Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69.771
Filtrar
1.
Medicine (Baltimore) ; 100(35): e27162, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477172

RESUMO

ABSTRACT: Cancer-associated fibroblasts (CAFs) have been attracting attention in recent years, but their nature has not been fully elucidated. Although CAFs have been recognized as an important therapeutic target, therapeutic agents have not been developed to date. CAFs are characterized by their high migration rate and involvement in epithelial-to-mesenchymal transition with some displaying a dendritic morphology that is reminiscent of fascin expression.The present study was designed to immunohistochemically investigate fascin expression in lung adenocarcinoma including CAFs and compare the results with existing CAF markers.We immunohistochemically investigated fascin expression in not only cancer tissue but also CAFs from 26 autopsy cases of lung adenocarcinoma. Immunohistochemistry of α-smooth muscle actin and fibroblast activation protein was also performed.Fascin-positive staining in CAFs was observed in all cases, with a strong correlation observed with existing CAF markers α-smooth muscle actin and fibroblast activation protein (P < .001). In addition, the proportion of tumor cells showing fascin-positive staining was found to correlate with its expression in CAFs (P < .05).We propose that CAFs express fascin, and that fascin may mediate crosstalk between cancer tissue and CAFs. Fascin might be a novel therapeutic target for treatments that target the cancer stroma.


Assuntos
Adenocarcinoma/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas dos Microfilamentos/metabolismo , Actinas/metabolismo , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Endopeptidases/metabolismo , Feminino , Humanos , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade
2.
Medicine (Baltimore) ; 100(35): e27174, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477176

RESUMO

ABSTRACT: Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients' clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.


Assuntos
Adenocarcinoma/patologia , Neoplasias dos Genitais Femininos/patologia , Genitália Feminina/patologia , Mesonefroma/patologia , Adenocarcinoma/mortalidade , Adulto , Idoso , China/epidemiologia , Feminino , Neoplasias dos Genitais Femininos/mortalidade , Humanos , Mesonefroma/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Ann Palliat Med ; 10(8): 8818-8826, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488370

RESUMO

BACKGROUND: Roughly 30-40% of lung cancer (LC) patients develop bone metastasis during the course of disease. The genetic differences between primary LC and matched bone metastasis are not yet fully understood. METHODS: A total of 40 LC patients with bone metastasis were collected and 450 targeted cancer-related genes were sequenced for genomic-alteration (GA) identification. RESULTS: Among the 40 LC patients, 33 had adenocarcinomas and 7 had squamous cell carcinomas. The metastatic sites of the 33 lung adenocarcinomas (LUADs) were the pelvis (6 patients), spine (16 patients), and limbs (11 patients). A total of 425 and 422 GAs were detected in the primary and metastatic lesions, respectively. The most common GAs were epidermal growth factor receptor (EGFR) mutations, which had mutation rates of 85.0% and 72.5% in the primary and metastatic lesions, respectively, and tumor protein 53 (TP53) mutations, which had mutation rates of 52.5% and 67.5% in the primary and metastatic lesions, respectively. Metastases to the pelvis and spine were most commonly accompanied by factor receptor substrate 2 (FRS2), cyclin-dependent kinase 4 (CDK4), and murine double minute 2 (MDM2) amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletion. The concordance between primary lung squamous cell carcinoma (LUSC) and corresponding metastasis was significantly higher than that of primary LUAD and corresponding metastasis (P=0.033). Compared to limb and pelvis metastases, the shared mutation in spine metastasis was significantly lower (P=0.016 and P=0.023, respectively). In matched primary LUSCs and bone metastasis lesions, there was no significant difference in the distribution of the tumor mutational burden (TMB) (P=0.9). Conversely, a significant difference of the TMB distribution was detected in pairs of primary LUAD and corresponding bone metastasis lesions (P=0.021). CONCLUSIONS: The consistency of mutation patterns between primary LC lesions and matched bone metastases may vary in terms of metastatic sites, but is very high in general. There was a significant difference in the TMB between primary LUAD and matched bone metastatic lesions. Our findings contribute to molecular understandings of primary LC and matched bone metastatic lesions.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Ósseas/genética , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Metástase Neoplásica/genética
4.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360996

