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1.
Clín. investig. ginecol. obstet. (Ed. impr.) ; 51(1): [100926], Ene-Mar, 2024. ilus
Artigo em Espanhol | IBECS | ID: ibc-229785

RESUMO

Introducción: El carcinoma metaplásico de mama (CMM) es un tipo raro y agresivo de cáncer de mama que suele diagnosticarse en etapas avanzadas, con tumores de gran tamaño y grado histológico elevado. En este estudio, presentamos un caso de CMM, y realizamos una revisión y discusión de la literatura relacionada. Principales síntomas o hallazgos clínicos: Paciente de 35 años, sin antecedentes personales ni familiares relevantes, que consulta por tumoración mamaria de 2cm, de crecimiento progresivo, que agrega en la evolución umbilicación del pezón y dolor mamario. Se realiza ecografía mamaria que evidencia masa sólida polilobulada con características sospechosas. En suma: masa en mama izquierda BI-RADS 5. Diagnósticos principales, intervenciones terapéuticas y resultados: Se realiza core biopsia y la anatomía patológica evidencia un carcinoma ductal infiltrante, variedad metaplásico, triple negativo y con expresión PDL1>1%. Se realiza mastectomía radical modificada. En la evolución se diagnostica un secundarismo pulmonar, y la paciente recibió tratamiento sistémico de primera y segunda línea. Conclusiones: Dada la naturaleza agresiva de este tipo de tumor, y las limitadas opciones de tratamiento disponibles, la participación en ensayos clínicos puede considerarse para mejorar los resultados en estas pacientes. Un enfoque multidisciplinario, y la revisión en un comité de tumores son fundamentales para guiar las decisiones terapéuticas y proporcionar la mejor atención posible a estas pacientes(AU)


Introduction: Metaplastic breast carcinoma (MBC) is a rare and aggressive type of breast cancer that is often diagnosed in advanced stages, with large tumors and a high histological grade. In this study, we present a case of MBC, and conduct a review and discussion of the related literature. Main symptoms or clinical findings: A 35-year-old patient with no relevant personal or family history presents with a progressively growing 2 cm breast mass, which, over time, develops into nipple retraction and breast pain. A breast ultrasound reveals a suspicious-looking polilobulated solid mass. In summary: a BI-RADS 5 mass in the left breast. Main diagnoses, therapeutic interventions, and outcomes: A core biopsy is performed, and the pathology report reveals an infiltrating ductal carcinoma, metaplastic variety, triple-negative with PDL1 expression > 1%. A modified radical mastectomy is performed. During follow-up, pulmonary metastasis is diagnosed, and the patient receives first and second-line systemic treatment. Conclusions: Given the aggressive nature of this type of tumor and the limited treatment options available, participation in clinical trials may be considered to improve outcomes in these patients. A multidisciplinary approach, and review in a tumor committee are essential to guide therapeutic decisions and provide the best possible care for these patients.(AU)


Assuntos
Humanos , Feminino , Adulto , Mastectomia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Carcinoma/cirurgia , Ultrassonografia Mamária , Pacientes Internados , Exame Físico , Ginecologia , Obstetrícia
2.
Med Oncol ; 41(3): 73, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372827

RESUMO

Cancer stands as the reigning champion of life-threatening diseases, casting a shadow with the highest global mortality rate. Unleashing the power of early cancer treatment is a vital weapon in the battle for efficient and positive outcomes. Yet, conventional screening procedures wield limitations of exorbitant costs, time-consuming endeavors, and impracticality for repeated testing. Enter bio-marker-based cancer diagnostics, which emerge as a formidable force in the realm of early detection, disease progression assessment, and ultimate cancer therapy. These remarkable devices boast a reputation for their exceptional sensitivity, streamlined setup requirements, and lightning fast response times. In this study, we embark on a captivating exploration of the most recent advancements and enhancements in the field of electrochemical marvels, targeting the detection of numerous cancer biomarkers. With each breakthrough, we inch closer to a future where cancer's grip on humanity weakens, guided by the promise of personalized treatment and improved patient outcomes. Together, we unravel the mysteries that cancer conceals and illuminate a path toward triumph against this daunting adversary. This study celebrates the relentless pursuit of progress, where electrochemical innovations take center stage in the quest for a world free from the clutches of carcinoma.


