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2.
Med. oral patol. oral cir. bucal (Internet) ; 29(2): e280-e287, Mar. 2024. mapas, tab
Artigo em Inglês | IBECS | ID: ibc-231232

RESUMO

Background: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs.Material and Methods: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. Results: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cysticcarcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. Conclusions: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST. (AU)


Assuntos
Humanos , Preparações Farmacêuticas , Carcinoma Adenoide Cístico , Sunitinibe , Androgênios , Neoplasias , Leuprolida , Carcinoma
3.
Biomark Med ; 18(5): 169-179, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38440866

RESUMO

Objective: This study aimed to assess the value of PLK4 as a biomarker in papillary thyroid carcinoma (PTC). Methods: This study reviewed 230 PTC patients receiving surgical resections. PLK4 was detected in tumor tissues and samples of normal thyroid gland tissues by immunohistochemistry. Results: PLK4 was elevated in tumor tissues versus normal thyroid gland tissues (p < 0.001). Tumor PLK4 was linked with extrathyroidal invasion (p = 0.036), higher pathological tumor stage (p = 0.030), node stage (p = 0.045) and tumor/node/metastasis stage (p = 0.022) in PTC patients. Tumor PLK4 immunohistochemistry score >3 was linked with shortened disease-free survival (p = 0.026) and overall survival (p = 0.028) and independently predicted poorer disease-free survival (hazard ratio: 2.797; p = 0.040). Conclusion: Tumor PLK4 reflects extrathyroidal invasion, higher tumor stage and shortened survival in PTC.


Assuntos
Carcinoma Papilar , Carcinoma , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Carcinoma/patologia , Carcinoma/cirurgia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Prognóstico , Proteínas Serina-Treonina Quinases/genética
4.
Acta Orthop Traumatol Turc ; 58(1): 62-67, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38525512

RESUMO

OBJECTIVE: This study aimed to investigate the factors affecting the survival of patients with bone carcinoma metastases and assess the clinical applicability of existing prognostic models. METHODS: We retrospectively evaluated 247 patients who presented to our hospital between 2011 and 2021 diagnosed with bone carcinoma metastasis. Demographic data, general health status, primary diagnoses, laboratory and radiological findings, pathological fracture status, treatment methods, and survival times of the patients were recorded, and the effects of these variables on survival time were evaluated. Previously developed Katagiri, Janssen, 2013-Spring, PathFX, and SORG prognostic models were applied, and the predictive performances of these models were evaluated by comparing the predicted survival time with the actual survival time of our patients. RESULTS: After the multivariate analysis, the following factors were shown to be significantly associated with the survival time of patients: blood hemoglobin and leukocyte levels, lactate dehydrogenase concentration, prognostic nutritional index, body mass index, performance status, medium and fast-growing groups of primary tumors, presence of extraspinal and visceral or brain metastases, and pathological fractures. According to receiver operating characteristics and Brier scores, SORG had the overall highest performance scores, while the Janssen nomogram had the lowest. CONCLUSION: Our report showed that all prognostic models were clinically applicable, but their performances varied. Among them, the SORG predictive model had the best performance scores overall and is the model the authors suggested for survival prediction among patients with carcinoma bone metastases. LEVEL OF EVIDENCE: Level IV, Prognostic Study.


Assuntos
Neoplasias Ósseas , Carcinoma , Fraturas Espontâneas , Humanos , Prognóstico , Estudos Retrospectivos , Neoplasias Ósseas/secundário
5.
J Pathol Clin Res ; 10(2): e12365, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38436543

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial-mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT-related genes and transcription factors are associated with poor prognosis in ccRCC. EMT-related factors suppress E-cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), ß-catenin, and E-cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan-Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm-c levels compared to those with low MIFn and MIFm-c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p < 0.0001). In conclusion, this study provides further evidence for the biological and prognostic value of MIF in the context of EMT as a potential early prognostic marker for advanced-stage ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Fatores Inibidores da Migração de Macrófagos , Humanos , Caderinas , Carcinoma de Células Renais/genética , Epigênese Genética , Oxirredutases Intramoleculares/genética , Neoplasias Renais/genética , Fatores Inibidores da Migração de Macrófagos/genética , Prognóstico
6.
J Pediatr Hematol Oncol ; 46(3): 117-124, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38447121