RESUMO

ß-Casomorphin-7 (BCM) is a degradation product of ß-casein, a milk component, and has been suggested to affect the immune system. However, its effect on mucosal immunity, especially anti-tumor immunity, in cancer-bearing individuals is not clear. We investigated the effects of BCM on lymphocytes using an in vitro system comprising mouse splenocytes, a mouse colorectal carcinogenesis model, and a mouse orthotopic colorectal cancer model. Treatment of mouse splenocytes with BCM in vitro reduced numbers of cluster of differentiation (CD) 20+ B cells, CD4+ T cells, and regulatory T cells (Tregs), and increased CD8+ T cells. Administration of BCM and the CD10 inhibitor thiorphan (TOP) to mice resulted in similar alterations in the lymphocyte subsets in the spleen and intestinal mucosa. BCM was degraded in a concentration- and time-dependent manner by the neutral endopeptidase CD10, and the formed BCM degradation product did not affect the lymphocyte counts. Furthermore, degradation was completely suppressed by TOP. In the azoxymethane mouse colorectal carcinogenesis model, the incidence of aberrant crypt foci, adenoma, and adenocarcinoma was reduced by co-treatment with BCM and TOP. Furthermore, when CT26 mouse colon cancer cells were inoculated into the cecum of syngeneic BALB/c mice and concurrently treated with BCM and TOP, infiltration of CD8+ T cells was promoted, and tumor growth and liver metastasis were suppressed. These results suggest that by suppressing the BCM degradation system, the anti-tumor effect of BCM is enhanced and it can suppress the development and progression of colorectal cancer.


Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Endorfinas/uso terapêutico , Linfócitos/imunologia , Fragmentos de Peptídeos/uso terapêutico , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Células Cultivadas , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Endorfinas/farmacologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Linfócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica , Fragmentos de Peptídeos/farmacologia , Inibidores de Proteases/farmacologia , Baço/citologia , Baço/imunologia , Tiorfano/farmacologia
5.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360883

RESUMO

Understanding the mechanisms of colorectal cancer progression is crucial in the setting of strategies for its prevention. δ-Valerobetaine (δVB) is an emerging dietary metabolite showing cytotoxic activity in colon cancer cells via autophagy and apoptosis. Here, we aimed to deepen current knowledge on the mechanism of δVB-induced colon cancer cell death by investigating the apoptotic cascade in colorectal adenocarcinoma SW480 and SW620 cells and evaluating the molecular players of mitochondrial dysfunction. Results indicated that δVB reduced cell viability in a time-dependent manner, reaching IC50 after 72 h of incubation with δVB 1.5 mM, and caused a G2/M cell cycle arrest with upregulation of cyclin A and cyclin B protein levels. The increased apoptotic cell rate occurred via caspase-3 activation with a concomitant loss in mitochondrial membrane potential and SIRT3 downregulation. Functional studies indicated that δVB activated mitochondrial apoptosis through PINK1/Parkin pathways, as upregulation of PINK1, Parkin, and LC3B protein levels was observed (p < 0.0001). Together, these findings support a critical role of PINK1/Parkin-mediated mitophagy in mitochondrial dysfunction and apoptosis induced by δVB in SW480 and SW620 colon cancer cells.


Assuntos
Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Suplementos Nutricionais , Mitofagia/efeitos dos fármacos , Proteínas Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 3/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Valeratos/farmacologia , Adenocarcinoma/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Humanos , Concentração Inibidora 50 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo
6.
APMIS ; 129 Suppl 142: 1-30, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34399444

