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BACKGROUND: There is currently a limited number of studies on transglutaminase type 1 (TGM1) in tumors. The objective of this study is to perform a comprehensive analysis across various types of cancer to determine the prognostic significance of TGM1 in tumors and investigate its role in the immune environment. METHOD: Pan-cancer and mutational data were retrieved from the TCGA database and analyzed using R (version 3.6.4) and its associated software package. The expression difference and prognosis of TGM1 were examined, along with its correlation with tumor heterogeneity, stemness, mutation landscape, and RNA modification. Additionally, the relationship between TGM1 expression and tumor immunity was investigated using the TIMER method. RESULTS: TGM1 is expressed differently in various tumors and normal samples and is associated with the overall survival and progression-free time of KIRC, ACC, SKCM, LIHC, and STES. In LICH, we found a negative correlation between TGM1 expression and 6 indicators of tumor stemness. The mutation frequencies of BLCA, LIHC, and KIRC were 1.7%, 0.3%, and 0.3% respectively. In BLCA and BRCA, there was a significant correlation between TGM1 expression and the infiltration of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells. CONCLUSION: TGM1 has the potential to serve as both a prognostic marker and a drug target.
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Neoplasias , Humanos , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , TransglutaminasesRESUMO
BACKGROUND: Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE: This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN: systematic review METHODS: PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION: These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.
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Produtos Biológicos , Carcinoma de Células de Transição , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Neoplasias da Bexiga Urinária , Masculino , Humanos , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Testiculares/tratamento farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Transdução de Sinais , Microambiente TumoralRESUMO
The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pan-cancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.
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Neoplasias , Proteínas Nucleares , Proteínas de Ligação a RNA , Fatores de Transcrição , Humanos , 5-Metilcitosina , Neoplasias/metabolismoRESUMO
Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.
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Proteínas de Ciclo Celular , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/cirurgia , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Proteínas Associadas aos Microtúbulos/metabolismoRESUMO
Prolyl 4-hydroxylase subunit beta (P4HB) can catalyze the formation, breakage and rearrangement of disulfide bonds through two thioredoxin domains, which is important for the maintenance of oxidizing environment in endoplasmic reticulum. Recently, P4HB has been demonstrated its oncogenic role of tumorigenesis and development in cancers. Therefore, we comprehensively deciphered P4HB in human cancer from various aspects, including pan-cancer analysis and narrative summary. We also provided some possible interacted molecules and the top 10 predicted drugs targeting P4HB to contribute to future research. We proposed that P4HB was a potential target and brought new therapeutic opportunities for cancer patients.
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In Japan, only single-unit cord blood transplantations (CBTs) are typically performed, and their number has increased over the last 23 years, with ongoing improvement in results. In most cases, CBTs with multiple HLA mismatches are used, owing to a low HLA barrier, and lower engraftment rate is a problem that must be overcome. Here, as part of an effort to improve guidelines for the selection and processing of CB units for transplantation, we sought to assess the present status of CBT in Japan and to elucidate factors contributing to the favorable outcomes, focusing in particular on selection by cell components of CB unit and HLA allele matching. We conducted a nationwide study analyzing 13,443 