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1.
Nat Commun ; 12(1): 4230, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244494

RESUMO

Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXß2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXß2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXß2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXß2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.


Assuntos
Processamento Alternativo , Carcinoma Epitelial do Ovário/genética , Proteínas da Matriz Extracelular/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas da Matriz Extracelular/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Integrina alfaXbeta2/genética , Integrina alfaXbeta2/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Ovário/patologia , Ovário/cirurgia , Fosforilação/genética , Prognóstico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA-Seq , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de Xenoenxerto
2.
World J Surg Oncol ; 19(1): 205, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238296

RESUMO

PURPOSE: To assess the value of adjuvant radiotherapy for treatment of gastric adenocarcinoma and to investigate subgroups of patients suitable for adjuvant radiotherapy. METHODS AND MATERIALS: Data from 785 patients with gastric adenocarcinoma who had undergone D1/D2 radical resection and adjuvant chemotherapy were collected, the site of first progression was determined, and the relationship between the rate of local recurrence and clinicopathologic features was analyzed. RESULTS: By the end of the follow-up period, progression was observed in 405 patients. Local recurrence was observed as the first progression in 161 cases. The local recurrence rate was significantly lower than the non-local progression rate (20.5% vs 31.5%, p=0.007). Multivariate Cox regression analysis showed a significant relationship among degree of differentiation, T stage, N stage, and rate of local recurrence. CONCLUSIONS: Not all patients with gastric carcinoma required adjuvant radiotherapy. However, patients with poorly differentiated cancer cells, advanced T stage (T3/T4), and positive lymph nodes, which included patients in the T4N1-2M0 subgroup, were recommended for adjuvant radiotherapy.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Quimioterapia Adjuvante , Gastrectomia , Humanos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/radioterapia
3.
Urologiia ; (3): 104-109, 2021 Jun.
Artigo em Russo | MEDLINE | ID: mdl-34251110

RESUMO

PURPOSE: To investigate long-term results after radical cystectomy in patients with bladder cancer. MATERIALS AND METHODS: Since 1997 to 2020 yy. we have performed 404 radical cystectomy with different methods of derivation for patients with bladder cancer in our clinic. There were 342 (86,4%) men and 62 (13,6%) women. Laboratory study, ultrasound, X-ray, CT. MRI investigations were performed in all patients. RESULTS: Mortality rate was 2,9%. Early and late postoperative complications have occurred in 136 (33,6%) and 98 (41,8%) cases, respectively. Local recurrence has occurred in 33 (8,5%) patients. 10-years overall and cancer-specific survival were 43,4% and 47,2%, respectively. In lymph-negative patients 2-years and 5-years overall survival were 81,2% and 67,2%, respectively. In lymph positive patients 2-years and 5-years overall survival were 46,9% and 13,9%, respectively. In lymph-negative patients 2-years and 5-years cancer-specific survival were 83,6% and 70,7%, respectively. In lymph positive patients 2-years and 5-years cancer-specific survival were 51,0% and 15,1%, respectively. Overall and cancer -specific survival decreased according to increasing pT-stage and histopathologic grade. CONCLUSIONS: pT-stage (pT), lymp nodes status (pN), histopathologic grade ( pG) have a significant independent influence on overall and cancer-specific survival of bladder cancer patients after radical cystectomy.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Carcinoma de Células de Transição/patologia , Cistectomia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
4.
Zhonghua Zhong Liu Za Zhi ; 43(6): 691-695, 2021 Jun 23.
Artigo em Chinês | MEDLINE | ID: mdl-34289563

