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We previously reported on two women with breast lesions in whom radiological examination could not exclude malignancy. In both cases, mastectomy was performed, and histological analyses revealed papillary lesions lined by fibrovascular stroma and nuclear inverse polarity. Hematoxylin-eosin, p63, and calponin staining indicated an absence of myoepithelial cells. However, it was concluded that the lesions had been non-malignant. These women have now been under long-term surveillance (74 months for one case and 62 months for the other) and have had no disease recurrence. Mucin (MUC)1, MUC2, MUC4, MUC5AC, MUC5B, and MUC6 immunostaining has also been performed in these women to investigate further whether their tumors were malignant or benign. In both cases, the tumors were only positive for MUC1 in apical luminal apical cells, as in normal breast tissue. MUC5B immunostaining, even when weak, can detect early breast cancer but was completely negative in our two cases. Therefore, both tumors were considered benign. Our findings in these cases suggest that nuclear inverse polarity papillary lesions lacking myoepithelial cells are benign. This knowledge should decrease the number of unnecessary operations performed for this tumor and their negative impact on patients' quality of life.
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Neoplasias da Mama , Mucinas , Humanos , Feminino , Neoplasias da Mama/patologia , Qualidade de Vida , Mastectomia , Biomarcadores Tumorais/análise , Recidiva Local de Neoplasia , Mucina-1RESUMO
Recent experimental studies have examined the efficacy of statins in preventing cancer, but the findings of clinical studies are inconsistent, and studies on Japanese patients are limited. This study aimed to clarify the association between statins and cancer risk among Japanese patients. We conducted a large population-based retrospective cohort study using the Japanese health insurance claims database, including patients newly diagnosed with dyslipidemia between 2005 and 2015. Patients who were on newly prescribed statins during the study period were designated as statin users. They were matched 1:1 with randomly selected drug nonusers who were not prescribed drugs for dyslipidemia according to age, sex, and year of first diagnosis of dyslipidemia. There were 23,746 patients in each group. The mean duration of follow-up for statin users and drug nonusers was approximately 2 years. Using a Cox proportional hazards model, significant reduction in cancer risk was observed in statin users compared with that in drug nonusers [adjusted HR = 0.84; 95% confidence interval (CI), 0.72-0.97; adjusted for patient background factors]. The results of subgroup analyses suggested that prescribed statins reduced the incidence of cancer of the digestive organs (adjusted HR = 0.79; 95% CI, 0.63-0.99) as well as reduced cancer risk in patients with nonsmokers (adjusted HR = 0.78, 95% CI = 0.65-0.92). Our results suggest that statin use may reduce cancer risk in patients with dyslipidemia. PREVENTION RELEVANCE: This study clarified the relationship between statin use and cancer risk in patients with dyslipidemia. Our study will contribute to medicine selection in patients with hypercholesterolemia level. See related Spotlight, p. 1.
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Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Incidência , Estudos Retrospectivos , Neoplasias/epidemiologia , Neoplasias/etiologia , Neoplasias/prevenção & controle , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Seguro SaúdeRESUMO
IMPORTANCE: To enable community-dwelling older adults to continue to live satisfying lives, a feasible health promotion program is needed that consists of relatively few sessions and can be implemented over a brief period. OBJECTIVE: To verify the relationship between a short-duration group program using an occupational diary and changes in satisfaction with occupation, a sense that life is worth living, and life satisfaction among community-dwelling older adults 3 mo after program cessation and to identify factors associated with changes in satisfaction with occupation after the program. DESIGN: Before-and-after comparison study and case-control study. SETTING: Public university in Japan. PARTICIPANTS: Community-dwelling older adults (N = 144). INTERVENTION: Four weekly group sessions and daily occupational diary keeping. OUTCOMES AND MEASURES: Activity and Daily Life Satisfaction Scale for the Elderly, K-I Scale for the Feeling that Life is Worth Living among the Aged, and Life Satisfaction Index-Z. RESULTS: Scores 3 mo postprogram were significantly higher than the pretest scores. Continued use of the diary was selected as a factor associated with changes in participants' satisfaction with occupation after the program. CONCLUSIONS AND RELEVANCE: The program may improve satisfaction with occupation, a sense that life is worth living, and life satisfaction among community-dwelling older adults 3 mo after conclusion. Continued use of the diary may increase the possibility of maintaining or improving older adults' satisfaction with occupation beyond the duration of the program. What This Article Adds: The program consists of a small number of sessions and can be implemented in a short period. Occupational therapists can include it as an option for promoting the health of community-dwelling older adults.
