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1.
Clin Lab ; 70(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38747933

RESUMEN

BACKGROUND: The aim was to evaluate the consistency of the results between the UF-1500 and UF-5000, fully automated urine particle analyzers. METHODS: A total of 554 randomly selected inpatient and outpatient urine samples were collected for analysis using the UF-1500, the UF-5000, and by manual microscopic examination. The coincidence rate, intraday repeatability, and interday reproducibility were evaluated on the UF-1500 and UF-5000. To analyze the review flags from the UF-1500, the UF-1500 results were compared to manual microscopy as the gold standard. RESULTS: The repeatability of red blood cells (RBCs), white blood cells (WBCs), epithelial cells (ECs), casts, and bacteria using the UF-1500 and UF-5000 is expressed as the relative standard deviations of the intraday and inter-day measurements. For the UF-1500, the relative standard deviation values ranged from 5.9% to 12.6% and 4.9% to 17.2% for the low and 1.6% to 9.3% and 2.3% to 16.9% for the high samples, respectively. The correlation co-efficient for RBCs, WBCs, ECs, SECs, casts, crystals, and bacteria for the UF-1500 were 0.981, 0.993, 0.968, 0.963, 0.821, 0.783, and 0.992, respectively. Review samples from the UF-1500 were confirmed by microscopic examination. Review flags for all 554 samples included 3 samples with "DEBRIS High" and 23 samples with "RBCs/YLC Abnormal classification". CONCLUSIONS: The identification of various urine components by both instruments meets laboratory requirements. These two instruments with different performances have specific characteristics and should be used based upon the needs of each laboratory.


Asunto(s)
Urinálisis , Humanos , Urinálisis/métodos , Urinálisis/instrumentación , Reproducibilidad de los Resultados , Automatización de Laboratorios , Recuento de Leucocitos/instrumentación , Recuento de Leucocitos/métodos
2.
Jpn J Clin Oncol ; 53(6): 457-462, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36974683

RESUMEN

BACKGROUND: The number of breast cancer patients of childbearing age has been increasing. Therefore, we investigated the characteristics and the childbearing status of the patients who received systemic therapy for breast cancer during their childbearing age to better understand the clinical impact of childbirth. METHODS: Female patients with breast cancer younger than 40 years old who underwent surgery and received perioperative systemic therapy from 2007 to 2014 were included in this study. We compared the characteristics of patients with and without childbirth after treatment. RESULT: Of 590 patients, 26 delivered a child, and 355 did not bear a child during the median observation period of 8.1 years, whilst 209 had unknown childbirth data. The childbirth group had a lower mean age at surgery (32.2 vs. 35.1, P < 0.001). The proportion of patients who desired childbirth and used assisted reproductive technology was significantly higher in the childbirth group (65.4 vs. 23.9% and 45.2 vs. 5.1%, respectively, P < 0.001). The patients in the childbirth group had significantly less advanced disease (P = 0.002). In the childbirth group, the age at childbirth was significantly older in patients who received combined endocrine therapy and chemotherapy (40.8 years) than in patients who received either alone (endocrine therapy: 36.9 years, chemotherapy: 36.7 years, P = 0.04). However, survival was not different between those with and without childbirth. CONCLUSION: It is critical to recognize the desire for childbirth in patients with breast cancer who are receiving systemic therapy and to provide them with necessary fertility information before treatment to support their decision-making.


Asunto(s)
Neoplasias de la Mama , Niño , Embarazo , Humanos , Femenino , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Estudios Retrospectivos , Japón
3.
Breast Cancer Res Treat ; 196(2): 341-348, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36153381