patients who underwent first CBT between in Japan between December 1997 and December 2019 using multivariate regression analysis. Both patient- and transplantation-related variables, such as age and Hematopoietic Cell Transplantation Comorbidity Index, as well as selected CB unit characteristics, were included in the analysis. The interaction analysis elucidated that CB unit selection favoring higher counts of CD34+ cells and granulocyte macrophage colony-forming units (GM-CFU)/kg, but not of total nucleated cells, contributed to improved engraftment after transplantation. Moreover, a higher CD34+ cell dose was associated with improved overall survival (OS). Distinctive HLA allele matching was observed. A 0 or 1 HLA allele mismatch between patient and donor had favorable engraftment and carried significantly lower risks of acute GVHD and chronic GVHD but had a significantly higher leukemia relapse rate, compared with a 3-HLA allele mismatch. HLA-DRB1 mismatches were associated with reduced risk of leukemia relapse. Notably, the number of HLA allele mismatches had no incremental effect on engraftment, acute and chronic GVHD, or relapse incidence. As a result, 5-year overall survival did not differ significantly among patients receiving CB units with 0 to 7 HLA allele mismatches. The main points of CB unit selection are as follows. First, selection according to a higher number of CD34+ cells/kg and then of CFU-GM/kg is recommended to obtain favorable engraftment. A unit with .5 × 105 CD34+ cells/kg is minimally acceptable. For units with a CD34+ cell dose of .5 to 1.0 × 105 cells/kg, applying the parameter of ≥20 to 50 × 103 GM-CFU/kg (66.5% of transplanted CB units in this cohort) is associated with a neutrophil engraftment rate of approximately 90%. A unit with ≥1.0 × 105 CD34+ cells/kg can achieve a ≥90% mean neutrophil engraftment rate. Subsequently, HLA allele matching of HLA-A, -B, -C, and -DRB1 at the 2-field level should be searched for units with 0 or 1 HLA allele mismatch in the host-versus-graft direction for favorable engraftment. Units with 2 to 6 HLA allele mismatches are acceptable in patients age ≥15 years and units with 2 to 4 HLA allele mismatches are acceptable in patients age ≤14 years. Units with HLA-DRB1 and/or -B allele mismatch(es) might not be preferable owing to an increased GVHD risk. Our analysis demonstrates that single-unit CBT with the selection of adequate CD34+/kg and GM-CFU/kg and HLA allele matching showed favorable outcomes in both pediatric and adult patients.
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BACKGROUND: The mechanism of metastasis-associated lung adenocarcinoma transcript 1 (Malat1) in triple-negative breast cancer (TNBC) is still unclear. OBJECTIVE: This study aimed to investigate the role of miR-141-3p and Malat1 in autophagy in TNBC under hypoxia. METHODS: The expression levels of Malat1 and miR-141-3p were detected via quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression levels of hypoxia-inducible factor 1α (HIF-1α), HIF-2α, MMP9, p62 and LC3 were determined via western blotting. A Cell Counting Kit-8 assay was used to detect cell viability, while a Transwell assay to detect cell proliferation and invasion. A luciferase assay was used to confirm the relationship between Malat1 and miR-141-3p. RESULTS: A significant increase was observed in the expression level of Malat1 and the autophagic activity in TNBC tissues and cells. The expression level of Malat1 was higher in a hypoxic environment, which can significantly promote the proliferation, migration, and invasion of TNBC cells by activating autophagy. HIF-1α, but not HIF-2α, was identified to induce the upregulation of Malat1 in TNBC cells. The dual-luciferase assay results identified a miR-141-binding site in Malat1. Malat1 knockdown and miR-141-3p overexpression were demonstrated to significantly inhibit autophagy, thereby inhibiting cell proliferation, invasion, and migration. Moreover, hypoxia can inhibit the effect of miR-141-3p on TNBC cells. CONCLUSION: miR-141-3p could suppress autophagy and inhibit proliferation, migration, and invasion by targeting Malat1 in TNBC cells under hypoxia. The existence of the HIF-1α/Malat1/miR-141 axis plays a vital role in the development of TNBC and may be a target for the diagnosis and treatment of TNBC.
