine treatment for advanced breast cancer patients, but the response to AG was not augmented by adding TAM.

Administration, Oral↗

[The inhibitory effects of platelet activating factor (PAF) on ciliary activity of human paranasal sinus mucosa].

The effect of platelet activating factor (PAF) on human paranasal ciliated cells was investigated in vitro. Normal human paranasal sinus mucosa was obtained by surgical procedure and incubated with Eagle's MEM containing 10% FCS in the form of tissue culture. Ciliary activity was viewed at 37 degrees C under an inverted microscope equipped with a thermoregulator and a humidified CO2 chamber, recorded on video tapes and photoelectrically measured. Ciliary inhibition was observed by the treatment with PAF, in a dose dependent manner, at concentrations from 10(-10) M to 10(-6) M. The inhibitory effect of 10(-8) M PAF on ciliary activity was completely blocked when the mucosa was treated with 10(-6) M CV-3988 or 10(-6) M CV-6209 (specific PAF receptor antagonists). By the radioimmunoassay, the concentration of PAF in tissue culture was reduced by half within 12.5 min, and within 60 min it was only 5% of the initial concentration. There was no significant difference in ciliary inhibition between irrigation after a 60 min incubation with 10(-8) M PAF and non-irrigation. These results indicate that PAF inhibited ciliary activity directly and specifically, and induced irreversible damage primarily within the first 60 min after the challenge.

Cilia↗

Platelet activating factor induced respiratory mucosal damage.

Human sinus mucosal specimens from eight normal individuals were exposed to platelet activating factor (PAF) at concentrations ranging from 10(-6) M to 10(-11) M in a humidified CO2 chamber at 37 degrees C. The mucosal surface of the specimens was recorded on video tapes and magnified 2,500 times on a 19-inch television (TV) monitor. Ciliary activity of each ciliated cell was photoelectrically measured on the TV monitor in real time. PAF induced mucosal damage which resulted in a coarse profile including ciliostasis and exfoliation of epithelial cells. The length of the incubation period in which the initial coarse profile occurred on the mucosal surface inversely correlated with the concentration of exposed PAF ranging from 10(-6) M to 10(-10) M with r = -0.712 (p less than 2 x 10(-4)). Both the control medium and 10(-8) M lysoPAF showed no effect on ciliary activity or mucosal surface alteration even after 24 hr of exposure. Significant ciliary inhibition was noted after 6 hr of exposure to PAF at concentrations of 10(-8) M and 10(-10) M (p less than 0.05). After 10 hr of exposure, significant ciliary inhibition (p less than 0.01) was noted at all concentrations. Inhibition occurred in a time- and dose-dependent manner. The length of the incubation period in which initial ciliostatis occurred and the level of PAF concentration showed an inverse correlation with r = -0.918 (p less than 10(-6)). These results indicate that PAF is cytotoxic to human respiratory mucosa.

Cilia↗

Platelet activating factor (PAF) effects on ciliary activity of human paranasal sinus mucosa in vitro.

The effect of PAF on ciliary activity was investigated in vitro. Normal human paranasal sinus mucosa was obtained from the ethmoid sinuses by surgical procedure and incubated in the form of tissue culture. Mucosal surface profile was viewed under an inverted microscope and ciliary activity was photoelectrically measured. Ciliary inhibition was significantly induced after a 60 min period of incubation with 10(-8) M PAF in vitro followed by irrigation. However, when the mucosa was irrigated after a 15 min incubation period the ciliary activity showed no remarkable change. The effect of 10(-8) M PAF on ciliary activity was completely blocked when pre-incubated and then incubated with 10(-6) M CV-3988 (a specific PAF receptor antagonist); however, it was moderately inhibited when only preincubated with CV-3988. These data indicate that PAF specifically affects ciliated cells in the first 60 min after the challenge.

Cells, Cultured↗

Differential effects of estrogen and antiestrogen on in vitro clonogenic growth of human breast cancers in soft agar.