RESUMO

Objective: To evaluate the recurrence and progression of patients with pT1 high grade urothelial carcinoma of bladder (UCB) and glandular differentiation. Methods: We retrospectively analyzed the clinical and pathological information of 208 patients diagnosed as pT1 high grade urothelial carcinoma in the Fifth Central Hospital of Tianjin from January 2006 to February 2019.Among them, 78 cases were diagnosed as glandular differentiation (UCGD), the other 130 patients without histologic variants were served as control. The UCGD group included 62 male and 16 female, whose median age was 67 years old (range 38-81 years old). The control group contained 105 male and 25 female, whose median age was 66 years old (range 40-82 years old). Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate the predictors of oncologic outcomes. Results: The disease recurrence rate and progression rate in UCGD group were 65.4% (51/78) and 28.2% (22/78), higher than 38.5%(50/130) and 14.6%(19/130) of control group (P<0.05). The median recurrence time in UCGD group was 41 months while 55 months in the control group. The median progression time in UCGD group was 39 months while 54 months in the control group. According to the univariate analysis, largest tumor size (P=0.030), UCGD (P=0.003) and lymphovascular invasion (LVI) (P=0.032) were associated with disease recurrence. UCGD (P=0.036) and LVI (P=0.011) were associated with progression. Additionally, Cox multivariate analysis revealed that UCGD (P=0.001), LVI (P=0.038) were the independent factors of disease recurrence. UCGD (P=0.007) and LVI (P=0.037) were also found to be the independent factors of disease progression. Conclusions: Patients with T1 stage UCB and UCGD are at higher risk of disease recurrence and progression. Therefore, these patients should be followed up closely after being diagnosed and undergo individual treatment according to the situation.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
5.
J Clin Neurosci ; 90: 82-88, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275586

RESUMO

OBJECTIVES: Recurrent high-grade glioma, a malignant tumor of the brain or spinal cord associated with poor prognosis with a median survival of <6 months. Recurrent high-grade glioma does not have standard treatment even if some strategies have some effect in recurrent gliomas. Apatinib, as a tyrosine kinase inhibitor shown to be effective in treating the lung and gastric cancer. The present study investigated the efficacy and safety of apatinib in combination with dose-dense regimens of temozolomide for treating recurrent glioma. PATIENTS AND METHODS: Eighteen patients with recurrent high-grade glioma were enrolled and treated with apatinib (500 mg/day) and TMZ (50 mg/m2/day). Patients who achieved partial response or stable disease continued treatment. Administration of drug was terminated for patients with progressive disease, who could not tolerate toxicity, and who required discontinuation due to other medical conditions. RESULTS: From the 18 cases, only 17 were included in the evaluation of the curative effect of the drug and in that four showed partial responses, ten had stable disease, remaining three exhibited progressive disease. The disease control rate was 82.3% (14/17). Progression-free and overall survival was found to be 4 months and 9.1 months, respectively. Three patients became transiently capable of self-care (Karnofsky performance status >70). Cognition and quality of life improved after treatment and from the safety perspective, three most common adverse reactions included epilepsy (24.1%), hypertension (20.7%), and fatigue (17.2%). CONCLUSION: Apatinib and TMZ may represent an alternative treatment option for patients with recurrent high-gradeglioma, especially those with a low Karnofsky performance status. However, studies using a larger sample size are required to confirm these findings.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Piridinas/uso terapêutico , Temozolomida/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Quimioterapia Combinada , Feminino , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Qualidade de Vida , Taxa de Sobrevida , Resultado do Tratamento
6.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198725

RESUMO

The molecular diversity of prostate cancer (PCa) has been demonstrated by recent genome-wide studies, proposing a significant number of different molecular markers. However, only a few of them have been transferred into clinical practice so far. The present study aimed to identify and validate novel DNA methylation biomarkers for PCa diagnosis and prognosis. Microarray-based methylome data of well-characterized cancerous and noncancerous prostate tissue (NPT) pairs was used for the initial screening. Ten protein-coding genes were selected for validation in a set of 151 PCa, 51 NPT, as well as 17 benign prostatic hyperplasia samples. The Prostate Cancer Dataset (PRAD) of The Cancer Genome Atlas (TCGA) was utilized for independent validation of our findings. Methylation frequencies of ADAMTS12, CCDC181, FILIP1L, NAALAD2, PRKCB, and ZMIZ1 were up to 91% in our study. PCa specific methylation of ADAMTS12, CCDC181, NAALAD2, and PRKCB was demonstrated by qualitative and quantitative means (all p < 0.05). In agreement with PRAD, promoter methylation of these four genes was associated with the transcript down-regulation in the Lithuanian cohort (all p < 0.05). Methylation of ADAMTS12, NAALAD2, and PRKCB was independently predictive for biochemical disease recurrence, while NAALAD2 and PRKCB increased the prognostic power of multivariate models (all p < 0.01). The present study identified methylation of ADAMTS12, NAALAD2, and PRKCB as novel diagnostic and prognostic PCa biomarkers that might guide treatment decisions in clinical practice.


