Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
1.
Biomed Pharmacother ; 175: 116805, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38781868

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cancer, accounting for approximately 80% of all renal cell cancers. Due to its exceptional inter- and intratumor heterogeneity, it is highly resistant to conventional systemic therapies. Targeting the evasion of cell death, one of cancer's hallmarks, is currently emerging as an alternative strategy for ccRCC. In this article, we review the current state of apoptosis-inducing therapies against ccRCC, including antisense oligonucleotides, BH3 mimetics, histone deacetylase inhibitors, cyclin-kinase inhibitors, inhibitors of apoptosis protein antagonists, and monoclonal antibodies. Although preclinical studies have shown encouraging results, these compounds fail to improve patients' outcomes significantly. Current evidence suggests that inducing apoptosis in ccRCC may promote tumor progression through apoptosis-induced proliferation, anastasis, and apoptosis-induced nuclear expulsion. Therefore, re-evaluating this approach is expected to enable successful preclinical-to-clinical translation.

2.
Clin Transl Oncol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769215

RESUMO

INTRODUCTION: Due to its lack of conventional surface receptors, triple-negative breast cancer (TNBC) is inherently resistant to most targeted therapies. MAL2 overexpression prompts endocytosis, conferring resistance to novel therapeutics. This study explores the role of MAL2 and PD-L1 in TNBC patients' prognosis. METHODS: We performed immunohistochemical analysis on 111 TNBC samples collected from 76 patients and evaluated the expression of MAL2 and PD-1. We expanded the study by including The Cancer Genome Atlas (TCGA) cohort. RESULTS: MAL2 expression did not correlate with stage, grade, tumor size, lymph node invasion, metastasis, and PD-1 expression. Patients with high MAL2 had significantly lower 5-year survival rates (71.33% vs. 89.59%, p = 0.0224). In the tissue microarray cohort (TMA), node invasions, size, recurrence, and low MAL2 (HR 0.29 [CI 95% 0.087-0.95]; p < 0.05) predicted longer patients' survival. In the TCGA cohort, patients with low MAL2 had significantly longer overall survival and disease-specific survival than patients with high MAL2. Older age and high MAL2 expression were the only independent predictors of shorter patient survival in the BRCA TCGA cohort. CONCLUSION: High MAL2 predicts unfavorable prognosis in triple-negative breast cancer, and its expression is independent of PD-1 levels and clinicopathological features of TNBC.

3.
Sci Rep ; 14(1): 9458, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658633

RESUMO

Male sex is a risk factor for colorectal cancer (CRC) with higher illness burden and earlier onset. Thus, we hypothesized that loss of chromosome Y (LOY) in the tumor micro-environment (TME) might be involved in oncogenesis. Previous studies show that LOY in circulating leukocytes of aging men was associated with shorter survival and non-hematological cancer, as well as higher LOY in CD4 + T-lymphocytes in men with prostate cancer vs. controls. However, nothing is known about LOY in leukocytes infiltrating TME and we address this aspect here. We studied frequency and functional effects of LOY in blood, TME and non-tumorous tissue. Regulatory T-lymphocytes (Tregs) in TME had the highest frequency of LOY (22%) in comparison to CD4 + T-lymphocytes and cytotoxic CD8 + T-lymphocytes. LOY score using scRNA-seq was also linked to higher expression of PDCD1, TIGIT and IKZF2 in Tregs. PDCD1 and TIGIT encode immune checkpoint receptors involved in the regulation of Tregs function. Our study sets the direction for further functional research regarding a probable role of LOY in intensifying features related to the suppressive phenotype of Tregs in TME and consequently a possible influence on immunotherapy response in CRC patients.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Linfócitos T Reguladores , Microambiente Tumoral , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/genética , Microambiente Tumoral/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Masculino , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Idoso , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/genética , Pessoa de Meia-Idade , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Feminino , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Fator de Transcrição Ikaros/genética , Fator de Transcrição Ikaros/metabolismo
4.
Cureus ; 16(2): e55029, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38550491

