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PURPOSE: The efficacy of carboplatin is non-equivalent to that of cisplatin (CDDP) for various tumor types in curative settings. However, the role of CDDP in operable triple-negative breast cancer (TNBC) patients remains unknown. We conducted a multicenter observational study to examine the effects of CDDP added to preoperative chemotherapy in patients with TNBC. METHODS: This retrospective study consecutively included previously untreated patients with stage I-III TNBC treated with preoperative chemotherapy with or without CDDP. The primary endpoint was distant disease-free survival (DDFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize confounding biases in comparisons between the two groups. RESULTS: A total of 138 patients were enrolled in the study. Of these, 52 were in the CDDP group and 86 in the non-CDDP group. DDFS was significantly better in the CDDP group than in the non-CDDP group (unadjusted hazard ratio (HR) 0.127 and p < 0.001, PSM HR 0.141 and p < 0.003, IPTW HR 0.123 and p = < 0.001). Furthermore, among the patients with residual cancer burden (RCB) class II/III, DDFS was better in the CDDP group than in the non-CDDP group (unadjusted HR 0.192 and p = 0.013, PSM HR 0.237 and p = 0.051, IPTW HR 0.124 and p = 0.059). CONCLUSION: Our study showed that CDDP-containing regimens achieved favorable prognoses in patients with operable TNBC, especially for the RCB class II/III population. Confirmative studies are warranted to elucidate the role of CDDP in TNBC treatment.
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Cisplatino , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/cirugía , Estudios Retrospectivos , Puntaje de Propensión , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia NeoadyuvanteRESUMEN
Flowering time is an agriculturally important trait that can be manipulated by various approaches such as breeding, growth control and genetic modifications. Despite its potential advantages, including fine-tuning the regulation of flowering time, few reports have explored the use of chemical compounds to manipulate flowering. Here, we report that sulfanilamide, an inhibitor of folate biosynthesis, delays flowering by repressing the expression of florigen FLOWERING LOCUS T (FT) in Arabidopsis thaliana. Transcriptome deep sequencing and quantitative polymerase chain reaction analyses showed that the expression of the circadian clock gene LUX ARRYTHMO/PHYTOCLOCK1 (LUX/PCL1) is altered by sulfanilamide treatment. Furthermore, in the lux nox mutant harboring loss of function in both LUX and its homolog BROTHER OF LUX ARRHYTHMO (BOA, also named NOX), the inhibitory effect of sulfanilamide treatment on FT expression was weak and the flowering time was similar to that of the wild type, suggesting that the circadian clock may contribute to the FT-mediated regulation of flowering by sulfanilamide. Sulfanilamide also delayed flowering time in arugula (Eruca sativa), suggesting that it is involved in the regulation of flowering across Brassicaceae. We propose that sulfanilamide is a novel modulator of flowering.
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Proteínas de Arabidopsis , Arabidopsis , Relojes Circadianos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Relojes Circadianos/genética , Ritmo Circadiano/genética , Flores , Regulación de la Expresión Génica de las Plantas , Fotoperiodo , Fitomejoramiento , Sulfanilamidas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Many organisms rely on a circadian clock system to adapt to daily and seasonal environmental changes. The mammalian circadian clock consists of a central clock in the suprachiasmatic nucleus that has tightly coupled neurons and synchronizes other clocks in peripheral tissues. Plants also have a circadian clock, but plant circadian clock function has long been assumed to be uncoupled. Only a few studies have been able to show weak, local coupling among cells. Here, by implementing two novel techniques, we have performed a comprehensive tissue-specific analysis of leaf tissues, and show that the vasculature and mesophyll clocks asymmetrically regulate each other in Arabidopsis. The circadian clock in the vasculature has characteristics distinct from other tissues, cycles robustly without environmental cues, and affects circadian clock regulation in other tissues. Furthermore, we found that vasculature-enriched genes that are rhythmically expressed are preferentially expressed in the evening, whereas rhythmic mesophyll-enriched genes tend to be expressed in the morning. Our results set the stage for a deeper understanding of how the vasculature circadian clock in plants regulates key physiological responses such as flowering time.