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Adenocarcinoma , Neoplasias Pulmonares , MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Hipóxia , Autofagia , Proliferação de Células , Movimento Celular , Regulação Neoplásica da Expressão GênicaRESUMO
Patients with chronic limb-threatening ischemia (CLTI) without other options for adequate arterial revascularization could undergo deep (or distal) venous arterialization for limb salvage. Additionally, patients with extensive foot wound with CLTI sometimes require free flap transfer for limb salvage. We herein report a case of successful reconstructive limb-salvage surgery for an extensively necrotic foot with CLTI, using a two-stage operation involving venous arterialization using foot-perforating veins and subsequent free flap transfer (with preservation of the arterialized vein). The patient was a 59-year-old man with CLTI. The patient's right foot had dry necrotic tissue after Lisfranc joint amputation. Only one straight-line to the posterior tibial artery was achieved after endovascular therapies (four times). At the first stage of surgery, an arterial-venous shunt bypass from the superficial femoral artery to the distal great saphenous vein (GSV) (near the foot-perforating vein) was created. Arterial blood supply reached the necrotic area via the foot venous circulation system. At the second stage of surgery, free latissimus dorsi musculocutaneous flap (8 × 27 cm) transfer with preservation of the arterialized vein was performed. The pedicle artery was anastomosed to the bypass graft (end-to-side). The pedicle vein was anastomosed to the proximal stump of the GSV (end-to-end). The flap and residual foot survived completely, at a one-year follow-up postoperatively. An indocyanine green bypass-through angiography revealed the angiosome through the venous arterialization bypass graft, which included the flap; entire forefoot; and partial regions of the midfoot and heel. This two-stage operation might be considered a useful option for limb-salvage and complete wound-healing in patients with severe non-healing wound with CLTI. The two methods could compensate and overcome the problems of either method: incomplete wound-healing after venous arterialization, and the absence of a recipient artery for free flap transfer.
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Retalho Miocutâneo , Doença Arterial Periférica , Músculos Superficiais do Dorso , Masculino , Humanos , Pessoa de Meia-Idade , Veia Safena/transplante , Isquemia Crônica Crítica de Membro , Retalho Miocutâneo/cirurgia , Músculos Superficiais do Dorso/transplante , Resultado do Tratamento , Salvamento de Membro/métodos , Isquemia/cirurgia , Doença Arterial Periférica/cirurgiaRESUMO
PURPOSE: To identify the risk factors for major adverse cardiovascular events (MACEs) in real-world practice for symptomatic peripheral artery disease in Japan. MATERIALS AND METHODS: Data on Japanese patients (N = 880) from the Observational Prospective Multicenter Registry Study on Outcomes of Peripheral Arterial Disease Patients Treated by Angioplasty Therapy for Aortoiliac Artery who underwent de novo aortoiliac stent placement. The 3-year risk of incident MACEs was investigated. RESULTS: The median age of the patients was 72.6 years (range, 34-97 years), and 83.1% of the patients were men. The patients had the following conditions: smoking (35.6%), hypertension (94.1%), dyslipidemia (81.7%), diabetes (48.0%), renal failure on dialysis (12.6%), myocardial infarction (12.7%), stroke (15.8%), and chronic limb-threatening ischemia (7.1%). Femoropopliteal lesions were present in 38.8% of the limbs with aortoiliac lesions. The 3-year rate of freedom from MACEs was 89.1%. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, were independently associated with the risk of incident MACEs. When the study population was stratified according to these risk factors, the rate of MACEs was highest in patients with at least 3 risk factors (32.9% at 3 years). CONCLUSIONS: The 3-year rate of freedom from MACEs was reported. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, are independent risk factors for MACEs after aortoiliac stent placement.
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Infarto do Miocárdio , Doença Arterial Periférica , Insuficiência Renal , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Artéria Femoral , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/terapia , Artéria Poplítea , Estudos Prospectivos , Fatores de Risco , Stents , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
There has been no systematic review evaluating the efficacy of electromyography (EMG) biofeedback after knee surgery recently. This meta-analysis aimed to determine whether EMG-biofeedback is effective for improving the range of motion (ROM), physical function, and pain relief in patients after knee. Randomized controlled trials (RCTs) assessing the effect of EMG-biofeedback after any knee surgery were retrieved from EMBASE, PubMed, Cochrane Library, Physiotherapy Evidence Database, ClinicalTrials.gov, ProQuest. This review identified 773 unique studies, and six RCTs were in the final meta-analysis. EMG-Biofeedback treatment has a significant difference compared to other rehabilitation therapy in knee ROM improving (SMD = -0.48, 95% CI = -0.82 to -0.14, p = 0.006, I2 = 37%). Moreover, there was no significant difference in pain (SMD = -0.33, 95% CI = -0.67 to0.02, p = 0.07, I2 = 41%) and physical function scores (MD = 1.83, 95% CI = -3.48 to7.14, p = 0.50, I2 = 0%). The results illustrate that EMG-biofeedback can improve knee ROM in patients after knee surgery. However, it is not superior to other rehabilitation methods for pain relief and physical function improvement.