RESUMEN

PURPOSE: This study investigated the clinical impact of pretreatment neutrophil-to-lymphocyte ratio (NLR) on survival in patients with oligometastatic breast cancer. PATIENTS AND METHODS: We collected data from 397 patients who underwent primary breast surgery from 2004 to 2015 and developed recurrence during the follow-up. We reviewed the images and clinical information and defined OMD according to the European Society for Medical Oncology advanced breast cancer guidelines. The NLR was calculated using pretreatment data of primary breast cancer. The cutoff value of the NLR was determined by receiver operating characteristic curve with Youden Index. RESULTS: Among 397 patients, 131 had OMD at recurrence. The low-NLR group included patients of significantly older age at primary cancer than those in the high-NLR group. A low NLR indicated a better overall survival (p = 0.023) after adjusting for relevant factors, including estrogen receptor status, surgical resection of metastatic disease, metastatic organ number, disease-free interval, and liver metastasis than did the high-NLR group. We developed prognostic models for OMD using six independent prognostic factors, including the NLR. The number of factors was associated with overall survival; patients with all six favorable factors showed a good overall survival of 90.9% at 8 years and those with four or more factors showed 70.4%. CONCLUSIONS: The NLR was an independent prognostic factor for overall survival in OMD. The number of favorable prognostic factors was associated with overall survival. A prognostic model, including the NLR, will help identify patients with a favorable prognosis.


Asunto(s)
Neoplasias de la Mama , Neutrófilos , Humanos , Femenino , Neutrófilos/patología , Neoplasias de la Mama/patología , Recuento de Linfocitos , Receptores de Estrógenos , Linfocitos/patología , Pronóstico , Estudios Retrospectivos
4.
Pediatr Cardiol ; 40(4): 841-847, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30830280

RESUMEN

This study aimed to clarify the characteristics of pulmonary arterial resistance (Rp)-compliance (Cp) coupling in individuals with Down syndrome (DS), who have increased risks of pulmonary arterial hypertension (PAH). We performed cardiac catheterization before and after corrective surgery in 85 DS infants and 85 controls with congenital heart disease and PAH. We retrospectively collected hemodynamic data and compared Rp and Cp between the groups. Age at surgery was 3.5 (2.6-4.6) months. The first and second catheterizations were performed 1 month before and after corrective surgery in both groups. Preoperative Cp in DS patients was significantly lower than that in controls [2.27 (1.62-3.0) vs. 2.50 (1.86-3.31) mL/mmHg/m2, p = 0.039], although there was no significant difference in mean pulmonary arterial pressure and Rp between the groups. Analysis of covariance revealed that the slopes of the preoperative regression lines for the logarithmic transformations of Rp and Cp were identical in DS patients and controls (p = 0.299). However, the postoperative regression line was shifted downward in DS patients after corrective surgery. Postoperative home oxygen therapy (HOT) was performed in 39 patients (36 DS patients) and multivariate logistic regression analysis revealed that postoperative HOT was significantly related to low preoperative Cp (p = 0.039) and DS (p = 0.0001). Individuals with DS have the unique pulmonary vasculature characterized with low Cp that is related to postoperative HOT.


Asunto(s)
Síndrome de Down/complicaciones , Cardiopatías Congénitas/complicaciones , Hipertensión Pulmonar/fisiopatología , Arteria Pulmonar/fisiopatología , Cateterismo Cardíaco/métodos , Estudios de Casos y Controles , Femenino , Cardiopatías Congénitas/cirugía , Hemodinámica/fisiología , Humanos , Lactante , Masculino , Estudios Retrospectivos
5.
Clin Exp Pharmacol Physiol ; 45(1): 27-33, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28762515

RESUMEN

Contact dermatitis is a form of delayed-type hypersensitivity characterized by localized thickening, papules, redness and vesicles of the skin. A model of contact dermatitis involving repeated challenge of a hapten is adapted to assess dermatitis as characterized by skin thickening. Recently, it was reported that neutrophils have crucial roles in contact hypersensitivity. We thus examined the involvement of CXC chemokines bearing the glutamic acid-leucine-arginine (ELR) motif ("ELR+ chemokines") and neutrophils in the ear swelling induced by 2,4,6-trinitrochlorobenzene (TNCB) challenges in the present study. Mice were sensitized by application of TNCB on their abdominal skin. They were then challenged thrice with TNCB to the ear. The CXCR2 antagonist SB225002 (9 mg/kg, i.p.) was administered before each TNCB challenge. Gene expressions and protein levels of the ELR+ chemokines CXCL1, 2 and 5 was increased markedly in mouse ear after the final TNCB challenge. In addition, we indicated that gene expression of CXCL1 was enhanced in the epidermis and dermis upon TNCB challenge. Expression of the CXCL2 gene was enhanced in the epidermis, and that of the CXCL5 gene was enhanced in the dermis. The swelling induced by TNCB challenges was significantly attenuated by SB225002. Furthermore, the increases in myeloperoxidase activity, and expression of myeloperoxidase and neutrophil elastase induced by TNCB challenge in mouse ear were inhibited by SB225002. These data suggest that ear swelling resulting from TNCB challenges might be concerned by upregulated ELR+ chemokine-induced neutrophil recruitment.