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Arabidopsis/fisiología , Relojes Circadianos/fisiología , Arabidopsis/citología , Arabidopsis/genética , Ritmo Circadiano/fisiología , Perfilación de la Expresión Génica , Células del Mesófilo/metabolismo , Especificidad de Órganos , Hojas de la Planta/genética , Hojas de la Planta/fisiologíaRESUMEN
Uterine leiomyosarcoma (ULMS) is the major subtype of uterine sarcoma (US) and contributes to uterine cancer deaths. Although preoperative diagnosis of US remains challenging, frequent application of laparoscopic surgery for benign uterine leiomyomas (ULM) requires precise exclusion of US. MicroRNAs are stably present in the bloodstream, and the application of circulating miRNAs as disease biomarkers has been recognized. In the present study, we aimed to identify diagnostic biomarkers for distinguishing US from ULM by focusing on circulating miRNAs. All serum samples were collected preoperatively between 2009 and 2017, and all cases were histopathologically diagnosed. Whole miRNA profiles were obtained using a miRNA microarray. By analyzing expression levels of the miRNAs, candidate miRNAs were selected based on diagnostic performance in discriminating US from ULM, and a diagnostic model was then constructed. A total of 90 serum samples were analyzed, and clustering analyses revealed that the profiles of ULMS were distinct from those of controls. Based on leave-one-out cross-validation, seven miRNAs were selected as biomarker candidates. Based on model construction, the optimal model consisted of two miRNAs (miR-1246 and miR-191-5p), with an area under the receiver operating characteristic curve (AUC) for identifying ULMS of 0.97 (95% confidence interval [CI], 0.91-1.00). In contrast, serum lactate dehydrogenase had an AUC of only 0.64 (95% CI, 0.34-0.94). Seven serum miRNAs with high diagnostic performance for preoperative US screening were detected, and a promising diagnostic model for ULMS was generated.
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MicroARN Circulante/análisis , Leiomiosarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Biomarcadores de Tumor/sangre , Análisis por Conglomerados , Femenino , Humanos , Leiomiosarcoma/sangre , Neoplasias Uterinas/sangreRESUMEN
Cornelia de Lange syndrome (CdLS) is a cohesinopathy, which is characterized by multiple structural anomalies as well as mental and growth retardation. A 36-yr-old nulliparous woman with oligomenorrhea was referred to us due to a mass in the uterine corpus. She had been clinically diagnosed with CdLS during infancy based on her specific facial features as well as growth and intellectual retardation. Imaging examinations and an endometrial biopsy revealed endometrial endometrioid carcinoma and polycystic ovary syndrome (PCOS). She underwent a hysterectomy and bilateral salpingo-oophorectomy. The tumor was mainly located at the uterine isthmus and exhibited diffuse exophytic growth. Microscopically, the grade 1 endometrioid carcinoma consisted of extremely well-differentiated glands and showed myometrial invasion. Both swollen ovaries had a thick fibrous cortex and multiple follicles. To the best of our knowledge, this is the first case report of a gynecologic malignancy in an adult patient with CdLS. Several gene mutations have been reported to be causative of CdLS; however, a potential role of these mutations in the pathogenesis of PCOS and subsequent endometrial cancer remains controversial. In this case, PCOS seemed to underlie the endometrial carcinogenesis and then concurrent loss of PTEN and PAX2 expression, confirmed by immunohistochemistry, can facilitate tumor progression. Our case suggests that adult female patients with CdLS can have PCOS and subsequent endometrial carcinoma. As patients with CdLS often have difficulties recognizing and/or reporting menstrual disorder, their care providers should pay particular attention to menstrual cycle irregularities due to the risk of endometrial cancer.
