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1.
Acta Neuropathol Commun ; 8(1): 8, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32019606

RESUMO

Diffuse midline glioma, H3 K27M-mutant is a lethal brain tumor located in the thalamus, brain stem, or spinal cord. H3 K27M encoded by the mutation of a histone H3 gene such as H3F3A plays a pivotal role in the tumorigenesis of this type of glioma. Although several studies have revealed comprehensive genetic and epigenetic profiling, the prognostic factors of these tumors have not been identified to date. In various cancers, oncogenic driver genes have been found to exhibit characteristic copy number alterations termed mutant allele specific imbalance (MASI). Here, we showed that several diffuse midline glioma, H3 K27M-mutant exhibited high variant allele frequency (VAF) of the mutated H3F3A gene using droplet digital polymerase chain reaction (ddPCR) assays. Whole-genome sequencing (WGS) revealed that these cases had various copy number alterations that affected the mutant and/or wild-type alleles of the H3F3A gene. We also found that these MASI cases showed a significantly higher Ki-67 index and poorer survival compared with those in the lower VAF cases (P < 0.05). Our results indicated that the MASI of the H3F3A K27M mutation was associated with the aggressive phenotype of the diffuse midline glioma, H3 K27M-mutant via upregulation of the H3 K27M mutant protein, resulting in downregulation of H3K27me3 modification.

2.
Hematol Oncol ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922287

RESUMO

Mogamulizumab (Mog) and lenalidomide (Len) are new therapeutic candidates for relapsed adult T-cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the present study, we retrospectively analyzed 12 patients who received Mog or Len monotherapy for relapsed ATL after allo-HSCT. Eight and three patients received Mog and Len, respectively. The remaining patient received Mog for the first relapse and Len for the third relapse. A complete response was achieved by three and two patients who received Mog and Len, respectively, two and one of whom remained alive with a complete response for more than 20 months. In terms of adverse events, the emergence or progression of graft-versus-host disease was observed in three out of four patients treated with Len and in none of the patients treated with Mog. The development or progression of cytomegalovirus reactivation was detected in four out of eight patients treated with Mog and in none of those treated with Len. The present results suggest that Mog and Len would be promising treatment options for relapsed ATL after allo-HSCT and need to be selected based on adverse event profiles.

3.
Anticancer Res ; 40(1): 413-419, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892595

RESUMO

BACKGROUND/AIM: In patients with lung cancer, there has been no study that treated 'distant metastases' as 'metastatic patterns'. This study aimed to evaluate if specific 'metastatic patterns' exist in lung cancer patients. PATIENTS AND METHODS: Data were collected from lung cancer patients between 2009 and 2018. Metastatic patterns were analyzed using cluster analysis in patients with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, those with small cell lung cancer (SCLC), and those with squamous cell lung cancer (SqCLC). RESULTS: In 313 patients (127 patients with EGFR mutation, 87 patients with SCLC, and 99 patients with SqCLC), metastatic patterns existed in each of the three subset groups, and metastatic patterns of these groups were statistically different. CONCLUSION: The knowledge of the metastatic patterns might be useful for clinical practice in the foreseeable future, as it enables a more efficient detection of metastatic disease through imaging, and a more effective treatment at predicted metastatic sites.


Assuntos
Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/genética , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Metástase Neoplásica , Probabilidade
4.
Anticancer Res ; 40(1): 421-426, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892596

RESUMO

BACKGROUND/AIM: Distant organ metastases do not occur at random in lung cancer. A retrospective study was conducted in order to evaluate 1) what kinds of metastatic patterns exist in three different types of lung cancer, and 2) whether metastatic patterns affected prognosis in the different types of lung cancer. PATIENTS AND METHODS: Data were collected from all consecutive patients with diagnosed lung cancer between April 2009 and October 2018 in our hospitals. Cluster analysis was performed to classify patients. Kaplan-Meier analysis, log-rank test, and Cox proportional hazards model were used. RESULTS: Epidermal growth factor-mutated adenocarcinoma, small cell lung cancer, and squamous cell lung cancer had different 'metastatic patterns', survival, and unfavorable prognostic factors, respectively. CONCLUSION: There might be different metastatic patterns, survival, and unfavorable prognostic factors in each pathological and genetic type of lung cancer. It is worthwhile carrying out diagnostic imaging and treatment considering information on metastatic patterns.