Asunto(s)
Quimiocinas CXC/química , Quimiocinas CXC/metabolismo , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Cloruro de Picrilo/efectos adversos , Secuencias de Aminoácidos , Animales , Dermatitis por Contacto/etiología , Femenino , Ratones Endogámicos BALB C , Receptores de Interleucina-8B/antagonistas & inhibidores
6.
Cancer Sci ; 108(3): 455-460, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28075526

RESUMEN

Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin-eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four-point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin-eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (P < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (P = 0.003), CD8+ (P = 0.003) and CD56+ (P = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune-enhancing effect. As such, the immune-related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides.


Asunto(s)
Antineoplásicos/uso terapéutico , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Complejo CD3/metabolismo , Antígeno CD56/metabolismo , Antígenos CD8/metabolismo , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Capecitabina , Neoplasias Colorrectales/inmunología , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/análogos & derivados , Fluorouracilo/uso terapéutico , Humanos , Inflamación/inmunología , Irinotecán , Leucovorina/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Oxaloacetatos
7.
Gan To Kagaku Ryoho ; 44(12): 1278-1280, 2017 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-29394606

RESUMEN

We report 2 cases of laparoscopic simultaneous resection for synchronous liver metastasis of colon cancer. Case 1: A 76- year-old woman was diagnosed with advanced cecum cancer(type 3)with synchronous liver metastasis(segment 5: 23mm), Laparoscopic ileocecal resection and partial liver resection were performed for 414 minutes, with 20 mL of blood loss. The patient was discharged 11 days after the operation. Case 2: A 78-year-old woman was diagnosed with advanced sigmoid colon cancer(type 2)with synchronous liver metastasis(segment 2: 70mm). Laparoscopic sigmoidectomy and extrahepatic resection were performed for 382 minutes, with 10 mL of blood loss. Portal vein thrombus(umbilicus)was recognized but relieved with warfarin. The patient was discharged 15 days after the operation. Simultaneous laparoscopic colon and hepatectomy for synchronous liver metastasis of colorectal cancer can be safely performed for selected indications.


Asunto(s)
Neoplasias del Apéndice/cirugía , Neoplasias Hepáticas/cirugía , Neoplasias del Colon Sigmoide/cirugía , Anciano , Neoplasias del Apéndice/patología , Femenino , Humanos , Laparoscopía , Neoplasias Hepáticas/secundario , Neoplasias del Colon Sigmoide/patología , Resultado del Tratamiento
8.
Cancer Sci ; 107(12): 1825-1829, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27663862

RESUMEN

We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA-A*2402-restricted CTL in combination with oxaliplatin-containing chemotherapy (FXV study) as first-line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five-peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell-free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small-sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi-quantitative real-time PCR. Progression-free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA-A*2402-matched group, patients with a low plasma cfDNA integrity value had significantly better progression-free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA-A*2402-unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , ADN de Neoplasias , Inmunoterapia , Anciano , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , ADN de Neoplasias/sangre , Femenino , Humanos , Inmunoterapia/métodos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Resultado del Tratamiento
9.
Gan To Kagaku Ryoho ; 43(12): 2341-2343, 2016 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-28133315

RESUMEN

A 51-year-old woman was seen in our hospital because an ascending colon tumor with extensive abdominal wall abscess was detected on computed tomography(CT). On the same day, we performed open drainage and laparoscopic assisted ileocolostomy. Postoperative day 35, we performed right hemicolectomy with abdominal wall resection and closure of the colostomy as a radical surgery. After surgery, we started(negative pressure wound therapy: NPWT)to the surgical wound site; hence, the abdominal wall defect could be healed without a musculocutaneous flap. Laparoscopic assisted open drainage, a two-stage operation, and NPWT are useful in a case of colon cancer with abdominal wall abscess.