RESUMO

Nasopharyngeal carcinoma (NPC) is a rare and locally aggressive form of childhood cancer. Treatment of pediatric NPC includes chemotherapy and radiotherapy. Most studies on the treatment of pediatric NPC are single-arm studies. With current treatment protocols survival rates for patients with nonmetastatic disease exceed 80%, although most children will have long-term treatment-related late effects. Efforts to reduce early and late toxicities include reduced radiotherapy doses in children with good responses to induction chemotherapy. Further studies are needed to evaluate the role of immunotherapy in both the primary setting and in children with progressive or relapsed disease. This review summarizes current clinical approaches to the treatment of pediatric NPC.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Criança , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma/tratamento farmacológico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia
7.
Sci Rep ; 14(1): 5569, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448646

RESUMO

This is a comprehensive retrospective study to characterize female dogs with canine mammary tumors (CMTs) using a dataset retrieved from the archives of the Division of Animal Pathology, Institute of Veterinary Medicine in Warsaw, and to identify prognostic factors. Clinical and histopathological data of 1447 dogs with CMTs were included. Malignant tumours were found in 83.3% (n = 1206), benign tumours in 11.7% (n = 169), and non-neoplastic lesions in 5.0% (n = 72) of dogs. Dogs most often had grade II carcinomas (38.2%, 215/562) of a single histological subtype (88.5%, 1281/1447), mostly simple carcinoma (35.3%, 510/1447). Dogs with a median age of 10 years significantly often had larger (≥ 3 cm) and malignant CMTs, whereas intact females had smaller tumours (median size 2.0 cm). However, the threshold value for the age of the dog in the differentiation of malignant and non-neoplastic/benign masses could not be determined. Most females were hormonally active (76.4%, 372/487). Hormonally active dogs significantly more often had multiple tumours. Multiple tumours were significantly smaller (median 2.5 cm) than single ones. Among pedigree dogs, small-breed dogs were mostly recorded (43%, 428/1006). Twelve breeds had an increased risk of CMTs, regardless of tumour behaviour, compared with the theoretical distribution of pedigree dogs in Poland. Four breeds were often affected only by malignant and other four breeds only by non-neoplastic/benign CMT. Large-breed dogs were significantly younger and affected by larger CMT (median 4 cm) compared with small- and medium-breed dogs. Ninety dogs with a malignant CMT and complete records were included in the full analysis of CMT-specific survival (CMT-SS) with a median follow-up time of 20.0 months. We showed that the timing of ovariohysterectomy in relation to mastectomy was significantly associated with grade, CMT-SS, and CMT-related death. We indicated the low diagnostic accuracy of palpation of regional lymph nodes (RLN) in the prediction of their metastatic involvement. By multivariable analysis, dogs with neoplastic emboli, tumour ulceration, and simple or complex carcinoma had a significantly higher risk of local recurrence. Tumour size > 3 cm was as a strong independent predictor of lung metastases. Compared with dogs with an easily separated localized tumour, dogs with a multiple/diffuse malignant CMT pattern had a fivefold higher risk of death. The risk of death was significantly higher in the presence of neoplastic emboli (~ fivefold) and tumour ulceration (~ fourfold). Furthermore, the presence of neoplastic emboli and large tumour size were independent predictors of CMT-related death.