Assuntos
Técnicas Biossensoriais , Carcinoma , Humanos , Biomarcadores Tumorais , Progressão da Doença
3.
Cell Biochem Funct ; 42(2): e3945, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38362935

RESUMO

MicroRNAs (miRNA) are small and conserved noncoding RNA molecules that regulate gene expression at the posttranscriptional level. These groups of RNAs are crucial in various cellular processes, especially in mediating disease pathogenesis, particularly cancer. The dysregulation of miRNAs was reported in many cancer types, including nasopharyngeal cancer (NPC), which is a malignant tumor of the nasopharynx. In this review, miRNAs involvement in crucial signaling pathways associated with NPC such as PTEN/PI3K/AKT, TGFß/SMAD, RAS/MAPK, Wnt/ß-catenin and pRB-E2F was investigated. miRNAs could function as tumor suppressor-miR or onco-miR in NPC profoundly influenced cell cycle, apoptosis, proliferation, migration, and metastasis. This comprehensive review of current literature provided a thorough profile of miRNAs and their interplay with the aforementioned signaling pathways in NPC. Understanding these molecular interactions could remarkably impact the diagnosis, prognosis, and therapeutic strategies for NPC.


Assuntos
Carcinoma , MicroRNAs , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , beta Catenina/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Transdução de Sinais , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Movimento Celular/genética , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo
6.
Aging (Albany NY) ; 16(3): 2715-2735, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309289

RESUMO

BACKGROUND: The relationship between clear cell renal cell carcinoma (ccRCC) and branched-chain amino acids (BCAA) metabolism has yet to be thoroughly explored. METHODS: The BCAA metabolism-related clusters were constructed using non-negative matrix factorization (NMF). The features of BCAA metabolism in ccRCC were evaluated by building a prognostic model using least absolute shrinkage and selection operator (LASSO) regression algorithm. Real-time quantitative PCR (RT-qPCR) was employed to analyze differential expression of branched-chain amino acid transaminase 1 (BCAT1) between cancer and paracancer tissues and between different cell lines. Cell counting kit-8, wound healing and Transwell chamber assays were conducted to determine changes in proliferative and metastatic abilities of A498 and 786-O cells. RESULTS: Two BCAA metabolism-related clusters with distinct prognostic and immune infiltration characteristics were identified in ccRCC. The BCAA metabolic signature (BMS) was capable of distinguishing immune features, tumor mutation burden, responses to immunotherapy, and drug sensitivity among ccRCC patients. RT-qPCR revealed overexpression of BCAT1 in ccRCC tissues and cell lines. Additionally, single-gene RNA sequencing analysis demonstrated significant enrichment of BCAT1 in macrophages and tumor cells. BCAT1 played tumor-promoting role in ccRCC and was closely associated with immunosuppressive cells and checkpoints. BCAT1 promoted ccRCC cell proliferation and metastasis. CONCLUSIONS: The BMS played a crucial role in determining the prognosis, tumor mutation burden, responses to immunotherapy and drug sensitivity of ccRCC patients, as well as the immune cell infiltration features. BCAT1 was linked to immunosuppressive microenvironments and may offer new sights into ccRCC immunotherapeutic targets.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Prognóstico , Aminoácidos de Cadeia Ramificada , Imunossupressores , Neoplasias Renais/genética , Microambiente Tumoral/genética , Transaminases/genética
7.
Sci Rep ; 14(1): 3893, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365923

RESUMO

Clear cell renal cell carcinoma (ccRCC) is characterized by high heterogeneity and recurrence rates, posing significant challenges for stratification and treatment. Basement membrane-related genes (BMGs) play a crucial role in tumor initiation and progression. Clinical and transcriptomic data of ccRCC patients were extracted from TCGA and GEO databases. We employed univariate regression and LASSO-Cox stepwise regression analysis to construct a BMscore model based on BMGs expression level. A nomogram combining clinical features and BMscore was constructed to predict individual survival probabilities. Further enrichment analysis and immune-related analysis were conducted to explore the enriched pathways and immune features associated with BMGs. High-risk individuals predicted by BMscore exhibited poorer overall survival, which was consistent with the validation dataset. BMscore was identified as an independent risk factor for ccRCC. Functional analysis revealed that BMGs were related to cell-matrix and tumor-associated signaling pathways. Immune profiling suggests that BMGs play a key role in immune interactions and the tumor microenvironment. BMGs serve as a novel prognostic predictor for ccRCC and play a role in the immune microenvironment and treatment response. Targeting the BM may represent an alternative therapeutic approach for ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Membrana Basal , Prognóstico , Fatores de Risco , Microambiente Tumoral/genética , Neoplasias Renais/genética
8.
Sci Rep ; 14(1): 3922, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365953