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Carcinoma Endometrioide/diagnóstico por imagen , Síndrome de Cornelia de Lange/diagnóstico por imagen , Neoplasias Endometriales/diagnóstico por imagen , Síndrome del Ovario Poliquístico/diagnóstico por imagen , Adulto , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/cirugía , Síndrome de Cornelia de Lange/genética , Síndrome de Cornelia de Lange/patología , Síndrome de Cornelia de Lange/cirugía , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Imagen por Resonancia Magnética , Mutación , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/patología , Síndrome del Ovario Poliquístico/cirugíaRESUMEN
Although S-1 is an effective oral anticancer drug in patients with metastatic breast cancer, it is difficult for some patients to continue taking S-1 because of its side effects in the approved regimen of 4 weeks of administration followed by a 2-week rest. When S-1 is administered for 5 days followed by a 2-day rest(5-day on/2-day off), the drug concentration is almost equal to that of the approved regimen, and it can be administered for longer without deterioration of its clinical effect. We retrospectively analyzed the effect and safety in 25 cases in which S-1 was administered using the "5-day on/2-day off" regimen in patients with metastatic breast cancer between November 2006 and August 2014 in our hospital. Patients were all female, and their median age was 68 years(44-87). ER was positive/negative in 15/10 cases, and PS 0/1/2were found in 8/ 10/7 cases. They had no prior chemotherapy and had measurable lesions. S-1 was administered at a dose of 80mg/m2 twice a day on a "5-day on/2-day off" schedule and was reduced when its side effects were appeared. The median treatment duration was 25(3-214)weeks, and CR/PR/long SD/SD/PD as clinical responses were observed in 0/8/5/5/7 cases. The overall response rate was 32% and clinical benefit rate was 52%. There was no difference in response rates whether visceral metastases were present or not. In terms of hematologic toxicity, anemia was seen in one case, and there were no cases of neutropenia. In non-hematologic toxicity, no more than Grade 3 side effects were shown. Discontinuance was observed in only one case because of diarrhea. A "5-day on/2-day off" regimen of S-1 in metastatic breast cancer is well tolerated, and we can continue administering it to elderly patients or those with poor PS without reducing QOL; thus, it can be considered as one of the effective metronomic treatments. In the future, a prospective study is warranted to ascertain these results.
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Neoplasias de la Mama , Ácido Oxónico , Tegafur , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Combinación de Medicamentos , Femenino , Humanos , Persona de Mediana Edad , Ácido Oxónico/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Tegafur/uso terapéuticoRESUMEN
INTRODUCTION: Diagnostic imaging modalities to evaluate the three-dimensional distribution of thoracodorsal artery perforators (TDAPs) are lacking. In this study, TDAPs were visualized and characterized using photoacoustic imaging. MATERIAL AND METHODS: In this study, 34 sites in the lateral chest wall of 18 individuals were analyzed. The region extending 5 cm ventral and 5 cm dorsal to the lateral edge of the latissimus dorsi (LD) and 5-15 cm from the posterior axillary fold was scanned using photoacoustic imaging. The largest perforator closest to the edge of the LD was characterized. The location of the stem portion and the orientation of the longest cutaneous branch of the perforator were described. The relationship between the maximal depth of delineation on photoacoustic images and the depth of the deep fascia was assessed. RESULTS: On average, 2.6 perforators (range, 1-5 perforators) were visualized in the region of interest. The distribution of the TDAP stem portion was similar to that in previous studies. Cutaneous branches were preferentially oriented in a medial-caudal direction. The length of delineated cutaneous branches varied (range, 7-78 mm) depending on the thickness of the subcutaneous layer. Vessels under the LD were observed when the subcutaneous layer was thin. CONCLUSION: Photoacoustic imaging can successfully visualize TDAPs in three dimensions. Visualization of TDAPs varied by the thickness of the subcutaneous layer. A thin deep fascia of the LD might be a cause of deep laser penetration.