RESUMO

Over the past decade, 3D culture models of human and animal cells have found their way into tissue differentiation, drug development, personalized medicine and tumour behaviour studies. Embryoid bodies (EBs) are in vitro 3D cultures established from murine pluripotential stem cells, whereas tumoroids are patient-derived in vitro 3D cultures. This thesis aims to describe a new implication of an embryoid body model and to characterize the patient-specific microenvironment of the parental tumour in relation to tumoroid growth rate. In this thesis, we described a high-throughput monitoring method, where EBs are used as a dynamic angiogenesis model. In this model, digital image analysis (DIA) is implemented on immunohistochemistry (IHC) stained sections of the cultures over time. Furthermore, we have investigated the correlation between the genetic profile and inflammatory microenvironment of parental tumours on the in vitro growth rate of tumoroids. The EBs were cultured in spinner flasks. The samples were collected at days 4, 6, 9, 14, 18 and 21, dehydrated and embedded in paraffin. The histological sections were IHC stained for the endothelial marker CD31 and digitally scanned. The virtual whole-image slides were digitally analysed by Visiopharm® software. Histological evaluation showed vascular-like structures over time. The quantitative DIA was plausible to monitor significant increase in the total area of the EBs and an increase in endothelial differentiation. The tumoroids were established from 32 colorectal adenocarcinomas. The in vitro growth rate of the tumoroids was followed by automated microscopy over an 11-day period. The parental tumours were analysed by next-generation sequencing for KRAS, TP53, PIK3CA, SMAD4, MAP2K1, BRAF, FGFR3 and FBXW7 status. The tumoroids established from KRAS-mutated parental tumours showed a significantly higher growth rate compared to their wild-type counterparts. The density of CD3+ T lymphocytes and CD68+ macrophages was calculated in the centre of the tumours and at the invasive margin of the tumours. The high density of CD3+ cells and the low density of CD68+ cells showed a significant correlation with a higher growth rate of the tumoroids. In conclusion, a novel approach for histological monitoring of endothelial differentiation is presented in the stem cell-derived EBs. Furthermore, the KRAS status and density of CD3+ T cells and macrophages in the parental tumour influence the growth rate of the tumoroids. Our results indicate that these parameters should be included when tumoroids are to be implemented in personalized medicine.


Assuntos
Adenocarcinoma/patologia , Técnicas de Cultura de Células/métodos , Neoplasias Colorretais/patologia , Animais , Diferenciação Celular/fisiologia , Corpos Embrioides/patologia , Células Endoteliais/patologia , Humanos , Macrófagos/patologia , Camundongos , Células-Tronco/patologia , Linfócitos T/patologia , Microambiente Tumoral/fisiologia
7.
Science ; 373(6556): 760-767, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34385390

RESUMO

The origin of human metaplastic states and their propensity for cancer is poorly understood. Barrett's esophagus is a common metaplastic condition that increases the risk for esophageal adenocarcinoma, and its cellular origin is enigmatic. To address this, we harvested tissues spanning the gastroesophageal junction from healthy and diseased donors, including isolation of esophageal submucosal glands. A combination of single-cell transcriptomic profiling, in silico lineage tracing from methylation, open chromatin and somatic mutation analyses, and functional studies in organoid models showed that Barrett's esophagus originates from gastric cardia through c-MYC and HNF4A-driven transcriptional programs. Furthermore, our data indicate that esophageal adenocarcinoma likely arises from undifferentiated Barrett's esophagus cell types even in the absence of a pathologically identifiable metaplastic precursor, illuminating early detection strategies.


Assuntos
Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Cárdia/citologia , Neoplasias Esofágicas/patologia , Esôfago/patologia , Esôfago de Barrett/genética , Esôfago de Barrett/metabolismo , Cárdia/química , Diferenciação Celular , Linhagem da Célula , Transformação Celular Neoplásica , Epigênese Genética , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Esôfago/citologia , Esôfago/metabolismo , Glândulas Exócrinas/química , Glândulas Exócrinas/citologia , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Queratina-7/análise , Metaplasia , Fenótipo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA-Seq , Análise de Célula Única , Transcrição Genética , Transcriptoma
8.
Zhonghua Zhong Liu Za Zhi ; 43(8): 856-860, 2021 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-34407591