Assuntos
Proteínas ADAMTS/genética , Glutamato Carboxipeptidase II/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Proteína Quinase C beta/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Regiões Promotoras Genéticas/genética , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Fatores de Transcrição/genética
7.
Int J Mol Sci ; 22(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199232

RESUMO

Non-muscle-invasive bladder cancer is the most common form of bladder cancer. The main problem in managing bladder tumors is the high recurrence after the transurethral resection of bladder tumors (TURBT). Our study aimed to examine the fate of intravesically applied cancer cells as the implantation of cancer cells after TURBT is thought to be a cause of tumor recurrence. We established an orthotopic mouse bladder tumor model with MB49-GFP cancer cells and traced them during the first three days to define their location and contacts with normal urothelial cells. Data were obtained by Western blot, immunolabeling, and light and electron microscopy. We showed that within the first two hours, applied cancer cells adhered to the traumatized epithelium by cell projections containing α3ß1 integrin on their tips. Cancer cells then migrated through the epithelium and on day 3, they reached the basal lamina or even penetrated it. In established bladder tumors, E-cadherin and desmoplakin 1/2 were shown as feasible immunohistochemical markers of tumor margins based on the immunolabeling of various junctional proteins. Altogether, these results for the first time illustrate cancer cell implantation in vivo mimicking cellular events of tumor recurrence in bladder cancer patients.


Assuntos
Epitélio/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Animais , Caderinas/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Modelos Animais de Doenças , Feminino , Integrina alfa3beta1/metabolismo , Junções Intercelulares/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Bexiga Urinária/ultraestrutura , Neoplasias da Bexiga Urinária/ultraestrutura , Urotélio/patologia , Urotélio/ultraestrutura
8.
Anticancer Res ; 41(7): 3615-3624, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230158

RESUMO

BACKGROUND/AIM: The aim of this study was to investigate the efficacy and safety of adjuvant chemotherapy in elderly patients with stage III colorectal cancer in a real-world setting. PATIENTS AND METHODS: A total of 165 patients of ≥70 years of age with stage III colorectal cancer who underwent a curative operation between 2008 and 2020 were enrolled in this study. RESULTS: Among septuagenarians, the relapse-free and overall survival rates in the single-agent therapy group and the combination therapy group were significantly better than those in the group treated by surgery alone. However, no significant differences were observed in the relapse-free and overall survival rates of the single-agent therapy group and the combination therapy group. Among octogenarians in whom all regimens were single-agent therapy, adjuvant chemotherapy tended to improve the relapse-free and overall survival rates but not the time to recurrence or cancer-specific survival. CONCLUSION: Single-agent adjuvant chemotherapy may be a useful treatment option for septuagenarians with stage III colorectal cancer. However, the efficacy of adjuvant chemotherapy in octogenarians was not shown in this study.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/métodos , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias/métodos , Taxa de Sobrevida
9.
Anticancer Res ; 41(7): 3625-3634, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230159

RESUMO

BACKGROUND/AIM: Stage III breast cancer comprises a broad spectrum of disease, including the extent of supraclavicular/internal mammary lymph node metastasis. In this study, we evaluated the usefulness of the absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of patients with stage III breast cancer. PATIENTS AND METHODS: Seventy-five patients with stage III breast cancer who underwent surgery were included. We compared their clinicopathological factors according to the presence or not of supraclavicular/internal mammary lymph node metastasis, and pretreatment ALC or NLR. RESULTS: Patients with metastasis of the studied lymph nodes had a poorer prognosis in comparison to those without metastasis. In patients without these types of lymph node metastasis, both the ALC and NLR were predictive factors for relapse-free and overall survival. Among these patients, those with a low ALC or high NLR had recurrence-free and overall survival comparable to those of patients with supraclavicular/internal mammary lymph node metastasis. CONCLUSION: Pretreatment ALC and NLR were prognostic factors for patients with stage III breast cancer.