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Colgajo Perforante , Técnicas Fotoacústicas , Arterias , Humanos , Imagenología Tridimensional , Colgajo Perforante/irrigación sanguínea , Colgajos Quirúrgicos/irrigación sanguínea , TóraxRESUMEN
Circadian rhythms and progression of cell differentiation are closely coupled in multicellular organisms. However, whether establishment of circadian rhythms regulates cell differentiation or vice versa has not been elucidated due to technical limitations. Here, we exploit high cell fate plasticity of plant cells to perform single-cell RNA sequencing during the entire process of cell differentiation. By analyzing reconstructed actual time series of the differentiation processes at single-cell resolution using a method we developed (PeakMatch), we find that the expression profile of clock genes is changed prior to cell differentiation, including induction of the clock gene LUX ARRYTHMO (LUX). ChIP sequencing analysis reveals that LUX induction in early differentiating cells directly targets genes involved in cell-cycle progression to regulate cell differentiation. Taken together, these results not only reveal a guiding role of the plant circadian clock in cell differentiation but also provide an approach for time-series analysis at single-cell resolution.
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Proteínas de Arabidopsis , Arabidopsis , Relojes Circadianos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Diferenciación Celular/genética , Relojes Circadianos/genética , Ritmo Circadiano/genética , Regulación de la Expresión Génica de las Plantas , Análisis de Secuencia de ARN , Factores de TiempoRESUMEN
This study aimed to evaluate the predictions of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for prognosis of triple-negative breast cancer (TNBC), especially with residual disease (RD) after preoperative chemotherapy. This retrospective analysis included 74 TNBC patients who received preoperative chemotherapy. DCE-MRI findings from three timepoints were examined: at diagnosis (MRIpre), at midpoint (MRImid) and after chemotherapy (MRIpost). These findings included cancer lesion size, washout index (WI) as a kinetic parameter using the difference in signal intensity between early and delayed phases, and time-signal intensity curve types. Distant disease-free survival was analysed using the log-rank test to compare RD group with and without a fast-washout curve. The diagnostic performance of DCE-MRI findings, including positive predictive value (PPV) for pathological responses, was also calculated. RD without fast washout curve was a significantly better prognostic factor, both at MRImid and MRIpost (hazard ratio = 0.092, 0.098, p < 0.05). PPV for pathological complete remission at MRImid was 76.7% by the cut-off point at negative WI value or lesion size = 0, and 66.7% at lesion size = 0. WI and curve types derived from DCE-MRI at the midpoint of preoperative chemotherapy can help not only assess tumour response but also predict prognosis.
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Imagen por Resonancia Magnética/métodos , Neoplasia Residual/diagnóstico por imagen , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Anciano , Antineoplásicos/uso terapéutico , Medios de Contraste/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Cinética , Imagen por Resonancia Magnética/instrumentación , Persona de Mediana Edad , Neoplasia Residual/química , Neoplasia Residual/mortalidad , Neoplasia Residual/patología , Pronóstico , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Spermatogenesis in Drosophila commences with cell division of germline stem cells (GSCs) to produce male germline cells at the tip of the testis. However, molecular mechanisms inducing division of male GSCs have not been reported. Insulin-like peptides are known to play an essential role in stimulation of proliferation and growth of somatic cells, and it has recently been reported that such peptides promote cell division in female Drosophila GSCs. However, their effects on male germline cells have not been characterized. We found that inhibition of insulin production and insulin signaling mutations resulted in decreased numbers of germline cells in Drosophila testes. GSC numbers were maintained in young mutant males, with a gradual decrease in abundance of GSCs with age. Furthermore, in mutants, fewer germline cysts originated from GSCs and a lower frequency of GSC division was seen. Insulin signaling was found to promote cell cycle progression of the male GSCs at the G(2)/M phase. The cell volume of spermatocytes increases up to 25 times before initiation of meiosis in Drosophila. We examined whether insulin signaling extrinsically induces the greatest cell growth in Drosophila diploid cells and found that spermatocyte growth was affected in mutants. The results indicate that in addition to its function in somatic cells, insulin signaling plays an essential role in cell proliferation and growth during male Drosophila gametogenesis and that sperm production is regulated by hormonal control via insulin-like peptides.