RESUMO

Objective: To evaluate the expression of semaphorin 5B (SEMA5B) in gastric adenocarcinoma and its relationship with prognosis. Methods: In November 2019, the clinicopathological characteristics and SEMA5B mRNA expression data of 341 patients with gastric adenocarcinoma were collected through TCGA database. The relationship between SEMA5B expression in gastric adenocarcinoma tissues and clinical pathologic features and overall survival were analyzed. Gene Set Enrichment Analysis (GSEA) was used to analyze the signaling pathways regulated by SEMA5B. Results: The expression level of SEMA5B mRNA in 341 gastric adenocarcinoma tissues was 0.577±0.587, in adjacent normal tissues was 0.132±0.075, the difference was statistically significant (P<0.001). The median survival time of 109 patients with high expression of SEMA5B mRNA was 14.5 months, 232 patients with low expression of SEMA5B mRNA was 17.9 months (P=0.047). Univariate analysis showed that the expression of SEMA5B mRNA was correlated with histological grade and T stage (P<0.05). The multivariate analysis revealed that age<65 years remained independently associated with overall survival, with a hazard ratio(HR) of 1.042 (95%CI: 1.021-1.064). The multivariate analysis revealed that high expression of SEMA5b mRNA remained independently associated with overall survival, with a HR of 1.195 (95%CI: 0.925-2.551). GSEA showed that malignant tumor signaling pathways (P=0.008), MAPK signaling pathways (P=0.047) and Notch signaling pathways (P=0.029) were differentially enriched in SEMA5B highly expressed phenotype. Conclusions: SEMA5B expression may be a potential prognostic molecular marker for prognosis of GAC patients. Moreover, malignant tumor signaling pathway, MAPK signaling pathway and Notch signaling pathway may be the key pathway regulated by SEMA5B in GAC.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Humanos , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
9.
Medicine (Baltimore) ; 100(33): e26951, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414959

RESUMO

ABSTRACT: An overexpression of S-phase kinase-associated protein 2 (SKP2) is frequently observed in human cancer progression and metastasis, and evidence suggests that SKP2 plays a proto-oncogenic role both in vitro and in vivo. However, the function of SKP2 in gastric adenocarcinoma remains largely obscure. We investigated SKP2 expression in human gastric carcinomas.Tissue samples were acquired from 182 cases of gastric adenocarcinoma that were surgically resected from 2006 to 2012. Immunohistochemical staining for SKP2, Beclin-1, and forkhead box protein P3 (FOXP3) was performed. Pearson chi-square test was used to evaluate the associations among clinicopathological variables. The Kaplan-Meier method, the log-rank test, and the Cox proportional-hazards model were used in the analysis of the overall survival (OS) and disease-free survival (DFS).As a result, SKP2 overexpression in gastric adenocarcinomas showed a significant correlation with several favorable clinical factors, including the tumor size, T category, N category, lymphatic invasion, vascular invasion, OS, and DFS. SKP2 expression was positively correlated with the tumoral FOXP3, Beclin-1 expression, and regulatory T cell (Treg) infiltration. The difference in DFS between the SKP2 positive and negative group was attenuated by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration. Attenuation of the difference in OS by FOXP3 high expression, Beclin-1 high expression, and Tregs infiltration was not significant. In multivariable analysis, SKP2 expression was not correlated with OS and DFS.Our study showed a complex interrelationship between SKP2 and Beclin-1 and FOXP3 expression in gastric adenocarcinoma. The antioncogenic effect of Beclin-1 and FOXP3 expression in gastric adenocarcinoma is related to SKP2 expression.


Assuntos
Adenocarcinoma/metabolismo , Proteína Beclina-1/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas Quinases Associadas a Fase S/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Análise Serial de Tecidos
10.
Pan Afr Med J ; 39: 12, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394803

RESUMO

Introduction: published data on oesophageal cancer (EC) in Zambia is limited and our study is the only study in Zambia evaluating the demographics and clinicopathologic features of patients presenting with EC at time of diagnosis. Methods: a retrospective analysis of data from Cancer Diseases Hospital (CDH) database was conducted on EC patients diagnosed between 2007 and December 2018. Medical records of EC patients were manually retrieved and reviewed using medical record numbers identified from the CDH database. Demographics, clinicopathologic features and modes of treatment were extracted. A coding sheet was created a priori, and data analysed in SAS version 9.3. Results: two hundred and seventy eight (278) complete EC medical records were included in the analysis, 183 (66%) were males, mean age was 55 years (range 21-89). One hundred and fifty six (156) (56%) resided in Lusaka, the location of CDH. The age-standardized incidence for EC was 5.5 per 100,000 people (95% CI, 4.3-6.6). The commonest symptom was dysphagia (83%), 97% were diagnosed endoscopically, squamous cell carcinoma and adenocarcinoma accounted for 90% and 8.3% respectively, 65% received treatment. One hundred and twenty four (124) medical records had missing cancer staging. Of 154 medical records with complete cancer staging, 98 (35%) were diagnosed at stage 4 of which 33% were between 40 and 49 years. Conclusion: the age-standardized incidence for EC is high at CDH. Patients with EC are predominantly male, reside in Lusaka and present with late stage EC at time of diagnosis; mostly between the ages of 40-49 years. Robust prospective research and improved data recording is needed.


