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BACKGROUND: Endothelial nitric oxide synthase (eNOS) has been reported to be involved in the atherosclerotic process. A number of studies have investigated the association between eNOS gene polymorphisms and the risk of carotid atherosclerosis (CAS). However, the results are conflicting and inconclusive. The aim of this study was to evaluate precisely the association between the eNOS T786C, G894T, and 4a/4b polymorphisms and CAS risk. MATERIAL AND METHODS: A meta-analysis was carried out by retrieving relevant studies from PubMed, Embase, China National Knowledge Infrastructure (CNKI), and Cochrane databases without a restriction on publication year. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to describe the strength of the association with CAS. RESULTS: Data were obtained from eight case-control studies comprising 2975 cases and 2624 controls. Significant associations were detected between the allelic and recessive models of the eNOS T786C polymorphism (allelic: pâ¯= 0.04; OR, 95% CIâ¯= 1.57 [1.01, 2.44]; recessive: pâ¯= 0.03; OR, 95% CIâ¯= 1.53 [1.04, 2.24]), as well as the allelic and dominant models of the eNOS 4a/4b polymorphism, and CAS risk in an Asian subgroup (allelic: pâ¯= 0.02; OR, 95% CIâ¯= 1.49 [1.07, 2.07]; dominant: pâ¯= 0.01; OR, 95% CIâ¯= 1.50 [1.09, 2.05]), but not in a Caucasian subgroup (pâ¯> 0.05). No association was observed between the eNOS G894T polymorphism and CAS risk (pâ¯> 0.05). CONCLUSION: Our study provides evidence that the allelic and recessive models of the eNOS T786C polymorphism and the allelic and dominant models of the eNOS 4a/4b polymorphism may increase the risk of CAS in Asian populations.
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Doenças das Artérias Carótidas , Óxido Nítrico Sintase Tipo III , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/genética , Predisposição Genética para Doença/genética , Humanos , Óxido Nítrico Sintase Tipo III/genética , Razão de Chances , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
INTRODUCTION: Because of the increasing age of the general population, there is an increasing number of older patients with lung cancer. Cancer chemotherapy often causes severe hematological toxicity in older patients. OBJECTIVE: This study aimed to explore the risk factors affecting the hematological toxicity of cytotoxic anticancer drugs in patients with lung cancer. METHODS: Data were retrospectively collected from 194 patients with lung cancer at Niigata University Medical and Dental Hospital, Japan, between April 2011 and March 2016, when the patients underwent their first round of cytotoxic chemotherapy. The patients were divided into three groups on the basis of age: <65, 65-74, and ≥75 years. Physiological functions and laboratory data before treatment, as well as hematological adverse events following chemotherapy, were compared among the groups. RESULTS: Patients aged ≥75 years were significantly more likely to experience grade 3 or 4 neutropenia, compared with patients aged <65 years. However, there were no differences in the incidence of anemia or thrombocytopenia among the age groups. The frequency of febrile neutropenia tended to increase with age. Multivariate analysis showed that age ≥75 years, male sex, and a performance status of ≥2 were independent factors for grade 3 or 4 neutropenia. Patients with 2 or 3 of these factors had a significantly higher frequency of neutropenia, compared with patients who had 0 or 1 of these factors. CONCLUSION: We found that age ≥75 years, male sex, and a performance status of ≥2 were independent risk factors for grade 3 or 4 neutropenia.