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Drosophila/metabolismo , Insulina/metabolismo , Espermatocitos/crecimiento & desarrollo , Espermatogénesis , Espermatozoides/citología , Células Madre/metabolismo , Animales , División Celular , Drosophila/citología , Fase G2 , Masculino , Meiosis , Proteínas Mutantes/metabolismo , Transducción de Señal , Espermatocitos/metabolismo , Espermatozoides/metabolismo , Células Madre/citologíaRESUMEN
OBJECTIVE: To assess the PP13 expression in the cellular component of blood in both preeclamptic patients and asymptomatic pregnant women during the early second trimester. METHODS: In the case-control study, peripheral blood samples were obtained from pregnant women with preeclampsia (n = 24) and controls (n = 22). PP13 RNA expression was quantified in the cellular component of the blood by reverse transcription PCR assay. Next, as a cohort study of asymptomatic pregnant women at early gestation, cellular RNA from 41 cases who developed preeclampsia at later gestation and 123 cases of control were analysed, and the possibility of prediction of preeclampsia was assessed. RESULTS: In symptomatic patients, PP13 level in preeclampsia was significantly lower than that in controls (p < 0.001). In the asymptomatic pregnant women, the PP13 level in preeclampsia was significantly lower than that in the controls (p = 0.008). A receiver-operating characteristics (ROC) curve yielded a detection rate of 24 and 31% at a false positive rate of 5 and 10% respectively. CONCLUSION: An alteration in the cellular PP13 RNA expression would affect the placental pathophysiological change. The cellular PP13 expression level could therefore potentially be one of the key markers to predict the clinical onset of preeclampsia.
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Galectinas/sangre , Preeclampsia/sangre , Proteínas Gestacionales/sangre , Adolescente , Adulto , Biomarcadores/sangre , Células Sanguíneas/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , ARN Mensajero/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: To assess the alterations of mRNA expressions associated with oxidative stress in the cellular component of blood from pregnant women with pre-eclampsia. METHODS: Peripheral blood samples were obtained from pregnant women with and without pre-eclampsia. Cellular RNA was subjected to a reverse transcription polymerase chain reaction (PCR) assay in order to examine the mRNA distribution among women with pre-eclampsia (n = 24) and control subjects (n = 24) during 35-41 weeks of gestation. The data were analyzed by non-parametric statistics. RESULTS: Significant differences between the pre-eclampsia subjects and the controls were observed in the gene expressions associated with oxidative stress. Lower values in the pre-eclampsia group were found for heme oxygenase (HO)-1, HO-2, catalase and superoxide dismutase (SOD). The HO-1, HO-2 and the catalase levels significantly correlated with proteinuria, and the HO-2 level with systolic blood pressure. CONCLUSION: Significantly lower concentrations of HO-1, HO-2, SOD and catalase are found in the cellular component of blood from pre-eclamptic patients. The values correlate with the severity of pre-eclampsia. These findings indicate that enhanced oxidative stress and a decrease in the number of anti-oxidant enzymes may be associated with pre-eclampsia.
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Antioxidantes/metabolismo , Células Sanguíneas/metabolismo , Preeclampsia/sangre , Preeclampsia/genética , ARN Mensajero/sangre , Adolescente , Adulto , Presión Sanguínea , Catalasa/genética , Catalasa/metabolismo , Femenino , Síndrome HELLP/sangre , Síndrome HELLP/genética , Síndrome HELLP/metabolismo , Síndrome HELLP/fisiopatología , Hemo Oxigenasa (Desciclizante)/genética , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Humanos , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Preeclampsia/metabolismo , Preeclampsia/fisiopatología , Embarazo , ARN Mensajero/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Adulto JovenRESUMEN
OBJECTIVE: Gynecologists occasionally encounter synchronous endometrial and ovarian endometrioid carcinoma (SEO-EC) patients who show favorable prognosis than locally advanced or metastatic disease patients. This study aimed to elucidate prognostic factors of SEO-EC and identify patients who have a sufficiently low risk of recurrence without receiving adjuvant chemotherapy. METHODS: We retrospectively reviewed 46 patients with pathologically confirmed SEO-EC who underwent surgery at the National Cancer Center Hospital between 1997 and 2016. Immunohistochemical evaluation of DNA mismatch repair (MMR) protein expression were performed for both endometrial and ovarian tumors. Patient outcomes were analyzed according to clinicopathologic factors. RESULTS: From the multivariate analysis, cervical stromal invasion indicated a worse prognosis for progression-free survival (hazard ratio [HR]=6.85; 95% confidence interval [CI]=1.50-31.1) and overall survival (HR=6.95; 95% CI=1.15-41.8). Lymph node metastasis and peritoneal dissemination did not significantly affect survival. MMR deficiency was observed in 13 patients (28.3%), with both endometrial and ovarian tumors showing the same MMR expression status. MMR deficiency was not significantly associated with survival. Of 23 patients with lesions confined to only the uterine body and adnexa, only 2 had recurrence in the group receiving adjuvant therapy, while none of the 10 patients who did not receive adjuvant therapy had recurrence. CONCLUSION: SEO-EC patients with tumors localized to the uterine body and adnexa lesions had a low risk for recurrence and may not require adjuvant therapy. SEO-EC may have prognostic factors different from those of endometrial and ovarian cancer.