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Promoção da Saúde , Vida Independente , Idoso , Estudos de Casos e Controles , Humanos , Japão , Satisfação Pessoal , Qualidade de VidaRESUMO
Background: Treatments for acute cholecystitis include cholecystectomy and percutaneous drainage. However, some patients are at high risk for surgery, and prolonged drainage can decrease their quality of life. Purpose: To determine the feasibility of percutaneous transhepatic gallbladder filling (PTGBF) with n-butyl-cyanoacrylate (NBCA) in a swine model. Material and methods: After the induction of general anesthesia, percutaneous transhepatic gallbladder puncture to a pig weighing 49 kg using a 20-G-percutaneous transhepatic cholangio drain (PTCD) needle was performed under ultrasound guidance. A 2.1 F-microcatheter was inserted through the outer PTCD needle, then the cystic duct was coil-embolized. The microcatheter was removed, the gallbladder was filled with 25% NBCA-Lipiodol, then the PTCD needle was withdrawn without complications. Blood was sampled and CT images were acquired from the pig immediately after the procedure and on postoperative day 7. The pig was euthanized on postoperative day 7 and the gallbladder was evaluated by microscopy. Results: Vital signs were stable, and the CT images showed that the gallbladder contained NBCA-Lipiodol without complications such as leakage. Hepatobiliary enzymes were not elevated. Histological findings demonstrated loss of most mucosa with partial regeneration, and lymphocytic infiltration. The muscle layer was intact. Conclusion: This technique might offer a feasible alternative to surgery for high-risk patients with acute cholecystitis, but further studies are needed to determine the safety and long-term effects of this procedure.
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Colecistite Aguda , Embucrilato , Animais , Colecistite Aguda/cirurgia , Drenagem/métodos , Óleo Etiodado , Estudos de Viabilidade , Vesícula Biliar/cirurgia , Qualidade de Vida , Suínos , Resultado do TratamentoRESUMO
Pilomatrical carcinosarcomas are very rare tumors. To the best of our knowledge, only nine cases diagnosed with pilomatrical carcinosarcomas have been reported. The present study reported on a case of pilomatrical carcinosarcoma in the posterior part of the left auricle of a 100-year-old male patient. The tumor histologically comprised the following two components: Pilomatrical carcinoma and undifferentiated spindle cell sarcoma. The pilomatrical carcinoma comprised atypical basaloid cells and shadow cells. The basaloid cells had basophilic cytoplasm, clear nucleoli and deeply stained nuclear chromatin. The undifferentiated spindle cell sarcoma comprised atypical spindle cells. Both components contained numerous mitotic cells. The boundary area between the carcinoma and sarcoma smoothly transitioned into each other. The carcinoma cells and a portion of the sarcoma cells were positive for ß-catenin in the cytoplasm with or without the nuclei. These results suggested that the two components developed from the same origin.