Assuntos
Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mutação/genética , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida
5.
J Gastroenterol Hepatol ; 35(1): 76-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31385352

RESUMO

BACKGROUND AND AIM: Patients with cirrhosis usually experience muscle cramps of varying severity. Although diuretics have been reported to cause muscle cramps, clinical evidence is limited. Also, it has been pointed out that the use of diuretics is associated with the progression of sarcopenia in patients with cirrhosis. We conducted a questionnaire survey to clarify the effects of diuretics and skeletal muscle loss on muscle cramps. METHODS: Overall, we enrolled 152 adults with cirrhosis in this study. Cramp questionnaires were obtained after informed consent. Study variables (demographics, physical findings, serum metabolic panel, and drugs taken that affect muscle cramps) were extracted from medical records. Body composition, including muscle volume, was analyzed using a bioelectrical impedance analysis method, and muscle strength (handgrip) was evaluated at enrollment. Cross-sectional skeletal muscle area was evaluated on computed tomography imaging at the L3 vertebral level to investigate the relationship between muscle cramps and sarcopenia. RESULTS: The proportion of furosemide administration was higher in patients with cramping compared with those without. On a multivariate logistic regression analysis, furosemide use was a significant factor in the presence of muscle cramps. Furthermore, regarding factors contributing to muscle cramp severity, furosemide use was extracted by multivariate logistic regression analysis. In the presence or severity of muscle cramps, skeletal muscles did not show any significant difference. CONCLUSIONS: Furosemide use for patients with cirrhosis was considered a risk factor for occurrence and severity of muscle cramps. On the other hand, skeletal muscle mass loss was not associated with muscle cramps.

6.
Int J Hematol ; 111(2): 311-316, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31515708

RESUMO

A 68-year-old male was diagnosed with acute promyelocytic leukemia (APL). A G-banding chromosomal analysis revealed the co-existence of two clones: one with del(20q) and t(15;17)(q22;q12) and another with del(20q) alone. During the remission of APL following treatment with all-trans-retinoic acid, del(20q) was persistently identified, indicating a diagnosis of cytogenetic abnormalities of undetermined significance (CCAUS) with isolated del(20q). Bicytopenia developed 48 months after the remission of APL. The presence of isolated del(20q) was detected in the G-banding analysis, whereas morphological dysplasia of hematopoietic cells was not confirmed. This case showed indolent progression from CCAUS after the remission of APL to clonal cytopenia of undetermined significance (CCUS). CCUS with isolated del(20q) persisted for 24 months without any finding of hematological malignancies. At the most recent follow-up, targeted capture sequencing showed the U2AF1 S34F mutation. Considerable attention needs to be paid in follow-ups for CCAUS with del(20q) after the treatment of leukemia.

7.
Haematologica ; 105(2): 358-365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31101757

RESUMO

Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. Our previous analyses demonstrated that MDS among these survivors had a significantly higher frequency of complex karyotypes and structural alterations of chromosomes 3, 8, and 11. However, there was no difference in the median survival time between MDS among survivors compared with those of de novo origin. This suggested that a different pathophysiology may underlie the causative genetic aberrations for those among survivors. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM were significantly more frequent in proximally exposed group with mutations identified on the remaining allele in 2 out of 5 cases. TP53, which is frequently mutated in therapy-related myeloid neoplasms, was equally affected between proximally and distally exposed patients. These results suggested that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo origin. Considering the role of ATM in DNA damage response after radiation exposure, further studies are warranted to elucidate how 11q deletion and aberrations of ATM contribute to the pathogenesis of MDS after radiation exposure.