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Doenças Hematológicas/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Fatores Etários , Idoso , Anemia/induzido quimicamente , Neutropenia Febril/induzido quimicamente , Feminino , Doenças Hematológicas/fisiopatologia , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Trombocitopenia/induzido quimicamenteRESUMO
BACKGROUND: The timing, location, and level of gene expression are crucial for normal organ development, because morphogenesis requires strict genetic control. MicroRNAs (miRNAs) are noncoding small single-stranded RNAs that play a critical role in regulating gene expression level. Although miRNAs are known to be involved in many biological events, the role of miRNAs in organogenesis is not fully understood. Mammalian eyelids fuse and separate during development and growth. In mice, failure of this process results in the eye-open at birth (EOB) phenotype. RESULTS: It has been shown that conditional deletion of mesenchymal Dicer (an essential protein for miRNA processing; Dicer fl/fl ;Wnt1Cre) leads to the EOB phenotype with full penetrance. Here, we identified that the up-regulation of Wnt signaling resulted in the EOB phenotype in Dicer mutants. Down-regulation of Fgf signaling observed in Dicer mutants was caused by an inverse relationship between Fgf and Wnt signaling. Shh and Bmp signaling were down-regulated as the secondary effects in Dicer fl/fl ;Wnt1Cre mice. Wnt, Shh, and Fgf signaling were also found to mediate the epithelial-mesenchymal interactions in eyelid development. CONCLUSIONS: miRNAs control eyelid development through Wnt. Developmental Dynamics 248:201-210, 2019. © 2019 Wiley Periodicals, Inc.
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Pálpebras/crescimento & desenvolvimento , MicroRNAs/fisiologia , Via de Sinalização Wnt , Animais , RNA Helicases DEAD-box/deficiência , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Organogênese , Fenótipo , Ribonuclease III/deficiênciaRESUMO
The prognostic nutrition index (PNI), calculated based on serum albumin and lymphocyte counts, predicts the prognosis of several cancers, including operated esophageal cancers. In this study, we determined whether PNI could predict the occurrence of severe adverse events by chemotherapy and chemoradiotherapy, and overall survival in esophageal cancer. We collected data from 191 patients with esophageal cancer treated with at least one course of cisplatin and 5-fluorouracil from 2005 to 2016. We compared the incidences of severe adverse events and overall survival between a high- and a low-PNI group. The optimal cut-off value of the Onodera PNI was 43.2. Patients with low PNIs suffered more frequent severe adverse events than did those with high PNIs, and the latter patients survived longer. The PNI was independently prognostic of overall survival and stage. The PNI predicted the development of severe adverse events caused by chemotherapy or chemoradiotherapy, and overall survival, in esophageal cancer patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/tratamento farmacológico , Doenças Hematológicas/induzido quimicamente , Avaliação Nutricional , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/radioterapia , Feminino , Fluoruracila/administração & dosagem , Doenças Hematológicas/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Lesões por Radiação/etiologia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Background: Palliative chemotherapy is commonly used for advanced cancer patients. The timing of chemotherapy termination is crucial for efforts to maintain quality of life. Patients and Methods: This retrospective study included gastrointestinal cancer patients who were treated with chemotherapy and died between 2013 and 2022 at Niigata University Medical and Dental Hospital. Data were reviewed regarding age, gender, cancer type, reason for chemotherapy termination, cause of death, survival after chemotherapy termination, and place of death. Results: In total, 388 patients were included; the median survival after chemotherapy was 73 days. Patients aged <67 years had shorter survival durations (59 days), compared with patients aged >67 years (82 days). Ten (2.6%) patients began a new chemotherapy regimen, whereas 17 (4.4%) patients received chemotherapy, within 4 weeks before death. The most common reason for chemotherapy termination was disease progression, and most deaths occurred in hospitals. Conclusion: The rates of chemotherapy and initiation of new chemotherapeutic regimens near the end of life were lower than previously reported. Most deaths occurred in hospitals, highlighting the need for development of hospices.