Of 534 human primary breast cancers provided for clonogenic assay in vitro, 276 (51.7%) developed distinctive colony formation by the soft-agar method. Estrogen receptors (ERs) were assayed by dextran-coated charcoal methods. A total of 65 (23.7%) of 274 breast cancers responded to added 10 nM 17 beta-estradiol (E2) by an increase in the number of colonies per dish of 150% or more of that in the controls treated with dextran-coated charcoal. The ER-positive and ER-negative tumors differed significantly in their response to E2: 55 (29.9%) of 184 ER-positive tumors responded versus 10 (11.1%) of 90 ER-negative tumors. The cancers in which the number of colonies increased to 150% or more of that of the controls were considered to be estrogen dependent; those in which the number of colonies increased to less than 150% of the control values were considered to be estrogen independent. When 1 microM tamoxifen (TMX) was added to the medium, 48 (21.3%) of 225 cancers showed a decreased in the number of colonies to 50% or less of that of the controls. Thus, we could separate breast cancers that were TMX sensitive (No. of colonies less than or equal to 50% of that of controls) from those that were TMX resistant (No. of colonies greater than 50% of that of controls). The response to TMX of the ER-positive cancers was significantly higher than that of the ER-negative tumors: 39 (25.5%) of 153 ER-positive tumors responded versus nine (12.5%) of 72 ER-negative tumors. In 153 ER-positive and 71 ER-negative tumors, we evaluated the correlation between the response to E2 and the response to TMX. ER-positive and ER-negative tumors differed significantly in their sensitivities to the two drugs. The TMX sensitivity did not completely correlate with the E2 dependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Cytotoxicity of human eosinophil granule major basic protein to human nasal sinus mucosa in vitro.

The toxic effects of the human eosinophil granule major basic protein (MBP), reduced and alkylated, were studied on human nasal mucosa in vitro. With a microscope coupled with a television monitor (magnification x 2500) and videotape recorder, we investigated the effects of MBP on the mucosa and the ciliary activity of single cells. In nasal mucosal specimens from normal individuals, MBP, 5 mumol/L and 10 mumol/L, significantly inhibited (p less than 0.01) ciliary activity by 4 and 1 hours of exposure, respectively. At these same MBP concentrations, the mucosal surface profiles were altered by 4 hours of exposure, and ciliostasis was 75% to 100% complete by 9 and 6 hours, respectively. In a mucosal specimen from a patient with nasal allergy, 1 mumol/L of MBP significantly inhibited (p less than 0.01) ciliary activity by 1 hour; alteration of the mucosal surface profile appeared by 3 hours of exposure, and ciliostasis was 75% to 100% by 13 hours. Similar alterations of the mucosal surface profile were observed with specimens from a second patient with allergies; in contrast, 1 mumol/L of MPB had no effect on specimens from a nonallergic patient. These results indicate that MBP damages human upper respiratory epithelium, causing ciliostasis and alteration of the epithelial surface at concentrations likely achieved in vivo. Furthermore, the mucosal specimens from two allergic patients were damaged by concentrations of MBP that had no effect on mucosal specimens from a normal individual.

Blood Proteins↗

[The reliability of fine needle aspiration cytology in the diagnosis of breast cancer].

Between September 1981 and December 1987, 1023 palpable breast tumors were submitted for cytological evaluation by fine needle aspiration before surgery (carcinoma: 793 cases, benign breast diseases: 230 cases). Clinical factor relating to the success of the aspirations were evaluated. Cases were regarded as positive when patients had a grade IV or more rating by Papanicolaou classification. The sensitivity was shown to be 73% (578/793); the specificity being 98% (226/230). A significantly lower rate of positive cancer identification occurred in smaller tumors (less than 2 cm, P less than 0.01) or scirrhous carcinomas (P less than 0.05). The comparison of positive rates between the aspiration cytology (66%) and the stamp cytology (95%) in 258 breast cancers (P less than 0.01) indicates the limited value of cytological diagnosis of breast cancers by fine needle aspiration.

Adenocarcinoma, Scirrhous↗

[A randomized trial of endocrine therapy, chemotherapy, and chemo-endocrine therapy in advanced breast cancer].

A randomized trial of endocrine therapy (adreno-oophorectomy, H), chemotherapy (FAC, C), chemoendocrine therapy (FAC + tamoxifen, H'C, or FAC + adreno-oophorectomy, HC) was performed in 114 advanced breast cancer patients from September, 1979 to December, 1983, and 106 were evaluable. The response to H, C, H'C, and HC was shown to be 33% (10/30), 54% (14/26), 59% (17/29), and 76% (16/21), respectively. There was a significantly higher response rate in HC group than H group. Higher but not significantly different response was obtained by H'C as compared with H. There were no significant differences in the overall survival among the treatment arms. However, patients treated with H survived longer (greater than 5 years). These results suggest that higher response obtained by chemotherapy, alone or in combination with endocrine therapy does not seem to contribute to the prolongation of survival of the patients.

