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1.
Int J Urol ; 31(1): 82-87, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37803911

RESUMEN

OBJECTIVES: To investigate who needs a careful postoperative monitoring for prostate cancer (PCa) after holmium laser enucleation of the prostate (HoLEP). We examined characteristics and oncological outcomes of HoLEP-related PCa. METHODS: Patients who underwent HoLEP during 2002-2017 in a Japanese tertiary center were retrospectively analyzed. Patients were divided into non-PCa, PCa with HoLEP specimen (PCa-Ope), and PCa diagnosed during follow-up (PCa-Post). Outcomes of all HoLEP-related PCa were monitored. RESULTS: Of the total 758, 60 (7.9%) were diagnosed with PCa from resected specimen of HoLEP and 9 (1.2%) were diagnosed postoperatively. Preoperative prostate-specific antigen (iPSA), postoperative PSA (pPSA), and PSA density were significantly higher in both PCa groups than those in non-PCa group. While iPSA significantly correlated to prostate volume (PV), pPSA was not associated with PV. A receiver-operating-characteristics curve demonstrated that pPSA 1.2 ng/mL achieved the optimal cut-off (AUC 0.95) for the incidence of PCa-Post. In addition to the incidence of PCa and iPSA, lower enucleation efficiency (enucleated volume /PV) was significantly associated with pPSA >1.2 ng/mL. Among PCa-Ope, 51 were Grade Group (GG) ≤2 and 42 were followed-up with active surveillance, whereas 8 of 9 PCa-Post were GG ≥3 and 2 progressed to death. CONCLUSIONS: Patients undergoing HoLEP are associated with some risk of potential PCa. While oncological outcomes were favorable among PCa-Ope, postoperative PSA should be carefully monitored even if not diagnosed with PCa with HoLEP specimen. Enucleation efficiency should be also considered not to misread pPSA value.


Asunto(s)
Terapia por Láser , Láseres de Estado Sólido , Hiperplasia Prostática , Masculino , Humanos , Antígeno Prostático Específico , Próstata/cirugía , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Estudios de Seguimiento , Estudios Retrospectivos , Láseres de Estado Sólido/uso terapéutico , Terapia por Láser/efectos adversos , Resultado del Tratamiento
2.
Gan To Kagaku Ryoho ; 50(12): 1339-1341, 2023 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-38247077

RESUMEN

An 86-year-old woman was referred to our hospital after an incidental CT scan of the trunk revealed a mass in the left breast and enlarged axillary lymph nodes. A core needle biopsy(CNB)from a 2 cm mass in the left breast revealed invasive ductal carcinoma, weakly positive result for ER, negative result for PgR, and negative result for HER2. She also had multiple enlarged left supraclavicular lymph nodes and was T2N3cM0, Stage ⅢC on pretreatment evaluation. She was given the S-1 oral drug of choice, starting with 80 mg/day/4-week dosing with a 2-week rest. Eight months after the start of S-1, a partial mastectomy and sentinel lymph node biopsy were performed. Pathological findings showed a pathological complete response(ypTis/ypN0)with only a 2 mm non-invasive carcinoma remnant in the left mammary gland. S-1 is weakly recommended as primary chemotherapy for HER2-negative metastatic recurrent breast cancer, but there are no reports to date of complete response in resection cases. S-1 may be administered to patients with locally advanced breast cancer who cannot tolerate standard drug therapy and may be converted to resection after a successful response.