RESUMO

The influence of lipid metabolism on tumorigenesis and progression has garnered significant attention. However, the role of Glycerol Kinase (GK), a key enzyme in glycerol metabolism, in Esophageal Carcinoma (ESCA) remains unclear. To further elucidate the relationship between GK and ESCA, we investigated GK expression levels using database information. Controlled studies employing immunohistochemistry were conducted on clinical ESCA tumor samples and normal specimens, confirming GK's elevated expression in ESCA. Analysis of The Cancer Genome Atlas (TCGA) data via Kaplan-Meier (KM) survival plots revealed that increased GK expression correlates with poorer ESCA patient outcomes, particularly in overall survival (OS) and disease-specific survival (DSS). Multiple regression analysis indicated that elevated GK expression is an independent risk factor affecting ESCA prognosis. Statistical analysis of prognostic data from clinical samples further corroborated this finding. Moreover, there appears to be a significant correlation between GK expression and immune infiltration, specifically involving certain T and B lymphocytes. In conclusion, elevated GK expression in ESCA is strongly linked to poor prognosis and increased immune cell infiltration, highlighting its potential as an independent prognostic biomarker and a viable therapeutic target.


Assuntos
Carcinoma , Neoplasias Esofágicas , Humanos , Glicerol Quinase , Prognóstico , Neoplasias Esofágicas/genética , Linfócitos B
9.
Indian J Pathol Microbiol ; 67(1): 15-20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358183

RESUMO

Background: With no unified system for tumor associated macrophages (TAMs) density assessment, limited information is available on their relationship with ß-catenin expression. Aim: To evaluate the density of CD68+ TAMs in gastric adenocarcinoma samples by immunohistochemistry and correlate it with grade, stage, invasion, and beta-catenin. Designs and Settings: Formalin fixed paraffin embedded (FFPE) blocks from gastrectomy specimens of proven gastric adenocarcinoma were prospectively and retrospectively were studied over a period of two years. Materials and Methods: Immunohistochemistry with CD68 and ß-catenin was performed. TAM density was qualitatively compared in "tumor" versus "stroma" and "tumor" versus "non-tumor" regions. Quantitative CD68+ TAM density was assessed using different methods and compared. Cases were classified as high and low TAM based on the median value and correlated with histologic type, location, grade, stage and ß-catenin expression pattern. Statistical Analysis: Spearman's rank correlation test was used to compare the different methods of TAM density evaluation. The categorical variables were studied using Pearson's Chi-square or Fisher's exact test. CD68+ TAM density and ß-catenin expression were correlated by analysis of variance. A P value ≤ 0.05 was taken as statistically significant. Results: The CD68+ TAMs in the "tumor" versus "non-tumor" area (p = 0.34) and "tumor" versus "stroma distribution" (p = 0.81) did not show any statistical significance. All methods of TAM density were found to be comparable. High TAM group is significantly associated with lymphovascular invasion, tumor depth, lymph node metastasis, and abnormal ß-catenin expression. Conclusion: TAMs density plays an important role in the tumor stage. Macrophages may possibly induce gastric cancer invasiveness by activating ß-catenin pathway.


Assuntos
Adenocarcinoma , Carcinoma , Neoplasias Gástricas , Humanos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Neoplasias Gástricas/patologia , Antígenos CD/metabolismo , beta Catenina , Estudos Retrospectivos , Prognóstico
10.
Indian J Pathol Microbiol ; 67(1): 189-191, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358219

RESUMO

The synchronous occurrence of bilateral ovarian tumors and breast malignancy often raise the suspicion of a Krukenberg tumor or a hereditary breast and ovarian cancer syndrome, both of which are uncommon in clinical practice. A 58-years-old postmenopausal woman had a right breast lump and was diagnosed as infiltrating duct carcinoma, no special type, and incidentally detected bilateral adnexal mass with the clinical suspicion of Krukenberg tumor. However, following the radical surgical excision of the right breast and bilateral ovaries, the right breast showed invasive micropapillary carcinoma (IMPC) while the ovaries showed mature cystic teratoma (MCT) with benign Brenner tumor. IMPC of the breast along with bilateral ovarian MCT with benign Brenner tumor is an unusual clinical occurrence in a postmenopausal female and thus worthy of documentation. It should be categorized as a non-hereditary synchronous tumor. The histomorphology augmented by immunohistochemistry and appropriate clinical context is pivotal in rendering a correct diagnosis.