Adrenalectomy↗

[Clinico-pathological study of elderly women with malignant ovarian tumors].

Twenty-five elderly women (those 70 years or older) with borderline and malignant ovarian tumors during the past 20 years were reviewed clinico-pathologically in comparison with 160 younger women (those 69 years or younger). The following results were obtained: 1) The incidence rate of elderly women for all patients of borderline and malignant ovarian tumors was 13.5%, and did not tend to increase in the past several years. 2) The rate that the elderly woman visited first at the other department excepting the department of obstetrics and gynecology was 36%, and which was statistically higher than that of the younger woman (p less than 0.01). 3) Fifty-two % of elderly patients had some complications and the incidence was significantly higher than that (23.1%) of younger patients (p less than 0.005). 4) Histopathologically in elderly patients, 9 patients (36%) were of serous cystadenocarcinoma and 17 patients (68%) were of malignant epithelial tumor (primary ovarian cancer and malignant Brenner tumor). 5) Of elderly patients, 8 (47.1%) were in Stage III and IV, and it was higher incidence than that (33.3%) of younger patients. In advanced cases, the histological grades became more poorly. 6) The survival rate of elderly patients in Stage III and IV was significantly lower than that in Stage I and II. The various treatment for Stage III and IV patients did not demonstrate the correlation in prognosis. In contrast, the survival rate for the group treated surgically in Stage I and II was significantly higher than that of non-surgical group (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

In vitro clonogenic growth and metastatic potential of human operable breast cancer.

In 254 patients with operable [International Union against Cancer (1972) Stages I, II, and III] breast cancer, the relations between in vitro clonogenic growth in soft agar of primary breast cancer tumors and their metastatic potential expressed by the relapse-free survivals (RFS) as well as overall survivals were studied. Sixty-four % (163 of 254) of cancers formed distinct colonies (30 or more colonies in a single dish, or 10 or more colonies in plural dishes). Other breast cancers (36%, 91 of 254) were designated to be negative for the clonogenicity. There was no correlation between the positive or negative clonogenicity and clinicopathological characteristics in breast cancer patients, including the age of patients, menopausal status, tumor size, T classification, International Union against Cancer stage, histological type (Japanese Breast Cancer Society), histologically proved axillary lymph node metastasis, and estrogen receptor (ER). At the time of median follow-up of 43 mo (range, 25 to 61 mo) after mastectomy, a recurrence of malignancy occurred in 19.0% (31 of 163) of the patients with positive clonogenic tumors, and in 8.8% (8 of 91) of those with negative clonogenic tumors (P = 0.03). There also was a significant difference (P less than 0.03 by log rank test, P less than 0.05 by generalized Wilcoxon test) in RFS curves between positive and negative clonogenicity groups. These differences in RFS were also noted in Stage II patients in favor of the negative colony formation group. In ER-negative cancer patients, the RFS of patients with positive clonogenic cancers was shown to be worse (P less than 0.03 by log rank test, P less than 0.05 by generalized Wilcoxon test) than patients with negative clonogenic cancers. There was no difference in RFS in ER-positive cancer patients. There was a trend (P = 0.09 by log rank test) of worse overall survival rate in patients with positive clonogenic growth. In a multivariate comparison using the principal component analysis composed of factors including positive node, T classification, histological type, age, ER, and colony formation, the clonogenicity showed a significant effect on the recurrence of malignancy and also on the survival of the patients after mastectomy. In conclusion, in vitro clonogenic growth of the primary tumor of breast cancer was shown to be one of the independent factors of metastatic potential in operable breast cancer patients after mastectomy.

Breast Neoplasms↗

[Systemic adjuvant therapy in patients with operable breast cancer].