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Biorretroalimentação Psicológica , Articulação do Joelho , Eletromiografia , Humanos , Articulação do Joelho/cirurgia , Dor , Amplitude de Movimento ArticularRESUMO
BACKGROUND: The study aims to identify whether Platelet-rich plasma (PRP) combined with early physiotherapy has an advantage over PRP alone for rotator cuff injury patients, regarding pain release, function score, tear size, and quality of life improvement. METHODS: This is a single-center prospective non-randomized study implemented in July 2019 at the Affiliated Hospital of Southwest Medical University in Sichuan. Three hundred-forteen patients with rotator cuff injury aged over 18 years were recruited. Participants were assigned to the experiment group (PRP plus physiotherapy) or control group (PRP) by their desire. We used the Constant-Murley score to assess the shoulder function, the Visual Analogue Scale to evaluate shoulder pain, and the MOS Item Short-form Health Survey (SF-12) to measure the quality of life. MRI was applied to measure tear size, and the follow-up duration is 12 months. DISCUSSION: Our findings will give information on the effects of PRP and physiotherapy on rotator cuff injuries. Physiotherapy might be added to improve the effects of PRP in patients with rotator cuff injuries. TRIAL REGISTRATION: This study was registered in the Chinese clinical trial registry on September 1st, 2019 ( ChiCTR1900025563 ).
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Plasma Rico em Plaquetas , Lesões do Manguito Rotador , Adulto , Artroscopia , Humanos , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Estudos Prospectivos , Qualidade de Vida , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Clinical research on the rotator cuff tendon is increasing, and new approaches are being applied to rotator cuff disease. Considering the integration of research resources and research trends, it is necessary to conduct an analysis of recent research on the topic. PURPOSE: To identity the research trends, influential journals, key researchers, and core countries of rotator cuff tendon research between 2000 and 2019. STUDY DESIGN: Cross-sectional study. METHODS: All the literature related to rotator cuff tendon research was retrieved from the Web of Science Core Collection on January 7, 2020. Qualitative and quantitative analyses were processed based on Web of Science and CiteSpace. RESULTS: A total of 4131 studies, which included 3830 articles and 301 reviews, were obtained. There was an upward trend of studies on the topic, with small fluctuations in the past 2 decades. The United States had the most studies, and the number of studies from other countries increased over the study period. Most of the funding sources came from the United States. Articles in the Journal of Shoulder and Elbow Surgery had the most citations for rotator cuff research. Frontier topics, such as arthroscopic repair, mesenchymal stem cell, and "platelet-rich plasma, were identified. The number of citations in 2018 (r = 0.280; P = .005) and 2019 (r = 0.307; P = .002) had a weak positive correlation with publication date, indicating that the more recently published articles had a higher number of citations. CONCLUSION: Valuable information on rotator cuff research based on bibliometric analysis was identified. Arthroscopic repair, mesenchymal stem cell, and platelet-rich plasma might be the research frontiers in this field, and researchers should focus on these topics in future studies.