Assuntos
Carcinoma , Neoplasias Mamárias Animais , Feminino , Cães , Animais , Estudos Retrospectivos , Polônia/epidemiologia , Mastectomia , Análise Fatorial
8.
Biol Direct ; 19(1): 20, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454507

RESUMO

CircLRIG1, a newly discovered circRNA, has yet to have its potential function and biological processes reported. This study explored the role of circLRIG1 in the development and progression of bladder carcinoma and its potential molecular mechanisms. Techniques such as qRT-PCR, Western blot, various cellular assays, and in vivo models were used to investigate mRNA and protein levels, cell behavior, molecular interactions, and tumor growth. The results showed that both circLRIG1 and LRIG1 were significantly reduced in bladder carcinoma tissues and cell lines. Low circLRIG1 expression was associated with poor patient prognosis. Overexpressing circLRIG1 inhibited bladder carcinoma cell growth, migration, and invasion, promoted apoptosis, and decreased tumor growth and metastasis in vivo. Importantly, circLRIG1 was found to sponge miR-214-3p, enhancing LRIG1 expression, and its overexpression also modulated protein levels of E-cadherin, N-cadherin, Vimentin, and LRIG1. Similar effects were observed with LRIG1 overexpression. Notably, a positive correlation was found between circLRIG1 and LRIG1 expression in bladder carcinoma tissues. Additionally, the tumor-suppressing effect of circLRIG1 was reversed by overexpressing miR-214-3p or silencing LRIG1. The study concludes that circLRIG1 suppresses bladder carcinoma progression by enhancing LRIG1 expression via sponging miR-214-3p, providing a potential strategy for early diagnosis and treatment of bladder carcinoma.


Assuntos
Carcinoma , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Carcinoma/genética , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Glicoproteínas de Membrana/metabolismo
9.
Cancer Med ; 13(4): e6578, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38457191

RESUMO

PURPOSE: Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. MATERIALS AND METHODS: From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. RESULTS: Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. CONCLUSION: The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma/tratamento farmacológico , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , Quimiorradioterapia/efeitos adversos , Náusea/tratamento farmacológico , Vômito/tratamento farmacológico , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento
10.
Cancer Med ; 13(4): e7055, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38457255

RESUMO

BACKGROUND: CD2-associated protein (CD2AP) is a podocyte-associated gene and its reduced expression is associated with the development of proteinuria and glomerulosclerosis. However, few studies have focused on the correlation between the expression and prognosis of CD2AP in renal clear cell carcinoma (ccRCC). Therefore, we aimed to assess the regulation of CD2AP expression and prognostic value in ccRCC. METHODS: Multiple databases were employed to examine the expression of CD2AP in ccRCC. RT-qPCR, Western Blot and immunohistochemistry were used to validate CD2AP expression in different cell lines and tissue samples. Kaplan-Meier analysis and ROC curve analysis were performed on the predictive prognostic performance of CD2AP. COX regression was used to construct CD2AP-related prognostic models. The TIMER and TISIDB databases were used to analyze the correlation of tumor-infiltrating immune cells with gene expression, mutations, somatic copy number variation, and immune molecules. Mass spectrometry was used to detect methylation status of the promoter CpG site of CD2AP in multiple cells. RESULTS: We found that CD2AP expression was downregulated in ccRCC and its lower expression level was correlation with worse patient prognosis, higher tumor stage and grade and distant metastasis through analysis of databases, ccRCC cell lines and clinical tissue samples. Moreover, database and mass spectrometry techniques identified and validated cg12968598 hypermethylation as one of the key reasons for the downregulation of CD2AP expression. CD2AP expression was also associated with macrophage and neutrophil infiltration. CONCLUSIONS: Taken together, our results suggest that CD2AP can be used as a diagnostic and prognostic biomarker in ccRCC patients and that DNA hypermethylation plays an important role in reducing CD2AP expression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Carcinoma de Células Renais , Carcinoma , Proteínas do Citoesqueleto , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Variações do Número de Cópias de DNA , Prognóstico , Neoplasias Renais/genética , Biomarcadores
12.
Zentralbl Chir ; 149(1): 46-55, 2024 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-38442883

RESUMO

Today, endoscopy plays a decisive role not only in the detection of colorectal adenomas and carcinomas, but also in the treatment of precancerous lesions, in particular flat adenomas and early carcinomas. In recent years, endoscopic submucosal dissection (ESD) has become increasingly important alongside classic polypectomy and mucosal resection after saline injection using a snare (EMR). Using ESD the lesion is marked, injected submucosally using viscous substances and the mucosa incised and tunneled with a transparent cap and a fine diathermy knife. Particularly in the case of widespread and high-risk lesions ESD enables a quasi-surgical "en bloc" resection almost regardless of size, with a histological R0 resection rate of far over 90% in specialized centers. ESD enables an excellent histopathological evaluation and has a low recurrence risk of 1-3%. Endoscopic full-thickness resection using a dedicated device (FTRD system) represents another addition to the armamentarium. It can be used for circumscribed submucosal, suspicious or scarred changes up to 2 cm in the middle and upper rectum. Endoscopic intermuscular dissection (EID) enables histopathological analysis of the complete submucosa beyond the mucosa and upper submucosal layer by including the circular inner muscle layer within the resection specimen. It reduces basal R1 situations and offers a new perspective for T1 carcinomas through curative, organ-preserving endoscopic therapy, especially in the case of deep submucosal infiltration alone, without other risk factors for metastases. Indications, the procedure itself and significance of the various techniques for premalignant and early malignant lesions in the rectum are presented.


Assuntos
Adenoma , Carcinoma , Lesões Pré-Cancerosas , Humanos , Reto/cirurgia , Endoscopia , Lesões Pré-Cancerosas/cirurgia , Adenoma/cirurgia
13.
J Cell Mol Med ; 28(6): e18186, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38445803

RESUMO

Clear cell renal cell carcinoma (ccRCC) represents a significant challenge in oncology, primarily due to its resistance to conventional therapies. Understanding the tumour microenvironment (TME) is crucial for developing new treatment strategies. This study focuses on the role of amyloid precursor protein (APP) in tumour-associated macrophages (TAMs) within the ccRCC TME, exploring its potential as a prognostic biomarker. Basing TAM-related genes, the prognostic model was important to constructed. Employing advanced single-cell transcriptomic analysis, this research dissects the TME of ccRCC at an unprecedented cellular resolution. By isolating and examining the gene expression profiles of individual cells, particularly focusing on TAMs, the study investigates the expression levels of APP and their association with the clinical outcomes of ccRCC patients. The analysis reveals a significant correlation between the expression of APP in TAMs and patient prognosis in ccRCC. Patients with higher APP expression in TAMs showed differing clinical outcomes compared to those with lower expression. This finding suggests that APP could serve as a novel prognostic biomarker for ccRCC, providing insights into the disease progression and potential therapeutic targets. This study underscores the importance of single-cell transcriptomics in understanding the complex dynamics of the TME in ccRCC. The correlation between APP expression in TAMs and patient prognosis highlights APP as a potential prognostic biomarker. However, further research is needed to validate these findings and explore the regulatory mechanisms and therapeutic implications of APP in ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Precursor de Proteína beta-Amiloide , Biomarcadores , Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica , Neoplasias Renais/genética , Microambiente Tumoral/genética
14.
PLoS One ; 19(3): e0299404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38446776

RESUMO

Otariid gammaherpesvirus 1 (OtGHV1) is associated with high rates of urogenital carcinoma in free-ranging California sea lions (Zalophus californianus; CSL), and until recently was reported only in the Northern Hemisphere. The objective of this study was to survey free-ranging South American sea lions (Otaria byronia; SASL) and South American fur seals (Arctocephalus australis: SAFS) in Punta San Juan, Peru for OtGHV1 and to determine prevalence characteristics. Twenty-one percent (14/67) of urogenital swabs collected over three years (2011, 2014, 2015) from live pinnipeds of both species tested positive with a pan-herpesvirus conventional PCR. Sequencing of SAFS amplicons revealed 100% homology to OtGHV1 at the DNA polymerase, glycoprotein B, and viral bcl2-like genes. Sequencing of SASL amplicons revealed a novel related virus, herein called Otariid gammaherpesvirus 8 (OtGHV8). For comparison of sample sites, urogenital, conjunctival, and oropharyngeal swabs collected from 136 live pinnipeds of both species at Punta San Juan between 2011-2018 were then assayed using quantitative PCR for a segment of the OtGHV1/8 DNA polymerase gene using a qPCR assay now determined to cross-react between the two viruses. In total, across both species, 38.6% (51/132) of urogenital swabs, 5.6% (4/71) of conjunctival swabs, and 1.1% (1/90) of oropharyngeal swabs were positive for OtGHV1/8, with SASL only positive on urogenital swabs. Results from SASL were complicated by the finding of OtGHV8, necessitating further study to determine prevalence of OtGHV1 versus OtGHV8 using an alternate assay. Results from SAFS suggest a potential relationship between OtGHV1 in SAFS and CSL. Though necropsy surveillance in SAFS is very limited, geographic patterns of OtGHV1-associated urogenital carcinoma in CSL and the tendency of herpesviruses to cause more detrimental disease in aberrant hosts suggests that it is possible that SAFS may be the definitive host of OtGHV1, which gives further insight into the diversity and phyogeography of this clade of related gammaherpesviruses.


Assuntos
Caniformia , Carcinoma , Otárias , Gammaherpesvirinae , Herpesviridae , Leões-Marinhos , Animais , Humanos , Prevalência , Gammaherpesvirinae/genética , Peru/epidemiologia , DNA Polimerase Dirigida por DNA
15.
Commun Biol ; 7(1): 262, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438714

RESUMO

Potassium Channel Tetramerization Domain Containing 15 (KCTD15) participates in the carcinogenesis of several solid malignancies; however, its role in colorectal cancer (CRC) remains unclear. Here we find that KCTD15 exhibits lower expression in CRC tissues as compared to para-carcinoma tissues. Tetracycline (tet)-induced overexpression and knockdown of KCTD15 confirms KCTD15 as an anti-proliferative and pro-apoptotic factor in CRC both in vitro and in xenografted tumors. N6-methyladenosine (m6A) is known to affect the expression, stabilization, and degradation of RNAs with this modification. We demonstrate that upregulation of fat mass and obesity-associated protein (FTO), a classical m6A eraser, prevents KCTD15 mRNA degradation in CRC cells. Less KCTD15 RNA is recognized by m6A 'reader' YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) in FTO-overexpressed cells. Moreover, KCTD15 overexpression decreases protein expression of histone deacetylase 1 (HDAC1) but increases acetylation of critical tumor suppressor p53 at Lys373 and Lys382. Degradation of p53 is delayed in CRC cells post-KCTD15 overexpression. We further show that the regulatory effects of KCTD15 on p53 are HDAC1-dependent. Collectively, we conclude that KCTD15 functions as an anti-growth factor in CRC cells, and its expression is orchestrated by the FTO-YTHDF2 axis. Enhanced p53 protein stabilization may contribute to KCTD15's actions in CRC cells.


Assuntos
Adenina/análogos & derivados , Carcinoma , Neoplasias Colorretais , Humanos , Proteína Supressora de Tumor p53 , Carcinogênese , Neoplasias Colorretais/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Canais de Potássio , Proteínas de Ligação a RNA/genética
16.
Diagn Pathol ; 19(1): 48, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431604

RESUMO

BACKGROUND: Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon. METHODS: PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis's mechanism. RESULTS: Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis. CONCLUSIONS: Our findings suggest that PKM2 may be a tumor's promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.