The results of adjuvant trials conducted from April, 1972 to August, 1978 showed that chemotherapy was more effective to premenopausal patients and endocrine therapy prolonged disease-free survival of postmenopausal patients compared with premenopausal ones. Preliminary analysis of randomized trial now on going suggests that endocrine therapy is best candidate for receptor-positive patients and chemotherapy for receptor-negative patients. Prognostic factors of primary breast cancer was discussed.

Androstanols↗

[Characteristic ultrasonographic findings of the Krukenberg tumor].

Researching into the possibility of ultrasonographic differential diagnosis between the Krukenberg tumor and primary ovarian cancer, we investigated ultrasonograms of 14 Krukenberg tumors, 14 primary ovarian cancers and 5 rare ovarian tumors. Specifically we examined in each the echo pattern of the tumor wall, solid part and cystic part. The results were as follows. 1) Thirteen of the 14 cases of Krukenberg tumor demonstrated a clear tumor margin, irregular hyperechoic solid pattern and moth-eaten cyst formation. These characteristic ultrasonographic features might reflect the specific pathological findings of the Krukenberg tumor. In only one case was there a clear tumor margin, large central cyst formation and diffuse thick solid part around the cysts. 2) The primary ovarian cancers had an indistinct tumor margin, irregular low echoic solid pattern, clear small cyst formation, papillary proliferation and irregular thickness of the septum. Taking the ultrasonographic characteristic findings of the Krukenberg tumors into consideration, eleven of 14 primary ovarian cancers (78.6%) could be distinguished ultrasonographically from the Krukenberg tumor. 3) In rare cases, only a carcinosarcoma was unable to be distinguished ultrasonographically from the Krukenberg tumor. that make it possible to distinguished it ultrasonographically from primary ovarian cancer.

Adult↗

[A comparative study of the treatment of vulvar carcinomas].

The results of treatment in our department of 24 patients with various vulvar carcinomas between 1969 and 1987 are described. There were 8 patients in stage I, 3 patients in stage II, 10 patients in stage III, 2 patients in stage IV and one patient in recurrence. Eighteen patients could be followed for more than 5 years. Particular attention was given to stage and treatments. The 5-year survival rate was 87% for stage I patients, 28% for stage III patients, 0% for stage IV patient and 0% for a recurrent patient. The 5-year survival rate was 80% (4/5) for operation group, 60% (3/5) for radiation group and 20% (1/5) for radiation and chemotherapy group.

Adenocarcinoma↗

A randomized trial of adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy for operable breast cancer stratified by estrogen receptors.

Based on estrogen receptor (ER) status and menopausal status, operable breast cancer (International Union Against Cancer [UICC] Stage I, II, and III) patients were randomized for adjuvant endocrine therapy, chemotherapy, and chemoendocrine therapy, and the effects on the disease-free survival (DFS) and overall survival (OS) were compared. Adjuvant endocrine therapy was composed of tamoxifen (TAM) 20 mg/day orally for 2 years in postmenopausal patients. In premenopausal patients, oophorectomy (OVEX) was done before TAM administration. In the chemotherapy arm, the patients were given 0.06 mg/kg of body weight of mitomycin C (MMC) intravenously (IV) and then an oral administration of cyclophosphamide (CPA) 100 mg/body orally in an administration of a 3-month period and a 3-month intermission. This 6-month schedule was repeated four times in 2 years. As the chemoendocrine therapy arm, TAM with MMC + CPA chemotherapy was added. The patients were randomized according to ER and menopausal status. Estrogen receptor-positive (ER+) cancer patients were randomized to three arms: TAM +/- OVEX, MMC + CPA, or MMC + CPA + TAM. For estrogen receptor-negative (ER-) patients, there were two arms: MMC + CPA, or MMC + TAM. The study started in September 1978, and 692 patients entered until the end of 1984 were evaluated. The median follow-up was about 46 months. Totally, a 9.8% rate (68/692) of recurrence was noted, a 7.5% rate (52/692) of mortality. There were no significant differences in DFS or OS among the treatment arms in ER+ or ER- patients. There was significant differences in adverse effects such as bone marrow suppression, gastrointestinal disturbances, cystitis, hair loss between endocrine therapy and chemotherapy or chemoendocrine therapy groups. In this preliminary study, it was concluded that because of less adverse effects of endocrine therapy, it seems rational to select the operable breast cancer patients by the presence or absence of ER, namely, endocrine therapy for ER+ and chemotherapy for ER- cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