Asunto(s)
Neoplasias de la Mama , Linfadenopatía , Anciano , Femenino , Humanos , Anciano de 80 o más Años , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Mastectomía , Terapia Neoadyuvante , Axila , Respuesta Patológica Completa
3.
J Infect Chemother ; 28(3): 420-425, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34924283

RESUMEN

INTRODUCTION: Invasive pneumococcal disease (IPD) is often fatal, requiring prompt diagnosis and treatment. To evaluate the factors associated with IPD in adults, we retrospectively investigated its characteristics compared to pneumococcal pneumonia without confirmation of invasion (PP). METHODS: Patients >18 years with PP (n = 79) and IPD (n = 53) from whom Streptococcus pneumoniae was isolated were enrolled from two hospitals between 2011 and 2017. Clinical backgrounds, blood test results at admission, initial antimicrobials administered, isolate serotypes, and outcomes were compared between the PP and IPD groups. RESULTS: Patients with IPD exhibited higher mortality (28.3%) than those with PP (2.5%) (p<0.001), regardless of the type of antimicrobials first administered. The majority (80.0%) of fatal cases of IPD were due to vaccine serotypes. Almost all patients with PP (97.4%) and IPD (88.7%) had underlying disease. C-reactive protein (CRP) ≥17.0 mg/dL (odds ratio [OR], 7.1; 95% CI, 2.7-19.0; p<0.001), white blood cell counts <11.0 × 103/µL (OR, 3.2; 95% CI, 1.3-8.4; p = 0.016), and platelet (PLT) counts <16.2 × 104/µL (OR, 2.8; 95% CI, 1.1-7.4; p = 0.036) were significantly more common in IPD. Moreover, 89.5% of cases with both CRP ≥23.8 mg/dL and PLT <18.5 × 104/µL were diagnosed with IPD. CONCLUSION: Laboratory blood test findings at admission, particularly high CRP and low PLT values, are useful early indicators of IPD in adults. These results could be used to initiate rapid and intensive treatment and improve prognosis.


Asunto(s)
Infecciones Neumocócicas , Neumonía Neumocócica , Pruebas Hematológicas , Humanos , Lactante , Infecciones Neumocócicas/diagnóstico , Infecciones Neumocócicas/tratamiento farmacológico , Vacunas Neumococicas , Neumonía Neumocócica/diagnóstico , Neumonía Neumocócica/tratamiento farmacológico , Estudios Retrospectivos , Serogrupo
4.
J Infect Chemother ; 26(11): 1198-1204, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32682683

RESUMEN

INTRODUCTION: Streptococcus pneumoniae is a commensal bacterium of the human nasopharynx and a major causative pathogen of bacterial diseases worldwide. Pilus of S. pneumoniae is one of the virulence factors which enhance the adhesion to the host epitherial cells in the upper respiratory tract. METHODS: We analyzed the serotype distribution and presence of pilus genes, rrgC and sipA, among 785 S. pneumoniae isolates from specimens of patients with invasive or non-invasive disease in a regional Japanese hospital between October 2014 and August 2018. We next performed multilocus sequence typing and penicillin-resistant genotyping for 86 isolates of serotype 35B. RESULTS: Serotype 35B was the most frequent serotype which accounted for 11.0% of total isolates and had pilus genes at high rate (80.2%). Clonal complex (CC) 558 isolates accounted for 77.9% of serotype 35B and were highly positive for rrgC and gPRSP (98.5%). In contrast, all CC2755 isolates (19.8%) were rrgC-negative and gPISP. CONCLUSIONS: Our results suggest that CC558 may assist the prevalence of serotype 35B after the introduction of vaccines, as that clone has pili as adhesins in addition to non-susceptibility against penicillin. These results may be useful information for development of optimal preventive strategies. Continuous studies on serotype distribution and virulence factors of S. pneumoniae are necessary.