Assuntos
Carcinoma , Neoplasias Hipofaríngeas , Piruvato Quinase , Animais , Humanos , Carcinoma/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Metástase Linfática/genética , Prognóstico , Piruvato Quinase/metabolismo , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patologia
17.
Zhongguo Fei Ai Za Zhi ; 27(2): 157-160, 2024 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-38453449

RESUMO

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant tumor, which includes the following five pathologic types: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. The onset of PSC is occult with non-specific clinical symptoms and signs. The clinical manifestations include irritating cough, bloody sputum, dyspnea, chest pain and so on, which are closely related to the growth and invasion site of the tumor. PSC tends to metastasize early, so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit. A patient with primary PSC which led to 90% stenosis in central airway was treated by combined method of vascular and tracheoscopic intervention in our respiratory center. This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery. Herein we report the case for clinical reference.
.


Assuntos
Carcinoma , Carcinossarcoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico , Prognóstico , Carcinoma/patologia , Carcinossarcoma/cirurgia , Carcinossarcoma/patologia , Pulmão/patologia
18.
J Cell Mol Med ; 28(7): e18165, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38494845

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a commonly occurring and highly aggressive urological malignancy characterized by a significant mortality rate. Current therapeutic options for advanced ccRCC are limited, necessitating the discovery of novel biomarkers and therapeutic targets. Carboxypeptidase A4 (CPA4) is a zinc-containing metallocarboxypeptidase with implications in various cancer types, but its role in ccRCC remains unexplored. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized in order to investigate the differential expression patterns of CPA4. The expression of CPA4 in ccRCC patients was further verified using immunohistochemical (IHC) examination of 24 clinical specimens. A network of protein-protein interactions (PPI) was established, incorporating CPA4 and its genes that were expressed differentially. Functional enrichment analyses were conducted to anticipate the contribution of CPA4 in the development of ccRCC. To validate our earlier study, we conducted real-time PCR and cell functional tests on ccRCC cell lines. Our findings revealed that CPA4 is overexpressed in ccRCC, and the higher the expression of CPA4, the worse the clinical outcomes such as TNM stage, pathological stage, histological grade, etc. Moreover, patients with high CPA4 expression had worse overall survival, disease-specific survival and progress-free interval than patients with low expression. The PPI network analysis highlighted potential interactions contributing to ccRCC progression. Functional enrichment analysis indicated the involvement of CPA4 in the regulation of key pathways associated with ccRCC development. Additionally, immune infiltration analysis suggested a potential link between CPA4 expression and immune response in the tumour microenvironment. Finally, cell functional studies in ccRCC cell lines shed light on the molecular mechanisms underlying the role of CPA4 in promoting ccRCC formation. Overall, our study unveils CPA4 as a promising biomarker with prognostic potential in ccRCC. The identified interactions and pathways provide valuable insights into its implications in ccRCC development and offer a foundation for future research on targeted therapies. Further investigation of CPA4's involvement in immune responses may contribute to the development of immunotherapeutic strategies for ccRCC treatment.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Biomarcadores , Neoplasias Renais/genética , Proliferação de Células/genética , Microambiente Tumoral/genética
19.
Technol Cancer Res Treat ; 23: 15330338241237439, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497139

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a widespread urogenital neoplasm. However, the therapeutic efficacy of these methods is unsatisfactory. In-depth screening of biomarkers could aid early diagnosis and therapy and predict patient prognosis. METHODS: The GEO datasets were selected with specific criteria. Differentially expressed gene (DEG), weighted gene coexpression network analysis (WGCNA), protein-protein interaction, LASSO, random forest, and Cox regression analyses were applied to identify the independent prognostic biomarkers. Survival analysis, correlation with clinical features, gene set enrichment analysis (GSEA), GO enrichment, immune infiltration analysis, and correlation with cuproptosis-related genes were carried out to determine the prognostic value and possible molecular mechanisms of the TSVR. Wound healing assays, transwell assays, cell colony formation experiments, flow cytometry, and immunohistochemistry (IHC) analysis were used to validate the functional attributes of CRYL1. RESULTS: Four GEO datasets were included to screen for hub genes. DEG combined with WGCNA showed a key module with 300 genes having the strongest correlation with "survival state" (R2 = -0.24 and P = 7e-8); six genes were identified by LASSO, random forest, and Cytoscape. Finally, CRYL1 (hazard ratio (HR) = 2.01, P < 0.001) was selected as an independent prognostic biomarker. The higher CRYL1 expression group had better DFS and overall survival (OS). GSEA demonstrated that the CRYL1-related DEGs were enriched mainly in the metabolism of sugar, fat, and amino acids. CRYL1 is positively correlated with FDX1 and the LIAS pathway, which are important molecule involved in cuproptosis. CRYL1 affects the infiltration abundance of four immune cells and can predict a positive OS. Wound healing, transwell, cell colony formation, and flow cytometry assays demonstrated that CRYL1 silencing enhances migration and proliferation and leads to a decreased apoptotic ratio. IHC analysis suggested that CRYL1 was highly expressed in adjacent tissues. CONCLUSIONS: CRYL1 is a robust predictive marker for clinicopathological characteristics and survival status in ccRCC patients.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Prognóstico , Aminoácidos , Neoplasias Renais/genética
20.
PeerJ ; 12: e17077, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500523