RESUMO

Bronchogenic cysts, benign congenital malformations resulting from abnormal tracheobronchial tree budding, primarily manifest in the mediastinum, with retroperitoneal occurrence being exceedingly rare. Typically incidental findings on imaging, and their diagnosis pose challenges, particularly when malignancy is suspected. We present a case involving a 55-year-old woman diagnosed with chronic back pain. Physical examination revealed a painful mass in the left renal region. Subsequent MRI identified a smooth mass in the left adrenal gland without infiltration of surrounding structures. Laparoscopic surgery successfully removed the lesion without complications. Pathomorphological examination confirmed a gelatinous-filled cyst, identified as a retroperitoneal bronchogenic cyst in the left adrenal gland. Increasing reports of retroperitoneal bronchogenic cysts contribute to a better understanding of their characteristics, aiding preoperative diagnosis. However, given potential malignancy and definitive diagnosis through histopathological examination, surgical resection remains the preferred method.

5.
Clin Chim Acta ; 552: 117651, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37980974

RESUMO

PURPOSE: Despite its limitations, the cytology of body fluids is widely used in diagnosing neoplastic cells. Flow cytometry detects and identifies individual cells, enabling the detection of circulating tumor cells and facilitating diagnosis. This study compared the diagnostic utility of flow cytometry and cytology for detecting cancer cells in peritoneal and pleural fluids. METHODOLOGY: We used flow cytometry and cytology to examine 119 pleural and peritoneal effusions received for routine screening. Antibodies against clusters of differentiation 45 (CD45), 14 (CD14), and Epithelial cell adhesion molecule (EpCAM) were used to detect malignant cells. Based on combined clinical and diagnostic information, 37 fluid specimens were malignant, and 77 were benign. RESULTS: Flow cytometry correctly identified 34 cancers, while cytology identified 26 cancers (sensitivity 91.89 % vs. 70.27, respectively). Both methods had equal specificity (98.7 %). At a cut-off of > 0.29 % EpCAM(+) cells to all cells in the samples, flow cytometry accurately detected cancer cells, achieving 89.2 % sensitivity, 90.9 % specificity, and an AUC of 0.959 (p < 0.001). CONCLUSION: Flow cytometry improves the detection of epithelial cancer cells in peritoneal and pleural fluids compared to conventional cytology. Due to similar specificity and higher sensitivity, flow cytometry offers a promising alternative to cytology for patient screening.


Assuntos
Células Neoplásicas Circulantes , Derrame Pleural Maligno , Humanos , Molécula de Adesão da Célula Epitelial/metabolismo , Células Neoplásicas Circulantes/patologia , Citometria de Fluxo/métodos , Líquido Ascítico , Derrame Pleural Maligno/diagnóstico
6.
Biomol Biomed ; 24(1): 14-29, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-37877810

RESUMO

Anti-programmed cell death ligand 1 (anti-PD-L1)  immunotherapy is an increasingly crucial in cancer treatment. To date, the Federal Drug Administration (FDA) has approved four PD-L1 immunohistochemistry (IHC) staining protocols, commercially available in the form of "kits", facilitating testing for PD-L1 expression. These kits comprise four PD-L1 antibodies on two separate IHC platforms, each utilizing distinct, non-interchangeable scoring systems. Several factors, including tumor heterogeneity and the size of the tissue specimens assessed, can lead to PD-L1 status misclassification, potentially hindering the initiation of therapy. Therefore, the development of more accurate predictive biomarkers to distinguish between responders and non-responders prior to anti-PD-1/PD-L1 therapy warrants further research. Achieving this goal necessitates refining sampling criteria, enhancing current methods of PD-L1 detection, and deepening our understanding of the impact of additional biomarkers. In this article, we review potential solutions to improve the predictive accuracy of PD-L1 assessment in order to more precisely anticipate patients' responses to anti-PD-1/PD-L1 therapy, monitor disease progression and predict clinical outcomes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/metabolismo , Imuno-Histoquímica , Antígeno B7-H1 , Biomarcadores Tumorais/metabolismo , Imunoterapia
7.
Hum Cell ; 37(1): 101-120, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37874534