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BACKGROUND: Osteoarthritis is a degenerative disease that commonly occurs in middle-aged and elderly people. High-quality articles in the field of osteoarthritis rehabilitation have not been studied in detail. OBJECTIVE: To identify and conduct a qualitative and quantitative analysis of the 50 most-cited articles on osteoarthritis rehabilitation and provide valuable scientific information for researchers. METHODS: Fifty articles related to the rehabilitation of individuals with osteoarthritis were retrieved from the Web of Science Core Collection. Basic information, such as the authors, title, number of citations, year of publication, journal, country/territory, and research type, was extracted. CiteSpace was used to visualize the keywords. RESULTS: The average number of citations per article was 244.54. The top 50 articles were published in 27 journals and published by 262 authors. Most of the top 50 articles were published in the United States. The top 50 articles included 23 randomized controlled trials, 21 cohort studies, 2 case series, and 4 expert opinion articles. The most commonly studied topics in osteoarthritis rehabilitation included rehabilitation for pain, gait abnormalities, muscle strength deficiencies, and other functional impairments caused by osteoarthritis in elderly people. CONCLUSIONS: The top articles in the field of osteoarthritis rehabilitation have a high level of evidence. Collaboration between authors was high for highly-cited articles. Moreover, the eminent articles can provide important information for the education of doctors and therapists specializing in osteoarthritis rehabilitation.
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We report the case of a 71-year-old female presenting with deep vein thrombosis (DVT) of the left lower extremity secondary to a huge uterine myoma, who was successfully managed by hysterectomy and staged endovascular treatment. Her DVT was caused by left common iliac vein compression as a result of both the huge uterine myoma and preexisting May-Thuner syndrome. Although reported to put patients at high risk for DVT, coexisting large uterine myomas and May-Thurner syndrome are considered extremely rare.
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Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.
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Heparina/efeitos adversos , Neoplasias Pulmonares/cirurgia , Trombocitopenia/induzido quimicamente , Idoso , Feminino , Humanos , Contagem de Plaquetas , Procedimentos Cirúrgicos Pulmonares , Trombocitopenia/diagnóstico por imagem , UltrassonografiaRESUMO
A 61-year-old male who noticed muscular weakness of his extremities, diplopia and slur his words was found to have a thymic tumor on computed tomography. The immunological examination showed incremental of anti Acetylcholine receptor antibody titer and anti P/Q-type voltage-gated calcium channels antibody titer. Electromyography showed decremental response to low frequency stimulations, and incremental response to high frequency stimulations. So he was diagnosed with thymic tumor combined with myasthenia gravis and Lambert-Eaton myasthenic syndrome. He treated with extended thymomectomy resulting in the improvement of his neurological symptoms. Five years after operation, the patient is well without any malignant diseases.
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Síndrome Miastênica de Lambert-Eaton/complicações , Síndrome Miastênica de Lambert-Eaton/cirurgia , Miastenia Gravis/complicações , Miastenia Gravis/cirurgia , Timectomia , Timo/anormalidades , Humanos , Masculino , Pessoa de Meia-Idade , Timo/cirurgiaRESUMO
The patients was 63-year-old man. He had a chest abnormally shadow pointed out in examination of March, 2012 and referred to our hospital for a close inspection. The chest computed tomography(CT)revealed a mass shadow of 60 mm in left lung. Bronchoscopic examination was done and it was diagnosed as non-small-cell lung cancer by cytology. The clinical stage was cT2bN1M0 and video-assistedthoracic surgery (VATS) left pneumonectomy with mediastinal lymph node dissection was performed. A lot of neoplastic cells which contained melanin in cytoplasm were recognized by pathology and the diagnosis of malignant melanoma was comfirmed. Lymph node metastasis were recognized in #10, #11, #12 and the pathological stage of a disease was pT2bN1M0, pStage IIB. Further examination to find another lesion after surgery was in vain suggesting primary site to be left lung. A adjuvant chemotherapy has not been done. Surgical resection of primary pulmonary malignant melanoma is reported with reference to literatures.