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BACKGROUND: The Keap1-Nrf2 pathway has been reported to be impaired in several cancers. However, the status of Keap1-Nrf2 system in human colorectal cancer (CRC) has not been elucidated. METHODS: We used colorectal cancer (CRC) cell lines and surgical specimens to investigate the methylation status of the KEAP1 promoter region as well as expression of Nrf2 and its downstream antioxidative stress genes, NQO-1 and AKR1C1. RESULTS: DNA sequencing analysis indicated that all mutations detected were synonymous, with no amino acid substitutions. We showed by bisulfite genomic sequencing and methylation-specific PCR that eight of 10 CRC cell lines had hypermethylated CpG islands in the KEAP1 promoter region. HT29 cells with a hypermethylated KEAP1 promoter resulted in decreased mRNA and protein expression but unmethylated Colo320DM cells showed higher expression levels. In addition, treatment with the DNA methyltransferase inhibitor 5-Aza-dC combined with the histone deacetylase inhibitor trichostatin A (TSA) increased KEAP1 mRNA expression. These result suggested that methylation of the KEAP1 promoter regulates its mRNA level. Time course analysis with the Nrf2-antioxidant response element (ARE) pathway activator t-BHQ treatment showed a rapid response within 24 h. HT29 cells had higher basal expression levels of NQO-1 and AKR1C1 mRNA than Colo320DM cells. Aberrant promoter methylation of KEAP1 was detected in 53% of tumor tissues and 25% of normal mucosae from 40 surgical CRC specimens, indicating that cancerous tissue showed increased methylation of the KEAP1 promoter region, conferring a protective effect against cytotoxic anticancer drugs. CONCLUSION: Hypermethylation of the KEAP1 promoter region suppressed its mRNA expression and increased nuclear Nrf2 and downstream ARE gene expression in CRC cells and tissues.
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Neoplasias Colorretais/genética , Metilação de DNA , Peptídeos e Proteínas de Sinalização Intracelular/genética , Regiões Promotoras Genéticas/genética , 20-Hidroxiesteroide Desidrogenases/metabolismo , Western Blotting , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , RNA/metabolismo , RNA Mitocondrial , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
Neuroendocrine neoplasms of the colon and rectum are colorectal epithelial neoplasms with neuroendocrine differentiation. A platinum regimen used for small cell lung cancer is the currently recommended chemotherapy for gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), regardless of the organ. The BRAF V600E mutation has been recently reported as a druggable driver mutation in colorectal NECs. In BRAF V600E mutant colorectal cancer, a combination of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody, with or without a MEK inhibitor, is recommended. Here, we report the case of 77-year-old man who had lymph node recurrence after surgery for primary ascending colonic NEC. Two cytotoxic regimens, cisplatin plus irinotecan and modified FOLFOX6, were administered as first- and second-line chemotherapies with no remarkable response observed. At this point, genetic analysis confirmed the tumor harbored a BRAF V600E mutation. Thus, a regimen of BRAF inhibitor plus anti-EGFR antibody was administered. After commencing this regimen, carcinoembryonic antigen levels decreased within normal range, and there was dramatic shrinkage of the lymph node metastases observed by chest and abdominal computed tomography scans. To our knowledge, this is the first reported case of a colorectal NEC responding to a BRAF inhibitor and anti-EGFR antibody.
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Carcinoma Neuroendócrino , Neoplasias Colorretais , Idoso , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Recém-Nascido , Masculino , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genéticaRESUMO
Lannea coromandelica (Houtt.) Merr. is a deciduous tree in the family Anacardiaceae, which grows in lowland and hill forests; 100-1800 m. SW Guangdong, S Guangxi, S Yunnan [Bhutan, India, Myanmar, Nepal, Sri Lanka; cultivated elsewhere in continental SE Asia, such as in Cambodia, Laos, Malaysia, Thailand, Vietnam, where it is probably naturalized]. The length of the complete plastome is 162,460 bp, including 130 genes consisting of 85 protein-coding genes, 37 tRNA genes and 8 rRNA genes. The assembled plastome has the typical structure and gene content of angiosperms plastome, which includes two inverted repeats (IRs) regions of 26,877 bp, a large single copy (LSC) region of 89,599 bp and a small single-copy (SSC) region of 19,107 bp. The total G/C content in the plastome of L. coromandelica is 37.7%. The complete plastome sequence of L. coromandelica will provide contributions to the conservation genetics of this species as well as to phylogenetic studies in Anacardiaceae.
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BACKGROUND: Colorectal mucinous adenocarcinoma is a rare subtype of colorectal cancer and is characterized by an abundance of mucin in the tumor. In addition, the colorectal mucinous adenocarcinoma often demonstrates poor differentiation in the histology of tumor cells and poor prognosis compared with those with adenocarcinoma. Here, we present the case of a young woman with colonic mucinous adenocarcinoma showing significantly rapid progression within four months of immunosuppressant therapy for Henoch-Schönlein purpura. CASE SUMMARY: Here we report a rare case of ascending colon mucinous adenocarcinoma with lymph node and liver metastases which developed and progressed rapidly within four months during the treatment of Henoch-Schönlein purpura using corticosteroids. The systemic screening examinations showed no tumors before the immunosuppressant therapy. Fortunately, the patient was successfully treated with chemotherapy. CONCLUSION: While no direct evidence that the immunosuppressants accelerated the tumor development, the case presenta tion and review of the literature demonstrated that surveillance for malignancies before and during treatment with immunosuppressive agents is essential.
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Circulating tumor cells (CTCs) derived from primary tumors and/or metastatic tumors are markers for tumor prognosis, and can also be used to monitor therapeutic efficacy and tumor recurrence. Circulating tumor cells enrichment and screening can be automated, but the final counting of CTCs currently requires manual intervention. This not only requires the participation of experienced pathologists, but also easily causes artificial misjudgment. Medical image recognition based on machine learning can effectively reduce the workload and improve the level of automation. So, we use machine learning to identify CTCs. First, we collected the CTC test results of 600 patients. After immunofluorescence staining, each picture presented a positive CTC cell nucleus and several negative controls. The images of CTCs were then segmented by image denoising, image filtering, edge detection, image expansion and contraction techniques using python's openCV scheme. Subsequently, traditional image recognition methods and machine learning were used to identify CTCs. Machine learning algorithms are implemented using convolutional neural network deep learning networks for training. We took 2300 cells from 600 patients for training and testing. About 1300 cells were used for training and the others were used for testing. The sensitivity and specificity of recognition reached 90.3 and 91.3%, respectively. We will further revise our models, hoping to achieve a higher sensitivity and specificity.
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The generation of mature, functional, thyroid follicular cells from pluripotent stem cells would potentially provide a therapeutic benefit for patients with hypothyroidism, but in vitro differentiation remains difficult. We earlier reported the in vivo generation of lung organs via blastocyst complementation in fibroblast growth factor 10 (Fgf10), compound, heterozygous mutant (Fgf10 Ex1mut/Ex3mut) mice. Fgf10 also plays an essential role in thyroid development and branching morphogenesis, but any role thereof in thyroid organogenesis remains unclear. Here, we report that the thyroids of Fgf10 Ex1mut/Ex3mut mice exhibit severe hypoplasia, and we generate thyroid tissues from mouse embryonic stem cells (ESCs) in Fgf10 Ex1mut/Ex3mut mice via blastocyst complementation. The tissues were morphologically normal and physiologically functional. The thyroid follicular cells of Fgf10 Ex1mut/Ex3mut chimeric mice were derived largely from GFP-positive mouse ESCs although the recipient cells were mixed. Thyroid generation in vivo via blastocyst complementation will aid functional thyroid regeneration.
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Blastocisto , Células-Tronco Embrionárias Murinas , Glândula Tireoide/crescimento & desenvolvimento , Animais , Quimera , Exoma/genética , Feminino , Fator 10 de Crescimento de Fibroblastos/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Mutação , Gravidez , Disgenesia da Tireoide/genética , Glândula Tireoide/ultraestrutura , Microtomografia por Raio-XRESUMO
The shortage of donor lungs hinders lung transplantation, the only definitive option for patients with end-stage lung disease. Blastocyst complementation enables the generation of transplantable organs from pluripotent stem cells (PSCs) in animal models. Pancreases and kidneys have been generated from PSCs by blastocyst complementation in rodent models. Here, we report the generation of lungs using mouse embryonic stem cells (ESCs) in apneumic Fgf10 Ex1mut/Ex3mutmice by blastocyst complementation. Complementation with ESCs enables Fgf10-deficient mice to survive to adulthood without abnormalities. Both the generated lung alveolar parenchyma and the interstitial portions, including vascular endothelial cells, vascular and parabronchial smooth muscle cells, and connective tissue, largely originate from the injected ESCs. These data suggest that Fgf10 Ex1mut/Ex3mutblastocysts provide an organ niche for lung generation and that blastocyst complementation could be a viable approach for generating whole lungs.