Asunto(s)
Pared Abdominal/patología , Absceso/etiología , Colon Ascendente/patología , Neoplasias del Colon/patología , Absceso/terapia , Colon Ascendente/cirugía , Neoplasias del Colon/cirugía , Colostomía , Drenaje , Femenino , Humanos , Laparoscopía , Persona de Mediana Edad
10.
Gan To Kagaku Ryoho ; 43(12): 1724-1726, 2016 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-28133111

RESUMEN

A 65-year-old woman who was diagnosed with unresectable Stage IV sigmoid colon cancer underwent transverse colostomy with double orifices. Although KRAS gene mutation was observed, we could not administer bevacizumab because of the risk of bleeding from the primary tumor and peritumoral abscess. We started bi-weekly XELOX therapy but bloody bowel discharge continued. We planned extended resection of the primary tumor in order to control the bleeding and perforation. Sigmoidectomy, partial resection of the left ureter and small intestine, partial hysterectomy, bilateral salpingo-oophorectomy, and umbilical tumor resection were performed and the patient was discharged on the 10th day after surgery. After surgery, bloody bowel discharge disappeared and bevacizumab was administered in the 55th day. Extended resection for a primary tumor may contribute to bleeding control and broaden treatment options.


Asunto(s)
Neoplasias del Colon Sigmoide/terapia , Anciano , Colectomía , Femenino , Humanos , Histerectomía , Metástasis de la Neoplasia , Estadificación de Neoplasias , Ovariectomía , Neoplasias del Colon Sigmoide/diagnóstico por imagen , Resultado del Tratamiento
11.
Gan To Kagaku Ryoho ; 43(12): 1821-1823, 2016 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-28133143

RESUMEN

We present a case of Fournier's gangrene secondary to rectal cancer that was managed with perineal reconstruction using a posterior thigh flap after debridement and tumor resection. A 67-year-old man was admitted with disturbed consciousness as well as hip and right thigh pain. His perineal and gluteal skin was necrotic. CT revealed subcutaneous emphysema that had spread from the rectum to the gluteal region and right thigh. We diagnosed him with Fournier's gangrene, and then removed the necrotic tissue and constructed a sigmoidostomy. A diagnosis of rectal cancer was later confirmed. Fifty-nine days after the initial operation, a laparoscopic abdominoperineal resection was performed. The perineal defect was repaired using a posterior thigh flap with the gluteus maximus. There were no postoperative complications, and the patient was discharged ahead of schedule. We concluded that the use of a posterior thigh flap is a good choice for perineal reconstruction, because it is simple to perform, can cover a large area, and has a low risk of infection.


Asunto(s)
Gangrena de Fournier/cirugía , Perineo/cirugía , Neoplasias del Recto/cirugía , Muslo , Anciano , Gangrena de Fournier/etiología , Humanos , Masculino , Procedimientos de Cirugía Plástica , Neoplasias del Recto/complicaciones , Colgajos Quirúrgicos , Muslo/cirugía , Resultado del Tratamiento
12.
Gan To Kagaku Ryoho ; 42(12): 1971-3, 2015 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-26805234

RESUMEN

A 56-year-old man who underwent a radical operation and adjuvant chemotherapy for recurrent rectal cancer had been followed-up and had no recurrence for one and a half years. Thereafter, CT and upper endoscopy showed a submucosal tumor with a central recess developing in the stomach wall. It was suspected that the gastric tumor was either a metastasis of rectal cancer or a submucosal tumor-like gastric cancer. We performed a radical operation to remove the lesion. In the resected specimen, immunohistopathological findings including HER2 status suggested that the gastric tumor was a primary gastric cancer resembling a submucosal tumor.


Asunto(s)
Mucosa Gástrica/patología , Neoplasias Primarias Secundarias/patología , Neoplasias del Recto/patología , Neoplasias Gástricas/patología , Antimetabolitos Antineoplásicos/uso terapéutico , Combinación de Medicamentos , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Secundarias/cirugía , Ácido Oxónico/uso terapéutico , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía , Neoplasias Gástricas/secundario , Neoplasias Gástricas/cirugía , Tegafur/uso terapéutico
13.
Gan To Kagaku Ryoho ; 42(10): 1310-2, 2015 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-26489582

RESUMEN

BACKGROUND AND OBJECTIVES: Cetuximab has shown efficacy in patients with metastatic colorectal cancer (mCRC). Recent studies have demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC), mediated via the fragment c gamma receptors(FcgR)in mCRC. Since the establishment of KRAS mutations as a major negative predictor of efficacy, additional biomarkers have been found to be useful for the improvement of selection of patients likely to be responsive to cetuximab. We investigated the relationship between polymorphisms and the outcome of mCRC patients treated with cetuximab. METHODS: In this study, 57 patients were evaluated. The relationships of FcgR polymorphisms with response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The FcgR polymorphisms were not significantly related to RR, PFS, and OS. Compared with the other haplotypes, the haplotype containing the 131H and 158V alleles was related to a lower RR (p=0.018). The diplotypes containing 131H and 158V alleles had significantly lower RR than the other diplotypes (p=0.038). CONCLUSION: Our data suggest that FcgR polymorphisms may be associated with the outcome of mCRC patients treated with cetuximab and FOLFIRI. However, these results are currently controversial, and detailed investigations are needed to confirm the relationship between FcgRs polymorphisms and cetuximab efficacy.


Asunto(s)
Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Polimorfismo Genético , Receptores Fc/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras) , Proteínas ras/genética
14.
J Transl Med ; 12: 63, 2014 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-24612787

RESUMEN

BACKGROUND: To evaluate the safety of combination vaccine treatment of multiple peptides, phase I clinical trial was conducted for patients with advanced colorectal cancer using five novel HLA-A*2402-restricted peptides, three peptides derived from oncoantigens, ring finger protein 43 (RNF43), 34 kDa-translocase of the outer mitochondrial membrane (TOMM34), and insulin-like growth factor-II mRNA binding protein 3 (KOC1), and the remaining two from angiogenesis factors, vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2. METHODS: Eighteen HLA- A*2402-positive colorectal cancer patients who had failed to standard therapy were enrolled in this study. 0.5 mg, 1.0 mg or 3.0 mg each of the peptides was mixed with incomplete Freund's adjuvant and then subcutaneously injected at five separated sites once a week. We also examined possible effect of a single site injection of "the cocktail of 5 peptides" on the immunological responses. ELISPOT assay was performed before and after vaccinations in the schedule of every 4 weeks. RESULTS: The vaccine treatment using multiple peptides was well tolerated without any severe treatment-associated systemic adverse events. Dose-dependent induction of peptide-specific cytotoxic T lymphocytes was observed. The single injection of "peptides cocktail" did not diminish the immunological responses. Regarding the clinical outcome, one patient achieved complete response and 6 patients revealed stable disease for 4 to 7 months. The median overall survival time (MST) was 13.5 months. Patients, in which we detected induction of cytotoxic T lymphocytes specific to 3 or more peptides, revealed significantly better prognosis (MST; 27.8 months) than those with poorer immune responses (MST; 3.7 months) (p = 0.032). CONCLUSION: Our cancer vaccine treatment using multiple peptides is a promising approach for advanced colorectal cancer with the minimum risk of systemic adverse reactions. CLINICAL TRIAL REGISTRATION: UMIN-CTR number UMIN000004948.


Asunto(s)
Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/inmunología , Epítopos/inmunología , Vacunas Combinadas/efectos adversos , Vacunas de Subunidad/efectos adversos , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Relación Dosis-Respuesta Inmunológica , Femenino , Humanos , Interferón gamma/metabolismo , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Monitorización Inmunológica , Análisis Multivariante , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Vacunación , Vacunas Combinadas/uso terapéutico , Vacunas de Subunidad/uso terapéutico
15.
J Transl Med ; 12: 108, 2014 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-24884643

