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1.
J Nanosci Nanotechnol ; 19(3): 1445-1450, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30469203

ABSTRACT

p-Type Si/intrinsic Si/n-type nanocrystalline iron disilicide heterojunctions were created by utilizing facing targets direct-current sputtering at the pressure of 1.33×10-1 Pa that investigated the photovoltaic properties. They exhibited a large leakage current and a small energy conversion efficiency of 0.62%. From using the method of Nicollian and Brews, the series resistance (Rs) values at zero bias voltage were 7.40 Ω at 2 MHz and 7.57 Ω at 50 kHz, respectively, which were in agreement with that estimated by the means of Norde. From applying the method of Hill-Coleman, the interface state density (nss) values were 3.15×1015 cm-2 eV-1 at 50 kHz and 8.93×1013 cm-2 eV-1 at 2 MHz. The obtained results revealed the presence of Rs and nss at the junction interface, which should be the potential cause of spoiled photovoltaic performance in the heterojunctions.

2.
Gan To Kagaku Ryoho ; 46(1): 145-147, 2019 Jan.
Article in Japanese | MEDLINE | ID: mdl-30765669

ABSTRACT

The patient was a 59-year-old man with type 2 advanced gastric cancer in the antrum. Abdominal computed tomography revealed the primary tumor with regional lymph node metastasis. Distal gastrectomy and D2 lymph node dissection were performed. Histopathological findings indicated gastric small cell carcinoma. Lymph node metastasis was observed microscopically in the #6 lymph nodes. Peritoneal lavage cytology was positive. The pathologic stage of the disease was pT2(MP), med, INF b, ly2, v2, pPM0, pDM0, pN2(6/33: #5, #6), M1, P0, CY1, H0, stage Ⅳ, R1(cy+). After surgery, he received chemotherapy with capecitabine plus oxaliplatin. However, after 1 course of therapy the disease had progressed, and the patient was diagnosed with peritoneal metastasis. Chemotherapy of CDDP plus CPT-11 was initiated, and after 5 courses the patient died.


Subject(s)
Carcinoma, Small Cell , Stomach Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/pathology , Carcinoma, Small Cell/surgery , Cisplatin , Drug Combinations , Gastrectomy , Humans , Lymphatic Metastasis , Male , Middle Aged , Oxonic Acid , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Tegafur
3.
Gan To Kagaku Ryoho ; 46(13): 1954-1956, 2019 Dec.
Article in Japanese | MEDLINE | ID: mdl-32157024

ABSTRACT

Laparoscopy and endoscopy cooperative surgery(LECS)is the surgical procedure used to avoid excessive resection of the gastrointestinal wall and preserve its function. We report the case of a patient who was successfully treated with inverted LECS for gastrointestinal stromal tumor(GIST)in the remnant stomach and underwent distal gastrectomy. The patient was a 75- year-old man who received distal gastrectomy for gastric ulcer 28 years before. Three years before he was diagnosed as having gastric submucosal tumor(SMT)as a gastrointestinal tumor(GIST)by using EUS. As the tumor increased, he was admitted to our hospital. Upper gastrointestinal endoscopy revealed a 30mm SMT just below the cardiac part of the remnant stomach. Biopsy by EUS-FNA revealed CD34(-), c-kit(+), S-100(-), and a-SMA(-), which indicated gastric GIST. Inverted LECS was performed. His postoperative course was good, and he was discharged from the hospital 9 days after the surgery.


Subject(s)
Gastric Stump , Gastrointestinal Stromal Tumors , Laparoscopy , Stomach Neoplasms , Aged , Gastrectomy , Gastrointestinal Stromal Tumors/surgery , Humans , Male , Stomach Neoplasms/surgery
4.
Breast Cancer Res Treat ; 167(1): 39-47, 2018 01.
Article in English | MEDLINE | ID: mdl-28905250

ABSTRACT

PURPOSE: The present study evaluated whether morphological-measured stromal and intra-tumour tumour-infiltrating lymphocytes (TILs) levels were associated with gene expression profiles, and whether TILs-associated genomic signature (GS) could be used to predict clinical outcomes and response to therapies in several breast cancer subtypes. METHODS: We retrospectively evaluated haematoxylin eosin (HE)-TILs levels and gene expression profiling data from 40 patients with primary breast cancer and extracted the 22 overexpressed genes in cases with high TILs scores as the TILs-GS. The TILs-GS were compared with breast cancer subtype and were evaluated predictive values for prognosis and response to therapies. RESULTS: Higher TILs-GS expressions were observed for triple-negative and human epidermal growth factor receptor 2 (HER2) positive (+) breast cancers, compared to the luminal types (P < 0.001). With the exception of HER2+, the TILs-GS had no prognostic value in subtypes of breast cancers. The Wilcoxon test revealed significantly different TILs-GS levels between the cases with pathological complete response (pCR) and residual disease after anthracycline and taxane-based neoadjuvant chemotherapy, with the exception of the luminal-low proliferation subtype. In the multivariate analysis, pCR was independently associated with smaller tumour size, higher histological grade, ER negativity, HER2 positivity and higher TILs-GS scores (OR 2.02, 95% CI 1.30-3.14, P = 0.025). CONCLUSIONS: TILs-GS was associated with stromal and intra-tumour TILs levels, as evaluated using HE, which predicted prognosis and chemotherapy response in several breast cancer subtypes. Further studies are needed to perform stratification according to TILs-GS levels and the conventional breast cancer subtypes.


Subject(s)
Breast Neoplasms/drug therapy , Breast/drug effects , Lymphocytes, Tumor-Infiltrating/drug effects , Prognosis , Aged , Breast/pathology , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Female , Gene Expression Regulation, Neoplastic/drug effects , Genomics , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Middle Aged , Neoadjuvant Therapy/adverse effects , Receptor, ErbB-2/genetics , Trastuzumab/adverse effects
5.
Gan To Kagaku Ryoho ; 45(13): 2461-2463, 2018 Dec.
Article in Japanese | MEDLINE | ID: mdl-30692498

ABSTRACT

A 71-year-old man visited our hospital because ofepigastralgia and anorexia. Upper gastrointestinal endoscopy revealed type 1 gastric cancer. Contrast-enhanced abdominal CT revealed gastric wall thickening in the midgastric region and direct invasion ofthe transverse colon. CT findings also revealed a suspicion ofdissemination on the omentum and para-aortic lymph node swelling. We diagnosed gastric cancer with transverse colon invasion. Therefore, we performed distal gastrectomy with transverse colectomy and D2+No.16b1 lymph node dissection after obtaining patient consent. We observed direct tumor invasion into the transverse colon and seeding nodules on the omentum. Liver metastasis was not seen, and ascitic cytology was negative. He was discharged 16 days postoperatively, without any complications. Histopathological analysis revealed poorly differentiated adenocarcinoma and gastrocolic fistula. Postoperatively, S-1 was administered for 4 years as adjuvant chemotherapy. There has been no recurrence for 9 years after surgery.


Subject(s)
Colon, Transverse , Stomach Neoplasms , Aged , Colon, Transverse/diagnostic imaging , Colon, Transverse/pathology , Colon, Transverse/surgery , Disease-Free Survival , Gastrectomy , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Neoplasm Invasiveness/diagnostic imaging , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery
6.
Gan To Kagaku Ryoho ; 44(12): 1281-1283, 2017 Nov.
Article in Japanese | MEDLINE | ID: mdl-29394607

ABSTRACT

A79 -year-old woman underwent colonoscopic examination for positive occult blood. Aneoplastic lesion was seen in the orifice of the vermiform appendix. She was referred to our hospital and underwent colonoscopic examination again. The biopsy revealed poorly differentiated adenocarcinoma or mixed adenoneuroendocrine carcinoma(MANEC), and she was diagnosed with carcinoma of the appendix. She was treated by laparoscopic ileocecal resection with lymph node dissection (D3). Histopathological examination revealed goblet cell carcinoid(GCC)of the appendix with serosal invasion. No metastasis was detected in the dissected lymph nodes. This patient has been followed-up for 6 months after surgery and no recurrences have been detected.


Subject(s)
Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/surgery , Carcinoid Tumor/surgery , Cecum/surgery , Ileum/surgery , Aged , Colectomy , Colonoscopy , Female , Humans , Laparoscopy , Occult Blood , Treatment Outcome
7.
Gan To Kagaku Ryoho ; 44(12): 1248-1250, 2017 Nov.
Article in Japanese | MEDLINE | ID: mdl-29394596

ABSTRACT

A 25-year-old woman presented to our hospital with left flank pain and diarrhea. Contrast-enhanced abdominal computed tomography(CT)showed a target sign in the descending colon. She was diagnosed with intussusception of the colon. Colonoscopy revealed a tumor at the splenic flexure. We performed surgery and found an invaginated transverse colon at the splenic flexure. Reduction was unsuccessful with Hutchinson's maneuver, and we performed partial resection of the invaginated colon. Histopathological diagnosis was adenocarcinoma, tub1, SM2. Adult intussusception is uncommon, especially in young adults. It is usually caused by a polyp or tumor. We report a case of intussusception caused by colon cancer in a young female patient, and review the literature.


Subject(s)
Adenocarcinoma , Colon, Transverse/pathology , Colonic Neoplasms/pathology , Intussusception/surgery , Adenocarcinoma/complications , Adenocarcinoma/surgery , Adult , Colon, Transverse/surgery , Colonic Neoplasms/complications , Colonic Neoplasms/surgery , Colonoscopy , Female , Humans , Treatment Outcome
8.
Gan To Kagaku Ryoho ; 44(12): 1251-1253, 2017 Nov.
Article in Japanese | MEDLINE | ID: mdl-29394597

ABSTRACT

Combined modality therapy is sufficient to treat advanced rectal cancer with multiple metastases. Her, we report a case of long-term survival in a patient with multiple metastases from rectal cancer. A5 8-year-old man had previously undergone low anterior resection for advanced rectal cancer. Multiple liver and lung metastases were identified prior to operation; therefore, we initiated chemotherapy(FOLFOX). Partial resection of metastatic lesions and radiofrequency ablation(RFA)were also administered, but newly developed liver, lung, and adrenal gland metastases were identified. We changed the chemotherapy regimen and administered topical therapies(partial resection, RFA, hepatic arterial infusion chemotherapy, radiotherapy)for each chemotherapy-refractory metastatic lesion. Although the patient is in a tumor-bearing state, he is still alive 10 years after his first operation. This combined modality therapy is an option for patients with chemotherapy-refractory metastases from rectal cancer.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/therapy , Lung Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Adenocarcinoma/secondary , Combined Modality Therapy , Hepatectomy , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Male , Middle Aged , Pneumonectomy , Time Factors
9.
Acta Med Okayama ; 70(5): 425-427, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27777441

ABSTRACT

Docetaxel is a standard treatment for patients with advanced or recurrent breast cancer. The recommended dose is 60 to 100 mg/m2. Previous study have shown that the tumor response rates of patients who received docetaxel monotherapy at doses of 60, 75, and 100 mg/m2 were 22.1% , 23.3% , and 36.0% , respectively, and there was a significant relationship between the dose and response. In Europe and the United States, docetaxel is approved at a dose of 100 mg/m2, and Japanese guidelines also recommend a dose of 100 mg/m2. However, the approved dose in Japan is up to 75 mg/m2. We have launched a phase I trial evaluating 100 mg/m2 docetaxel in patients with advanced or relapsed breast cancer. The major eligibility criteria are as follows: age 20 years, pathologically diagnosed breast cancer, recurrent or advanced breast cancer, a good performance status, and HER2 [human epidermal growth factor receptor 2] negative. The primary endpoint is demonstrated safety of 100 mg/m2 docetaxel. This study will clarify whether 100mg/m2 docetaxel can be administrated safely in Japanese patients with advanced or recurrent breast cancer.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Taxoids/therapeutic use , Adult , Antineoplastic Agents/administration & dosage , Clinical Protocols , Docetaxel , Dose-Response Relationship, Drug , Female , Humans , Taxoids/administration & dosage , Young Adult
10.
Acta Med Okayama ; 69(6): 333-8, 2015.
Article in English | MEDLINE | ID: mdl-26690243

ABSTRACT

We evaluated the usefulness of preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) examinations to predict the pathological features in primary breast cancer. In particular, we evaluated the correlation between the maximum standardized uptake values (SUVmax) obtained by 18F-FDG PET/CT and the Ki67 expression in estrogen receptor (ER)-positive invasive ductal carcinoma (IDC). Primary IDC patients operated between March 2009 and July 2013 at Okayama University Hospital were enrolled. We evaluated the correlations between the SUVmax and age, postoperative pT, histological grade, lymph vascular invasion, status of hormone receptor, human epidermal growth factor receptor 2 (HER2), Ki67 expression and node status. The Ki67 expression was classified as high (> 14%) versus low (< 14%). We enrolled 138 patients with IDC. Their median SUVmax was 3.85 (range:0-52.57). In a univariate analysis, the SUVmax was significantly related to age, pT, histological grade, lymphovascular invasion, hormone receptor status, HER2 status, node status and Ki67. In the 113 patients with ER-positive IDC, there was a significant correlation between Ki67 and SUVmax (p = 0.0030). The preoperative 18F-FDG PET/CT results of IDC patients had significant relationships with pathological status parameters. The determination of the preoperative SUVmax might help classify Luminal A and Luminal B patients among luminal-type breast cancer patients.


Subject(s)
Breast Neoplasms/diagnostic imaging , Carcinoma, Ductal, Breast/diagnostic imaging , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Adult , Aged , Aged, 80 and over , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Female , Humans , Ki-67 Antigen/analysis , Middle Aged , Receptor, ErbB-2/analysis , Receptors, Estrogen/analysis
11.
Breast Cancer Res Treat ; 143(2): 403-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24337596

ABSTRACT

We examined estrogen receptor (ER) mRNA expression and molecular subtypes in stage I-III breast cancers that are progesterone receptor (PR) positive but ER and HER2 negative by immunohistochemistry (IHC) or fluorescent in situ hybridization. The ER, PR, and HER2 status was determined by IHC as part of routine clinical assessment (N = 501). Gene expression profiling was done with the Affymetrix U133A gene chip. We compared expressions of ESR1 and MKI67 mRNA, distribution of molecular subtypes by the PAM50 classifier, the sensitivity to endocrine therapy index, and the DLDA30 chemotherapy response predictor signature among ER/PR-positive (n = 223), ER-positive/PR-negative (n = 73), ER-negative/PR-positive (n = 20), and triple-negative (n = 185) cancers. All patients received neoadjuvant chemotherapy with an anthracycline and taxane and had adjuvant endocrine therapy only if ER or PR > 10 % positive. ESR1 expression was high in 25 % of ER-negative/PR-positive, in 79 % of ER-positive/PR-negative, in 96 % of ER/PR-positive, and in 12 % of triple-negative cancers by IHC. The average MKI67 expression was significantly higher in the ER-negative/PR-positive and triple-negative cohorts. Among the ER-negative/PR-positive patients, 15 % were luminal A, 5 % were Luminal B, and 65 % were basal like. The relapse-free survival rate of ER-negative/PR-positive patients was equivalent to ER-positive cancers and better than the triple-negative cohort. Only 20-25 % of the ER-negative/PR-positive tumors show molecular features of ER-positive cancers. In this rare subset of patients (i) a second RNA-based assessment may help identifying the minority of ESR1 mRNA-positive, luminal-type cancers and (ii) the safest clinical approach may be to consider both adjuvant endocrine and chemotherapy.


Subject(s)
Breast Neoplasms/genetics , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Adult , Aged , Anthracyclines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Breast Neoplasms/classification , Breast Neoplasms/drug therapy , Bridged-Ring Compounds/therapeutic use , Female , Gene Expression Profiling , Humans , Ki-67 Antigen/genetics , Middle Aged , Neoadjuvant Therapy , Neoplasm Recurrence, Local/drug therapy , RNA, Messenger/biosynthesis , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics , Survival Rate , Taxoids/therapeutic use , Young Adult
12.
BMC Cancer ; 13: 565, 2013 Dec 01.
Article in English | MEDLINE | ID: mdl-24289300

ABSTRACT

BACKGROUND: Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk. METHODS: A case-control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses. RESULTS: High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR=1.37 [95% CI: 1.11-1.70]), rs3757318 (OR=1.33[1.05-1.69]), and rs3803662 (OR=1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers. CONCLUSION: In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers.


Subject(s)
Asian People , Breast Neoplasms/epidemiology , Life Style , Polymorphism, Single Nucleotide , Adult , Age Factors , Aged , Asian People/genetics , Breast Neoplasms/genetics , Case-Control Studies , Female , Humans , Japan/epidemiology , Middle Aged , Odds Ratio , Population Surveillance , Risk
13.
Acta Med Okayama ; 67(3): 145-51, 2013.
Article in English | MEDLINE | ID: mdl-23804137

ABSTRACT

A high mammographic breast density is considered to be a risk factor for breast cancer. However, only a small number of studies on the association between breast density and lifestyle have been performed. A cross-sectional study was performed using a survey with 29 questions on life history and lifestyle. The breast density on mammography was classified into 4 categories following the BI-RADS criteria. The subjects were 522 women with no medical history of breast cancer. The mean age was 53.3 years old. On multivariate analysis, only BMI was a significant factor determining breast density in premenopausal women (parameter estimate, -0.403; p value, 0.0005), and the density decreased as BMI rose. In postmenopausal women, BMI (parameter estimate, -0.196; p value, 0.0143) and number of deliveries (parameter estimate, -0.388; p value, 0.0186) were significant factors determining breast density;breast density decreased as BMI and number of deliveries increased. Only BMI and number of deliveries were identified as factors significantly influencing breast density. BMI was inversely correlated with breast density before and after menopause, whereas the influence of number of deliveries on breast density was significant only in postmenopausal women in their 50 and 60s.


Subject(s)
Asian People/statistics & numerical data , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/ethnology , Life Style , Adult , Alcohol Drinking/ethnology , Body Mass Index , Breast Density , Breast Neoplasms/epidemiology , Cross-Sectional Studies , Female , Humans , Mammary Glands, Human/abnormalities , Middle Aged , Multivariate Analysis , Parity , Postmenopause , Premenopause , Radiography , Risk Factors , Smoking/ethnology
14.
Acta Med Okayama ; 66(4): 357-61, 2012.
Article in English | MEDLINE | ID: mdl-22918209

ABSTRACT

Ectopic thymoma is considered to arise from ectopic thymus tissue deposited as a result of the abnormal mislocalization of thymus tissue during the embryonic stage. An 86-year-old man visited our hospital with chief complaints of hoarseness and a mass in his anterior neck. A preoperative needle biopsy of the mass did not yield a definitive diagnosis. A positron emission tomography (PET) study revealed heterogeneous accumulation of (18)F-fluorodeoxyglucose (FDG) in the tumor. The tumor, affecting the left sternocleidomastoid muscle, the recurrent laryngeal nerve, the internal carotid vein, and the brachiocephalic vein, was resected using a combination of a collar incision in the neck and a median incision in the sternum. Immunohistochemically, the tumor was diagnosed as an ectopic thymoma of the neck. To date, only a few cases of ectopic thymoma presenting with FDG accumulation have been reported. Our experience indicates that ectopic thymoma should be kept in mind during the differential diagnosis of neck tumors with FDG accumulation appearing on PET images.


Subject(s)
Fluorodeoxyglucose F18 , Head and Neck Neoplasms/diagnostic imaging , Thymoma/diagnostic imaging , Thymus Neoplasms/diagnostic imaging , Aged, 80 and over , Head and Neck Neoplasms/pathology , Humans , Male , Positron-Emission Tomography , Thymoma/pathology , Thymus Neoplasms/pathology
15.
Cancer Sci ; 102(11): 2038-42, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21801281

ABSTRACT

Patients with estrogen receptor (ER)-positive breast cancers have a better prognosis than those with ER-negative breast cancers, but often have low sensitivity to chemotherapy and a limited survival benefit. We have previously shown a combination effect of taxanes and fulvestrant and suggested that this treatment may be useful for ER-positive breast cancer. In this study, we evaluated the effects of combinations of hormone drugs and chemotherapeutic agents. In vitro, the effects of combinations of five chemotherapeutic agents (doxorubicin, paclitaxel, docetaxel, vinorelbine, and 5-fluorouracil) and three hormone drugs (fulvestrant, tamoxifen, and 4-hydroxytamoxifen) were examined in ER-positive breast cancer cell lines using CalcuSyn software. Changes in chemoresistant factors such as Bcl2, multidrug resistance-associated protein 1, and microtubule-associated protein tau were also examined after exposure of the cells to hormone drugs. In vivo, tumor sizes in mice were evaluated after treatment with docetaxel or doxorubicin alone, fulvestrant alone, and combinations of these agents. Combination treatment with fulvestrant and all five chemotherapeutic agents in vitro showed synergistic effects. In contrast, tamoxifen showed an antagonistic effect with all the chemotherapeutic agents. 4-Hydroxytamoxifen showed an antagonistic effect with doxorubicin and 5-fluorouracil, but a synergistic effect with taxanes and vinorelbine. Regarding chemoresistant factors, Bcl2 and microtubule-associated protein tau were downregulated by fulvestrant. In vivo, a combination of fulvestrant and docetaxel had a synergistic effect on tumor growth, but fulvestrant and doxorubicin did not show this effect. In conclusion, fulvestrant showed good compatibility with all the evaluated chemotherapeutic agents, and especially with docetaxel, in vitro and in vivo.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Estradiol/analogs & derivatives , Estrogens , Neoplasms, Hormone-Dependent/pathology , Animals , Antineoplastic Agents, Hormonal/pharmacology , Antineoplastic Combined Chemotherapy Protocols/antagonists & inhibitors , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Docetaxel , Doxorubicin/administration & dosage , Doxorubicin/antagonists & inhibitors , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Drug Synergism , Estradiol/administration & dosage , Estradiol/pharmacology , Estrogen Receptor Modulators/pharmacology , Female , Fluorouracil/administration & dosage , Fluorouracil/antagonists & inhibitors , Fluorouracil/pharmacology , Fulvestrant , Humans , Mice , Mice, Nude , Neoplasm Proteins/biosynthesis , Paclitaxel/administration & dosage , Paclitaxel/antagonists & inhibitors , Paclitaxel/pharmacology , Random Allocation , Tamoxifen/analogs & derivatives , Tamoxifen/pharmacology , Taxoids/administration & dosage , Taxoids/antagonists & inhibitors , Taxoids/pharmacology , Tumor Cells, Cultured/drug effects , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinblastine/antagonists & inhibitors , Vinblastine/pharmacology , Vinorelbine , Xenograft Model Antitumor Assays
16.
Acta Med Okayama ; 65(4): 231-7, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21860529

ABSTRACT

Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC) has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and prolongation of survival. Here, a retrospective review was conducted of MBC patients administered XC at the Okayama University Hospital (OUH), to evaluate responses to XC, adverse events and time to progression (TTP). Twenty patients with MBC received XC between 2006 and 2009. With the exception of 2 elderly patients who were over the age of 70 at the initial examination, all of the patients had received prior treatment with an anthracycline and/or a taxane. No complete response (CR) cases were observed, but partial response (PR) was achieved in 6 patients (30%) and SD in 9 (45%), of whom 5 (20%) sustained SD status for >12 months. The median TTP was 6 months (range:3-27 mo.). Three patients developed Grade 3 adverse events (diarrhea, nausea and stomatitis), but no other patients developed adverse reactions causing interruption of the therapy. XC was safe even in previously treated and elderly MBC patients;moreover, it yielded remarkable clinical responses.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents, Alkylating/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cyclophosphamide/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Adult , Aged , Aged, 80 and over , Capecitabine , Deoxycytidine/therapeutic use , Disease Progression , Female , Fluorouracil/therapeutic use , Humans , Middle Aged , Neoplasm Metastasis , Retrospective Studies
17.
Intern Med ; 60(8): 1183-1190, 2021 Apr 15.
Article in English | MEDLINE | ID: mdl-33191320

ABSTRACT

Objective This study examined the pharmacokinetics, safety and anti-tumor activity of docetaxel at a dose of 100 mg/m2 in Japanese patients with advanced or recurrent breast cancer. Methods Japanese patients with advanced or recurrent breast cancer received docetaxel at a dose of 100 mg/m2 intravenously every three weeks. The pharmacokinetics were assessed during the first cycle. The patients were allowed to receive supportive care drugs based on the indications and dosages in Japan. Results Six eligible patients aged 39-65 years old and 27 treatment cycles were analyzed. All patients experienced one or more adverse events (AEs). The common AEs were neutropenia, thrombocytopenia, alopecia, rash, diarrhea, neuropathy (sensory), fatigue, nausea, fever, hypoalbuminemia, alanine transaminase (ALT) increased, constipation, and taste alteration. Grade 3 or 4 AEs included neutropenia, leukopenia, anemia, lymphopenia, decreased appetite, γ-glutamyl transpeptidase (GTP) increased, aspartate transaminase (AST) increased, ALT increased, hypertension and cellulitis which were all reversible. There were no cases of febrile neutropenia, serious AEs or deaths. The median number of cycles was six. Dose reductions were not observed and most cycles were administered at their intended doses. No complete response and three partial responses were observed in four assessable patients with evaluable lesions. The maximum concentration and area under the blood concentration-time curve were 3,417.5 ng/mL and 4.35 µg・hr/mL (mean), respectively. Conclusion Docetaxel at a dose of 100 mg/m2 was tolerable with acceptable safety profiles and effective for Japanese patients with advanced or recurrent breast cancer with appropriate supportive therapies, and pharmacokinetic (PK) profiles which corresponded approximately with the findings of previous clinical studies.


Subject(s)
Breast Neoplasms , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms/drug therapy , Docetaxel/therapeutic use , Drug Administration Schedule , Humans , Japan/epidemiology , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Taxoids/therapeutic use
18.
Breast Cancer Res ; 12(3): R43, 2010.
Article in English | MEDLINE | ID: mdl-20579400

ABSTRACT

INTRODUCTION: Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT. METHODS: The correlation between MAPT expression and sensitivity to taxanes was investigated in 12 human breast cancer cell lines. Alterations in cellular sensitivity to taxanes were evaluated after knockdown of MAPT expression. ER expression was knocked down or stimulated in MAPT- and ER-positive cell lines to examine the relationship between ER and MAPT. The cells were also treated with hormone drugs (tamoxifen and fulvestrant) and taxanes. RESULTS: mRNA expression of MAPT did not correlate with sensitivity to taxanes. However, expression of MAPT protein isoforms of less than 70 kDa was correlated with a low sensitivity to taxanes. Downregulation of MAPT increased cellular sensitivity to taxanes. MAPT protein expression was increased by stimulation with 17-beta-estradiol or tamoxifen, but decreased by ER downregulation and by fulvestrant, an ER inhibitor. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect. CONCLUSIONS: Expression of MAPT protein isoforms of less than 70 kDa is correlated with a low sensitivity to taxanes in breast cancer cells. ER influences MAPT expression and fulvestrant increases the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells.


Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Estradiol/analogs & derivatives , Estrogen Antagonists/pharmacology , Receptors, Estrogen/metabolism , Taxoids/pharmacology , tau Proteins/metabolism , Blotting, Western , Breast Neoplasms/pathology , Cell Line, Tumor , Down-Regulation , Drug Synergism , Estradiol/pharmacology , Estrogen Receptor Modulators/pharmacology , Female , Fluorescent Antibody Technique , Fulvestrant , Humans , Protein Isoforms , RNA, Messenger/genetics , RNA, Small Interfering/pharmacology , Receptors, Estrogen/antagonists & inhibitors , Reverse Transcriptase Polymerase Chain Reaction , Tamoxifen/pharmacology , tau Proteins/antagonists & inhibitors , tau Proteins/genetics
19.
Breast Cancer ; 24(2): 288-298, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27179527

ABSTRACT

BACKGROUND: An understanding of health-related quality of life (HRQOL) is of utmost importance in both oncological and esthetic breast surgery. The BREAST-Q is a patient-reported outcome (PRO) measure that investigates HRQOL and patient satisfaction before and after breast surgery. The aim of this study was to develop a Japanese version of the BREAST-Q including the mastectomy module, the reconstruction module, the augmentation module and the reduction/mastopexy module, and to assess the psychometric properties of the mastectomy module among Japanese women. METHODS: The Japanese version of the BREAST-Q was developed through forward translation, backward translation and patient testing. Traditional psychometric testing of the mastectomy module was administered to 45 post-mastectomy patients. RESULTS: The mastectomy, reconstruction, augmentation and reduction/mastopexy modules were formally developed into Japanese. Despite cultural difference between Japanese women and original target population, the contents were considered to be valid among Japanese woman. With the exception of the sexual well-being subscale, good reliability and validity were evident for the mastectomy module (Test-retest reliability 0.76-0.95, Chronbach's alpha coefficient 0.77-0.98). CONCLUSIONS: The BREAST-Q Japanese version is a useful PRO measure for investigating the impact of breast surgery on HRQOL and patient satisfaction. Further validation in younger Japanese women is needed to determine the usefulness of the sexual well-being subscale.


Subject(s)
Breast Neoplasms/surgery , Patient Satisfaction , Psychometrics/methods , Quality of Life , Adult , Aged , Female , Humans , Japan , Mammaplasty , Mastectomy , Mastectomy, Segmental , Middle Aged , Psychometrics/standards , Reproducibility of Results , Surveys and Questionnaires
20.
Breast Cancer ; 24(2): 254-262, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27068825

ABSTRACT

BACKGROUND: Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia. METHODS: We conducted a case-control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype. RESULTS: In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38-3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype. CONCLUSION: Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.


Subject(s)
Arylamine N-Acetyltransferase/genetics , Breast Neoplasms/genetics , Polymorphism, Single Nucleotide , Smoking/genetics , Adult , Aged , Aged, 80 and over , Asian People/genetics , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Middle Aged , Smoking/adverse effects
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