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Neoplasias Pulmonares/patologia , Melanoma/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Mutation causes inactivation of 'p53' tumor suppressor protein in almost fifty percent of cancers in humans. Outside the DNA-binding surface of p53, Y220C is the most common cancerous mutation. Previous studies have shown that a surface cavity is created by this mutation which destabilizes p53. PhiKan083, a carbazole derivative capable of binding with that cavity, and slows down its thermal denaturation rate. We investigated, theoretically, on mechanisms of structural stability loss due to Y220C mutation and mechanisms of stability restoration by PhiKan083 at the atomic level. From this study it is found that in Tp53C, Tyr220 has five electrostatic interactions with residues Val 147, Prol51, Pro153 and Pro223 located on S3/S4 loop and S7/S8 loop. The S7/S8 loop is stabilized by these electrostatic interactions. Due to the Y220C mutation all these electrostatic interactions are lost. As a result the structural fluctuation occurs at S7/S8 loop, and the loop is displaced from its original position after 6 ns MD simulation. When PhiKan083 is present (inserted) at the mutation site it provides five electrostatic interactions with Pro155, Glu221 and Thr230, and two hydrogen bonds with Leu145 and Asp228, respectively. These interactions provided by Pkikan083 stabilized the S7/S8 loop, and as a result it couldn't be displaced. Our results showed that due to Y220C mutation p53 became destabilized through structural fluctuations surrounding the mutation site. When PhiKan083 is present at the Y220C mutation site (in 2vuk), it provides electrostatic and hydrogen bonding interactions among residue-220, its neighboring residues and PhiKan08. These interactions give additional stability to Y220C mutant p53, thus Y220C mutant p53 doesn't destabilize.
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Mutação de Sentido Incorreto , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/genética , Biologia Computacional , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Estabilidade Proteica , Eletricidade EstáticaRESUMO
Critical limb ischaemia (CLI) is known to be associated with high mortality. In some patients, surgery cannot be performed due to high risk of perioperative death and complications. In other cases, there is only pain at rest but no wound. Therefore, it is difficult to accurately predict the prognosis of individual patients. We examined the prognosis of CLI cases in which therapeutic footwear was made for ambulation after wounds healed. The subjects were 31 haemodialysis patients with diabetic foot wounds, which were treated with percutaneous transluminal angioplasty and minor amputation. The subjects were 22 men and 9 women. Female patients were significantly older than male patients (P = 0.046). Two-year postoperative outcomes were survival in 19 patients and death in 12 patients. Eight of twelve deceased patients had a history of coronary intervention. There were 8 deaths among 13 patients with such history, indicating a marginally significant increase in the mortality rate (P = 0.060). Re-amputation was performed in 6 of 19 patients who survived. Two years postoperatively, 41.9% of patients overall survived without re-amputation. It is important to increase the number of cases for further study to improve the well-being of CLI patients and to examine medical economics.
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Amputação Cirúrgica/métodos , Angioplastia , Pé Diabético/terapia , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Pé Diabético/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reoperação , Resultado do TratamentoRESUMO
PURPOSE: In this study, we evaluated the risk factors for postoperative complications in elderly patients with intractable pneumothorax and constructed a risk assessment model. MATERIALS AND METHODS: Between January 2004 and December 2011, 83 elderly patients( age, 75 years or older) underwent an operation at our hospital for intractable pneumothorax. Preoperative factors of these cases were assessed to clarify which is contributory to the development of postoperative complications by using univariate analysis and multivariate logistic regression analysis. RESULTS: Thirty-five patients (42.2%) developed postoperative complications. In univariate analysis, total protein, albumin level, blood urea nitrogen, creatinine level, Paco2, body mass index, performance status, and preoperative respiratory complications showed statistically significant associations with the occurrence of postoperative complications. In the multivariate analysis, the performance status showed a statistically significant association( 95% confidence interval, 1.17ã4.44;odds ratio, 2.28;p=0.0157). CONCLUSION: The results suggested that the preoperative examinations were useful in predicting postoperative complications in the elderly patients with intractable pneumothorax. Poor performance status, low nutrition, respiratory failure, and preoperative respiratory complications are risk factors for postoperative complications in elderly patients with intractable pneumothorax.