RESUMO

Circulating tumor cells (CTCs) are cancer cells that detach from the primary tumor, enter the bloodstream or body fluids, and spread to other body parts, leading to metastasis. Their presence and characteristics have been linked to cancer progression and poor prognosis in different types of cancer. Analyzing CTCs can offer valuable information about tumors' genetic and molecular diversity, which is crucial for personalized therapy. Epithelial-mesenchymal transition (EMT) and the reverse process, mesenchymal-epithelial transition (MET), play a significant role in generating and disseminating CTCs. Certain proteins, such as EpCAM, vimentin, CD44, and TGM2, are vital in regulating EMT and MET and could be potential targets for therapies to prevent metastasis and serve as detection markers. Several devices, methods, and protocols have been developed for detecting CTCs with various applications. CTCs interact with different components of the tumor microenvironment. The interactions between CTCs and tumor-associated macrophages promote local inflammation and allow the cancer cells to evade the immune system, facilitating their attachment and invasion of distant metastatic sites. Consequently, targeting and eliminating CTCs hold promise in preventing metastasis and improving patient outcomes. Various approaches are being explored to reduce the volume of CTCs. By investigating and discussing targeted therapies, new insights can be gained into their potential effectiveness in inhibiting the spread of CTCs and thereby reducing metastasis. The development of such treatments offers great potential for enhancing patient outcomes and halting disease progression.


Assuntos
Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética , Microambiente Tumoral
8.
Clin Exp Med ; 23(8): 5121-5127, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37804360

RESUMO

PD-L1 expression is known to predict the benefits of immune checkpoint inhibitor therapy for triple-negative breast cancer (TNBC). We examined whether the PD-L1 expression evaluated in biopsy specimens accurately reflects its expression in the whole tumor. Immunohistochemistry was performed on 81 biopsy and resection specimens from patients with TNBC to determine their PD-L1 status. We found PD-L1-positive tumors in 23 (28%) biopsy specimens and primarily PD-L1-negative tumors in 58 (72%). The PD-L1 status was reevaluated in matching postoperative specimens of primarily PD-L1-negative tumors. Of them, 31% (18/58) were positive, whereas 69% (40/58) were negative. Considering the pre- and postoperative analyses, 41 (51%) patients had PD-L1-positive tumors, while 40 had PD-L1-negative tumors. We found 18 (22%) more PD-L1-positive tumors while examining the resection specimens compared to biopsies, and the difference was statistically significant (p = 0.0038). Diagnostic biopsies do not fully reflect the PD-L1 expression in TNBC. Our results suggest that a significant subset of TNBC patients may be misclassified as PD-L1-negative and disqualified from anti-PD-L1 therapy.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/metabolismo , Antígeno B7-H1/metabolismo , Imuno-Histoquímica , Biópsia
9.
Cells ; 12(10)2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37408208

RESUMO

Prostate cancer remains a leading cause of cancer-related death in men worldwide. Recent research advances have emphasized the critical roles of mismatch repair (MMR) and double-strand break (DSB) in prostate cancer development and progression. Here, we provide a comprehensive review of the molecular mechanisms underlying DSB and MMR defects in prostate cancer, as well as their clinical implications. Furthermore, we discuss the promising therapeutic potential of immune checkpoint inhibitors and PARP inhibitors in targeting these defects, particularly in the context of personalized medicine and further perspectives. Recent clinical trials have demonstrated the efficacy of these novel treatments, including Food and Drugs Association (FDA) drug approvals, offering hope for improved patient outcomes. Overall, this review emphasizes the importance of understanding the interplay between MMR and DSB defects in prostate cancer to develop innovative and effective therapeutic strategies for patients.


