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1.
Jpn J Clin Oncol ; 54(3): 292-296, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-37995280

RESUMO

BACKGROUND: Gynecologic cancers are one of the most common types of malignancies in working-age women. We aimed to determine the factors that impede women from returning to the same workplace after treatment for such cancers. METHODS: A questionnaire-based survey was conducted on 194 women who underwent treatment for gynecologic cancer at the Okayama University (≥1 year after cancer treatment and <65 years of age). We performed a logistic regression analysis to determine the relationship between returning to the same workplace and not taking sick leave. RESULTS: The median age at diagnosis was 49.0 years, and the median time from cancer treatment to questionnaire completion was 3.8 years. Not returning to the same workplace was positively associated with not being regularly employed (P = 0.018), short work time per day (P = 0.023), low personal income (P = 0.004), not taking sick leave (P < 0.001), advanced cancer stage (P = 0.018) and long treatment time (P = 0.032). Interestingly, not taking sick leave was strongly associated with not returning to the same workplace in the multivariable analysis (P < 0.001). CONCLUSIONS: Not taking sick leave likely was negatively associated with returning to the same workplace after the treatment for gynecologic cancer. Therefore, we suggest that steps be taken to formally introduce a sick leave system over and above the paid leave system in Japan.


Assuntos
Neoplasias dos Genitais Femininos , Licença Médica , Humanos , Feminino , Emprego , Local de Trabalho , Neoplasias dos Genitais Femininos/terapia , Japão
2.
J Med Genet ; 58(8): 505-513, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732225

RESUMO

BACKGROUND: Variants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear. METHODS: We examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail. RESULTS: Pathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly. CONCLUSIONS: Prenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.


Assuntos
Colágeno Tipo IV/genética , Mutação/genética , Síndrome de Dandy-Walker/genética , Feminino , Humanos , Masculino , Gravidez , Ultrassonografia Pré-Natal/métodos
3.
J Obstet Gynaecol Res ; 48(5): 1076-1090, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35229413

RESUMO

Gynecologic cancers are more often caused by genetic factors than other cancers. Genetic testing has become a promising avenue for the prevention, prognosis, and treatment of cancers. This review describes molecular features of gynecologic tumors linked to hereditary syndromes, gives an overview of the current state of clinical management, and clarifies the role of gynecology in the treatment of hereditary tumors. Typical hereditary gynecologic tumors include hereditary breast and ovarian cancer, Lynch syndrome, Peutz-Jeghers syndrome, and Cowden syndrome. Multigene panel testing, which analyzes a preselected subset of genes for genetic variants, has recently become the first-choice test because it can provide more accurate risk assessment than a single test. Furthermore, comprehensive genomic cancer profiling enables personalized cancer treatment and aids in germline findings.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias dos Genitais Femininos , Ginecologia , Síndromes Neoplásicas Hereditárias , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Feminino , Predisposição Genética para Doença , Testes Genéticos , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/terapia , Humanos , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia
4.
Acta Med Okayama ; 76(2): 129-135, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503440

RESUMO

Cancer patients have increased risk of venous thromboembolism (VTE) that must be assessed before treatment. This study aimed to determine effective VTE biomarkers in gynecologic cancer (GC). We investigated the correlation between D-dimer levels, Khorana risk score (KRS), Glasgow prognostic score (GPS), and VTE in 1499 GC patients (583 cervical cancer (CC), 621 endometrial cancer (EC), and 295 ovarian cancer (OC) patients) treated at our institution between January 2008 and December 2019. χ2 and Mann-Whitney U-tests were used to determine statistical significance. We used receiver operating characteristic-curve analysis to evaluate the discriminatory ability of each parameter. D-dimer levels were significantly correlated with KRS and GPS in patients with GC. VTE was diagnosed in 11 CC (1.9%), 27 EC (4.3%), and 39 OC patients (13.2%). Optimal D-dimer cut-off values for VTE were 3.1, 3.2, and 3.9 µg/ml in CC, EC and OC patients, respectively. D-dimer could significantly predict VTE in all GC patients. Furthermore, D-dimer combined with GPS was more accurate in predicting VTE than other VTE biomarkers in stage IIIC and IVA OC (AUC: 0.846; p<0.001). This study demonstrates that combined D-dimer and GPS are useful in predicting VTE in patients with OC.