8.
Oncol Res Treat ; : 1-5, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842017

RESUMO

INTRODUCTION: Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B-cell lymphoma for which no optimal treatment has been established and prognosis remains poor. Here, we describe a human immunodeficiency virus-uninfected patient with PBL that was refractory to conventional chemotherapies but was successfully controlled with a bortezomib-based regimen followed by a lenalidomide-based regimen. CASE PRESENTATION: A 64-year-old man suffered from nasal bleeding and occlusion. Whole-body computed tomography results revealed a large lesion occupying his nasal cavity. He was diagnosed with PBL based on a tumor biopsy and was treated with two lines of conventional chemotherapy. A dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH) regimen and an ifosfamide, carboplatin, and etoposide (ICE) regimen were ineffective, but the bortezomib-based regimen CyBorD (bortezomib, cyclophosphamide orally, and dexamethasone orally) provided a clinical response. Due to peripheral neuropathy, the patient was then treated with a lenalidomide-based regimen (Ld; lenalidomide and dexamethasone). Although a complete response was not achieved, the Ld regimen was tolerated and was continued with a partial response (PR) for over 2 years. DISCUSSION/CONCLUSION: In the present case, PBL that was refractory to conventional chemotherapies responded to the CyBorD regimen and a long-term Ld-based regimen without severe adverse effects. This strategy provided and maintained a PR for over 2 years. Despite not resulting in tumor reduction and only maintaining a PR, continued Ld treatment contributed to long-term survival of the present patient with PBL.

9.
Intern Med ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31875636

RESUMO

Secondary pulmonary alveolar proteinosis (sPAP) is a complication of myelodysplastic syndrome (MDS). A 60-year-old woman was diagnosed with MDS with excess blasts-1. Fifty-four months after the initial diagnosis, treatment with azacitidine was initiated. Seventy-three months after the diagnosis, a bone marrow examination revealed increased myeloblasts, at which time computed tomography showed diffuse ground-glass opacities and interlobular septal thickening in the bilateral lower lung fields. A lung biopsy revealed the presence of PAP; therefore, the clinical diagnosis of MDS/sPAP was confirmed. Careful attention should be paid to the development of sPAP in MDS patients with pulmonary lesions during azacitidine treatment.

10.
No Shinkei Geka ; 47(11): 1129-1141, 2019 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-31761774
11.
Int J Clin Oncol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728682

RESUMO

BACKGROUND: The proportion of elderly Japanese people (age ≥ 65 years) is currently 27.7%, and the average life span of women is 87.14 years, both of which are unprecedented. In gynecologic cancer, evidence of treatment for the elderly is scarce, and treatment policies are determined by each facility. The aim of the present study was to investigate the status of treatment policies for elderly patients with gynecologic cancer. METHODS: A web-based questionnaire regarding how treatment strategies are currently determined for elderly patients with gynecologic cancer was conducted on gynecologic oncologists to develop a tool for the objective evaluation of treatment policy decisions for elderly patients. RESULTS: The responses showed that 48% of the gynecologic oncologists were aware of comprehensive geriatric assessment (CGA), but only 6% had actually conducted CGA. Age, comorbidities, performance status, and pretreatment evaluations were regarded as important in determining the treatment strategy. Invasive treatments such as radical hysterectomy and para-aortic lymph node dissection tended to have age limits. CONCLUSIONS: These findings suggest that awareness of CGA is low in Japan, and that elderly people may not be given standard therapy, which highlights the importance of building on these findings by gathering further evidence and developing a new tool for predicting treatment outcomes for elderly patients with gynecologic cancer.

12.
Sci Rep ; 9(1): 16718, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723215

RESUMO

This study investigated whether the sex difference in fatigability of the knee extensors (KE) is explained by the sex difference in fatigue-induced changes in the shear modulus of one or more muscles of KE in 18 young men and 23 young women. The shear moduli of the resting rectus femoris and medial and lateral vastus muscles (VL) were measured before and after a sustained contraction at 20% peak torque during a maximal voluntary isometric contraction of KE until the endurance limit, in addition to evoked torque and voluntary activation (VA%). The fatigue-induced decrease in maximal muscle strength was more prominent in men than in women. Only the VL shear modulus for men increased after the fatiguing task, and a sex difference was observed in the percentage change in the VL shear modulus before and after the fatiguing task. The fatigue-induced decreased ratio was greater for men than for women in evoked torque, but not in VA%. These results suggest that although peripheral and central fatigue both influenced the fatigue-induced decrease in maximal muscle strength regardless of sex, the sex difference in KE fatigability is explained by that in peripheral fatigue, particularly the degree of peripheral VL fatigue.