Assuntos
Reparo de Erro de Pareamento de DNA , Neoplasias da Próstata , Masculino , Humanos , Reparo do DNA , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
10.
Front Oncol ; 13: 1158261, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37228491

RESUMO

Introduction: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of death worldwide. Efficient non-invasive blood-based biomarkers for CRC early detection and prognosis are urgently needed. Methods: To identify novel potential plasma biomarkers, we applied a proximity extension assay (PEA), an antibody-based proteomics strategy to quantify the abundance of plasma proteins in CRC development and cancer-associated inflammation from few µL of plasma sample. Results: Among the 690 quantified proteins, levels of 202 plasma proteins were significantly changed in CRC patients compared to age-and-sex-matched healthy subjects. We identified novel protein changes involved in Th17 activity, oncogenic pathways, and cancer-related inflammation with potential implications in the CRC diagnosis. Moreover, the interferon γ (IFNG), interleukin (IL) 32, and IL17C were identified as associated with the early stages of CRC, whereas lysophosphatidic acid phosphatase type 6 (ACP6), Fms-related tyrosine kinase 4 (FLT4), and MANSC domain-containing protein 1 (MANSC1) were correlated with the late-stages of CRC. Discussion: Further study to characterize the newly identified plasma protein changes from larger cohorts will facilitate the identification of potential novel diagnostic, prognostic biomarkers for CRC.

11.
Arch Med Sci ; 19(2): 499-506, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37034507

RESUMO

Introduction: The purpose of this research was to explore the correlation between Gleason score and pattern and the expression of the MLH1, MSH2, MDC1, TP53BP1 proteins in prostate cancer (PC). Prostate cancer development is related to errors in DNA, among others double-strand breaks (DSB) and changes in the base sequence of the DNA. These errors should be repaired through mismatch (MMR) or DSB repair proteins such as MSH2, MLH1, MDC1 and TP53BP1. Material and methods: A total of 500 prostate cancer specimens were recruited in this study. From among all gathered specimens the 52 most suitable cases were selected. The expression of examined proteins was detected by immunohistochemistry, and its correlation with the Gleason score and pattern were further analyzed through standard statistical algorithms. Results: The results show a significant correlation between Gleason pattern and the nuclear expression of the MSH2 protein and the cytoplasmic expression of the MLH1 protein. Gleason score significantly correlates with the nuclear and the cytoplasmic expression of the MSH2 protein and the cytoplasmic expression of the MDC1 protein. There is no correlation between the nuclear or cytoplasmic expression of the TP53BP1 protein and Gleason pattern or score. Conclusions: Our study suggests that the aberration in the MMR repair mechanism may be significantly more important regarding the grading among PC cells in comparison to the impact of alterations in the DSB repair mechanism. The lack of correlation between expression of the TP53BP1 protein and Gleason pattern and Gleason score suggests that the radiation resistance of PC is independent of alterations connected with TP53BP1.

12.
Anticancer Res ; 43(4): 1503-1511, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36974831

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) continues to pose a challenge due to our limited understanding of its underlying pathophysiology. Aconitase 2 (ACO2) is a mitochondrial Fe-S cluster enzyme that catalyzes the stereospecific isomerization of citrate to isocitrate in the second step of the Krebs cycle. We investigated the relationship between ACO2 protein expression and the clinical course of RCC. MATERIALS AND METHODS: Tumor samples were evaluated in a commercial tissue microarray for ACO2 expression using the H-score. The tissue microarrays contained a total of 96 cores from primary tumors, matched metastases, and matched adjacent tissues derived from 32 patients with RCC. The mean follow-up was 82.74 months. Correlation analysis of clinicopathological data and survival was performed. Expression levels of ACO2 mRNA were compared using publicly available data. RESULTS: All the tissue samples showed cytoplasmic ACO2 expression, with median H-scores of 139.7, 130.3 and 166.7 in primary tumor, metastatic tissue, and matched control tissue, respectively. A significantly higher ACO2 expression was found in normal tissues compared to primary and metastatic RCC. The analysis demonstrated a significantly positive correlation between ACO2 expression in primary tumors and their metastases. The results also showed a significant correlation between the expression of ACO2 and worse overall survival among patients with RCC. CONCLUSION: ACO2 may be used as a prognostic factor in RCC. Significant alterations in ACO2 expression are thought to occur in the early stages of RCC carcinogenesis. Considering the physiological role of ACO2, its dysregulation may constitute an adaptive trait of RCC for escaping the equilibrium phase of immunoediting.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Prognóstico , Biomarcadores Tumorais/metabolismo , RNA Mensageiro , Aconitato Hidratase
13.
J Med Virol ; 95(1): e28303, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36369954