Assuntos
Neoplasias Ovarianas , Tromboembolia Venosa , Biomarcadores , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Neoplasias Ovarianas/complicações , Prognóstico , Fatores de Risco , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia
5.
Acta Med Okayama ; 76(4): 479-483, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36123164

RESUMO

A hereditary breast and ovarian cancer (HBOC) pedigree was detected via liquid biopsy, and cancer prevention was initiated for the patient's daughter, after receiving a definitive result from BRCA genetic testing. A 48-yearold woman with ovarian cancer was administered precision medicine, which used cell-free DNA from plasma. The results revealed a pathogenic variant of BRCA1 as a presumed germline pathogenic mutation. We confirmed the germline pathological variant BRCA1 c.81-1G> A and suggested treatment with a PARP inhibitor. One of her three children had the variant, was diagnosed as an unaffected pathogenic variant carrier, and was advised to initiate surveillance.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Ovarianas , Proteína BRCA2/genética , Neoplasias da Mama , Criança , Feminino , Humanos , Biópsia Líquida , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Linhagem , Inibidores de Poli(ADP-Ribose) Polimerases
6.
Acta Med Okayama ; 75(6): 745-750, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34955544

RESUMO

NIPT is non-definitive testing to estimate the possibility that fetuses have trisomy 21, trisomy 18, or trisomy 13. However, in NIPT-positive and indeterminate cases, rare chromosomal disease may become apparent, requiring advanced genetic considerations and counseling skills. We experienced two such cases, a trisomy 21 mosaicism case triggered by NIPT-positive status and 18q deletion syndrome triggered by NIPT-indeterminate status. These cases have two clinical implications for NIPT. First, it was revealed that trisomy mosaicism might be found in NIPT-positive cases that have lower Z-Scores than those inferred from the fraction of fetal cfDNA in the case of standard trisomy. Second, it is possible that microdeletion syndrome could be the reason for an indeterminate NIPT result. Today's genetic counseling requires more expertise in ethics and communication as well as genetic science because NIPT can lead to totally unexpected results.


Assuntos
Transtornos Cromossômicos/diagnóstico , Síndrome de Down/diagnóstico , Mosaicismo , Teste Pré-Natal não Invasivo/métodos , Adulto , Deleção Cromossômica , Cromossomos Humanos Par 18 , Feminino , Humanos , Gravidez
7.
Acta Med Okayama ; 74(2): 109-114, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32341584

RESUMO

This study aimed to determine whether the risk conferred by gynecologic cancer (GC) as second primary cancer (SPC) differs from that associated with GC as first primary cancer (FPC). We investigated the correlations between FPC/SPC and the characteristics and prognoses of 1,645 GC patients (701 with cervical cancer [CC], 641 with endometrial cancer [EM], and 303 with ovarian cancer [OV]). The χ2 test and the Kaplan-Meier method were used to determine whether FPC/SPC and the characteristics and prognoses of GC patients. Of the SPC patients, 26 (3.7%) had CC, 53 (8.3%) had EM, and 31 (10.2%) had OV. The most common previous cancer type in SPC of GC patients was breast cancer, which was observed in 13 patients (50.0%) with CC, 23 (43.4%) with EM, and 16 (51.6%) with OV. In all patients with CC, EM, and OV as SPC, the stage was significantly associated with recurrence. There were no significant differences in the morbidity or mortality of CC, EM, or OV patients between those with FPC and those with SPC. The risk of SPC development in GC patients varied, ranging from 3.5% (CC) to 10.3% (OV) of patients.


Assuntos
Neoplasias do Endométrio/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias Ovarianas/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias/estatística & dados numéricos , Intervalo Livre de Progressão , Estudos Retrospectivos
8.
Epilepsia ; 59(2): 440-448, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29315514

RESUMO

OBJECTIVE: To clarify longitudinal changes in white matter microstructures from the onset of disease in patients with West syndrome (WS) of unknown etiology. METHODS: Diffusion tensor imaging (DTI) was prospectively performed at onset and at 12 and 24 months old in 17 children with WS of unknown etiology. DTI was analyzed using tract-based spatial statistics (TBSS) and tract-specific analysis (TSA) of 13 fiber tracts, and fractional anisotropy (FA) and mean diffusivity (MD) were compared with those of 42 age-matched controls. Correlations of FA and MD with developmental quotient (DQ) at age 24 months were analyzed. Multiple comparisons were adjusted for using the false discovery rate (q-value). RESULTS: TBSS analysis at onset showed higher FA and lower MD in the corpus callosum and brainstem in patients. TSA showed lower MD in bilateral uncinate fasciculi (UF) (right: q < 0.001; left: q = 0.03) at onset in patients. TBSS showed a negative correlation between FA at onset and DQ in the right frontal lobe, whereas FA at 24 months old exhibited a positive correlation with DQ in the diffuse white matter. MD for bilateral UF at 24 months old on TSA correlated positively with DQ (q = 0.04, both). SIGNIFICANCE: These findings may indicate the existence of cytotoxic edema in the immature white matter and dorsal brainstem at onset, and subsequent alterations in the diffuse white matter in WS of unknown etiology. Microstructural development in the UF might play important roles in cognitive development in WS.


Assuntos
Edema Encefálico/diagnóstico por imagem , Deficiências do Desenvolvimento/fisiopatologia , Espasmos Infantis/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Anisotropia , Encéfalo/diagnóstico por imagem , Tronco Encefálico/diagnóstico por imagem , Estudos de Casos e Controles , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Imagem de Tensor de Difusão , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Lactente , Estudos Longitudinais , Masculino , Estudos Prospectivos , Espasmos Infantis/complicações , Espasmos Infantis/fisiopatologia
9.
Int J Gynecol Cancer ; 28(7): 1394-1402, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30095701

RESUMO

OBJECTIVE: The aim of this observational study was to investigate correlations between long-term chemotherapy-induced peripheral neurotoxicity (CIPN) and quality of life (physical well-being, social well-being, emotional well-being, and functional well-being [FWB]) among survivors of gynecologic cancer (GC). METHODS: We aimed to assess the correlation of quality of life and long-term CIPN with the temporal change in recurrence-free GC survival. Questionnaire responses and clinical data of 259 GC survivors were collected and assessed according to treatment received. The χ test was used to determine the significance of correlations. RESULTS: Of 165 evaluable patients treated by chemotherapy, 36 patients (21.8%) developed CIPN of Common Toxicity Criteria for Adverse Events grade 1 or higher during the study. Chemotherapy-induced peripheral neurotoxicity had significantly improved over time in the domain of FWB at 61 months or more after the end of chemotherapy (posttreatment 4) among GC survivors (P = 0.003). Furthermore, CIPN treated by more than 6 courses of the paclitaxel and carboplatin regimen among GC survivors showed significant improvement over time in the emotional well-being domain at 25 to 60 months and 61 months or more after the end of chemotherapy (posttreatments 3 and 4) (P = 0.037 and P = 0.023) and in FWB at posttreatment 4 (P < 0.001). CONCLUSIONS: Emotional and functional domains of CIPN improved over time among GC survivors treated by more than 6 courses of the paclitaxel and carboplatin regimen. Based on these results, further research is required to identify additional preventative or curative approaches.


Assuntos
Sobreviventes de Câncer/psicologia , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/psicologia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/psicologia , Adulto , Idoso , Feminino , Neoplasias dos Genitais Femininos/fisiopatologia , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/fisiopatologia , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
10.
Int J Gynecol Cancer ; 25(7): 1306-14, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26067860