RESUMEN

BACKGROUND: We previously conducted a phase I trial for advanced colorectal cancer (CRC) using five HLA-A*2402-restricted peptides, three derived from oncoantigens and two from vascular endothelial growth factor (VEGF) receptors, and confirmed safety and immunological responses. To evaluate clinical benefits of cancer vaccination treatment, we conducted a phase II trial using the same peptides in combination with oxaliplatin-based chemotherapy as a first-line therapy. METHODS: The primary objective of the study was the response rates (RR). Progression free survival (PFS), overall survival (OS), and immunological parameters were evaluated as secondary objective. The planned sample size was more than 40 patients for both HLA2402-matched and -unmatched groups. All patients received a cocktail of five peptides (3 mg each) mixed with 1.5 ml of IFA which was subcutaneously administered weekly for the first 12 weeks followed by biweekly administration. Presence or absence of the HLA-A*2402 genotype were used for classification of patients into two groups. RESULTS: Between February 2009 and November 2012, ninety-six chemotherapy naïve CRC patients were enrolled under the masking of their HLA-A status. Ninety-three patients received mFOLFOX6 and three received XELOX. Bevacizumab was added in five patients. RR was 62.0% and 60.9% in the HLA-A*2402-matched and -unmatched groups, respectively (p=0.910). The median OS was 20.7 months in the HLA-A*2402-matched group and 24.0 months in the unmatched group (log-rank, p=0.489). In subgroup with a neutrophil/lymphocyte ratio (NLR) of <3.0, patients in the HLA-matched group did not survive significantly longer than those in the unmatched group (log-rank, p=0.289) but showed a delayed response. CONCLUSIONS: Although no significance was observed for planned statistical efficacy endpoints, a delayed response was observed in subgroup with a NLR of <3.0. Biomarkers such as NLR might be useful for selecting patients with a better treatment outcome by the vaccination. TRIAL REGISTRATION: Trial registration: UMIN000001791.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Femenino , Antígenos HLA/análisis , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Péptidos/administración & dosificación , Análisis de Supervivencia
16.
Surg Today ; 44(11): 2037-44, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24150099

RESUMEN

PURPOSE: We compared the safety, invasiveness and cosmetic outcomes between endoscopic breast-conserving surgery (endoscopic group) and surgery under direct vision (direct vision group) for treating breast cancer. METHODS: We compared 100 cases of endoscopic surgery with 150 cases of direct vision surgery. The safety was evaluated in terms of the blood loss, length of the operation and presence or absence of complications, whereas the degree of invasiveness was assessed using preoperative and postoperative leukocyte counts, neutrophil counts, interleukin (IL-6) levels and fever. The cosmetic outcome was assessed on the basis of a breast evaluation by the medical staff and the patient's subjective satisfaction. RESULTS: In both groups, serious postoperative complications were absent. No significant differences were observed in the leukocyte counts, neutrophil counts, IL-6 level or fever between the groups. An evaluation of the cosmetic outcomes by the staff showed a more favorable breast size, breast shape and scar condition in the endoscopic group. A significantly higher level of patient satisfaction was also observed in the endoscopic group. Postoperative local recurrence was absent. CONCLUSIONS: The endoscopic approach showed comparable safety and invasiveness, and provided better postoperative cosmetic outcomes than direct vision surgery. Our results suggest that endoscopic breast-conserving surgery is a potentially useful surgical method for the treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama/cirugía , Endoscopía , Mastectomía Segmentaria/métodos , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Femenino , Fiebre , Humanos , Interleucina-6/sangre , Recuento de Leucocitos , Persona de Mediana Edad , Tempo Operativo , Satisfacción del Paciente , Seguridad , Resultado del Tratamiento
17.
Cancer Sci ; 104(12): 1662-9, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24033692