RESUMO

Recurrent respiratory papillomatosis is strictly connected with human papillomavirus (HPV) infection of the epithelium of the upper respiratory tract. The main treatment of lesions located in the larynx or lower pharynx includes microsurgical excision by using a CO2 laser. To decrease the amount of surgical procedures gain in importance combined therapy with antiviral agents. The aim of this study was to investigate the effect of the intralesional application of Cidofovir on the tissue of laryngeal papillomas. We have shown that simultaneous microsurgery with adjuvant therapy of Cidofovir reduces chronic inflammation (by measuring the expression of CD4 and CD8 in tissue samples), cell proliferation, and regulates the cell cycle of HPV-infected cells by reducing the expression of p53 and p63 proteins. In addition, this strategy reduces the multiple surgical procedures and regrowth of the pathology.


Assuntos
Neoplasias Laríngeas , Organofosfonatos , Infecções por Papillomavirus , Humanos , Cidofovir/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Projetos Piloto , Organofosfonatos/uso terapêutico , Citosina/uso terapêutico , Antivirais/uso terapêutico , Neoplasias Laríngeas/patologia , Epitélio/patologia , Ciclo Celular , Imunomodulação
14.
Clin Transl Oncol ; 25(3): 830-840, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36374405

RESUMO

PURPOSE: The mutation of p53 is considered a pivotal step in bladder cancer pathogenesis. Recently, distinct interactions between p53 and CDK9, a transcription regulator, have been described. In this work, we explored the prognostic role of p53 expression and evaluated its associations with CDK9 in urothelial carcinoma. MATERIALS AND METHODS: The research group consisted of 67 bladder cancer samples and 32 normal urothelial mucosa samples. All specimens were analyzed using ImageJ and the IHC profiler plugin. To validate the results, 406 cases from The Cancer Genome Atlas database were analyzed. RESULTS: P53 and CDK9 are overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High p53 expression was observed in metastatic tumors and tumors with high CDK9 expression (p < 0,05). High p53 expression was predictive for shorter survival in patients with non-muscle-invasive bladder cancer (HR = 0.107 [0.012-0.96]; p = 0.046) but did not correlate with prognosis in the muscle-invasive group. In high CDK9 cancers, high p53 expression correlated with the occurrence of high-grade and muscle-invasive tumors (p < 0.05). CONCLUSION: High expression of p53 correlates with unfavorable clinical features of bladder cancer. CDK9 is associated with the expression of p53, possibly through interactions with p53 inhibitors. Since the blockade of CDK9 in other malignancies reactivates wild-p53 activity, confirming the crosstalk between p53 and CDK9 in bladder cancer may be another step to explain the mechanism of tumor progression in its early stages.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Prognóstico , Proteína Supressora de Tumor p53/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quinase 9 Dependente de Ciclina/metabolismo
15.
Int J Mol Sci ; 23(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36499030

RESUMO

Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Autofagia/genética , Transdução de Sinais , Processamento de Proteína Pós-Traducional , Neoplasias Renais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo
16.
Biomedicines ; 10(8)2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-36009577

RESUMO

Glioblastoma is the most malignant central nervous system tumor, which represents 50% of all glial tumors. The understanding of glioma genesis, prognostic evaluation, and treatment planning has been significantly enhanced by the discovery of molecular genetic biomarkers. This study aimed to evaluate survival in patients with primary glioblastoma concerning O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and other clinical factors. The study included 41 newly diagnosed glioblastoma patients treated from 2011 to 2014 in the 10th Military Research Hospital and Polyclinic, Poland. All patients underwent surgical resection followed by radiation and chemotherapy with alkylating agents. The MGMT promoter methylation was evaluated in all patients, and 43% were found to be methylated. In 26 and 15 cases, gross total resection and subtotal resection were conducted, respectively. Patients with a methylated MGMT promoter had a median survival of 504 days, while those without methylation had a median survival of 329 days. The group that was examined had a median age of 53. In a patient group younger than 53 years, those with methylation had significantly longer overall survival (639 days), compared to 433.5 days for patients without methylation. The most prolonged survival (551 days) was in patients with MGMT promoter methylation after gross total resection. The value of MGMT promoter methylation as a predictive biomarker is widely acknowledged. However, its prognostic significance remains unclear. Our findings proved that MGMT promoter methylation is also an essential positive prognostic biomarker.