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No therapeutic targets have been identified for lung squamous cell cancer (SqCC) which is the second most prevalent lung cancer because its molecular profiles remain unclear. This study aimed to unveil disease-related protein networks by proteomic and bioinformatic assessment of laser-microdissected cancerous cells from seven SqCCs compared with eight representative lung adenocarcinomas. We identified three network modules significant to lung SqCC using weighted gene co-expression network analysis. One module was intrinsically annotated to keratinization and cell proliferation of SqCC, accompanied by hypoxia-induced aerobic glycolysis, in which key regulators were activated (HIF1A, ROCK2, EFNA1-5) and highly suppressed (KMT2D). The other two modules were significant for translational initiation, nonsense-mediated mRNA decay, inhibited cell death, and interestingly, eIF2 signaling, in which key regulators, MYC and MLXIPL, were highly activated. Another key regulator LARP1, the master regulator in cap-dependent translation, was highly suppressed although upregulations were observed for hub proteins including EIF3F and LARP1 targeted ribosomal proteins, among which PS25 is the key ribosomal protein in IRES-dependent translation. Our results suggest an underlying progression mechanism largely caused by switching to the cap-independent, IRES-dependent translation of mRNA subsets encoding oncogenic proteins. Our findings may help to develop therapeutic strategies to improve patient outcomes.
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Adenocarcinoma de Pulmão/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteômica/métodos , Idoso , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Microdissecção e Captura a Laser , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Mapas de Interação de ProteínasRESUMO
Longitudinal investigations using ultrasound during pregnancy can be used to clarify the mechanisms and pathophysiology of abnormal fetal and placental development. In this report, we presented a case of a true knot that appeared to develop into a hypercoiled cord and circumvallate placenta, which we found through longitudinal ultrasound investigations during pregnancy. In the present case, ultrasonography proved that the true knot had existed at least 16 weeks of gestation. The true knot was presumed to develop into a hypercoiled cord based on the hypothesis of differential umbilical vascular growth rates.
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Doenças Placentárias , Cordão Umbilical , Feminino , Humanos , Placenta/diagnóstico por imagem , Doenças Placentárias/diagnóstico por imagem , Gravidez , Ultrassonografia , Ultrassonografia Pré-Natal , Cordão Umbilical/diagnóstico por imagemRESUMO
The tumourigenesis of early lung adenocarcinomas, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA), remains unclear. This study aimed to capture disease-related molecular networks characterising each subtype and tumorigenesis by assessing 14 lung adenocarcinomas (AIS, five; MIA, five; LPA, four). Protein-protein interaction networks significant to the three subtypes were elucidated by weighted gene co-expression network analysis and pairwise G-statistics based analysis. Pathway enrichment analysis for AIS involved extracellular matrix proteoglycans and neutrophil degranulation pathway relating to tumour growth and angiogenesis. Whereas no direct networks were found for MIA, proteins significant to MIA were involved in oncogenic transformation, epithelial-mesenchymal transition, and detoxification in the lung. LPA was associated with pathways of HSF1-mediated heat shock response regulation, DNA damage repair, cell cycle regulation, and mitosis. Genomic alteration analysis suggested that LPA had both somatic mutations with loss of function and copy number gains more frequent than MIA. Oncogenic drivers were detected in both MIA and LPA, and also LPA had a higher degree of copy number loss than MIA. Our findings may help identifying potential therapeutic targets and developing therapeutic strategies to improve patient outcomes.
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Adenocarcinoma in Situ/metabolismo , Adenocarcinoma de Pulmão/metabolismo , Redes Reguladoras de Genes , Neoplasias Pulmonares/metabolismo , Mapas de Interação de Proteínas , Proteogenômica/métodos , Adenocarcinoma in Situ/genética , Adenocarcinoma de Pulmão/genética , Transição Epitelial-Mesenquimal , Feminino , Dosagem de Genes , Humanos , Mutação com Perda de Função , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Invasividade NeoplásicaRESUMO
It is unclear how epidermal growth factor receptor EGFR major driver mutations (L858R or Ex19del) affect downstream molecular networks and pathways. This study aimed to provide information on the influences of these mutations. The study assessed 36 protein expression profiles of lung adenocarcinoma (Ex19del, nine; L858R, nine; no Ex19del/L858R, 18). Weighted gene co-expression network analysis together with analysis of variance-based screening identified 13 co-expressed modules and their eigen proteins. Pathway enrichment analysis for the Ex19del mutation demonstrated involvement of SUMOylation, epithelial and mesenchymal transition, ERK/mitogen-activated protein kinase signalling via phosphorylation and Hippo signalling. Additionally, analysis for the L858R mutation identified various pathways related to cancer cell survival and death. With regard to the Ex19del mutation, ROCK, RPS6KA1, ARF1, IL2RA and several ErbB pathways were upregulated, whereas AURK and GSKIP were downregulated. With regard to the L858R mutation, RB1, TSC22D3 and DOCK1 were downregulated, whereas various networks, including VEGFA, were moderately upregulated. In all mutation types, CD80/CD86 (B7), MHC, CIITA and IFGN were activated, whereas CD37 and SAFB were inhibited. Costimulatory immune-checkpoint pathways by B7/CD28 were mainly activated, whereas those by PD-1/PD-L1 were inhibited. Our findings may help identify potential therapeutic targets and develop therapeutic strategies to improve patient outcomes.
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Adenocarcinoma de Pulmão/genética , Regulação Neoplásica da Expressão Gênica , Genes erbB-1 , Neoplasias Pulmonares/genética , Mutação de Sentido Incorreto , Proteínas de Neoplasias/genética , Mutação Puntual , Adenocarcinoma de Pulmão/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Conjuntos de Dados como Assunto , Receptores ErbB/genética , Feminino , Redes Reguladoras de Genes , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteoma , Deleção de Sequência , TranscriptomaRESUMO
We report a rare case of a solitary synovial osteochondroma (SSO) in the cervical canal. A 37-year-old man presented with neck pain and the forearm dysesthesia developed immediately after a trivial motor accident. Because of aggravation he visited our hospital though he was treated conservatively for 3 months. A computed tomography (CT) scan showed an oval shaped small mass with high density rim in the cervical canal at the level of the C6/7 facet joint. This mass compressing the dural sac was visualized with a high intensity signal in T2-weighted magnetic resonance imaging (MRI) and, interestingly, with high intensity in T1-weighted images. A surgical removal was carried out. Macroscopically, it consists of a solitary, firm, juxta-articular mass associated with synobia but lacking connection with the adjacent bone. Microscopically, it is similar to conventional osteochondromas. It differs from this entity by not arising from a bone surface and by a whole coverage of synobial tissue. The final diagnosis was a SSO. There have been anecdotal case reports of a SSO in various site including knee, fingers, buttocks, wrist, and so on. To the best of our knowledge, this is the first case report of SSO arising in the spinal canal.
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Removability is one of the important features of biliary covered self-expandable metal stents (CSEMS). In this study, we evaluated the diagnostic ability of washing cytology of removed CSEMS. For 14 removed CSEMS that had been placed for the biliary strictures (12 malignant, 2 benign), the surface of CSEMS was washed with saline, and pathological examination of the washing liquid as cytology (CSEMS washing cytology) was performed. The specimen sampling rates and sensitivity for malignancy of CSEMS washing cytology were 92.9â% and 41.7â%, respectively. Sensitivity according to the primary disease was 60.0â% for bile duct cancer and 20â% for pancreatic cancer. Sensitivities based on the methods of stent removal were 16.7â% and 66.7â% for removal through the channel of the scope and with the scope, respectively. Therefore, it is possible that sensitivity of CSEMS washing cytology is higher in bile duct cancer and for removal with the scope. In conclusion, CSEMS washing cytology may have potential as a pathological diagnostic method.
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We report on a case of recurrent primary hyperparathyroidism possibly caused by parathyroid adenocarcinoma metastasizing to the lung. A 46-year-old woman with a history of parathyroid adenoma, which was extirpated 8 years ago, presented with symptoms of primary hyperparathyroidism, and was found to have a parathyroid and a lung nodule in radiographic assessments. Resections of the tumors in the parathyroid gland as well as the lung were required to improve her condition, and in pathology, both tumors demonstrated benign features consistent with adenoma. However, from the perspective of the clinical course and location of the tumors, we deduced that the tumors were malignant despite being identified as benign by conventional pathological examination. The integration of information based on clinical status and imaging studies is essential to evaluate the malignant potential of tumors if a patient with hyperparathyroidism has tumors located both inside and outside of the parathyroid gland.
