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1.
Sci Rep ; 11(1): 6255, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737617

RESUMO

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Nucleares/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Neoplasias Gástricas/patologia , Transfecção , Regulação para Cima/genética
2.
World J Clin Cases ; 7(14): 1865-1875, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31417933

RESUMO

BACKGROUND: Colorectal neuroendocrine carcinoma (NEC) is a rare tumor that demonstrates aggressive growth pattern with ingrowth into the tract, metastasis to the other organs, and invasion to the surrounding organs; these clinical characteristics result in poor prognosis. Surgical resection appears as an effective approach; however, because it is difficult to accurately diagnose NEC during the early stage and owing to its aggressive growth pattern, development of a reliable standard chemotherapy regimen and management strategies are essential. CASE SUMMARY: Here, we report the case of patient with NEC showing an aggressive growth pattern that resulted in the rupture of the tumor to the outside the colon after stenting of the internal colonic stenosis. In addition, the tumor invaded into the duodenum, thereby causing duodenal stenosis that required an additional stent in the duodenum. This aggressive growth pattern is one of the main features of the NEC that is different from adenocarcinoma. To clarify the clinical characteristics, we reviewed 60 recently reported cases, including data on tumor location, size, treatment, and prognosis. CONCLUSION: We consider that the information presented here is of great significance for the diagnosis, treatment, and management of symptoms of the patients with NEC.

3.
World J Hepatol ; 4(4): 139-48, 2012 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-22567186

RESUMO

AIM: To investigate the impact of hepatitis B virus (HBV) infection on cellular gene expression, by conducting both in vitro and in vivo studies. METHODS: Knockdown of HBV was targeted by stable expression of short hairpin RNA (shRNA) in huH-1 cells. Cellular gene expression was compared using a human 30K cDNA microarray in the cells and quantified by real-time reverse transcription-polymerase chain reaction (RT-PCR) (qRT-PCR) in the cells, hepatocellular carcinoma (HCC) and surrounding non-cancerous liver tissues (SL). RESULTS: The expressions of HBsAg and HBx protein were markedly suppressed in the cells and in HBx transgenic mouse liver, respectively, after introduction of shRNA. Of the 30K genes studied, 135 and 103 genes were identified as being down- and up-regulated, respectively, by at least twofold in the knockdown cells. Functional annotation revealed that 85 and 62 genes were classified into four up-regulated and five down-regulated functional categories, respectively. When gene expression levels were compared between HCC and SL, eight candidate genes that were confirmed to be up- or down-regulated in the knockdown cells by both microarray and qRT-PCR analyses were not expressed as expected from HBV reduction in HCC, but had similar expression patterns in HBV- and hepatitis C virus-associated cases. In contrast, among the eight genes, only APM2 was constantly repressed in HBV non-associated tissues irrespective of HCC or SL. CONCLUSION: The signature of cellular gene expression should provide new information regarding the pathophysiological mechanisms of persistent hepatitis and hepatocarcinogenesis that are associated with HBV infection.

4.
Gan To Kagaku Ryoho ; 39(4): 683-6, 2012 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-22504703

RESUMO

The patient was a 62-year-old man with bowel obstruction in a locally advanced rectal cancer. Computed tomography (CT) scan of the abdomen showed tumor enlargement(11.4 × 9.0 cm)that invaded the urinary bladder, but no distant metastasis. XELOX therapy was planned in order to shrink or eliminate the tumor after a sigmoid colostomy. Four courses of XELOX therapy were perfomed. Consequently, the level of the tumor marker had been restored to a normal range. CT scan revealed marked shrinkage of the tumor (6.1 × 5.2 cm) and a sharply-defined border between the tumor and the urinary bladder. Three weeks after chemotherapy, a low anterior resection as a radical surgery, and a temporary ileostomy were performed. The post-operative course was good. The histological effect was judged to be grade 3. There were no viable cancer cells in the rectal tumor and lymph nodes. The patient is alive and has been disease-free for 10 months after the operation. XELOX therapy as pre-operative chemotherapy might be safe and effective for patients with locally advanced rectal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Capecitabina , Antígeno Carcinoembrionário/sangue , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Oxaloacetatos , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia
5.
DNA Res ; 17(3): 123-37, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20189949

RESUMO

The complete genome sequence of the thermophilic sulphur-reducing bacterium, Deferribacter desulfuricans SMM1, isolated from a hydrothermal vent chimney has been determined. The genome comprises a single circular chromosome of 2,234,389 bp and a megaplasmid of 308,544 bp. Many genes encoded in the genome are most similar to the genes of sulphur- or sulphate-reducing bacterial species within Deltaproteobacteria. The reconstructed central metabolisms showed a heterotrophic lifestyle primarily driven by C1 to C3 organics, e.g. formate, acetate, and pyruvate, and also suggested that the inability of autotrophy via a reductive tricarboxylic acid cycle may be due to the lack of ATP-dependent citrate lyase. In addition, the genome encodes numerous genes for chemoreceptors, chemotaxis-like systems, and signal transduction machineries. These signalling networks may be linked to this bacterium's versatile energy metabolisms and may provide ecophysiological advantages for D. desulfuricans SSM1 thriving in the physically and chemically fluctuating environments near hydrothermal vents. This is the first genome sequence from the phylum Deferribacteres.