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Carcinoma Endometrioide/patología , Neoplasias Endometriales/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Adulto , Anciano , Carcinoma Endometrioide/terapia , Quimioterapia Adyuvante , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Neoplasias Primarias Múltiples/terapia , Neoplasias Ováricas/terapia , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Receptores Inmunológicos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To treat advanced ovarian cancer, interval debulking surgery (IDS) is performed after 3 cycles each of neoadjuvant chemotherapy (NAC) and postoperative chemotherapy (IDS group). If we expect that complete resection cannot be achieved by IDS, debulking surgery is performed after administering additional 3 cycles of chemotherapy without postoperative chemotherapy (Add-C group). We evaluated the survival outcomes of the Add-C group and determined their serum cancer antigen 125 (CA125) levels to predict complete surgery. METHODS: A retrospective chart review of all stage III and IV ovarian, fallopian tube, and peritoneal cancer patients treated with NAC in 2007-2016 was conducted. RESULTS: About 117 patients comprised the IDS group and 26 comprised the Add-C group. Univariate and multivariate analyses revealed that Add-C group had an equivalent effect on progression-free survival (PFS; p=0.09) and overall survival (OS; p=0.94) compared with the IDS group. Multivariate analysis revealed that patients who developed residual disease after surgery had worse PFS (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.45-3.28) and OS (HR=2.33; 95% CI=1.43-3.79), and those who received <6 cycles of chemotherapy had worse PFS (HR=5.30; 95% CI=2.56-10.99) and OS (HR=3.05; 95% CI=1.46-6.38). The preoperative serum CA125 cutoff level was 30 U/mL based on Youden index method. CONCLUSIONS: Administering 3 additional cycles of chemotherapy followed by debulking surgery exhibited equivalent effects on survival as IDS followed by 3 cycles of postoperative chemotherapy. Preoperative serum CA125 levels of ≤30 U/mL may be a useful predictor of achieving complete surgery.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias Ováricas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Antígeno Ca-125/metabolismo , Quimioterapia Adyuvante , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Supervivencia sin Enfermedad , Neoplasias de las Trompas Uterinas/mortalidad , Neoplasias de las Trompas Uterinas/terapia , Femenino , Humanos , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Ováricas/mortalidad , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/terapia , Estudios RetrospectivosRESUMEN
OBJECTIVES: Incidentally discovered lymphangioleiomyomatosis (LAM) in sampled lymph nodes are infrequent but intractable issues for gynecologists. The aims of this study were to elucidate the prevalence of incidental nodal LAM in a consecutive cohort of gynecologic surgical specimens from Japanese patients, to document clinicopathological features of nodal LAM cases, and to investigate the association between the subsequent development of pulmonary LAM and tuberous sclerosis complex (TSC). STUDY DESIGN: We retrospectively reviewed 1732 consecutive Japanese patients who underwent gynecologic surgery with lymph node sampling in the National Cancer Center Hospital between January 2004 and April 2017. The pathological diagnosis of LAM was performed by pathologists. Clinicopathological data were obtained from patients' electronic medical records. RESULTS: We found that 0.46% (8/1732) of gynecologic surgical specimens with lymph node sampling showed incidental nodal LAM. The size of the lesions was less than 10 mm, and external iliac and obturator nodes were frequently affected. Although there has been no report of a case of incidental nodal LAM developing pulmonary LAM, we identified the first case of a 36-year-old woman who developed pulmonary LAM 7 years after the diagnosis of incidental nodal LAM. None of the 8 patients had a personal or family history of TSC. CONCLUSIONS: Our case brings attention to the risk of developing subsequent pulmonary LAM. To date, insufficient long-term follow-up data of young patients have hindered us from drawing a definite conclusion that patients with incidental nodal LAM are not at risk for subsequent pulmonary LAM. Future studies should collect and share long-term follow-up data to elucidate the true risk of developing pulmonary LAM in women with incidental nodal LAM.