Asunto(s)
Infecciones Neumocócicas , Vacunas Neumococicas , Humanos , Japón/epidemiología , Tipificación de Secuencias Multilocus , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Serogrupo , Serotipificación , Streptococcus pneumoniae/genética
5.
J Infect Chemother ; 23(4): 234-240, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28161295

RESUMEN

Pneumococcal vaccines have reduced the incidences of Streptococcus pneumoniae infections among children and adults, but a relative increase in the prevalence of non-vaccine serotypes has been reported. To follow the changing epidemiology of pneumococcal diseases, capsular serotyping and antimicrobial susceptibility testing was performed on 534 pneumococcal isolates obtained from a hospital in Japan after routine immunization was launched, between October 2014 and May 2016. Serotype distributions and antimicrobial susceptibilities were evaluated among the total patient population, and were compared by age and sample groups and by serotype group, respectively. Serotypes targeted by the 13-valent pneumococcal conjugate vaccine (PCV13) were identified in 14.6%, 44.5%, and 40.2% of the samples from the <5, 5-64, and ≥65 year age groups, respectively. The 23-valent pneumococcal polysaccharide vaccine serotypes (PPSV23) were identified in 42.4%, 68.2%, and 63.1% of the samples, respectively; whereas non-PCV13 serotypes or non-PPSV serotypes (NVT) comprised 46.8% of all isolates. Among NVT, strain 35B was the most frequently isolated, followed by 15A, particularly in sputum samples collected from children <5 years old. Meanwhile, serotype 3, which is targeted by the PCV13 and PPSV23, was the most prevalent among patients aged ≥65 and 5-64 years. Antimicrobial susceptibility testing revealed that 88.9% and 81.0% of serotype 35B was non-susceptible to penicillin and meropenem, respectively, and 89.4% of 15A was non-susceptible to penicillin. Our data suggest rapid effects of pneumococcal vaccines and progression of serotype replacement. Besides invasive potential, the increased prevalence of non-vaccine serotypes with highly non-susceptible to penicillin was a concern. Continuous monitoring of pneumococcal serotypes and antimicrobial susceptibility is necessary for developing optimal preventive strategies.


Asunto(s)
Antibacterianos/inmunología , Antibacterianos/uso terapéutico , Infecciones Neumocócicas/tratamiento farmacológico , Infecciones Neumocócicas/inmunología , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/inmunología , Adolescente , Adulto , Anciano , Portador Sano/inmunología , Niño , Femenino , Vacuna Neumocócica Conjugada Heptavalente/inmunología , Humanos , Programas de Inmunización/métodos , Incidencia , Japón , Masculino , Meropenem , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Penicilinas/inmunología , Vacunas Neumococicas/inmunología , Prevalencia , Serogrupo , Serotipificación/métodos , Tienamicinas/inmunología , Vacunación/métodos , Adulto Joven
6.
Tohoku J Exp Med ; 230(2): 123-7, 2013 06.
Artículo en Inglés | MEDLINE | ID: mdl-23801051

RESUMEN

Juvenile xanthogranuloma (JXG) is a benign manifestation of non-Langerhans cell histiocytosis characterized by yellowish cutaneous nodules. Its occurrence in the larynx is very rare, but laryngeal JXG may cause severe respiratory distress. We report a patient with isolated laryngeal JXG treated by laryngomicrosurgery, and this is the first report of JXG extending to vocal fold. A 3-year-old girl presented with hoarseness and inspiration stridor. A bulky tumor was found in right glottic to subglottic region. Subtotal resection of the tumor was carried out by laryngomicrosurgery, and airway distress was diminished after the operation. In pathological examination, the resected specimen showed proliferation of histiocytic cells and spindle cells with Touton giant cells that are characterized by polynuclei or wreath nuclei and are known to appear in JXG but not in LCH. Immunohistochemistry of histiocytic cell markers demonstrated positivity for CD68, lysozyme, alpha1-anti-chymotrypsin, factor XIIIa and vimentin, and negativity for CD1a and S-100, leading to diagnosis of JXG, but not LCH. The patient was thus expected with benign prognosis, and additional resection of the tumor including vocal fold was not indicated in the initial treatment. Six weeks later, the JXG recurred and a second procedure using CO2 laser was needed. The tumor did not re-grow thereafter, and there was no residual voice handicap. Because of its favorable prognosis and tendency for spontaneous regression, JXG in the larynx needs to be considered carefully with regard to whether reduction surgery and/or tracheotomy are necessary, and thus precise diagnosis is required.