Assuntos
Neoplasias da Mama/patologia , Linfócitos/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Contagem de Linfócitos/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico
10.
Anticancer Res ; 41(7): 3683-3688, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230167

RESUMO

BACKGROUND/AIM: There are no clinically significant cutoff values of serum vitamin D levels and time points to predict the prognosis of colon cancer, particularly in patients who underwent curative surgical resection. PATIENTS AND METHODS: We retrospectively analyzed serum vitamin D levels in 795 patients with stages I to III colon cancer who underwent curative surgical resection. RESULTS: Patients with vitamin D levels below 12 ng/ml at one year after surgical resection demonstrated a significantly reduced disease-free survival (DFS) than those who did not have vitamin D deficiency (p=0.01). In the multivariate analysis, an age of 70 years or older [hazard ratio (HR)=1.992; p=0.001], pathologic stage (HR=3.739; p<0.001), and vitamin D deficiency (less than 12 ng/ml) at one year after surgery (HR=0.563; p=0.020) were factors unfavorably influencing DFS. CONCLUSION: In patients with stages I to III of colon cancer, vitamin D deficiency at one year after surgical resection was associated with increased disease relapse.


Assuntos
Neoplasias do Colo/patologia , Recidiva Local de Neoplasia/patologia , Deficiência de Vitamina D/patologia , Vitamina D/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias/métodos , Período Pós-Operatório , Prognóstico , Estudos Retrospectivos , Deficiência de Vitamina D/metabolismo , Adulto Jovem
11.
Anticancer Res ; 41(8): 3851-3857, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281845

RESUMO

BACKGROUND/AIM: Muscle invasive bladder cancer (MIBC) is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predictive biomarkers for recurrence patterns in patients undergoing RC for MIBC. PATIENTS AND METHODS: Our institutional cystectomy database containing cases from 1992-2014 was queried for patients with local only recurrence (LOR), and case-matched to patients with distant recurrence (DR) and no recurrence (NR). Clinicopathological data were collected and a tissue microarray was analyzed for presence of Ki-67, MRE11, and PD-L1 using immunofluorescence and immunohistochemistry. RESULTS: Pathologic specimens from 42 patients (18 NR, 16 LOR, and 8 DR) were reviewed. Compared to normal bladder tissue, tumors had increased expression of Ki-67 (p<0.01) and PD-L1 (p<0.05). High Ki-67 was associated with recurrence pattern (local vs. distant) on univariate analysis (p<0.05). Ki-67 cell density varied by recurrence type: LOR (1354 cells/mm2), DR (557 cells/mm2) and NR (1111 cells/mm2) (p=0.034). CONCLUSION: Our selected biomarkers could distinguish MIBC from normal bladder tissue but could not classify samples by recurrence pattern.


Assuntos
Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno Ki-67/metabolismo , Proteína Homóloga a MRE11/metabolismo , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade
12.
Anticancer Res ; 41(8): 4027-4032, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281869

RESUMO

BACKGROUND/AIM: We aimed to investigate the effectiveness of postoperative radiotherapy (RT) on local recurrence-free survival (LRFS) in high-grade infiltrative soft tissue sarcomas (STSs) and determine its prognostic factors. PATIENTS AND METHODS: This was a retrospective cohort study and included 132 patients with high-grade STSs. Patients were divided into two groups: Group RT (n=48) who underwent postoperative RT and Group No-RT (n=84) who underwent only surgery. We analysed 5-year LRFS and its prognostic factors between these groups. Furthermore, 5-year LRFS in infiltrative and non-infiltrative STSs were evaluated. RESULTS: Five-year LRFS was not significantly different in Group RT (83.6%) and Group No-RT (79.6%) (p=0.698). Overall, significant prognostic factors influencing LRFS were age at diagnosis (p=0.02) and tumour growth pattern (p=0.04). Postoperative RT was less effective in the infiltrative than in non-infiltrative pattern of STSs. CONCLUSION: Postoperative RT does not influence local recurrence outcomes in infiltrative STSs.


Assuntos
Neoplasias de Tecidos Moles/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Período Pós-Operatório , Estudos Retrospectivos , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Adulto Jovem
13.
Anticancer Res ; 41(8): 4133-4141, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281884

RESUMO

BACKGROUND/AIM: Advanced/recurrent breast cancer (ARBC) still has a poor prognosis; therefore, new treatment strategies are required. In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cell vaccination in combination with standard therapies in terms of the survival of patients with ARBC. PATIENTS AND METHODS: A total of 127 patients with ARBC were enrolled in this study. The correlation between overall survival and various clinical factors of each ARBC subset was examined by univariate and multivariate analyses. RESULTS: Multivariate analysis demonstrated that performance status (PS) 0, the absence of prior chemotherapy, liver/pleural metastasis, and the presence of combined surgery in ARBC and PS 0 or the absence of liver metastasis in the HR+/HER- subset are indications for immune-cell therapy. CONCLUSION: A survival benefit could be potentially obtained by a combination of immune-cell therapy with other therapies in ARBC patients.


Assuntos
Neoplasias da Mama/terapia , Terapia Baseada em Transplante de Células e Tecidos , Células Dendríticas/transplante , Imunoterapia , Recidiva Local de Neoplasia/terapia , Linfócitos T/transplante , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos
14.
Medicine (Baltimore) ; 100(25): e26388, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160418

RESUMO

ABSTRACT: Radioiodine-refractory thyroid cancers (IRTCs) are uncommon and have a poor prognosis. Treatment options for radioiodine-refractory and anaplastic tumors (ATCs) are limited. Although the genomic landscape of thyroid cancer has been studied, there is little evidence on whether next-generation sequencing (NGS) findings translate to tumor control.We analyzed all patients with IRTC and ATC who underwent commercially available NGS in 3 cancer centers.Twenty-two patients were identified, 16 patients with IRTCs and 6 patients with ATCs. Eighteen (82%) had targetable findings in NGS, nine patients were treated accordingly. Median progression-free survival for targeted treatment was 50 months [95% confidence interval (CI95%) 9.8-66.6] and2 months (CI95% 0.2-16.5) for IRTC and ATC, respectively. Of 4 patients who achieved durable responses of 7 to 50 months, 2 are ongoing. The estimated median OS of IRTC receiving targeted treatment was not reached (CI95% 89.7-111.4 months) and was 77.8 months (CI95% 52.5-114.6) for patients treated conventionally (P = .3).NGS may detect clinically significant genetic alterations and benefit patients with advanced thyroid cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Radioisótopos do Iodo/uso terapêutico , Recidiva Local de Neoplasia/terapia , Neoplasias da Glândula Tireoide/terapia , Adulto , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Análise Mutacional de DNA , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Radioisótopos do Iodo/farmacologia , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Tolerância a Radiação/efeitos dos fármacos , Tolerância a Radiação/genética , Estudos Retrospectivos , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/mortalidade
15.
Medicine (Baltimore) ; 100(25): e26450, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160440

RESUMO

RATIONALE: The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib. PATIENT CONCERNS: We described a 55-year-old man with good performance status (PS). DIAGNOSES: He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018. INTERVENTIONS: He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib. OUTCOMES: It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable. LESSIONS: This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.


Assuntos
Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação/métodos , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Quimiorradioterapia/métodos , Resistencia a Medicamentos Antineoplásicos , Substituição de Medicamentos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Radioterapia de Intensidade Modulada , Critérios de Avaliação de Resposta em Tumores Sólidos
16.
Eur J Radiol ; 141: 109802, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34090112

RESUMO

OBJECTIVES: To retrospectively investigate whether radiological and clinicopathological characteristics were associated with the presence of stage IA-IIA lung adenocarcinoma in patients at high risk for a postoperative recurrence. MATERIALS AND METHODS: Three hundred twelve patients with biopsy-proven node-negative early-stage (IA-IIA) lung adenocarcinoma met the inclusion criteria for this study. Demographics data and histopathological findings were collected from medical records. Computed tomography (CT) performed approximately 1 month before surgery was manually scored using 23 CT descriptors. Univariate analyses were applied to demonstrate an association between clinicopathological and radiological features and 2-/5-year recurrences. Multivariate logistic regression was performed to assess the ability of radiological and clinicopathological features to discriminate low and high-risk factors for recurrence. A ROC curve was used to evaluate prediction performance. RESULTS: Univariate analysis revealed that the 2-year recurrence was associated with six radiological features and two clinicopathological features, while 5-year recurrence was associated with five radiological features and two clinicopathological features. A multivariate logistic regression model of combined clinicopathological and radiological features showed that stage IIA (OR = 2.87), solid texture (solid part > 50 %: OR = 4.81; solid part = 100 %: OR = 3.61), pleural attachment (OR = 3.97) and bronchovascular bundle thickening (OR = 2.16) were associated with the independent predictors of 2-year recurrence, and stage IIA (OR = 3.52), solid texture (solid part > 50 %: OR = 3.56; solid part = 100 %: OR = 2.44) and pleural attachment (OR = 4.57) were associated with 5-year recurrence. Combined radiological and clinicopathological features could be significant indicators of 2- and 5-year recurrences (AUC = 0.784 and AUC = 0.815, respectively). CONCLUSIONS: The combination of radiological and clinicopathological features has the potential to help predict postoperative recurrence in patients with stage IA-IIA lung adenocarcinomas and guide oncologists and patients whether to undergo additional treatment after surgery.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
17.
Crit Rev Oncol Hematol ; 163: 103391, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34102286

RESUMO

PURPOSE: Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT. RESULTS: 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus. CONCLUSIONS: Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT.


Assuntos
Neoplasias da Mama , Radiodermatite , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Radioterapia Adjuvante/efeitos adversos
18.
J Med Life ; 14(2): 170-175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104239

RESUMO

Gangliogliomas are central nervous system tumors located in the temporal lobe of young patients, frequently associated with epilepsy. In this paper, we propose a grading system based solely on histopathological criteria. We reevaluated all cases of ganglioglioma, atypical ganglioglioma, and anaplastic ganglioglioma diagnosed between 2011 and 2020 in the Pathology Department of the Emergency Clinical Hospital Bagdasar-Arseni, based on the type of glial mitoses, the number of neuronal and glial mitoses, presence of necrosis, microvascular proliferation, eosinophilic granular bodies, hypercellularity, presence and disposition of inflammatory infiltrate and atypical pleomorphism. Based on the proposed grading system, a score of 0-4 corresponded to a benign ganglioglioma, 5-9 to an atypical ganglioglioma, and 10-18 to an anaplastic ganglioglioma. The survival rates were 90% for benign ganglioglioma, 71.43% for atypical ganglioglioma, and 62.54% for anaplastic ganglioglioma. One case of benign ganglioglioma underwent a malignant transformation into anaplastic ganglioglioma, and recurrences were noticed in 28.57% of atypical ganglioglioma cases and 30.7% of all anaplastic gangliogliomas. The presence of rare glial mitoses and hypercellularity was correlated with mortality in cases of atypical ganglioglioma. We believe this histopathological scoring system could be used as a three-tier system to identify atypical ganglioglioma cases that are bound to have an aggressive course of evolution and require close follow-up. The other option would be to convert it to a two-tier grading system that can separate low-grade gangliogliomas from high-grade ones. The latter category can encompass both atypical and anaplastic ganglioglioma due to the high mortality of both entities.


Assuntos
Neoplasias Encefálicas/patologia , Ganglioglioma/patologia , Adolescente , Adulto , Idoso , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/metabolismo , Criança , Pré-Escolar , Feminino , Ganglioglioma/complicações , Ganglioglioma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Adulto Jovem
19.
Int J Mol Sci ; 22(9)2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34066996

RESUMO

Glioblastomas (GBM)-the most common, therapy-resistant, and lethal tumors driven by populations of glioma stem cells (GSCs) are still on the list of the most complicated pathologies. Thus, deeper understanding and characterization of GSCs is indispensable to find suitable targets and develop more effective therapies. In the present study, we applied native glioblastoma cells and GSCs sequencing, screened for GSC-specific targets and checked if the signature is related to GBM patient pathological, clinical data as well as molecular subtypes applying TCGA cohort. Data analysis revealed that tumors of proneural and mesenchymal subtypes are branching in separate clusters based on screened gene expression. Samples of the same subtype revealed significantly different patient survival prognosis as well as recurrence chance between the clusters. Recently, different subpopulations of mesenchymal GSC demonstrating different properties were shown, which indicates possible internal heterogeneity of GBM subtypes as well. Current findings also revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Perfilação da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Mesoderma/patologia , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Análise por Conglomerados , Feminino , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Recidiva Local de Neoplasia/patologia , Análise de Componente Principal , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Int J Mol Sci ; 22(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063642

RESUMO

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low, and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabeled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.


Assuntos
Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/radioterapia , Animais , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Fatores Imunológicos/genética , Imunoterapia/métodos , Camundongos , Recidiva Local de Neoplasia/patologia , Neoplasias de Mama Triplo Negativas/imunologia , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação , Ensaios Antitumorais Modelo de Xenoenxerto
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