Assuntos
Tumor de Brenner , Carcinoma , Tumor de Krukenberg , Neoplasias Ovarianas , Teratoma , Feminino , Humanos , Pessoa de Meia-Idade , Tumor de Brenner/diagnóstico , Tumor de Brenner/cirurgia , Pós-Menopausa , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Teratoma/diagnóstico , Teratoma/cirurgia , Teratoma/patologia
11.
J Cancer Res Clin Oncol ; 150(2): 64, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300330

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the main type of renal cell carcinoma. Cyclin B2 (CCNB2) is a subtype of B-type cyclin that is associated with the prognosis of several cancers. This study aimed to identify the relationship between CCNB2 and progression of ccRCC and construct a novel lncRNAs-related model to predict prognosis of ccRCC patients. METHODS: The data were obtained from public databases. We identified CCNB2 in ccRCC using Kaplan-Meier survival analysis, univariate and multivariate Cox regression, and Gene Ontology analysis. External validation was then performed. The risk model was constructed based on prognostic lncRNAs by the LASSO algorithm and multivariate Cox regression. Receiver operating characteristics (ROC) curves were used to evaluate the model. Consensus clustering analysis was performed to re-stratify the patients. Finally, we analyzed the tumor-immune microenvironment and performed screening of potential drugs. RESULTS: CCNB2 associated with late clinicopathological parameters and poor prognosis in ccRCC and was an independent predictor for disease-free survival. In addition, CCNB2 shared the same expression pattern with known suppressive immune checkpoints. A risk model dependent on the expression of three prognostic CCNB2-related lncRNAs (SNHG17, VPS9D1-AS1, and ZMIZ1-AS1) was constructed. The risk signature was an independent predictor of ccRCC. The area under the ROC (AUC) curve for overall survival at 1-, 3-, 5-, and 8-year was 0.704, 0.702, 0.741, and 0.763. The high-risk group and cluster 2 had stronger immunogenicity and were more sensitive to immunotherapy. CONCLUSION: CCNB2 could be an important biomarker for predicting prognosis in ccRCC patients. Furthermore, we developed a novel lncRNAs-related risk model and identified two CCNB2-related molecular clusters. The risk model performed well in predicting overall survival and immunological microenvironment of ccRCC.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , RNA Longo não Codificante , Humanos , Carcinoma de Células Renais/genética , RNA Longo não Codificante/genética , Ciclina B2/genética , Regulação para Cima , Prognóstico , Neoplasias Renais/genética , Microambiente Tumoral
12.
J Cancer Res Clin Oncol ; 150(2): 76, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38310601

RESUMO

PURPOSE: Investigation of Microtubuli-associated Protein 2 (MAP2) expression and its clinical relevance in prostate cancer. MATERIAL AND METHODS: MAP2 expression was immunohistochemically analysed on radical prostatectomy specimens using whole block sections (n = 107) and tissue microarrays (TMA; n = 310). The staining intensity was evaluated for carcinoma, benign tissue and prostatic intraepithelial neoplasia. Expression data were correlated with clinicopathological parameters and biochemical recurrence-free survival. Additionally, MAP2 protein expression was quantitatively analysed in the serum of histologically confirmed prostate carcinoma patients and the control group using a commercial enzyme-linked immunosorbent assay. RESULTS: MAP2 staining was significantly stronger in neoplastic tissue than in non-neoplastic prostatic glands, both in whole block sections (p < 0.01) and in TMA sections (p < 0.05). TMA data revealed significantly stronger MAP2 staining in high-grade tumors. Survival analysis showed a significant correlation between strong MAP2 staining in carcinoma and shortened biochemical recurrence-free survival after prostatectomy (p < 0.001). Multivariate Cox regression analysis confirmed MAP2 as an independent predictor for an unfavourable course. Mean MAP2 serum levels for non-PCA vs. PCA patients differed significantly (non-PCA = 164.7 pg/ml vs. PCA = 242.5 pg/ml, p < 0.001). CONCLUSION: The present data support MAP2 as a novel biomarker in PCA specimens. MAP2 is correlated with tumor grade and MAP2 high-expressing PCA is associated with an increased risk of biochemical recurrence after radical prostatectomy. Future studies are necessary to evaluate MAP2 as a valuable immunohistochemical biomarker in preoperative PCA diagnostic procedures, in particular with regard to treatment modalities.