RESUMO

OBJECTIVE: The Glasgow prognostic score (GPS) determined at pretreatment is important in the prediction of prognosis in various cancers. We investigated if the GPS used both at pretreatment and during concurrent chemoradiotherapy (CCRT) could predict the prognosis of patients with cervical cancer. METHODS: We collected GPS and clinicopathological data from the medical records of 91 patients who underwent CCRT for cervical cancer; their GPSs at pretreatment and during CCRT were retrospectively analyzed for correlations with recurrence and survival. Statistical analyses were performed using the Mann-Whitney U test. Disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox's proportional hazard regression was used for univariate and multivariate analyses. RESULTS: The median follow-up for all patients who were alive at the time of last follow-up was 38.0 months (range, 1-108 months). The DFS and OS rates of patients with a high GPS during CCRT (GPS 1 + 2; 55 patients; 60.4%) were significantly shorter than those for patients with a low GPS (GPS 0; 36 patients; 39.6%) (DFS, P < 0.001; OS, P < 0.001). Furthermore, multivariate analyses showed that high GPS during CCRT was an independent prognostic factor of survival for OS (P = 0.008). CONCLUSIONS: During CCRT, a high GPS was revealed to be an important predictor of survival for cervical cancer.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adenocarcinoma/secundário , Adenocarcinoma/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Feminino , Seguimentos , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
11.
Acta Med Okayama ; 69(3): 183-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26101195

RESUMO

Pure ovarian choriocarcinoma is an extremely rare malignancy that can be gestational or non-gestational in origin. Silver-Russell syndrome (SRS) is a rare congenital developmental disorder characterized by pre- and postnatal growth failure, relative macrocephaly, a triangular face, hemihypotrophy, and fifth-finger clinodactyly. We report a rare case of pure ovarian choriocarcinoma occurring in a 19-year-old woman with SRS. Following surgery, multiple chemotherapy courses were effective and she was free of disease at the 10-month follow-up.


Assuntos
Coriocarcinoma/patologia , Neoplasias Ovarianas/patologia , Síndrome de Silver-Russell/patologia , Adulto , Coriocarcinoma/sangue , Coriocarcinoma/terapia , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/terapia , Gravidez
12.
Int J Gen Med ; 17: 541-551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371520

RESUMO

Purpose: Among the Organisation for Economic Co-operation and Development countries, Japan has one of the lowest cervical cancer screening coverages. Cancer screening coverage has worsened due to the coronavirus disease of 2019 (COVID-19) pandemic. This study investigated the relationship between socioeconomic background, COVID-19 infection history and vaccine status, and regular cervical cancer screening (CCS) during the two years of the COVID-19 era in Japan. Patients and Methods: We used data from the Japan COVID-19 and Society Internet Survey, a nationwide, Internet-based, self-report cohort observational study conducted in 2022. The outcome variable was identified by asking whether the participants had undergone CCS within the last two years. Cervical cytology was performed in Japan by brushing the external cervical os. This study used multivariate log-binomial regression models to evaluate inequalities during regular checkups for CCS. Adjusted prevalence ratios (APRs) with 95% confidence intervals (CIs) were estimated to incorporate the socioeconomic background variables. Results: Of the 12,066 participants, 5597 (46.4%) had undergone regular CCS for over two years. The prevalence ratio (PR) of patients who underwent CCS was 0.70 for those in their 20s and 0.78 for those in their 60s, compared to those in their 40s. Socioeconomic inequities were found in the following groups: unemployed/student, unmarried, high school graduate or lower, and household income below 4 million Yen. Our final multivariate analysis revealed that participants who were in their 20s or 60s, had a household income below 4 million Yen, were unmarried, had no annual health check-ups, and were unvaccinated with COVID-19 were at a higher risk of not undergoing CCS. Conclusion: The relationship between socioeconomic inequality and CCS hesitancy is prevalent among younger participants. The CCS coverage in Japan during the COVID-19 pandemic year (2020-2022) was not low compared with the pre-pandemic era.

13.
World J Clin Cases ; 11(16): 3899-3906, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37383118

RESUMO

BACKGROUND: Perinatal brain injury may lead to later neurodevelopmental disorders, whose outcomes may vary due to neuroplasticity in young children. Recent neuroimaging studies have shown that the left parietotemporal area (which includes the left inferior parietal lobe) is associated with phonological awareness and decoding skills, which are essential skills for reading acquisition in children. However, the literature on the effect of perinatal cerebral injury on the development of phonological awareness or decoding ability in childhood is limited. CASE SUMMARY: We report the case of an 8-year-old boy who presented with reading difficulty following a perinatal injury in the parieto-temporal-occipital lobes. The patient was born at term and was treated for hypoglycemia and seizures during the neonatal period. Diffusion-weighted brain magnetic resonance imaging on postnatal day 4 revealed cortical and subcortical hyperintensities in the parieto-temporo-occipital lobe. At the age of 8 years, physical examination was unremarkable, aside from mild clumsiness. Despite occipital lobe injury, the patient had adequate visual acuity, normal eye movement, and no visual field defects. Full-scale intelligence quotient and verbal comprehension index on Wechsler Intelligence Scale for Children-Fourth Edition were 75 and 90, respectively. Further assessment revealed adequate recognition of Japanese Hiragana letters. However, he had significantly slower reading speed in the Hiragana reading test than control children. The phonological awareness test revealed significant errors (standard deviation +2.7) in the mora reversal task. CONCLUSION: Patients with perinatal brain injuries in the parietotemporal area require attention and may benefit from additional reading instructions.

14.
Radiol Case Rep ; 18(7): 2447-2451, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37235086

RESUMO

The abscopal effect is a rare phenomenon, in which tumor shrinkage in the nonirradiated metastatic region is observed after radiotherapy. Certainly, this response is sometimes reported with the combined use of immune-checkpoint inhibitors, but a pure abscopal effect is extremely rare, especially in endometrial cancer. We present the case of a 79-year-old woman with an advanced endometrial carcinosarcoma. She was treated with surgical reduction of the primary lesion, followed by radiotherapy of the metastatic regional lymph nodes. Distant metastases were detected in radiological imaging test 2 months after the completion of radiotherapy, and we carefully followed up without any treatment considering the patient's tolerability for further procedures. Six months after recurrence, she experienced cytoreduction in the metastatic lesions confirmed through imaging findings, which was believed to be an abscopal effect, and maintained this shrinking state for 15 months. Herein, we describe this pure abscopal effect from the perspective of imaging, pathological and molecular findings, and therapeutic strategies.

15.
Pediatr Neurol ; 144: 1-4, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37087914

RESUMO

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder that often manifests after infections or vaccinations. We report two patients who developed MOGAD out of eight patients with juvenile myelomonocytic leukemia (JMML) that has never been reported. METHODS: We investigated two patients with JMML who developed MOGAD among 127 patients with leukemia from 2012 to 2021. RESULTS: Patient 1 was treated for JMML and developed fever and impaired consciousness at two years and one month of age. Magnetic resonance imaging revealed high-intensity lesions in the left frontal and left occipital white matter. The serum anti-MOG antibody test was positive, while the test was negative in the stored serum 45 days before the onset of encephalopathy. He had relapse of MOGAD after steroid therapy and plasmapheresis. Patient 2, who was treated for JMML, became apathetic and mute at three years and seven months of age. Magnetic resonance imaging revealed left frontoparietal subcortical high-intensity lesions. Anti-MOG antibody at the onset of encephalopathy was positive, while it was negative in stored serum 57 days before and 47 days after the onset. CONCLUSION: We treated two patients who developed MOGAD out of eight patients with JMML and none with MOGAD out of 119 patients with acute lymphocytic leukemia, acute myelocytic leukemia, or chronic myelocytic leukemia. The activated autoimmune process via the RAS pathway abnormality may have led to the formation of the anti-MOG antibody and the onset of MOGAD. MOGAD can occur in children with JMML, and abnormalities of the RAS pathway possibly contribute to its onset.


Assuntos
Doenças Autoimunes , Encefalopatias , Leucemia Mielomonocítica Juvenil , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Masculino , Leucemia Mielomonocítica Juvenil/terapia , Glicoproteína Mielina-Oligodendrócito , Febre , Autoanticorpos
16.
J Biol Chem ; 286(7): 5727-35, 2011 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-21138842

RESUMO

Toll-like receptors (TLRs) and nucleotide-binding domain, leucine-rich repeat (NLR) proteins are two major forms of innate immune receptors that trigger inflammatory responses by various biological mechanisms such as cytokine production, recruitment of inflammatory cells, or activation of adaptive immunity. Although the innate immune system is designed to fight against infectious pathogens, excessive activation of TLR or NLR signaling pathways may lead to unwarranted inflammation with hazardous outcomes, including septic shock or inflammatory diseases. As part of the search for effective therapeutics to regulate these responses, here we show that a novel aminosaccharide compound, named DFK1012, inhibits immune responses caused by TLR and NLR activation. Treatment with DFK1012, but not its derivatives DFK845 or DFK846, strongly inhibited pro-inflammatory cytokine production upon stimulation via either TLR or NLR proteins in macrophages. Importantly, we have not observed cytotoxicity in any range of its working concentration. Treatment with DFK1012 did not interfere with TLR- or NLR-induced activation of p38 and JNK, phosphorylation/degradation of IκB, and subsequent nuclear translocation of NF-κB subunit p65, suggesting that the inhibitory activity of DFK1012 is not due to the suppression of downstream signaling. Indeed, DFK1012 did not impair transcription of pro-inflammatory cytokine genes but rather promoted post-translational degradation of pro-inflammatory cytokines. Therefore, DFK1012 is a novel anti-inflammatory compound that drives proteolysis of proinflammatory cytokines induced by TLR and NLR stimulation. DFK1012 may represent a novel class of potential therapeutic agents aimed at the treatment of inflammatory disorders.


Assuntos
Acetilglucosamina/análogos & derivados , Amino Açúcares , Anti-Inflamatórios não Esteroides , Biotina/análogos & derivados , Imunidade Inata/efeitos dos fármacos , Proteínas/antagonistas & inibidores , Receptores Toll-Like/antagonistas & inibidores , Acetilglucosamina/química , Acetilglucosamina/farmacologia , Amino Açúcares/química , Amino Açúcares/farmacologia , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Biotina/química , Biotina/farmacologia , Linhagem Celular , Citocinas/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Proteínas de Repetições Ricas em Leucina , MAP Quinase Quinase 4/imunologia , Camundongos , Estrutura Terciária de Proteína , Proteínas/imunologia , Receptores Toll-Like/imunologia , Fator de Transcrição RelA/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
17.
Mol Clin Oncol ; 12(4): 336-342, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32190316

RESUMO

The aim of the present study was to determine whether chronic diseases (CD), such as hypertension, diabetes mellitus, dyslipidemia, heart diseases and cerebrovascular diseases, are occurrence risk factors and affect the survival of patients with gynecological cancers (GC). The correlations between CD and the characteristics and survival of 1,590 GC patients [685 with cervical cancer (CC), 613 with endometrial cancer (EM) and 292 with ovarian cancer (OV)] were investigated in the present study. Of the CD patients, 189 had CC (27.6%), 265 had EM (43.2%) and 72 had OV (24.7%). The incidence of CD increased with age in GC patients. The number of CD patients aged ≥70 years, was 8.6-fold higher in the CC group, 3.0-fold higher in the EM group, and 9.6-fold higher in the OV group compared with those aged <50 years. CD and excess body weight were associated with GC regardless of patient age. However, there was no correlation between CD and survival at any age in GC patients. These findings indicate that CD contribute to >24% of the occurrence risk factors in GC patients in Japan.

18.
Pediatr Neurol ; 109: 79-84, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32303390

RESUMO

OBJECTIVE: To investigate clinical risk factors for acute magnetic resonance imaging (MRI) abnormalities in patients with benign convulsions with mild gastroenteritis or benign infantile epilepsy. STUDY DESIGN: We investigated clinical and diffusion-weighted imaging findings in 32 patients with benign convulsions with mild gastroenteritis and 22 patients with benign infantile epilepsy who underwent MRI within seven days of seizure onset between 2010 and 2015. RESULTS: Diffusion-weighted imaging showed signal hyperintensity in the splenium of the corpus callosum in seven patients with benign convulsions with mild gastroenteritis, but no abnormalities in patients with benign infantile epilepsy. Patients with benign convulsions with mild gastroenteritis with splenial lesions showed a higher rate of rotavirus detection from feces (P = 0.006), higher serum level of C-reactive protein (P = 0.04), and shorter interval between seizure onset and MRI (P = 0.002) than patients with benign convulsions with mild gastroenteritis without splenial lesions. Multivariate analysis revealed rotavirus infection as a significant risk factor for splenial lesions on diffusion-weighted imaging in patients with benign convulsions with mild gastroenteritis (P = 0.02). CONCLUSIONS: Splenial lesions are often seen during acute period in patients with benign convulsions with mild gastroenteritis. Rotavirus infection is a risk factor for splenial lesions in patients with benign convulsions with mild gastroenteritis, suggesting the role of rotavirus to cause edema in the corpus callosum. From our observations, benign convulsions with mild gastroenteritis with a splenial lesion on diffusion-weighted imaging suggests good outcomes, and extensive evaluation of these patients may be unnecessary.


Assuntos
Corpo Caloso/patologia , Encefalite Viral/etiologia , Gastroenterite/etiologia , Infecções por Rotavirus/complicações , Convulsões/etiologia , Espasmos Infantis/etiologia , Corpo Caloso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Encefalite Viral/diagnóstico , Feminino , Gastroenterite/diagnóstico , Humanos , Lactente , Masculino , Estudos Retrospectivos , Infecções por Rotavirus/diagnóstico , Convulsões/diagnóstico , Espasmos Infantis/diagnóstico
19.
Epilepsia Open ; 5(3): 442-450, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32913952

RESUMO

OBJECTIVE: To elucidate the genetic background and genotype-phenotype correlations for epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy (MAE) or Doose syndrome. METHODS: We collected clinical information and blood samples from 29 patients with MAE. We performed whole-exome sequencing for all except one MAE case in whom custom capture sequencing identified a variant. RESULTS: We newly identified four variants: SLC6A1 and HNRNPU missense variants and microdeletions at 2q24.2 involving SCN1A and Xp22.31 involving STS. Febrile seizures preceded epileptic or afebrile seizures in four patients, of which two patients had gene variants. Myoclonic-atonic seizures occurred at onset in four patients, of which two had variants, and during the course of disease in three patients. Variants were more commonly identified in patients with a developmental delay or intellectual disability (DD/ID), but genetic status was not associated with the severity of DD/ID. Attention-deficit/hyperactivity disorder and autistic spectrum disorder were less frequently observed in patients with variants than in those with unknown etiology. SIGNIFICANCE: MAE patients had genetic heterogeneity, and HNRNPU and STS emerged as possible candidate causative genes. Febrile seizures prior to epileptic seizures and myoclonic-atonic seizure at onset indicate a genetic predisposition to MAE. Comorbid conditions were not related to genetic predisposition to MAE.

20.
Mol Clin Oncol ; 11(4): 376-382, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31497297

RESUMO

Low skeletal muscle mass (sarcopenia) is an important prognostic risk factor for the outcome of a variety of cancer types. The current study investigated whether skeletal muscle area (SMA), psoas area (PA) and psoas major volume (PV) are associated with progression-free survival (PFS) and overall survival (OS) in patients with epithelial ovarian cancer (OC). A total of 92 OC patients were enrolled in the present study. Pre-treatment with SMA and PA was assessed using computed tomography (CT) and PV was calculated using a three-dimensional-CT (3D-CT). The clinical factors associated with sarcopenia and prognosis were retrospectively evaluated. For all patients, the median PFS and OS were 19 and 32 months, respectively. Patients exhibiting lower PV (<195.6 cm3) had significantly poorer PFS and OS compared with patients exhibiting higher PV (≥195.6 cm3; P=0.018 and P=0.006), while those with low SMA (<92.92 cm2) had significantly worse OS than patients with higher SMA (≥92.92 cm2; P=0.030). PV was also demonstrated to be superior to SMA and PA in prognosis prediction. PV by 3D-CT can serve as an indicator of poor prognosis in patients with OC.

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