Assuntos
Genoma Bacteriano , Bactérias Anaeróbias Gram-Negativas/crescimento & desenvolvimento , Bactérias Anaeróbias Gram-Negativas/genética , Água do Mar/microbiologia , Adaptação Fisiológica , Movimento Celular , Quimiotaxia , Bactérias Anaeróbias Gram-Negativas/classificação , Temperatura Alta , Transdução de Sinais
6.
Hepatol Res ; 37(11): 914-22, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17610501

RESUMO

BACKGROUND: The aim of the present study was to establish L3 fraction before initial treatment as a useful prognostic factor in a prospective fashion in hepatocellular carcinoma (HCC) where the alpha-fetoprotein (AFP) was very low. METHODS: From 1990 to 2004, 298 HCC patients in whom L3 could be measured were examined in the present study. Enrolled patients with HCC underwent operation, transcatheter arterial chemoembolization and percutaneous ablation therapy. The current patient status was confirmed as of the end of March 2005. L3 was determined by crossed immuno-affinoelectrophoresis when AFP was >/=30 ng/mL. It was carried out by liquid-phase binding assay system on cases where AFP < 30 ng/mL. The tentative discriminating line of L3 was set at 15%. RESULTS: The HCC group included four subgroups: 110 patients with AFP concentrations 15% (high L3), was significantly lower than that in the HCC group whose L3 was

7.
Intern Med ; 45(5): 309-11, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16596000

RESUMO

A 48-year-old man was admitted to our hospital because of repeated episodes of epigastralgia. Endoscopy showed multiple whitish granules extending from the 2nd to 3rd portion of the duodenum. Biopsy specimens showed well circumscribed follicles with a monotonous population of predominantly small cleaved cells that were positive for CD20, CD10 and BCL2, but negative for CD5. A full staging study showed no abnormalities. The tumor was finally diagnosed according to the WHO classification as a stage I follicular lymphoma (FL), grade 1, of the duodenum and subsequently received irradiation to the involved area. After 3 years of followup, he is still in complete remission. Because FL arising in the duodenum has recently reported with increasing frequency, patients with multiple granules in the duodenum should be examined carefully.


Assuntos
Neoplasias Duodenais/radioterapia , Linfoma Folicular/radioterapia , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/patologia , Endoscopia Gastrointestinal , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica
8.
Clin Cancer Res ; 9(8): 3004-11, 2003 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-12912949

RESUMO

PURPOSE: We evaluated whether detection of human telomerase reverse transcriptase (hTERT) mRNA after immunomagnetic separation is useful to detect circulating cancer (CC) cells. EXPERIMENTAL DESIGN: Two ml of peripheral blood were collected from 55 cases with hepatocellular carcinoma (HCC), 20 cases with chronic liver diseases devoid of cancer, and 20 healthy volunteers. Then 1500 and 500 micro l were subjected to immunomagnetic separations using Ber-EP4 and anti-CD45 antibodies, harvested and supernatant cells were collected as epithelial and nonleukocyte fractions, respectively. Samples of each fraction were subjected to reverse transcription-PCR detecting beta-actin, interleukin-2 receptor (IL-2r), alpha-fetoprotein, and hTERT mRNAs. The cases were judged to be positive, equivocal, or negative for CC cells when hTERT positivity with IL-2r negativity, hTERT positivity with IL-2r positivity, or hTERT negativity was seen in epithelial and/or nonleukocyte fractions, respectively. RESULTS: The dilution experiments revealed that our system could detect 10(0-1) HeLa cells involved in 2 ml of blood. The Ber-EP4-harvested cells from cases with distant metastasis were positive for immunostaining using Hep Par 1 monoclonal antibody. CC cells were judged to be positive in 29 of 55 (53%) HCC cases. On the contrary, no cases without HCC were determined to be positive. The frequency of positivity was significantly correlated with disease extent of HCC. CONCLUSIONS: These results strongly suggest that detection of hTERT mRNA after immunomagnetic separation is a specific and sensitive tool to detect CC cells and that it would provide useful source for further investigation of cancer metastasis.


Assuntos
Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Separação Celular/métodos , Separação Imunomagnética/métodos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Células Neoplásicas Circulantes/metabolismo , RNA Mensageiro/metabolismo , Telomerase/genética , Idoso , Contagem de Células Sanguíneas , Proteínas de Ligação a DNA , Feminino , Células HeLa , Hepatócitos/metabolismo , Humanos , Antígenos Comuns de Leucócito/biossíntese , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade
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