13.
JCI Insight ; 4(23)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31661464

RESUMO

Angiogenesis is a key process that allows nutrient uptake and cellular trafficking and is coopted in cancer to enable tumor growth and metastasis. Recently, extracellular vesicles (EVs) have been shown to promote angiogenesis; however, it is unclear what unique features EVs contribute to the process. Here, we studied the role of EVs derived from head and neck squamous cell carcinoma (HNSCC) in driving tumor angiogenesis. Small EVs (SEVs), in the size range of exosomes (50-150 nm), induced angiogenesis both in vitro and in vivo. Proteomic analysis of HNSCC SEVs revealed the cell-to-cell signaling receptor ephrin type B receptor 2 (EPHB2) as a promising candidate cargo to promote angiogenesis. Analysis of patient data further identified EPHB2 overexpression in HNSCC tumors to be associated with poor patient prognosis and tumor angiogenesis, especially in the context of overexpression of the exosome secretion regulator cortactin. Functional experiments revealed that EPHB2 expression in SEVs regulated angiogenesis both in vitro and in vivo and that EPHB2 carried by SEVs stimulates ephrin-B reverse signaling, inducing STAT3 phosphorylation. A STAT3 inhibitor greatly reduced SEV-induced angiogenesis. These data suggest a model in which EVs uniquely promote angiogenesis by transporting Eph transmembrane receptors to nonadjacent endothelial cells to induce ephrin reverse signaling.

14.
BMC Gastroenterol ; 19(1): 167, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638892

RESUMO

BACKGROUND: To investigate the von Willebrand factor to ADAMTS13 ratio as a potential biomarker for early detection of hepatocellular carcinoma (HCC) in cirrhosis. METHODS: Serum levels of alpha-fetoprotein, des-γ-carboxy prothrombin, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (alpha-fetoprotein-L3%), vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, as well as the plasma levels of von Willebrand factor antigen (von Willebrand factor: Ag) and ADAMTS13 activity (ADAMTS13:AC), were evaluated in 41 cirrhotic patients with HCC undergoing radiofrequency ablation and in 20 cirrhotic patients without HCC. The diagnostic accuracy of each biomarker was evaluated using the receiver operating characteristic curve analysis. RESULTS: The von Willebrand factor: Ag and von Willebrand factor: Ag/ADAMTS13:AC ratios were significantly higher in cirrhotic patients with HCC than in those without HCC (p < 0.05 and p < 0.01, respectively), whereas ADAMTS13:AC was significantly lower in those with HCC than those without HCC (p < 0.05). However, no relationship was observed between the von Willebrand factor: Ag/ADAMTS13:AC ratio and serum tumor markers such as alpha-fetoprotein, des-γ-carboxy prothrombin, and alpha-fetoprotein-L3%. Multivariate regression analysis identified von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% as significant factors of HCC development. Receiver operating characteristic analysis showed that the von Willebrand factor: Ag/ADAMTS13:AC ratio and alpha-fetoprotein-L3% had a better performance than alpha-fetoprotein, des-γ-carboxy prothrombin, alpha-fetoprotein-L3%, vascular endothelial growth factor, and vascular endothelial growth factor receptor-2, von Willebrand factor: Ag, and ADAMTS13:AC. The von Willebrand factor: Ag/ADAMTS13:AC ratio was exclusively correlated with tumor volume and stage as well as serum vascular endothelial growth factor levels. CONCLUSIONS: The von Willebrand factor: Ag/ADAMTS13:AC ratio can potentially serve as a novel biomarker for early diagnosis of HCC in cirrhotic patients.

15.
World J Gastrointest Oncol ; 11(10): 887-897, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31662827

RESUMO

BACKGROUND: Early diagnosis of hepatocellular carcinoma (HCC) is necessary to improve the prognosis of patients. However, the currently available tumor biomarkers are insufficient for the early detection of HCC. Acylcarnitine is essential in fatty acid metabolic pathways. A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis (SH) patients. In contrast, another study reported that the level of acetylcarnitine (AC2) - one of the acylcarnitine species - in non-SH patients with HCC was decreased vs that reported in those without HCC. AIM: To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients. METHODS: Thirty-three non-SH patients (14 with HCC and 19 without HCC) were enrolled in this study. Blood samples were obtained from patients at the time of admission. The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry. The levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) were determined by enzyme-linked immunosorbent assay. Univariate and multivariate analyses were used to determine early diagnostic factors of HCC. RESULTS: The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC (P < 0.05). In contrast, the level of lens culinaris agglutinin-reactive fraction of α-fetoprotein (AFP) - AFP-L3% - was significantly higher in non-SH patients with HCC vs those without HCC (P < 0.05). However, the levels of total carnitine, free carnitine, AFP, des-γ-carboxy prothrombin, VEGF, and VEGFR-2 were not different between patients with and without HCC. The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC. The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2 (P < 0.05). CONCLUSION: The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC. Further studies are warranted to investigate these differences.