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Pulmonary hyalinizing granuloma is a very rare benign condition. This study describes a case involving pulmonary hyalinizing granuloma in a 76-year-old man who presented with a solitary pulmonary nodule, determined through chest radiography and computed tomography, that mimicked primary lung cancer. To establish a definitive diagnosis, tumor resection was performed with histopathological analysis indicating pulmonary hyalinizing granuloma. Radiographic findings in previously reported cases showed that most patients had well-defined margins and usually bilateral, multiple lesions. In our case; however, the solitary ill-defined tumor mimicking lung cancer is an uncommon location for this rare condition.
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BACKGROUND: Primary epithelial ovarian cancer is divided into several subtypes. The relationships between apparent diffusion coefficient (ADC) values and their subtypes have not yet been established. PURPOSE: To investigate whether ADC values of epithelial ovarian cancer vary according to histologic tumor cellularity and evaluate the difference of clear cell carcinoma (CCC), high-grade serous carcinoma (HGSC), and endometrioid carcinoma (EC). MATERIAL AND METHODS: This retrospective study included 51 cases of epithelial ovarian cancer (17 CCC, 20 HGSC, and 14 EC) identified by magnetic resonance imaging with pathological confirmation. All patients underwent diffusion-weighted imaging and the ADC values of lesions were measured. We counted the tumor cells in three high-power fields and calculated the average for each case. The Spearman's correlation coefficient test was used to analyze correlation between ADC values and tumor cellularity. The ADC values of HGSC, EC, and CCC were compared using the Steel-Dwass test. RESULTS: The ADC values of all cases were significantly inversely correlated with tumor cellularity (rs = -0.761; P < 0.001). The mean ± SD ADC values (×10-3 mm2/s) of CCC, HGSC, and EC were 1.24 ± 0.17 (range 0.98--1.65), 0.84 ± 0.10 (range 0.67--1.06), and 0.84 ± 0.10 (range 0.67--1.07). The mean ± SD tumor cellularity of CCC, HGSC, and EC was 162.88 ± 63.28 (range 90.33--305.67), 440.60 ± 119.86 (range 204.67--655.67), and 461.02 ± 81.86 (range 333.33--602.33). CONCLUSION: There is a significant inverse correlation between ADC values and tumor cellularity in epithelial ovarian cancer. The mean ADC value of CCC was higher than those of HGSC and EC, seemingly due to the low cellularity of CCC.