RESUMEN

UNLABELLED: Retrospective studies have suggested that UDP-glucuronosyltransferase (UGT)1A1, UGT1A7, and UGT1A9 predict severe toxicity and efficacy of irinotecan-containing regimens. We prospectively evaluated the impact of UGT1A genotypes and haplotypes on severe toxicity and efficacy in patients treated with fluorouracil, leucovorin, and irinotecan combination chemotherapy (FOLFIRI) for metastatic colorectal cancer (mCRC) from the two prospective multicenter phase II studies in Japan. The FLIGHT1 study was a first-line FOLFIRI trial, and FLIGHT2 was a FOLFOX-refractory, second-line FOLFIRI trial. A total of 73 patients agreed to additional analysis, and were genotyped for UGT1A polymorphisms, UGT1A1*28 (TA6>TA7), UGT1A1*6 (211G>A), UGT1A1*27 (686C>A), UGT1A1*60 (-3279T>G), UGT1A1*93 (-3156G>A), UGT1A7 (-57T>G), UGT1A7*3 (387T>G, 622T>C), and UGT1A9*22 (T9>T10). Of 73 patients, 34 developed G3/4 severe hematological toxicities. The toxicities were significantly more frequent in patients with UGT1A1*6 (211A), UGT1A7 (387G), and UGT1A9*22 reference alleles (T9). Haplotype I, which consists of all favorable alleles, was associated with a significant reduction in hematologic toxicity (P = 0.031). In contrast, haplotype II, which contains four high-risk alleles, showed significantly higher hematologic toxicity than the other haplotypes (P = 0.010). Six out of seven patients who were homozygous for UGT1A1*28 or *6 experienced severe hematological toxicity despite the fact that their response rate was not impaired (42.9%). We concluded that UGT1A polymorphisms, especially UGT1A1*6, are important for the prediction of severe toxicity of FOLFIRI in northeast Asian populations. In this regard, haplotype analyses should substantially impact the prediction of severe hematological toxicities of FOLFIRI. ( CLINICAL TRIAL REGISTRATION: UMIN000002388 and UMIN000002476).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/análogos & derivados , Neoplasias Colorrectales/tratamiento farmacológico , Glucuronosiltransferasa/genética , Neutropenia/inducido químicamente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Neoplasias Colorrectales/genética , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Frecuencia de los Genes , Genotipo , Haplotipos/genética , Humanos , Irinotecán , Japón , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Neutropenia/genética , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , UDP Glucuronosiltransferasa 1A9
18.
Gan To Kagaku Ryoho ; 40(12): 1837-9, 2013 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-24393939

RESUMEN

Curative resection can be achieved in some cases of multiple liver metastases that are initially unresectable by multistage hepatectomy. We report the case of a patient who underwent 2 hepatectomy procedures for liver metastases of advanced colon cancer after conversion chemotherapy and 2-stage hepatectomy; this treatment resulted in long-term survival.


Asunto(s)
Hepatectomía , Neoplasias Hepáticas/cirugía , Neoplasias del Colon Sigmoide/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Estadificación de Neoplasias , Neoplasias del Colon Sigmoide/tratamiento farmacológico , Neoplasias del Colon Sigmoide/cirugía , Resultado del Tratamiento
19.
Gan To Kagaku Ryoho ; 40(12): 1936-8, 2013 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-24393971

RESUMEN

Here, we report a case of a patient with overlap syndrome (systemic lupus erythematosus[SLE]and polymyositis[PM]) whose condition improved following treatment for coexisting descending colon cancer. A 75-year-old man experienced Raynaud symptoms and arthralgia. He was diagnosed as having overlap syndrome (SLE/PM) and was treated with steroids. However, the symptoms did not improve. Descending colon cancer was diagnosed by colonoscopy. After surgery, overlap syndrome improved immediately. Overlap syndrome was considered as a paraneoplastic event caused by the coexisting descending colon cancer.


Asunto(s)
Neoplasias del Colon/complicaciones , Lupus Eritematoso Sistémico/complicaciones , Polimiositis/complicaciones , Anciano , Neoplasias del Colon/patología , Neoplasias del Colon/cirugía , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Estadificación de Neoplasias , Polimiositis/diagnóstico , Pronóstico
20.
Nat Prod Res ; 37(24): 4089-4098, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36661112

RESUMEN

Four new natural compounds named hericenone O (1), hericenone P (2), hericenone Q (3), and hericenone R (4), two of them were reported synthetically (3-4), together with eleven known compounds were isolated from the fruiting bodies of Hericium erinaceus. The chemical structures of the isolated compounds were elucidated by using NMR analysis and mass spectrometry, as well as comparisons with the reported data in the literature. The bioactivity evaluation revealed that hericenone Q showed significant cytotoxic activity against Hep-G2 with IC50 values of 23.89 µM, and against HCT-116 with IC50 values of 65.64 µM.


Asunto(s)
Antineoplásicos , Basidiomycota , Basidiomycota/química , Benzaldehídos/farmacología , Antineoplásicos/farmacología , Antineoplásicos/análisis , Cuerpos Fructíferos de los Hongos/química
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