Assuntos
Adenocarcinoma/epidemiologia , Neoplasias Esofágicas/epidemiologia , Carcinoma de Células Escamosas do Esôfago/epidemiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Transtornos de Deglutição/etiologia , Endoscopia Gastrointestinal/métodos , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Adulto Jovem , Zâmbia
11.
Pan Afr Med J ; 39: 18, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34394809

RESUMO

Introduction: cancer is a major cause of death in the world. The purpose of this study is to evaluate the epidemiological, clinical, therapeutic and prognostic features of cancers of the pancreas (CP) at the National Hospital and University Center of Cotonou. Methods: we conducted a cross-sectional descriptive and analytical study with a prospective and retrospective data collection over a period of ten years, from 1 October 2009 to 31 October 2019. Results: out of 15.102 hospitalizations, we identified 72 cases of CP, reflecting a hospitalization rate of 0.5%. The average age of patients was 59 years. The sex-ratio (H/F) was 1.5. The main reason for consultation was abdominal pain. More than half (51.4%) of patients had metastatic tumor at the time of diagnosis. Histological evidence of adenocarcinoma was only reported in 15.1% of cases. The rate of operable patients was 37.5% while the rate of resectable patients was 2.7%. Palliative chemotherapy was given to 13.9% of patients. The average cost of treatment was 955.882,4 FCFA (23.9 times the Guaranteed Interprofessional Minimum Wage in Benin). Median overall survival was 6 months. Mortality rate was 86.9% (53/61), survival rate at one year was 31.4%, and zero at five years. Palliative surgery (p = 0.021) and chemotherapy (p = 0.023) improved patient survival. Conclusion: cancer of the pancreas, due to its non-specific signs and insidious outcome, is often diagnosed at a late stage. A metastatic tumor and the limited individual and institutional therapeutic possibilities lead to more pejorative prognosis.


Assuntos
Adenocarcinoma/epidemiologia , Hospitalização/estatística & dados numéricos , Cuidados Paliativos/métodos , Neoplasias Pancreáticas/epidemiologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Benin , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(3): 375-382, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34402250

RESUMO

To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance,epidemiology,and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (=283) and without chemotherapy (=229) (57.4% vs 55.6%, vs all >0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in survival rate and mOS between patients with and without chemotherapy (all >0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, vs all <0.05). Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Humanos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/tratamento farmacológico , Prognóstico , Pontuação de Propensão
13.
Zhonghua Bing Li Xue Za Zhi ; 50(7): 773-778, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34405613