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Adenocarcinoma de Células Claras/diagnóstico por imagem , Carcinoma Endometrioide/diagnóstico por imagem , Cistadenocarcinoma Seroso/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/patologia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Programmed cell death-1 (PD-1) immune checkpoint inhibitor antibody has proven to be effective in advanced non-small cell lung cancer (NSCLC) patients positive for programmed cell death-1 ligand-1 (PD-L1). However, there are currently no prospective studies evaluating PD-L1 expression for small biopsy samples. METHODS: To prospectively investigate the reliability of small samples for NSCLC, we included patients who underwent diagnostic biopsy by flexible bronchoscopy, computed tomography (CT) and ultra-sonography (US) guided core-needle to determine the PD-L1 expression status. In pathologically confirmed NSCLC, PD-L1 expression was evaluated using companion diagnostic PD-L1 immunohistochemistry. We evaluated: 1) tumor cell count and sample size, 2) tumor proportion score (TPS): <1, 1-49%, 50%â¦, and 3) the concordance rate of TPS by biopsy and surgical samples. RESULTS: Of the 153 cases of PD-L1 expression, 110 were assessed using endobronchial ultrasonography guided transbronchial biopsy (EBUS-TBB) (thin bronchoscopy 84 cases; normal bronchoscopy 26 cases), 23 were endobronchial ultrasonography guided transbronchial needle aspiration (EBUS-TBNA), and 20 cases of CT or US-guided core-needle biopsy. Tumor cell count and sample size were significantly larger for normal bronchoscopy than thin bronchoscopy or EBUS-TBNA samples. Moreover, tumor cell counts for each subsequent biopsy decreased. In all cases, TPS distribution (undiagnosed, <1%, 1-49, 50%â¦) was 2.6, 34.6, 31.4, 31.4%, respectively. TPS positive cases using thin bronchoscope was 55.9%, normal bronchoscope was 73.1% and EBUS-TBNA was 78.3%. In early stage adenocarcinoma, TPS was lower compared with advanced stages. Conversely, in squamous cell carcinoma, the rates of TPS were similar regardless of stage. The concordance rate of TPS by biopsy and surgical materials was 86.7%. CONCLUSION: Utilizing smaller samples for evaluation, the frequency of TPS was comparable to past clinical trials using larger samples. The differences in TPS were influenced by diagnostic tools, cancer histologic types and staging. The concordance of TPS between EBUS-TBB samples and surgical materials was high. TRIAL REGISTRATION: This study was performed at the Department of Respiratory Medicine at St. Marianna University School of Medicine Hospital, with ethics approval (#3590) and registered as a clinical trial ( UMIN000027030 ).
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Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Broncoscopia/métodos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Biópsia Guiada por Imagem , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Tomografia Computadorizada por Raios X , UltrassonografiaRESUMO
Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis. Weighted gene co-expression network analysis (WGCNA) identified co-expressed modules and hub genes. Of 34 identified modules, six were significant and selected for protein-protein interaction (PPI) network analysis and pathway enrichment. Within the six modules, the activation of cellular processes and complexes, such as alternative mRNA splicing, translation initiation, nucleosome remodeling and deacetylase (NuRD) complex, SWItch/Sucrose Non-Fermentable (SWI/SNF) superfamily-type complex, chromatin remodeling pathway, and mRNA metabolic processes, were significant to SCLC. Modules enriched in processes, including signal recognition particle (SRP)-dependent co-translational protein targeting to membrane, nuclear-transcribed mRNA catabolic process of nonsense-mediated decay (NMD), and cellular macromolecule catabolic process, were characteristically activated in LCNEC. Novel high-degree hub genes were identified for each module. Master and upstream regulators were predicted via causal network analysis. This study provides an understanding of the molecular differences in tumorigenesis and malignancy between SCLC and LCNEC and may help identify potential therapeutic targets.
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Carcinoma de Células Grandes/genética , Carcinoma Neuroendócrino/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Pulmonares/genética , Proteômica , Carcinoma de Pequenas Células do Pulmão/genética , Idoso , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mapeamento de Interação de Proteínas , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
BACKGROUND/AIM: Angiosarcoma is a rare and aggressive soft tissue sarcoma with poor prognosis. Chemotherapy and radiotherapy do not improve the prognosis. SIRT1, a class III histone deacetylase, is up-regulated in many malignant tumours. This study aimed at exploring the role of SIRTl in angiosarcoma. MATERIALS AND METHODS: The effect of suppressing SIRT1 expression with siRNA on the proliferation and invasion ability of ISO-HAS-B angiosarcoma cells was investigated. Additionally, SIRT1 expression in tissues from surgical specimens was immunohistochemically evaluated and compared to that from benign tumours. RESULTS: Suppression of SIRT1 expression by siRNA resulted in the down-regulation of cell growth, proliferation, migration, and invasion. An immunohistochemical analysis disclosed that SIRT1 expression in angiosarcoma was stronger than that in haemangioma. CONCLUSION: SIRT1 may be involved in the invasive proliferation and malignant transformation of angiosarcoma, and may be considered a future target for angiosarcoma therapy.