16.
Nutrients ; 11(9)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500257

RESUMO

Cirrhosis patients often have abnormal glucose metabolism. We investigated the effects of a late-evening snack (LES) with branched-chain amino acid-enriched nutrients (BCAA-EN) on glucose metabolism in cirrhosis patients. LES with BCAA-EN was administered for 1 week in 13 patients with cirrhosis and hypoalbuminemia. Blood glucose (BG) levels were measured every 15 min. The patients were divided into two groups based on BG levels: group 1 (G1, n = 11): nocturnal BG levels <200 mg/dL and group 2 (G2, n = 2): nocturnal BG levels ≥200 mg/dL. G1 had nocturnal BG levels <200 mg/dL, whereas G2 had nocturnal BG levels ≥200 mg/dL. The average BG levels did not significantly change after BCAA-EN administration in G1 (before 91.9 ± 29.0 mg/dL; after 89.0 ± 24.3 mg/dl). However, the average BG levels significantly increased after BCAA-EN administration in G2 (before 153.6 ± 43.3 mg/dL; after 200.9 ± 59.7 mg/dL) (p < 0.01). The glycated albumin level (16.6 ± 0.9% vs. 16.2 ± 2.1%), fasting immunoreactive insulin (F-IRI) level (53.9 ± 34.0 µU/mL vs. 16.5 ± 11.0 µU/mL), and homeostasis model assessment of insulin resistance (HOMA-IR) score (17.85 ± 10.58 vs. 4.02 ± 2.59) were significantly higher in G2 than in G1 (p < 0.05, p < 0.05, and p < 0.01, respectively). The quantitative insulin sensitivity check indices (0.32 ± 0.03 vs. 0.27 ± 0.02) were significantly higher in G1 than in G2 (p < 0.01). One patient in G2 was obese and had type 2 diabetes. The other patient was obese and had a high HOMA-IR score and F-IRI level. A LES with BCAA-EN does not inhibit overt diabetes in most cirrhosis patients. However, close attention should be paid to fluctuations in BG levels in cirrhosis patients who present with obesity and severe insulin resistance.

17.
Tuberk Toraks ; 67(2): 142-145, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31414646

RESUMO

The adrenal gland is a common site for metastasis from non-small-cell lung cancer (NSCLC). Adrenal metastases are usually solitary, asymptomatic and diagnosed incidentally during staging of patients with lung adenocarcinoma. Huge but sole adrenal gland metastasis with rapid growth and local invasion is extremely rare and those occurring in the setting of NSCLC have not been reported previously. Herein we describe a 66 year old male patient with NSCLC who had huge but sole adrenal gland metastasis with rapid growth and local invasion and extension into stomach, pancreas and left kidney. Interestingly there was no increase in the primary lesion of NSCLC. These findings were confirmed by autopsy. Despite the occurrence of an adrenal gland metastasis with considerable size being rare, it should be considered in the differential diagnosis, even if there is no involvement of the other organ and the primary lesion is of a small size.


Assuntos
Adenocarcinoma/patologia , Neoplasias das Glândulas Suprarrenais/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Adenocarcinoma/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Idoso , Autopsia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Achados Incidentais , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Radiografia , Tomografia Computadorizada por Raios X
18.
Clin Mol Hepatol ; 25(4): 381-389, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31405269