Asunto(s)
Histiocitosis de Células de Langerhans/diagnóstico , Histiocitosis de Células de Langerhans/cirugía , Laringe/patología , Xantogranuloma Juvenil/diagnóstico , Xantogranuloma Juvenil/cirugía , Preescolar , Femenino , Glotis/patología , Histiocitosis de Células de Langerhans/metabolismo , Humanos , Inmunohistoquímica , Pronóstico , Enfermedades Respiratorias/diagnóstico , Enfermedades Respiratorias/metabolismo , Enfermedades Respiratorias/cirugía , Resultado del Tratamiento , Xantogranuloma Juvenil/metabolismo
7.
IJU Case Rep ; 4(4): 204-206, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34258527

RESUMEN

INTRODUCTION: Basal cell carcinoma of the prostate is a rare prostate malignancy. Its diagnosis and treatment have not been well established yet. CASE PRESENTATION: An 80-year-old man was referred to our hospital for undergoing holmium laser enucleation of the prostate with persistent lower urinary tract symptoms. Ultrasonography showed enlarged prostate (41.3 cc) with mid-lobe hypertrophy. His prostate-specific antigen and testosterone levels were 0.437 ng/mL and 873 ng/dL, respectively. Histological examination of the enucleated tissue confirmed basal cell carcinoma. The cells were positive for bcl-2, 34ßE12, p63, and cytokeratin 5/6. Ki-67 labeling index was 5%. Subsequent staging computed tomography scan and bone scintigram showed neither lymph node nor distant metastasis. Currently, the patient is under close follow-up with imaging, endoscopy, and urodynamic study. CONCLUSION: It is difficult for physicians to detect prostate basal cell carcinoma before benign prostatic hyperplasia surgery. In case of organ-confined disease, age and Ki-67 labeling index could be suggestive of subsequent treatment decision-making.

8.
Sci Rep ; 10(1): 8682, 2020 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-32457307

RESUMEN

Symptoms of Staphylococcus lugdunensis infection are often similar to those of Staphylococcus aureus infection, including skin and soft-tissue lesions, bacteremia and infective endocarditis. Despite the severity of these infections, S. lugdunensis is regarded as a less important pathogen than drug-resistant S. aureus. To investigate its ability to cause infectious diseases, a methicillin-resistant S. lugdunensis (MRSL) strain JICS135 was isolated from a patient with bacteremia and subjected to whole genome sequencing. Similar to most strains of methicillin-resistant S. aureus (MRSA), this MRSL strain possessed the staphylococcal cassette chromosome mec (SCCmec) located close to the origin of replication. However, the SCCmec in this MRSL strain, with three ccr complexes, was structurally unique and currently untypable. Moreover, the SCCmec of this MRSL strain was found to carry two genes encoding microbial surface components recognizing adhesive matrix molecules (MSCRAMM)-like proteins accompanied by glycosyl transferases, one of which may have been derived from S. aureus and the other from S. epidermidis, indicating that this MRSL evolved to carry virulence factors from other staphylococci. The emergence of this strain, the first MRSL strain whose genome has been sequenced completely, may be of public concern.


Asunto(s)
Proteínas Bacterianas/genética , Cromosomas Bacterianos , Resistencia a la Meticilina/genética , Staphylococcus lugdunensis/genética , Anciano , Antibacterianos/farmacología , Bacteriemia/microbiología , Bacteriemia/patología , Cromosomas Bacterianos/genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Filogenia , Staphylococcus lugdunensis/clasificación , Staphylococcus lugdunensis/efectos de los fármacos , Secuenciación Completa del Genoma
9.
Kansenshogaku Zasshi ; 83(1): 52-5, 2009 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-19227225

RESUMEN

As the most common cause of neonatal sepsis, Lancefield Group B Streptococcus (GBS) must be diagnosed as early as possible in pregnant women is prevent neonatal infection. A selective enrichment broth medium has been widely recommended to optimally recover GBS from genital and anorectal samples. To establish a culture suitable for screening vaginal swab specimens, we compared subcultures of three selective enrichment media to direct culture on agar medium. Vaginal swab samples were inoculated directly onto 5% sheep blood agar and into New Granada medium (Eiken), Lim broth (Becton, Dickinson, and Company), and Todd Hewitt broth with gentamicin and nalidixic acid (Becton, Dickinson, and Company, Todd). Of the 288 specimens tested, GBS was recovered from 43 samples (14.9%) on direct agar media, with 82 (28.5%), positive on New Granada medium subculture, 67 (23.3%) on Lim broth subculture, and 61 (21.2%) on Todd, subculture. These results demonstrates that selective enrichment broth media provides more superior sensitivity than direct agar media for detection of GBS colonization in vaginal specimens, underscoring the usefulness of selective enrichment broth media in GBS screening for vaginal swabs in pregnant woman.


Asunto(s)
Medios de Cultivo , Streptococcus agalactiae/aislamiento & purificación , Vagina/microbiología , Femenino , Humanos
10.
Cancer Lett ; 461: 144-152, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31325530

RESUMEN

CD271, known as a neurotrophin receptor, is expressed in various cancers such as hypopharyngeal cancer (HPC) and melanoma. We recently reported that CD271 is a cancer-stem-cell biomarker of HPC, and that its expression is essential for cancer-cell proliferation and is correlated with a poor prognosis in this disease. Here, to develop a therapeutic antibody to CD271, we established a humanized anti-CD271 monoclonal antibody (hCD271 mA b). hCD271 mA b bound to the cysteine-rich domain 1 (CRD1) of human CD271 with high affinity (KD = 1.697 × 10-9 M). In vitro, hCD271 mA b exerted antibody-dependent cell-mediated cytotoxicity (ADCC) activity against SP2/0-CD271 (human CD271-transduced mouse cell line). Treatment with hCD271 mA b also exerted anti-tumor activity in graft models of three cell lines (HPCM2 (patient-derived xenograft cell line of hypopharyngeal cancer), MeWo-Luc (melanoma cell line), and SP2/0-CD271) in mice, resulting in smaller tumors compared to controls and reduced numbers of CD271-positive cells. Collectively, these data suggest that an antibody targeting CD271 is a promising therapeutic strategy.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Proteínas del Tejido Nervioso/inmunología , Receptores de Factor de Crecimiento Nervioso/inmunología , Animales , Anticuerpos Monoclonales Humanizados/inmunología , Apoptosis , Proliferación Celular , Femenino , Humanos , Neoplasias Hipofaríngeas/inmunología , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Melanoma/inmunología , Melanoma/metabolismo , Melanoma/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Ratones SCID , Células Madre Neoplásicas/inmunología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Endocr Relat Cancer ; 15(1): 113-24, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18310280

RESUMEN

It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.


Asunto(s)
17-Hidroxiesteroide Deshidrogenasas/metabolismo , Aromatasa/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Intraductal no Infiltrante/metabolismo , Dihidrotestosterona/metabolismo , Estradiol/metabolismo , Esteril-Sulfatasa/metabolismo , 17-Hidroxiesteroide Deshidrogenasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Aromatasa/genética , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/patología , Cromatografía Liquida , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Espectrometría de Masa por Ionización de Electrospray , Esteril-Sulfatasa/genética , Células del Estroma/metabolismo , Células del Estroma/patología , Tasa de Supervivencia
12.
Cancer Res ; 66(1): 535-42, 2006 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-16397270

RESUMEN

Steroid and xenobiotic receptor (SXR) or human pregnane X receptor (hPXR) has been shown to play an important role in the regulation of genes related to xenobiotic detoxification, such as cytochrome P450 3A4 and multidrug resistance gene 1. Cytochrome P450 enzymes, conjugation enzymes, and transporters are all considered to be involved in the resistance of breast carcinoma to chemotherapeutic or endocrine agents. However, the expression of SXR/hPXR proteins and that of its target genes and their biological or clinical significance have not been examined in human breast carcinomas. Therefore, we first examined SXR/hPXR expression in 60 breast carcinomas using immunohistochemistry and quantitative reverse transcription-PCR. We then searched for possible SXR/hPXR target genes using microarray analysis of carcinoma cells captured by laser microscissors. SXR/hPXR was detected in carcinoma tissues but not in nonneoplastic and stromal cells of breast tumors. A significant positive correlation was detected between the SXR/hPXR labeling index and both the histologic grade and the lymph node status of the carcinoma cases. Furthermore, in estrogen receptor-positive cases, SXR/hPXR expression was also positively correlated with expression of the cell proliferation marker, Ki-67. Microarray analysis showed that organic anion transporting polypeptide-A (OATP-A) was most closely correlated with SXR/hPXR gene expression, and both OATP-A mRNA and protein were significantly associated with SXR/hPXR in both breast carcinoma tissues and its cell lines. These results suggest that SXR/hPXR and its target gene, such as OATP-A, may play important roles in the biology of human breast cancers.


Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma Ductal/metabolismo , Transportadores de Anión Orgánico/biosíntesis , Receptores de Esteroides/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Ductal/genética , Carcinoma Ductal/patología , Línea Celular Tumoral , Análisis por Conglomerados , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/biosíntesis , Sistema Enzimático del Citocromo P-450/genética , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Transportadores de Anión Orgánico/genética , Receptor X de Pregnano , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptores de Esteroides/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
13.
Oncol Lett ; 15(1): 509-514, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29387231

RESUMEN

Accumulating evidence demonstrated that Hox antisense intergenic RNA (HOTAIR) serves essential roles in the development and metastasis of several types of cancer. In hepatocellular carcinoma (HCC), high expression of HOTAIR is associated with poor prognosis, and HOTAIR regulates cell migration and proliferation. However, the downstream molecular targets of HOTAIR depend on the cancer cell types, and little is known about the precise molecular mechanisms of HOTAIR involved in cancer development. The present study investigated the role of HOTAIR in HCC cell lines. Notably, the overexpression of HOTAIR in HCC cell lines did not affect cell migration and proliferation capability. In the microarray analysis, C-C motif chemokine ligand (CCL)2 was identified to be differentially expressed in HOTAIR-overexpressing cells, and it was confirmed that HOTAIR promotes the secretion of CCL2. Furthermore, it was revealed that the proportion of macrophages and myeloid-derived suppressor cells (MDSCs) were increased when peripheral blood mononuclear cells were co-cultured with HOTAIR-overexpressing cells. Collectively, these data suggest that HOTAIR regulates CCL2 expression, which may be involved in the recruitment of macrophages and MDSCs to the tumor microenvironment.

14.
Oncotarget ; 9(28): 20008-20017, 2018 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-29731999

RESUMEN

Inflammatory bowel diseases, which are multifactorial autoimmune colitis diseases, are occurring with increasing prevalence. One of the most serious complications of these diseases is colorectal cancer. Here we investigated the role of periostin (Postn), a matricellular protein that interacts with various integrin molecules on the cell surface, in colitis-induced colorectal cancer. Immunohistochemistry of mouse and human colorectal cancer samples revealed that Postn was expressed in the stroma and was upregulated in close proximity to the cancer cells. The colonic tumorigenesis in an inflammation-related colon carcinogenesis mouse model was increased in Postn knock-out (Postn-/-) mice compared to Postn+/+ mice. Although no difference was found in the degree of colitis between Postn+/+ and Postn-/- mice, Postn inhibited tumor growth and induced the apoptosis of mouse rectal cancer cells in vitro. Furthermore, fewer apoptotic colorectal cancer cells were observed in Postn-/- than in Postn+/+ mice. These data suggested that Postn has an anti-tumor effect on colitis-induced colorectal cancer.

15.
Oncotarget ; 9(58): 31187-31199, 2018 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-30131847

RESUMEN

Periostin is a matricellular protein that is secreted by fibroblasts and interacts with various cell-surface integrin molecules. Although periostin is known to support tumor development in human malignancies, little is known about its effect on lung-cancer progression. We here demonstrate that periostin is a negative prognostic factor that increases tumor proliferation through ERK signaling in non-small cell lung carcinoma. We classified 189 clinical specimens from patients with non-small cell lung-cancer according to high or low periostin expression, and found a better prognosis for patients with low rather than high periostin, even in cases of advanced-stage cancer. In a syngenic implantation model, murine Ex3LL lung-cancer cells formed smaller tumor nodules in periostin-/- mice than in periostin+/+ mice, both at the primary site and at metastatic lung sites. An in vitro proliferation assay showed that stimulation with recombinant periostin increased Ex3LL-cell proliferation. We also found that periostin promotes ERK phosphorylation, but not Akt or FAK activation. These findings suggest that periostin represents a potential target in lung-cancer tumor progression.

16.
Int J Oncol ; 52(3): 881-891, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29393401

RESUMEN

The majority of cancer cells maintain a high glycolytic activity and an increased lactate production, even in a well oxygenated environment. This phenomenon is known as the Warburg effect. Previous studies have revealed that various types of cancer selectively express the pyruvate kinase M2 isoform (PKM2), and that PKM2 plays a pivotal role in the Warburg effect. Although elevated PKM2 levels have been observed in pancreatic cancer and other types of cancer, little is known about the biological function of PKM2. In this study, in order to examine the expression and role of PKM2 in pancreatic ductal adenocarcinoma (PDAC), we knocked down PKM2 in PDAC cells by introducing small interfering and short hairpin RNAs, and examined the gene expression profiles in the cells by microarray analysis. We analyzed the energy-producing pathways in the cells by XFe Extracellular Flux Analyzers, and detected intracellular metabolites by capillary electrophoresis time-of-flight mass spectrometry. We found that the RNAi-mediated knockdown of PKM2 diminished the proliferative, migratory and tumorigenic ability of the PDAC cell-lines. PKM2 knockdown also resulted in lower glycolytic activities and decreased levels of some intracellular metabolites, such as pyruvate and polyamine; however, it led to elevated levels of reactive oxygen species. Microarray analysis revealed the functional association between PKM2 and the expression of genes that drive the cell cycle. On the whole, the findings of this study demonstrate that PKM2 plays an important role in metabolic activities, as well as in the malignancy of PDAC cells.


Asunto(s)
Carcinoma Ductal Pancreático/patología , Proteínas Portadoras/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Neoplasias Pancreáticas/patología , Especies Reactivas de Oxígeno/metabolismo , Hormonas Tiroideas/metabolismo , Animales , Carcinogénesis/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/cirugía , Proteínas Portadoras/genética , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Femenino , Perfilación de la Expresión Génica/métodos , Técnicas de Silenciamiento del Gen , Glucólisis/genética , Humanos , Isoenzimas/metabolismo , Proteínas de la Membrana/genética , Metabolómica/métodos , Ratones SCID , Páncreas/patología , Páncreas/cirugía , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirugía , ARN Interferente Pequeño/metabolismo , Hormonas Tiroideas/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas de Unión a Hormona Tiroide
17.
Sci Rep ; 7(1): 12016, 2017 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-28931862

RESUMEN

Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression. HOTAIR expression in tumors was significantly correlated with nuclear grade, lymph-node metastasis, and lung metastasis. High HOTAIR expression was associated with a poor prognosis in both our dataset and The Cancer Genome Atlas dataset. Migratory capacity was enhanced in RCC cell lines in a HOTAIR-dependent manner. HOTAIR overexpression accelerated tumorigenicity and lung metastasis in immunodeficient mice. Microarray analysis revealed that IGFBP2 expression was upregulated in HOTAIR-overexpressing cells compared with control cells. The enhanced migration activity of HOTAIR-overexpressing cells was attenuated by IGFBP2 knockdown. IGFBP2 and HOTAIR were co-expressed in clinical RCC samples. Our findings suggest that the HOTAIR-IGFBP2 axis plays critical roles in RCC metastasis and may serve as a novel therapeutic target for advanced RCC.


Asunto(s)
Carcinoma de Células Renales/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Neoplasias Renales/genética , ARN Largo no Codificante/genética , Animales , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica , Humanos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Estimación de Kaplan-Meier , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Persona de Mediana Edad , Interferencia de ARN , Trasplante Heterólogo , Regulación hacia Arriba
18.
Cancer Lett ; 244(1): 24-33, 2006 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-16427184

RESUMEN

Liver receptor homologue-1 (LRH-1) belongs to a class of nuclear orphan receptor. We examined immunolocalization of LRH-1 in 106 breast carcinomas. LRH-1 immunoreactivity was detected in 43% of the invasive ductal carcinoma. It was negatively correlated with clinical stage, histological grade and HER2 status, and positively associated with sex-steroid receptors, steroidogenic acute regulatory protein, P450 side-chain cleavage, and 3beta-hydroxysteroid dehydrogenase. LRH-1 immunoreactivity was also detected in 28% of the ductal carcinoma in situ. These results suggest that LRH-1 is frequently detected in breast carcinoma tissues, and plays important roles including the regulation of in situ steroidogenesis.


Asunto(s)
Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Proteínas de Unión al ADN/metabolismo , Fosfoproteínas/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/metabolismo , Carcinoma Intraductal no Infiltrante/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfoproteínas/genética , Receptor ErbB-2/metabolismo
20.
Endosc Int Open ; 4(8): E832-7, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27540569

RESUMEN

BACKGROUND AND STUDY AIMS: Intramucosal vascular density differs between differentiated and undifferentiated type gastric carcinomas. This study aimed to evaluate the microvascular density characteristics of these two types of carcinoma using magnifying endoscopy with narrow-band imaging (ME-NBI). PATIENTS AND METHODS: In total, 42 differentiated and 10 undifferentiated types were evaluated. The microvessels observed using ME-NBI were extracted from stored still images and the microvascular density in the two carcinoma types was analyzed. Histological vascular density in resected specimens was also evaluated using CD34 immunostaining. RESULTS: There were significant differences between the microvascular density in the differentiated and undifferentiated types of carcinoma (10.02 ±â€Š4.72 % vs 4.02 ±â€Š0.40 %; P < 0.001) using ME-NBI. Vascular density assessed histologically also differed significantly between differentiated and undifferentiated types in both the whole mucosal (5.81 ±â€Š3.17 % vs 3.25 ±â€Š1.21 %) and the superficial mucosal layers (0 - 100 µm) (6.38 ±â€Š3.73 % vs 3.66 ±â€Š1.46 %). However, the vascular density in the surrounding non-carcinomatous mucosa assessed using ME-NBI and histologically, was significantly lower in the differentiated than in the undifferentiated types (P < 0.001). There was good agreement between ME-NBI and histologically assessed microvascular density in both the whole (r = 0.740; P < 0.001) and superficial mucosal layers (r = 0.764; P < 0.001). White opaque substance (WOS) was seen in eight patients who had the differentiated type carcinoma. In almost all cases with WOS, the appearance of the carcinoma was discolored. CONCLUSIONS: There was a close relationship between ME-NBI assessed microvascular density and histologically assessed vascular density in the mucosal layer. Microvascular density differed significantly between the differentiated and undifferentiated types of carcinoma assessed using ME-NBI.

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