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Hemangiossarcoma/metabolismo , Sirtuína 1/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Hemangiossarcoma/patologia , Humanos , RNA Interferente Pequeno/administração & dosagem , Sirtuína 1/genética , CicatrizaçãoRESUMO
PURPOSE: Knowledge regarding programmed death-ligand 1 (PD-L1) expression in lung cancer is limited. We aim to clarify PD-L1-positive expression in non-small-cell lung cancer (NSCLC), including adenocarcinoma subtypes. METHODS: In all, 90 NSCLC specimens containing various adenocarcinoma subtypes, in addition to squamous cell carcinoma and large-cell carcinoma were selected. PD-L1 was immunohistochemically stained by murine monoclonal antibody clone 22C3. RESULTS: When PD-L1-positive expression was defined by tumor proportion score (TPS) ≥1%, the positive cases were 0/11 in adenocarcinoma in situ, 0/12 in minimally invasive adenocarcinoma, 1/10 in lepidic predominant adenocarcinoma, 1/13 in papillary predominant adenocarcinoma, 8/14 in acinar predominant adenocarcinoma, 6/11 in solid predominant adenocarcinoma, 0/3 in micropapillary predominant adenocarcinoma, 0/4 in invasive mucinous adenocarcinoma, 4/9 in squamous cell carcinoma, and 2/3 in large-cell carcinoma. PD-L1 positivity was higher in males, smokers, advanced pathologic stages, positive vessel invasion, and positive lymphatic invasion. Postoperative survival analysis revealed that PD-L1-positive expression was a significantly worse prognostic factor in univariate analysis for recurrence-free survival (RFS). CONCLUSION: PD-L1-positive tumors were frequent in acinar predominant adenocarcinoma and solid predominant adenocarcinoma than other adenocarcinoma subtypes. PD-L1 expression seemed to increase according to pathologic tumor progression, suggesting a worse postoperative prognosis in NSCLC patients.
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Adenocarcinoma de Pulmão/química , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/química , Neoplasias Pulmonares/química , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Pneumonectomia , Intervalo Livre de Progressão , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The so-called "double-hit" and "double-protein-expression" lymphoma with MYC and BCL2 rearrangements is a rare, mature B-cell neoplasm characterized by a germinal center B-cell phenotype, abundant protein expression of MYC and BCL2, rapid disease progression, and a poor prognosis. In this study, we showed the potential benefit of the BCL2 inhibitor venetoclax in the treatment of this disease. Immunohistochemical studies of the lymphoma tissues confirmed that overexpression of MYC and BCL2 was observed more frequently in this subtype than in other germinal center B-cell-like diffuse large B-cell lymphomas. In contrast, another pro-survival protein MCL1 was less expressed in this subtype, even when compared with its expression in the non-"double-hit" and "double-protein-expression" type. Furthermore, in vitro studies using two "double-hit" and "double-protein-expression" lymphoma-derived cell lines, Karpas231 and OCI-Ly8, clearly showed that a low concentration of venetoclax, but not the MCL1 inhibitor S63845, was sufficient to induce apoptosis in the two lines, compared with in other germinal center B-cell-derived cell lines, BJAB and SU-DHL10. These results indicate that the survival of this type of lymphoma depends predominantly on BCL2 rather than on MCL1. Unexpectedly, we found that venetoclax not only disrupts the interaction between BCL2 and the pro-apoptotic protein BIM, but also leads to dephosphorylation of BCL2 and further downregulates MCL1 protein expression, probably through modulation of the protein phosphatase 2A B56α activity in Karpas231 and OCI-Ly8. Indeed, a low concentration of venetoclax induced substantial apoptosis in the primary lymphoma cells, regardless of high protein expression of MCL1 associated with venetoclax resistance. Venetoclax clearly triggers the signal transduction related to BCL2 and MCL1 in "double-hit" and "double-protein-expression" lymphoma cells.