RESUMO

BACKGROUND AND AIM: We previously reported the comparable efficacy of bi-monthly hepatic arterial infusion chemotherapy (B-HAIC) to that of sorafenib chemotherapy for the treatment of advanced hepatocellular carcinoma (aHCC) in patients with compensated cirrhosis. In this study, we demonstrate the efficacy of B-HAIC in patients with decompensated cirrhosis. METHODS: Forty-five patients with aHCC refractory to transcatheter arterial chemo-embolization (TACE) were treated with B-HAIC and were divided into two groups according to hepatic functional reserve (Child-Pugh grade). Overall survival period, treatment response, and adverse events in each group were analyzed. RESULTS: Efficacy and disease control rates in the Child-Pugh B group (n=24; 21% and 71%, respectively) were not significantly impaired compared the Child-Pugh A group (n=21; 38% and 67%, respectively). Median survival time and survival rate at 12 months in the Child-Pugh B group were 422 days and 58.3%, respectively, whereas those in the ChildPugh A group were 567 days and 70.8%, respectively. Importantly, the hepatic functional reserve of patients did not worsen in either group during the treatment period. Furthermore, the occurrence rate of adverse events leading to discontinuation of anti-tumor treatment was not significantly increased in the Child-Pugh B group. CONCLUSION: Given the preservation of hepatic functional reserve afforded by B-HAIC chemotherapy in patients with decompensated cirrhosis, B-HAIC might be an acceptable alternative strategy for aHCC patients who do not respond to TACE.

19.
Cancer Res ; 79(19): 4814-4827, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31431463

RESUMO

Gliomas are classified by combining histopathologic and molecular features, including isocitrate dehydrogenase (IDH) status. Although IDH-wild-type diffuse astrocytic glioma (DAG) shows a more aggressive phenotype than IDH-mutant type, lack of knowledge regarding relevant molecular drivers for this type of tumor has hindered the development of therapeutic agents. Here, we examined human IDH-wild-type DAGs and a glioma mouse model with a mosaic analysis with double markers (MADM) system, which concurrently lacks p53 and NF1 and spontaneously develops tumors highly comparable with human IDH-wild-type DAG without characteristic molecular features of glioblastoma (DAG-nonMF). During tumor formation, enhancer of zeste homolog (EZH2) and the other polycomb repressive complex 2 (PRC2) components were upregulated even at an early stage of tumorigenesis, together with an increased number of genes with H3K27me3 or H3K27me3 and H3K4me3 bivalent modifications. Among the epigenetically dysregulated genes, frizzled-8 (Fzd8), which is known to be a cancer- and stem cell reprogramming-related gene, was gradually silenced during tumorigenesis. Genetic and pharmacologic inhibition of EZH2 in MADM mice showed reactivation of aberrant H3K27me3 target genes, including Fzd8, together with significant reduction of tumor size. Our study clarifies a pathogenic molecular pathway of IDH-wild-type DAG-nonMF that depends on EZH2 activity and provides a strong rationale for targeting EZH2 as a promising therapeutic approach for this type of glioma. SIGNIFICANCE: EZH2 is involved in the generation of IDH-wild-type diffuse astrocytic gliomas and is a potential therapeutic target for this type of glioma. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/19/4814/F1.large.jpg.

20.
Anticancer Res ; 39(8): 4555-4560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366559

RESUMO

BACKGROUND/AIM: Treatments for controlling delayed nausea after chemotherapy are inadequate, potentially inciting malnutrition. We sought to determine the incidence of nausea, anorexia, and food intake after chemotherapy. PATIENTS AND METHODS: Subjects were females with gynecological cancers who underwent chemotherapy between 2008 and 2013. Nausea, anorexia, and food intake in the acute (day 1) and delayed phases (days 2 and 3) were retrospectively evaluated. RESULTS: Subjects included 156 females. Chemotherapies were highly (HEC; n=24) and moderately emetogenic (MEC; n=132). There were no significant between-group differences for anorexia control during either the acute or the delayed phase and both groups demonstrated significantly worse control of nausea during the delayed phase. In the HEC group, food intake was significantly reduced on days 2 and 3 compared with day 1. CONCLUSION: Rates of nausea, anorexia, and food intake significantly worsened over time, particularly in the MEC group. Current supportive therapies appear inadequate and should be improved.


Assuntos
Anorexia/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Ingestão de Alimentos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Adulto , Idoso , Anorexia/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/epidemiologia , Náusea/patologia , Vômito/induzido quimicamente , Vômito/epidemiologia , Vômito/patologia
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