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Blastocisto/metabolismo , Fator 10 de Crescimento de Fibroblastos/deficiência , Pulmão/fisiopatologia , Animais , Quimerismo , Modelos Animais de Doenças , CamundongosRESUMO
The number of older patients with esophageal cancer (EC) is increasing due to the population aging and increasing life expectancy. However, no optimal treatment strategy for older patients with EC has been established to date. The aim of the present study was to review and compare the treatment modalities and outcomes of 990 younger and older patients diagnosed with EC in our institution. The patients were divided into younger (≤74 years) and older (≥75 years) groups. The majority of the patients in both groups had early-stage EC and were treated by endoscopic submucosal dissection (ESD). The older patients with locally advanced (stage II and III) EC were more likely to undergo chemoradiotherapy rather than esophagectomy. Among the older patients, 22% selected best supportive care. The disease-specific survival rate of the older patients was significantly lower compared with that of the younger patients, which was likely due to the less intense treatment modalities applied. The prognosis following esophagectomy was significantly better compared with that of chemoradiotherapy in the younger, but not in the older patients. In conclusion, the poorer prognosis of older patients (aged ≥75 years) with stage I EC may improve with multidisciplinary treatment after ESD. Although CRT is currently considered the optimal treatment for older patients with stage II/III EC, more efficient treatment modalities are urgently required.
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Two patients underwent hemodialysis. Case 1 with stage IV gastric cancer was treated with reduced doses of capecitabine (1,000 mg/m2/day, days 1 to 14) and oxaliplatin (65 mg/m2, day 1). Although grade 1 thrombocytopenia occurred in the first cycle, grade 3 thrombocytopenia developed in the second cycle because of increasing dosage. After the dosage was reduced, chemotherapy was continued safely. Case 2 with stage IA gastroesophageal cancer was treated with radiotherapy followed by chemotherapy. Treatment with the same dose of CapeOX therapy as in case 1 resulted in no severe toxicity. We conclude that a half-dose of the CapeOX regimen is safe for gastric cancer patients undergoing hemodialysis.
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Capecitabina/uso terapêutico , Neoplasias Esofágicas/terapia , Oxaliplatina/uso terapêutico , Diálise Renal/métodos , Neoplasias Gástricas/terapia , Idoso , Antineoplásicos/uso terapêutico , Quimioterapia Combinada , Endoscopia do Sistema Digestório/métodos , Neoplasias Esofágicas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Adolescents and young adults (AYAs) with cancer often live long lives following treatment and face many life events. No detailed studies of cancers in AYAs have described the epidemiology, treatment outcome, and social status in Japan. The present study defined AYAs as those aged 15-29 years old based on the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. Data was collected from the hospital-based cancer registry and electronic medical charts at Niigata University Medical and Dental Hospital from 2007 to 2015. The present study analyzed the types of cancer, treatment methods and outcomes, fertility preservation, marital status, raising children, school admission, and employment status. A total of 362 (1.9%) cancer cases in AYAs (males 119, females 243) were identified. Carcinoma was the most common type of cancer in both sexes. Females had a high incidence of carcinoma of the genitourinary tract (28.0%). Fertility-sparing surgery (16.0%) was the most common method of fertility preservation. The 5-year survival was better in females (88.4%) than in males (79.9%). The percentage of married AYAs increased following cancer treatment. The proportion of unemployment increased following cancer treatment in all age groups and was greatest (12.6%) in those aged 20-24 years old. Compared with SEER data from the United States, the incidence of carcinoma was high among AYAs, particularly genitourinary tract carcinomas in females, while the incidence of melanoma and skin carcinomas was low. Therefore, AYAs with cancer requires social and economic support.