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Procedimientos Quirúrgicos Ginecológicos , Hallazgos Incidentales , Ganglios Linfáticos/patología , Linfangioleiomiomatosis/patología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Japón/epidemiología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/patología , Linfangioleiomiomatosis/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Esclerosis Tuberosa/epidemiología , Esclerosis Tuberosa/patologíaRESUMEN
AIM: Uterine adenosarcoma is a rare malignancy with limited cohort data in Asian countries. This study evaluated the clinicopathologic features of Japanese patients with uterine adenosarcoma and their potential treatment challenges. METHODS: A retrospective chart review was performed at the National Cancer Center Hospital, Japan from 2000 to 2016. A literature search for Japanese cases of uterine adenosarcoma was conducted using PubMed, Japanese Central Review of Medicine, and the Annual of Pathological Autopsy Cases in Japan. Only histologically confirmed cases of uterine adenosarcoma were included. All collected data were analyzed. RESULTS: A total of 110 cases was identified (6 from our hospital and 104 from the literature review). Most baseline characteristics were similar to those reported in western countries. Death due to the disease was observed in 34% (29/86) of patients, whereas patients with stage IA disease showed a 13% (4/30) recurrence rate and a 3.3% (1/30) mortality rate. Preoperative radiological and pathological examinations occasionally failed to help reach the correct diagnosis. In cases of sarcomatous overgrowth, the recurrence and mortality rates were 45% (9/20) and 35% (7/20), respectively. Distant recurrence occurred in 44% (12/27) of cases, 75% of which included lung metastasis. CONCLUSIONS: This study showed the clinicopathologic features of Japanese patients with uterine adenosarcoma and suggested potential solutions for improving prognosis including early treatment based on a timely diagnosis, the development of effective adjuvant therapy for patients at high risk of recurrence, and optimal follow-up focusing on late recurrence and lung metastasis.
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Adenosarcoma/diagnóstico , Adenosarcoma/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Adenosarcoma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios de Cohortes , Femenino , Humanos , Japón , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Retrospectivos , Neoplasias Uterinas/patología , Adulto JovenRESUMEN
A major obstacle to improving prognoses in ovarian cancer is the lack of effective screening methods for early detection. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers that could lead to clinical applications. Here, to develop an optimal detection method, we use microarrays to obtain comprehensive miRNA profiles from 4046 serum samples, including 428 patients with ovarian tumors. A diagnostic model based on expression levels of ten miRNAs is constructed in the discovery set. Validation in an independent cohort reveals that the model is very accurate (sensitivity, 0.99; specificity, 1.00), and the diagnostic accuracy is maintained even in early-stage ovarian cancers. Furthermore, we construct two additional models, each using 9-10 serum miRNAs, aimed at discriminating ovarian cancers from the other types of solid tumors or benign ovarian tumors. Our findings provide robust evidence that the serum miRNA profile represents a promising diagnostic biomarker for ovarian cancer.