RESUMO

Background: Metastatic disease resulting from mammary gland tumors (MGTs) is a known cause of death among dogs and cats. Keys to successful prevention and management strategies involve the accurate recording of diagnostic data. Methods: This retrospective study reviewed the epidemiology and classification of canine mammary gland tumors (CMTs) and feline mammary gland tumors (FMTs), as well as the factors including sex, age, and breed related to the occurrence of these tumors. Accordingly, 1,736 tumor biopsy cases were reported from 2012 to 2019 at Chiang Mai University Small Animal Hospital, Thailand, with 1,639 canine tumor biopsy cases and 97 feline tumor biopsy cases. Results: The proportion of CMTs was reported at 24.5% (401/1,639) for all canine tumor biopsy cases. Benign and malignant tumors were reported at 14.5% (58/401) and 85.5% (343/401) for all CMT cases, respectively. The mean age of dogs affected by benign CMTs was 9.0 ± 3.0 years, which was significantly lower than for malignant CMTs at 9.9 ± 2.8 years (P = 0.0239). According to histopathological classification, benign mixed tumors and simple carcinoma types were highest among benign and malignant CMT cases, respectively. Moreover, female dogs were at significantly higher risk of developing mammary gland tumors (OR = 45.8, 95% CI [3.9-86.0], P < 0.0001) than male dogs, as well as older dogs (>8 years) (OR = 1.7, 95% CI [1.2-2.2], P = 0.0001) compared to young ones (≤8 years). The proportion of FMTs was 37.1% (36/97) for all feline tumor biopsy cases. Benign and malignant tumors for all FMTs were reported at 16.7% (6/36) and 83.3% (30/36), respectively. According to histopathological classifications, adenoma and simple carcinoma were present in the highest proportion among benign and malignant FMTs, respectively. Female cats were at a significantly higher risk of developing mammary gland tumors than male cats (OR = 25.7, 95% CI [3.9-272.8], P < 0.0001). Conclusions and clinical importance: There was a high proportion of MGT cases compared with other tumor cases reported in a secondary care hospital in Chiang Mai, Thailand from 2012 to 2019, and malignant tumor biopsies have been more frequently observed than benign tumor biopsies in both CMT and FMT cases. The resulting data originating from this study can be an aid for veterinary oncologists in better educating clients and planning treatment and prevention strategies and it can be used as a basis for further experimental studies in the oncology section.


Assuntos
Carcinoma , Doenças do Gato , Doenças do Cão , Glândulas Mamárias Humanas , Neoplasias Mamárias Animais , Neoplasias das Glândulas Sudoríparas , Humanos , Gatos , Cães , Animais , Masculino , Feminino , Criança , Doenças do Gato/epidemiologia , Tailândia/epidemiologia , Estudos Retrospectivos , Glândulas Mamárias Humanas/patologia , Atenção Secundária à Saúde , Doenças do Cão/diagnóstico , Carcinoma/patologia , Biópsia/veterinária , Neoplasias Mamárias Animais/epidemiologia , Hospitais
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