RESUMO

Objective: To pathologically evaluate the surgically resected specimens of three different therapies (neoadjuvant chemotherapy, neoadjuvant targeted therapy and neoadjuvant immunotherapy combined with chemotherapy) for non-small cell lung cancer. Methods: One-hundred and thirteen cases of post neoadjuvant therapy non-small cell lung cancer specimens were collected at Tongji University Affiliated Shanghai Pulmonary Hospital from January 2000 to March 2020. There were ninty patients receiving neoadjuvant chemotherapy (chemotherapy group;26 cases of adenocarcinoma and 64 cases of squamous cell carcinoma), 13 patients receiving neoadjuvant targeted therapy (targeted group;13 cases of adenocarcinoma) and 10 patients receiving neoadjuvant immunotherapy combined with chemotherapy (immune combined chemotherapy group;4 cases of adenocarcinoma and 6 cases of squamous cell carcinoma). They were evaluated for histologic tumor regression responses (necrosis, inflammatory cell infiltration, cholesterol crystal deposition, foam cell infiltration, reactive granuloma and interstitial collagenous formation) and pathological responses [main pathological response (MPR) and complete pathological response (PCR)]. Results: Chemotherapy group, targeted group and immune combined chemotherapy group all showed degenerative changes in residual tumor cells, increased atypia, various degrees of necrosis, foam cell aggregation, cholesterol cleft, inflammatory cell infiltration, and reactive granuloma in the tumor bed. Histologic characteristics of tumor regression reaction were not different between these three groups (P>0.05); the highest percentage of necrosis in the targeted group and immune combined chemotherapy group was only 10% and 20%, respectively, while that in the chemotherapy group was as high as 80%. One case of adenocarcinoma in immune combined chemotherapy group had tumor regression bed. The MPR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 35% (9/26) and 64% (41/64), respectively; the MPR ratio of targeted group was 2/13; the MPR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinoma in immune combined chemotherapy group were 2/4 and 2/6, respectively. The PCR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 11% (3/26) and 3% (2/64), respectively; the PCR ratio of targeted group was 0/13; the PCR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinomain immune combined chemotherapy group were 0/4 and 1/6, respectively. Conclusions: Different neoadjuvant therapy may cause various histopathological changes in non-small cell lung cancer: more necrosis is noted in the chemotherapy group and regression bed frequently appears in the immune combined chemotherapy group. In the immune combined chemotherapy group, there are significant lymphoplasmacytic infiltration and lymphoid follicle formation in the lung parenchyma beside the tumor bed.


Assuntos
Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , China , Humanos , Neoplasias Pulmonares/patologia , Terapia Neoadjuvante , Estadiamento de Neoplasias
14.
Zhonghua Bing Li Xue Za Zhi ; 50(7): 779-784, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34405614

RESUMO

Objective: To investigate the role of tumor budding (TB) in predicting lymph node metastasis of intestinal-type early gastric adenocarcinoma, and to determine the optimal cutoff value of TB number. Methods: A total of 202 patients with intestinal-type early gastric adenocarcinoma, who underwent surgical operation at the Affiliated Wuxi People's Hospital of Nanjing Medical University, Jiangsu, China from 2008 to 2018 were included. According to the International Tumor Budding Consensus Conference (ITBCC) criteria, the number of TB for each case was assessed. The receiver operating characteristic (ROC) curve was employed to determine the optimal cutoff value of TB number for predicting lymph node metastasis, and multivariate logistic regression was used to analyze whether a high TB number was an independent risk factor for lymph node metastasis. In addition, in the patients, who met the indications for endoscopic resection and developed lymph node metastasis, the association of a high number of TB with lymph node metastasis was examined. Results: TBs were observed in 63.4% (128/202) of intestinal-type early gastric adenocarcinomas. Using ROC curve, 4 TBs was found as the optimal cutoff value to predict lymph node metastasis (area under the curve 0.767; sensitivity 0.657; specificity 0.780). Therefore, the 202 cases were divided into two groups: the high-budding (≥4 TBs) group (n=60) and the low-budding (<4 TBs) group (n=142). The high-budding group exhibited a higher rate of lymph node metastasis than that of the low-budding group (41.7% vs 9.1%, P<0.01), and ≥4 TBs was associated with deeper invasion and lymph vessel invasion (P<0.01). The multivariate regression model showed that ≥4 TBs was an independent risk factor for lymph node metastasis (Hazard ratio=8.760, 95%CI 2.648-28.987; P<0.01). Meanwhile, 4 TBs as the cutoff value could better predict lymph node metastasis than the cutoff value advised by the ITBCC. In addition, 3 cases were found to have developed lymph node metastasis even that they met the expanded indications for endoscopic resection, and 2 of these 3 cases exhibited a higher TB number (≥4 TBs). Conclusions: More than 4 TBs are a useful indicator for predicting lymph node metastasis in intestinal-type early gastric adenocarcinoma. It may be used to as an endoscopic resection criterion for patients with a high risk of lymph node metastasis.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Humanos , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
15.
Molecules ; 26(13)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34279414

RESUMO

Malignant tumors have affected the human being since the pharaoh period, but in the last century the incidence of this disease has increased due to a large number of risk factors, including deleterious lifestyle habits (i.e., smoking) and the higher longevity. Many efforts have been spent in the last decades on achieving an early stage diagnosis of cancer, and more effective cures, leading to a decline in age-standardized cancer mortality rates. In the last years, our research groups have developed new metal-based complexes, with the aim to obtain a better selectivity for cancer cells and less side effects than the clinically established reference drug cisplatin. This work is focused on four novel Au(III) and Ru(III) complexes that share the piperidine dithiocarbamato (pipe-DTC) as the ligand, in a different molar ratio. The compounds [AuCl2(pipeDTC)], [Au(pipeDTC)2]Cl, [Ru(pipeDTC)3] and ß-[Ru2(pipeDTC)5] have been synthesized and fully characterized by several chemical analyses. We have then investigated their biological properties in two different cell lines, namely, AGS (gastric adenocarcinoma) and HCT116 (colon carcinomas), showing significant differences among the four compounds. First, the two gold-based compounds and ß-[Ru2(pipeDTC)5] display IC50 in the µM range, significantly lower than cisplatin. Second, we showed that [AuCl2(pipeDTC)] and ß-[Ru2(pipeDTC)5]Cl drive different molecular mechanisms. The first was able to induce the protein level of the DNA damage response factor p53 and the autophagy protein p62, in contrast to the second that induced the ATF4 protein level, but repressed p62 expression. This study highlights that the biological activity of different complexes bringing the same organic ligand depends on the electronic and structural properties of the metal, which are able to fine tune the biological properties, giving us precious information that can help to design more selective anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células , Complexos de Coordenação/farmacologia , Ouro/química , Rutênio/química , Neoplasias Gástricas/tratamento farmacológico , Tiocarbamatos/química , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Antineoplásicos/química , Complexos de Coordenação/química , Humanos , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas
16.
Zhonghua Zhong Liu Za Zhi ; 43(6): 686-690, 2021 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-34289562

RESUMO

Objective: To investigate the effect of the neoadjuvant chemotherapy course adjustment on the patients with esophageal cancer underwent delayed operation. Methods: The clinical data of patients with esophageal cancer treated in Cancer Hospital, Chinese Academy of Medical Sciences from 2019-2020, who underwent neoadjuvant chemotherapy strategy adjustment (multiple course chemotherapy group) or not (control group), were retrospectively studied. The clinical pathological characteristics and postoperative complication of these two group were compared and analyzed. Results: The cases who underwent the interval between chemotherapy and operation more than 4 weeks in multiple course chemotherapy group and control group were 17 and 6, with significant difference (P<0.05). The average operative blood loss of these two groups were 88.6 ml and 46.1 ml, the average postoperative hospital stays were 14.7 days and 10.0 days, with significant difference (P<0.05). The incidence rate of postoperative complication in the multiple course chemotherapy group was 40.9% (9/22), not significantly different from 31.8% (7/22) of control group (P>0.05). There were no death within postoperative 7 days and 30 days in both groups. Cases with apparent tumor regression [tumor regression grade (TRG) 1 to 3] in multiple course chemotherapy group were 14, with marginal tumor regression (TRG 4 to 5) were 8, while there were 7 and 15 in the control group, respectively, with significant difference (P<0.05). After multiple neoadjuvant chemotherapy, the imaging examination of patients indicated an almost total tumor degradation and the postoperative pathology showed no residual malignant tumor tissue was observed. Conclusions: Increased neoadjuvant chemotherapy course for patients with locally advanced esophageal cancer can obtain more obvious tumor degradation response. Neoadjuvant chemotherapy adjustment according to the operation schedule is recommended.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/patologia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
17.
Anticancer Res ; 41(8): 3885-3889, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281850

RESUMO

BACKGROUND/AIM: Currently, there is no established prognostic serum parameter except PSA in clinically regional lymph node-positive prostate cancer. The aim of this study was to identify serum prognostic factors in clinically regional lymph node-positive prostate cancer. PATIENTS AND METHODS: Patients diagnosed with regional lymph node-positive prostate cancer between 2008 and 2017 were included. The prognostic value of serum parameters for progression-free survival (PFS) and overall survival (OS) was investigated. RESULTS: Univariate and multivariate analyses showed a statistically significant increased hazard risk for PFS and OS for men with lactate dehydrogenase (LDH) ≥230 IU/l at diagnosis. PFS at 5 years for patients with high and low LDH levels were 69.9% (95% CI=56.8-79.8%) and 18.9% (95% CI=1.23-53.2%), respectively (p=0.003). OS at 5 years for low and high LDH levels were 89.2% (95% CI=78.6-94.7%) and 46.3 (95% CI=11.2-76.2%), respectively (p=0.006). CONCLUSION: This study shows that LDH is an independent predictor of PFS and OS in patients with regional lymph node metastatic prostate cancer.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , L-Lactato Desidrogenase/sangue , Metástase Linfática , Neoplasias da Próstata/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Idoso , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Metástase Linfática/radioterapia , Masculino , Prognóstico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia
18.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203589