Asunto(s)
Carcinoma/diagnóstico , MicroARNs/sangre , Neoplasias Ováricas/diagnóstico , Biomarcadores/sangre , Carcinoma/sangre , Análisis Discriminante , Femenino , Perfilación de la Expresión Génica , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Modelos Estadísticos , Neoplasias Ováricas/sangreRESUMEN
It is important for the proper execution of cell division in both mitosis and meiosis that the chromosome segregation, cytokinesis, and partition of cell organelles progress in smooth coordination. We show here that the mitochondria inheritance is closely linked with microtubules during meiotic divisions in Drosophila males. They are first clustered in a cell equator at metaphase associated with astral microtubules and then distributed along central spindle microtubules after anaphase. The molecular mechanism for the microtubule-dependent inheritance of mitochondria in male meiosis has not been demonstrated yet. We first isolated mutations for a larp gene that is highly conserved among eukaryotes and showed that these mutant males exhibited multiple meiotic phenotypes such as a failure of chromosome segregation, cytokinesis, and mitochondrial partition. Our cytological examination revealed that the mutants showed defects in spindle pole organization and spindle formation. The larp encodes a Drosophila orthologue of a La-related protein containing a domain exhibiting an outstanding homology with a La type RNA-binding protein. Surprisingly, the dLarp protein is localized in the cytoplasm of the male germ line cells, as observed by its distinct co-localization with mitochondria in early spermatocytes and during meiotic divisions. We discuss here the essential role that dLarp plays in multiple processes in Drosophila male meiosis.
Asunto(s)
Proteínas de Drosophila/genética , Proteínas de Drosophila/fisiología , Drosophila/genética , Meiosis , Espermatocitos/fisiología , Factores de Transcripción/genética , Factores de Transcripción/fisiología , Animales , Centrosoma/fisiología , Cromátides/fisiología , Segregación Cromosómica , Citocinesis , Drosophila/citología , Drosophila/fisiología , Masculino , Meiosis/genética , Microtúbulos/fisiología , Microtúbulos/ultraestructura , Mitocondrias/genética , Mitocondrias/fisiología , Proteínas Mutantes/fisiología , Mutación , Espermatocitos/citología , Huso Acromático/genética , Huso Acromático/fisiologíaRESUMEN
Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers is performed to reduce carcinogenesis. It decreases the ovarian, tubal, and peritoneal cancer risk to 3.5-4.3% and breast cancer risk to 30-40%. According to a previous study, despite RRSO, 3.4% of patients develop breast cancer and 0.8% develop peritoneal cancer. However, the long-term risk of recurrence and appropriate treatment for patients with unsuspected neoplasia after RRSO are unclear. Case: A 61-year-old woman who had a BRCA2 mutation underwent RRSO. Her pelvic washing cytology showed atypical cells, and similar atypical cells were identified on her fimbria. She underwent strict surveillance. Elevated CA125 levels and increased ascites in the pelvic cavity were detected by routine surveillance at 18 months after RRSO. She underwent staging laparotomy and was diagnosed with primary peritoneal carcinoma stage IIIC. It is helpful to perform surveillance by transvaginal ultrasound and serum CA125 analyses in cases that require strict management. The appropriate intervention should be considered for cases in which atypical cells or non-invasive carcinoma are detected after RRSO.
RESUMEN
To understand physiological phenomena at the tissue level, elucidation of tissue-specific molecular functions in vivo is required. As an example of the current state of affairs, many genes in plants have been reported to have discordant levels of expression between bulk tissues and the specific tissues in which the respective gene product is principally functional. The principal challenge in deciphering such tissue-specific functions lies in separating tissues with high spatiotemporal resolution to evaluate accurate gene expression profiles. Here, we provide a simple and rapid tissue isolation protocol to isolate all three major leaf tissues (mesophyll, vasculature and epidermis) from Arabidopsis within 30 min with high purity. On the basis of the different cell-to-cell connectivities of tissues, the mesophyll isolation is achieved by making protoplasts, and the vasculature and epidermis isolation is achieved through sonication and enzymatic digestion of leaves. We have successfully tested the protocol on several other plant species, including crop plants such as soybean, tomato and wheat. Furthermore, isolated tissues can be used not only for tissue-specific transcriptome assays but also potentially for tissue-specific proteome and methylome assays.