17.
Pol J Pathol ; 73(2): 82-87, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35979754

RESUMO

INTRODUCTION: Unresectable renal cell carcinoma continues to be a great challenge due to our limited understanding of its underlying pathophysiology. We explored the relationship between KIF11 protein expression and the clinical courses of clear cell renal cell carcinoma (ccRCC) using a tissue microarray. MATERIAL AND METHODS: The tissue microarray contained specimens derived from 90 patients, cancer and matched adjacent non-cancerous tissue (2 cores per case), followed up for 7 years. Tumour samples were evaluated for KIF11 expression using the H-score, and their correlations with clinicopathological data and survival data were analysed. RESULTS: 72.7% of ccRCC tissues presented KIF11 cytoplasmic expression with a median value of 20 (interquartile range 0-200). The nuclear staining was positive in 36.36% of ccRCC tissues. Among controls, nuclear KIF11 expression was absent, but cytoplasmic expression was identified in all cases, with a median value of 230 (interquartile range 45-290). Cytoplasmic KIF11 expression in ccRCC tissues was lower than in the control tissues and was positively correlated with tumour grade and mortality (p < 0.05). KIF11 nuclear expression did not correlate with overall survival. CONCLUSIONS: Elevated expression of KIF11 predicts poor clinical outcome in ccRCC patients. Downregulation of KIF11 may provide a new therapeutic strategy for ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Prognóstico , Biomarcadores Tumorais/análise , Cinesinas
18.
Biomedicines ; 10(7)2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35884907

RESUMO

Gastric cancer (GC) is the fourth most common cancer in the world in terms of incidence and second in terms of mortality. Chemotherapy is the main treatment for GC. The greatest challenge and major cause of GC treatment failure is resistance to chemotherapy. As such, research is ongoing into molecular evaluation, investigating mechanisms, and screening therapeutic targets. Several mechanisms related to both the tumor cells and the tumor microenvironment (TME) are involved in resistance to chemotherapy. TME promotes the secretion of various inflammatory cytokines. Recent studies have revealed that inflammatory cytokines affect not only tumor growth, but also chemoresistance. Cytokines in TME can be detected in blood circulation and TME cells. Inflammatory cytokines could serve as potential biomarkers in the assessment of chemoresistance and influence the management of therapeutics in GC. This review presents recent data concerning research on inflammatory cytokines involved in the mechanisms of chemoresistance and provides new clues in GC treatment.

19.
Biomedicines ; 10(7)2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35884974

RESUMO

The inflammatory process plays a significant role in the development of colon cancer (CRC). Intestinal cytokine networks are critical mediators of tissue homeostasis and inflammation but also impact carcinogenesis at all stages of the disease. Recent studies suggest that inflammation is of greater importance in the serrated pathway than in the adenoma-carcinoma pathway. Interleukins have gained the most attention due to their potential role in CRC pathogenesis and promising results of clinical trials. Malignant transformation is associated with the pro-tumorigenic and anti-tumorigenic cytokines. The harmony between proinflammatory and anti-inflammatory factors is crucial to maintaining homeostasis. Immune cells in the tumor microenvironment modulate immune sensitivity and facilitate cancer escape from immune surveillance. Therefore, clarifying the role of underlying cytokine pathways and the effects of their modulation may be an important step to improve the effectiveness of cancer immunotherapy.

20.
NPJ Breast Cancer ; 8(1): 76, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768433

RESUMO

The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation, and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population, and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor, and peripheral blood from 52 reportedly sporadic breast cancer patients. Targeted resequencing of 542 cancer-associated genes revealed subclonal somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3, and TSHR in the normal mammary gland at considerable allelic frequencies (9 × 10-2- 5.2 × 10-1), indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low-level subclonal (in 10-2-10-4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumorous mammary gland tissue of breast-conserving surgery patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA