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1.
Intern Med ; 60(8): 1183-1190, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33191320

RESUMO

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.


Assuntos
Neoplasias da Mama , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Docetaxel/uso terapêutico , Esquema de Medicação , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Taxoides/uso terapêutico
2.
Gan To Kagaku Ryoho ; 46(1): 145-147, 2019 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-30765669

RESUMO

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.


Assuntos
Carcinoma de Células Pequenas , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/cirurgia , Cisplatino , Combinação de Medicamentos , Gastrectomia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Ácido Oxônico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur
3.
Gan To Kagaku Ryoho ; 46(13): 1954-1956, 2019 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-32157024

RESUMO

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.


Assuntos
Coto Gástrico , Tumores do Estroma Gastrointestinal , Laparoscopia , Neoplasias Gástricas , Idoso , Gastrectomia , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Masculino , Neoplasias Gástricas/cirurgia
4.
J Nanosci Nanotechnol ; 19(3): 1445-1450, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30469203

RESUMO

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.

5.
Gan To Kagaku Ryoho ; 45(13): 2461-2463, 2018 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-30692498

RESUMO

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.


Assuntos
Colo Transverso , Neoplasias Gástricas , Idoso , Colo Transverso/diagnóstico por imagem , Colo Transverso/patologia , Colo Transverso/cirurgia , Intervalo Livre de Doença , Gastrectomia , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Invasividade Neoplásica/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
6.
Breast Cancer Res Treat ; 167(1): 39-47, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28905250

RESUMO

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.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Mama/efeitos dos fármacos , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Prognóstico , Idoso , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genômica , Humanos , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Receptor ErbB-2/genética , Trastuzumab/efeitos adversos
7.
Oncotarget ; 8(16): 26122-26128, 2017 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-28412725

RESUMO

BACKGROUND: The purpose of this study was to test whether immunohistochemical (IHC) Ki67 levels after short-term preoperative hormone therapy (post-Ki67) predict similar numbers of patients with favorable prognoses as genomic markers. RESULTS: Thirty paired cases (60 samples) were enrolled in this study. Post-Ki67 levels were significantly lower than pre-treatment Ki67 levels (P < 0.001). Post-Ki67 predicted more low-risk cases (83.3%, 25/30) than pre-genomic surrogate signature(GSS) (66.7%: 20/30), but the difference in predictive power was not significant (P = 0.233). Proliferation (MKI67, STK15, Survivin, CCNB1, and MYBL2) and estrogen (ER, PGR, BCL2, and SCUBE2) related signatures were significantly downregulated after therapy (P < 0.001 and 0.041, respectively). MATERIALS AND METHODS: Core needle biopsy specimens of primary breast cancer were collected at Okayama University Hospital from hormone receptor-positive and human epidermal growth factor 2-negative patients that subsequently received two weeks of neoadjuvant hormone therapy. Paired post-treatment specimens from surgical samples were also collected. IHC Ki67 levels and GSS were compared between pre- and post-hormone treatment samples. Changes of gene expression pattern in short-term hormone therapy were also assessed. CONCLUSIONS: IHC based post-Ki67 levels may have distinct predictive power compared with the naïve IHC Ki67. Future studies with larger cohorts and longer follow-up periods may be needed to validate our results.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Antígeno Ki-67/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Biópsia com Agulha de Grande Calibre , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Terapia Neoadjuvante , Gradação de Tumores , Prognóstico
8.
Breast Cancer ; 24(2): 288-298, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27179527

RESUMO

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.


Assuntos
Neoplasias da Mama/cirurgia , Satisfação do Paciente , Psicometria/métodos , Qualidade de Vida , Adulto , Idoso , Feminino , Humanos , Japão , Mamoplastia , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Psicometria/normas , Reprodutibilidade dos Testes , Inquéritos e Questionários
9.
Breast Cancer ; 24(2): 254-262, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27068825

RESUMO

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.


Assuntos
Arilamina N-Acetiltransferase/genética , Neoplasias da Mama/genética , Polimorfismo de Nucleotídeo Único , Fumar/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Fumar/efeitos adversos
10.
Gan To Kagaku Ryoho ; 44(12): 1248-1250, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29394596

RESUMO

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.


Assuntos
Adenocarcinoma , Colo Transverso/patologia , Neoplasias do Colo/patologia , Intussuscepção/cirurgia , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Adulto , Colo Transverso/cirurgia , Neoplasias do Colo/complicações , Neoplasias do Colo/cirurgia , Colonoscopia , Feminino , Humanos , Resultado do Tratamento
11.
Gan To Kagaku Ryoho ; 44(12): 1251-1253, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29394597

RESUMO

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.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Adenocarcinoma/secundário , Terapia Combinada , Hepatectomia , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Fatores de Tempo
12.
Gan To Kagaku Ryoho ; 44(12): 1281-1283, 2017 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-29394607

RESUMO

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.


Assuntos
Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Tumor Carcinoide/cirurgia , Ceco/cirurgia , Íleo/cirurgia , Idoso , Colectomia , Colonoscopia , Feminino , Humanos , Laparoscopia , Sangue Oculto , Resultado do Tratamento
13.
Case Rep Gastrointest Med ; 2016: 2085452, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27957354

RESUMO

A 52-year-old woman presented with stage IIB primary breast cancer (cT2N1M0), which was treated using neoadjuvant chemotherapy (epirubicin, cyclophosphamide, and paclitaxel). However, the tumor persisted in patchy areas; therefore, we performed modified radical mastectomy and axillary lymph node dissection. Routine endoscopy at 8 months revealed a depressed lesion on the gastric angle's greater curvature, and histology revealed signet ring cell proliferation. We performed endoscopic submucosal dissection for gastric cancer, although immunohistochemistry revealed that the tumor was positive for estrogen receptor, mammaglobin, and gross cystic disease fluid protein-15 (E-cadherin-negative). Therefore, we revised the diagnosis to gastric metastasis from the breast cancer.

14.
Acta Med Okayama ; 70(5): 425-427, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27777441

RESUMO

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.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Taxoides/uso terapêutico , Adulto , Antineoplásicos/administração & dosagem , Protocolos Clínicos , Docetaxel , Relação Dose-Resposta a Droga , Feminino , Humanos , Taxoides/administração & dosagem , Adulto Jovem
15.
Cancer Chemother Pharmacol ; 78(2): 289-94, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27316438

RESUMO

PURPOSE: Gemcitabine (Gem) with paclitaxel (Pac) is used for patients with metastatic breast cancer who require cytoreduction with manageable toxicities. Nanoparticle albumin-bound (nab)-Pac exhibits better efficacy and reduces the risk of hypersensitivity reactions associated with solvent-based Pac. Therefore, Gem plus nab-Pac (GA) therapy may be effective for metastatic breast cancer. The purpose of this study was to determine the maximum tolerated dose for GA therapy. METHODS: The subjects were patients with metastatic breast cancer with performance status 0 or 1 and normal hepatic, renal and marrow function. Leukopenia, neutropenia or thrombocytopenia of grade 4, neutropenic fever, or non-hematological toxicity of grade 3 or higher during the 1st cycle, and chemotherapy-induced peripheral neurotoxicity of grade 2 or higher at the end of the 1st cycle were defined as dose-limiting toxicities (DLTs). Gem (1250 mg/m(2)) was administered on days 1 and 8. nab-Pac was administered at a starting dose of 180 mg/m(2) (cohort 1) and escalated to 220 mg/m(2) (cohort 2) and 260 mg/m(2) (cohort 3) on day 1 of the 21-day cycle, using a 3 + 3 design. RESULTS: Nine patients (n = 3, 3, and 3 in cohorts 1, 2, and 3, respectively) were included in the study (median age 56 years; range 43-75 years). DLTs did not occur in any cohorts. CONCLUSIONS: The initial recommend dose in GA therapy is 1250 mg/m(2) Gem and 260 mg/m(2) nab-Pac. It is well known that nab-Pac has cumulative toxicities, and thus the efficacy and safety of GA therapy require validation in a phase 2 study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Gencitabina
16.
Breast Cancer ; 23(3): 437-44, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-25599843

RESUMO

BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells, and the expression of ALDH1 may be a prognostic factor of poor clinical outcome. The epithelial-mesenchymal transition may produce cells with stem-cell-like properties promoted by transcription factors. We investigated the expression of ALDH1 and transcription factors in both primary and metastatic lesions, and prognostic value of them in breast cancer patients with axillary lymph node metastasis (ALNM). METHOD: Forty-seven breast cancer patients with ALNM who underwent surgery at Okayama University Hospital from 2002 to 2008 were enrolled. We retrospectively evaluated the levels of ALDH1 and transcription factors, such as Snail, Slug and Twist, in both primary and metastatic lesions by immunohistochemistry. RESULTS: In primary lesions, the positive rate of ALDH1, Snail, Slug and Twist was 19, 49, 40 and 26%, respectively. In lymph nodes, that of ALDH1, Snail, Slug and Twist was 21, 32, 13 and 23%, respectively. The expression of ALDH1 or transcription factors alone was not significantly associated with a poor prognosis. However, co-expression of ALDH1 and Slug in primary lesions was associated with a shorter DFS (P = 0.009). CONCLUSIONS: The evaluation of the co-expression of ALDH1 and transcription factors in primary lesions may be useful in prognosis of node-positive breast cancers.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Isoenzimas/metabolismo , Retinal Desidrogenase/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Família Aldeído Desidrogenase 1 , Axila/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Transição Epitelial-Mesenquimal , Feminino , Humanos , Isoenzimas/análise , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Proteínas Nucleares/análise , Proteínas Nucleares/metabolismo , Prognóstico , Retinal Desidrogenase/análise , Fatores de Transcrição da Família Snail/análise , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição/análise , Proteína 1 Relacionada a Twist/análise , Proteína 1 Relacionada a Twist/metabolismo
17.
Clin Breast Cancer ; 16(2): 95-100.e1, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26631838

RESUMO

BACKGROUND: In estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, first-generation genomic signatures serve predominately as prognostic biomarkers and secondarily as predictors of response to chemotherapy. We compared both the prognostic and predictive value of histologic grades and genomic markers. METHODS: We retrieved publicly available cDNA microarray data from 1373 primary ER(+)/HER2(-) breast cancers and developed a genomic signature simulated from Recurrence Online (http://www.recurrenceonline.com/) to calculate the recurrence score and risk using predefined sets of genes in the cDNA microarray. We then compared the prognostic and predictive information provided by histologic grade and genomic signature. RESULTS: Based on genomic signatures, 55%, 28%, and 17% of breast cancers were classified as low, intermediate, and high risk, respectively, whereas the histologic grades were I, II, and III in 22%, 59%, and 19% of breast cancers, respectively. Univariate analysis in the untreated cohort revealed that both histologic grade (overall P = .007) and genomic signature (P < .001) could predict prognosis. Results were similar using the genomic signature, with pathologic complete response rates of 4.6%, 5.7%, and 16.5% for low-, intermediate-, and high-risk cancers, respectively. Neither biomarker was statistically significant in multivariate analysis for predictive response to neoadjuvant chemotherapy (NAC). CONCLUSION: Genomic signature was better at identifying low-risk cases compared to histologic grade alone, but both markers had similar predictive values for NAC response. Better predictive biomarkers for NAC response are still needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Perfilação da Expressão Gênica , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Receptores de Progesterona/metabolismo
18.
Acta Med Okayama ; 69(6): 333-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26690243

RESUMO

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.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Antígeno Ki-67/análise , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Receptores de Estrogênio/análise
19.
Breast Cancer ; 21(6): 698-702, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23338154

RESUMO

BACKGROUND: We evaluated the expression of aldehyde dehydrogenase 1 (ALDH1) between primary breast lesions and pulmonary metastatic (PM) lesions in breast cancer patients. METHODS: We retrospectively analyzed the clinicopathological features and the expression statuses of ER, PR, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions and evaluated the discordance rates in the expressions of these markers between the primary and metastatic lesions, and also the prognostic value of these factors. RESULTS: None of the PM patients had metastases at any other sites, and all had undergone curative breast cancer surgery. The pulmonary operation was partial resection in 15 (88 %) patients and lobectomy in 2 (12 %) patients. The median overall survival (OS) after resection of the PNs (OS) was 48 months. The discordance rates in the expressions of ER, PR, HER2, Ki67 and ALDH-1 between the primary and metastatic lesions were 0, 29, 21, 43 and 50 %, respectively. CONCLUSION: There was significant discordance in the biomarkers between the primary tumors and the metastatic lesions.


Assuntos
Neoplasias da Mama/patologia , Isoenzimas/metabolismo , Neoplasias Pulmonares/secundário , Retinal Desidrogenase/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Família Aldeído Desidrogenase 1 , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Análise de Sobrevida
20.
Breast Cancer Res Treat ; 143(2): 403-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24337596

RESUMO

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.


Assuntos
Neoplasias da Mama/genética , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/classificação , Neoplasias da Mama/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Humanos , Antígeno Ki-67/genética , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , RNA Mensageiro/biossíntese , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Taxa de Sobrevida , Taxoides/uso terapêutico , Adulto Jovem
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