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The outcomes of tracheal transplantation for the treatment of airway stenosis are unsatisfactory. We investigated the feasibility of regeneration of the trachea using a rat decellularized tracheal scaffold and mouse-induced pluripotent stem (iPS) cells for in vivo transplantation. The rat trachea was first decellularized using a detergent/enzymatic treatment method. We successfully established a centrifugation method that can transplant cells onto the luminal surface of the decellularized rat tracheal scaffold circumferentially. Two types of mouse iPS cells were differentiated into definitive endoderm cells and transplanted onto the luminal surface of the decellularized tracheal matrix scaffold using this centrifugation method. For in vivo study, normal rat tracheas, no-cell rat tracheal scaffolds, or rat tracheal scaffolds recellularized with rat tracheal epithelial cells (EGV-4T) were orthotopically transplanted on F344 rats, and rat tracheal scaffolds recellularized with mouse iPS cells were transplanted on F344/NJc1-rnu/rnu rats. Rats transplanted with no-cell scaffolds or scaffolds recellularized with EGV-4T survived for 1 month, although airway stenosis was observed. One of the F344/NJc1-rnu/rnu rats transplanted with rat trachea regenerated using mouse iPS cells survived over 5 weeks. Histological analysis indicated the cause of death was airway stenosis due to colonic cellular proliferation of undifferentiated iPS cells. Re-epithelialization with numerous ciliated epithelial cells was observed in one of the rats transplanted with trachea bioengineered using iPS cells. In this study, we present a simple and efficient tracheal tissue engineering model using a centrifugation method in a small-animal model. Tissue-engineered trachea using decellularized tracheal scaffolds and iPS cells is potentially applicable for tracheal transplantation.
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Centrifugação/métodos , Células-Tronco Pluripotentes Induzidas/citologia , Engenharia Tecidual/métodos , Traqueia/fisiologia , Animais , Linhagem Celular , Feminino , Camundongos , Ratos Endogâmicos F344 , Regeneração , Transplante de Células-Tronco , Alicerces Teciduais/química , Traqueia/transplanteRESUMO
Nowadays, the role of miRNA in tumorigenesis has been largely reported. It was found that miR-506 might be associated with tumorigenesis of various cancers. The present study was aimed to investigate the character of miR-506 and some related factors in human osteosarcoma (OS) carcinogenesis. The expression level of miR-506 was downregulated in OS compared with the normal control group by RT-PCR, both in vivo and in vitro. In addition, IL-1ß stimulation decreased the expression of miR-506. MiR-506 interfered with JAG1 gene transcription throughmiR-506 binding to the 3'-UTR region of JAG1 gene. Further siRNA strategy suggested that IL-1ß may regulate miR-506 level via NF-κB, and then alter the JAG1 expression. Besides, the suppression of JAG1 by miR-506 inhibited OS cell proliferation. Taken together, our data indicate a process of NF-κB-induced miR-506 suppression and JAG1 upregulation upon IL-1ß induction, which can be regarded as a new pathway for modulating cell proliferation via miR-506. It may be of clinical value in treating OS in the future.
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Regulação para Baixo/efeitos dos fármacos , Interleucina-1beta/farmacologia , Proteína Jagged-1/metabolismo , MicroRNAs/genética , NF-kappa B/metabolismo , Osteossarcoma/genética , Osteossarcoma/patologia , Regiões 3' não Traduzidas/genética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína Jagged-1/genética , MicroRNAs/metabolismoRESUMO
OBJECTIVE: Studying on the routes of vas deferens to provide anatomy basis for surgical operation, especially, reconstruction of long segment loss of vas deferens. METHODS: The routes of vas deferens were observed and anatomic distances along epididymal, infrainguinal, inguinal, retroperitoneal and ampullar segments of vas deferens, the distances from external ring to extremity of vas deferens were measured respectively in 18 formalin fixed adult cadavers. RESULTS: The vas deferens have a large curve from external ring to extremity in its route, draw it out from the external ring. Eliminating this curve will allow to shorten this segment of vas deferens for vasovasostomy by 6.1 - 12.9 (9.31 +/- 1.30) cm. The length of each segment of vas deferens, respectively, is epididymal: 3.2 - 5.6 (4.53 +/- 0.79) cm, infrainguinal: 4.5 - 9.5 (7.31 +/- 1.78) cm, inguinal: 4.4 - 7.5 (5.52 +/- 0.74) cm, retroperitoneal: 12.5 - 19.5 (16.75 +/- 1.87) cm and ampullar: 2.9 - 3.8 (3.63 +/- 0.23) cm. There was no significant differences in segment length and the distances from external ring to extremity of vas deferens between the right and left. CONCLUSION: Reconstruction of long segment loss of vas deferens can be performed by mobilization retroperitoneal vas deferens and draw it out from external ring. There were no significant differences in lengths of vas deferens and the distances from external ring to vassal extremity between the left and right in adults. The surgical operations of vas deferens are closely related each segment of vasa.