RESUMO

Pancreatic ductal adenocarcinoma is one of the deadliest tumors. This neoplasia is characterized by an important cellular and phenotypic heterogeneity. In particular, it has been shown that at least two subtypes can be found: basal-like, which presents stem-like properties, and classical. Cancer stem cells have been isolated and characterized from these tumors, showing their dependance on general and tissue-specific stem transcription factors and signaling pathways. Nevertheless, little is known about their tissue microenvironment and cell non-autonomous regulators, such as long-non-coding RNAs. (lncRNAs). In this review, we summarize the current knowledge about the positive and negative effects of lncRNAs in the stemness phenotype of pancreatic ductal adenocarcinoma cancer (PDAC).


Assuntos
Adenocarcinoma/genética , Carcinoma Ductal Pancreático/genética , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/metabolismo , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/patologia , Humanos , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/patologia , Fenótipo , RNA Longo não Codificante/genética
19.
Int J Mol Sci ; 22(12)2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203923

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), accounting for 90-95% of all pancreatic tumors, is a highly devastating disease associated with poor prognosis. The lack of accurate diagnostic tests and failure of conventional therapies contribute to this pejorative issue. Over the last decade, the advent of theranostics in nuclear medicine has opened great opportunities for the diagnosis and treatment of several solid tumors. Several radiotracers dedicated to PDAC imaging or internal vectorized radiotherapy have been developed and some of them are currently under clinical consideration. The functional information provided by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) could indeed provide an additive diagnostic value and thus help in the selection of patients for targeted therapies. Moreover, the therapeutic potential of ß-- and α-emitter-radiolabeled agents could also overcome the resistance to conventional therapies. This review summarizes the current knowledge concerning the recent developments in the nuclear medicine field for the management of PDAC patients.


Assuntos
Adenocarcinoma/patologia , Carcinoma Ductal Pancreático/patologia , Medicina Nuclear , Neoplasias Pancreáticas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/terapia , Animais , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/terapia , Diagnóstico por Imagem , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Compostos Radiofarmacêuticos/química
20.
Aging (Albany NY) ; 13(13): 17349-17369, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226299

RESUMO

miR-144-3p is aberrantly expressed in several types of human cancer and functions as a tumor suppressor by inhibiting metastasis. However, the clinical significance and biological function of miR-144-3p in colorectal adenocarcinoma (CRA) have yet to be elucidated. Here we reported that miR-144-3p expression level was significantly down-regulated in CRA tissues compared with matched noncancerous colorectal mucosae tissues. Low miR-144-3p expression was correlated with adverse clinicopathologic characteristics and poor prognosis of CRA patients. Cox regression analysis showed that low miR-144-3p expression was an independent risk factor for DFS and OS in CRA. In vitro and in vivo assays showed that miR-144-3p significantly inhibited proliferation, migration and invasion of CRA cells. In particular, miR-144-3p could suppress EMT process of CRA cells by regulating the cytoskeleton and EMT markers. Bioinformatics analysis indicated that EMT associated transcription factors ZEB1 and ZEB2 were potential targets of miR-144-3p, and miR-144-3p inhibited ZEB1 and ZEB2 expression and was negatively correlated with their expression in CRA. Finally, we confirmed that ZEB1 and ZEB2 down-regulation collaboratively mediated the inhibitory effect of miR-144-3p on proliferation, invasion and EMT of CRA cells. In conclusion, our study provided evidence that miR-144-3p could inhibit CRA cell proliferation, invasion and EMT by targeting ZEB1/2.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , MicroRNAs/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Mucosa Intestinal/química , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...