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Ducto Deferente/anatomia & histologia , Adulto , Autopsia , Humanos , MasculinoRESUMO
PURPOSE: The American Society of Clinical Oncology provides clinical practice guidelines for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer. The panel recommends that actual body weight should be used when selecting cytotoxic chemotherapy doses regardless of obesity status. However, there have been no reports regarding the appropriate cytotoxic chemotherapy dosing for obese Japanese patients with cancer. PATIENTS AND METHODS: We collected data from 216 gynecological cancer patients who were treated with at least one course of a paclitaxel and carboplatin (TC) regimen or a docetaxel and carboplatin (DC) regimen at Niigata University Medical and Dental Hospital from July 2006 to April 2014. Patients were divided into three groups according to body mass index (BMI): obese (BMI ≥ 25), normal (BMI 18.5-24.9), and underweight (BMI < 18.5), as defined by the Japan Society for the Study of Obesity. We analyzed hematological toxicities by full weight-based chemotherapy in each group. RESULTS: The rates of grade 3/4 leukocytopenia, neutropenia, and thrombocytopenia were not significantly different among the three BMI groups on all patient analyses. For the TC regimen, the obese and normal groups had significantly lower leukocytopenia (grade 3/4) rates than did the underweight group. Also, significant positive correlations between BMI and the nadirs of leukocytes, neutrophils, platelets, and hemoglobin were observed. For the DC regimen, no significant difference was observed among the BMI groups and the rate of grade 3/4 hematological toxicities. CONCLUSIONS: We did not observe stronger myelosuppression in obese cancer patients compared with non-obese cancer patients. Therefore, the cytotoxic chemotherapy dose should be calculated by the actual body weight and unnecessary dose reduction should be avoided.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias dos Genitais Femininos/tratamento farmacológico , Doenças Hematológicas/induzido quimicamente , Obesidade/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Índice de Massa Corporal , Carboplatina/administração & dosagem , Docetaxel , Relação Dose-Resposta a Droga , Feminino , Doenças Hematológicas/epidemiologia , Humanos , Peso Corporal Ideal/fisiologia , Japão , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Estudos Retrospectivos , Taxoides/administração & dosagem , Magreza/complicações , Adulto JovemRESUMO
BACKGROUND/AIM: Inhibition of glutaminolysis has been reported as a promising therapeutic strategy to target several solid carcinomas. We aimed to investigate the effects of glutaminolysis on cell proliferation in lung squamous cell carcinoma cell lines and to explore the potential of targeting glutaminolysis as an anticancer strategy. MATERIALS AND METHODS: Glutamine (Gln) dependence was assessed in six lung squamous cell carcinoma cell lines. Cell proliferation, mammalian target of rapamycin complex 1 (mTORC1) activity and the induction of autophagy were assessed after inhibition of glutaminolysis via Gln depletion or glutaminase (GLS) inhibition. RESULTS: Five of six lung squamous cell carcinoma cell lines exhibited glutamine-dependence. The extent of dependence was correlated with the mRNA levels of GLS1/GLS2. Inhibition of glutaminolysis inhibited cell proliferation by down-regulating of mTORC1 signaling and inducing autophagy in Gln-dependent lung squamous cell carcinoma cell lines. CONCLUSION: Targeting glutaminolysis may represent a potential therapeutic strategy for the treatment of Gln-dependent lung squamous cell carcinomas.