Assuntos
Carcinoma , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Neoplasias da Próstata/patologia , Prostatectomia/métodos , Carcinoma/cirurgia , Biomarcadores , Proteínas Associadas aos Microtúbulos , Biomarcadores Tumorais/metabolismo
13.
Int J Colorectal Dis ; 39(1): 27, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349566

RESUMO

PURPOSE: Sidedness has emerged as a prognostic factor for metastatic colorectal cancer treated with modern systemic therapies. This study investigates whether it is also relevant for an unselected patient cohort including all stages. METHODS: All consecutive patients admitted with colon cancer between 1995 and 2018 were retrieved from an institution-held database. Patients were divided into two cohorts. The first cohort included patients without distant metastases who were able to undergo curative resection. The second cohort presented with distant metastases (stage IV). Potentially prognostic factors were subjected to multivariate Cox Regression analysis. RESULTS: Overall, 1,606 patients met the inclusion and exclusion criteria. An R0-resection was achieved in 1,222 patients without distant metastases. Five-year cause-specific survival rate was 89.3% for this group. There was no difference between right- and left-sided cancers (88.2% vs. 90.1%, p = 0.220). However, prognosis of caecal carcinoma was significantly worse than that of all other sites combined (83.5% vs. 90.2%, p = 0.007). In multivariate analysis, pT-category, pN-category, grading, vascular invasion, emergency operation, adjuvant chemotherapy, and caecal carcinoma remained as independent prognostic factors. In the 384 patients with stage IV-disease, 3-year overall survival for right- vs. left-sided cancers differed only in univariate analysis (17.7% vs. 28.6%, p = 0.013). CONCLUSION: In non-metastatic colon cancer, location in the caecum is an independent prognostic factor. In unselected patients with stage IV colon cancer, sidedness was not found to be a prognostic factor. Differentiation into right- and left-sided tumors may be simplistic, and further studies on the biological behavior of different colonic sites are warranted.


Assuntos
Carcinoma , Neoplasias do Ceco , Neoplasias do Colo , Humanos , Prognóstico , Análise Multivariada
14.
Front Immunol ; 15: 1287632, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343544

RESUMO

Objective: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and is associated with high morbidity and mortality rates. Colorectal carcinogenesis occurs via the conventional adenoma-to-carcinoma and serrated pathways. Conventional T helper (Th) and innate lymphoid cells (ILCs) play vital roles in maintaining intestinal homeostasis. However, the contribution of these two major lymphoid cell populations and their associated cytokines to CRC development is unclear. Therefore, we aimed to analyze peripheral lymphocyte profiles during colorectal carcinogenesis. Methods: We collected 86 blood samples concurrently, and pathologists confirmed the presence of various pathological conditions (i.e., HPs, adenoma, and carcinoma) using hematoxylin and eosin staining. Ten healthy donors were recruited as healthy controls (HCs) from the physical examination center. We performed flow cytometry on peripheral blood mononuclear cells collected from patients with various pathological conditions and the HCs, and cytokines (interleukin-2, interleukin-4, interleukin-5, interleukin-13, interleukin-17A, interleukin-17F, interleukin-22, interferon-γ, and tumor necrosis factor-α) were quantified. We also analyzed the published single-cell RNA sequence data derived from tissue samples from different stages of colorectal carcinogenesis. Results: The cytokine response in peripheral CD4+ T cells was upregulated during the carcinoma process. The frequency of peripheral regulatory T cells (Tregs) increased in the adenoma and carcinoma stages. While the T follicular helper (Tfh) cell proportion was downregulated in the adenoma and carcinoma processes. Thus, Th cell subsets, especially Tregs and Tfh cells, were involved in colonic diseases. Moreover, the immunological profile characteristics in the HPs were clarified. Conclusion: We comprehensively analyzed circulating ILCs and adaptive T-cell lymphocyte subtypes in colorectal carcinoma progression. Our results show the immunological profile characteristics and support the involvement of Th subsets, especially Treg and Tfh cell populations, in colonic diseases. These findings significantly enhance our understanding of the immune mechanisms underlying CRC and its precancerous lesions. Further investigation of the Treg and Tfh cells' function in colorectal disease development will provide potential therapeutic targets for monitoring and preventing CRC development.


Assuntos
Adenoma , Carcinoma , Doenças do Colo , Neoplasias Colorretais , Humanos , Linfócitos T Reguladores/patologia , Leucócitos Mononucleares/patologia , Imunidade Inata , Linfócitos/patologia , Linfócitos T Auxiliares-Indutores , Citocinas/metabolismo , Neoplasias Colorretais/patologia , Doenças do Colo/metabolismo , Carcinoma/metabolismo , Carcinogênese/metabolismo , Adenoma/metabolismo
15.
BMC Genomics ; 25(1): 135, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308202

RESUMO

INTRODUCTION: Pseudogenes have been implicated for their role in regulating cellular differentiation and organismal development. However, their role in promoting cancer-associated differentiation has not been well-studied. This study explores the tumour landscape of oesophageal carcinoma to identify pseudogenes that may regulate events of differentiation to promote oncogenic transformation. MATERIALS AND METHOD: De-regulated differentiation-associated pseudogenes were identified using DeSeq2 followed by 'InteractiVenn' analysis to identify their expression pattern. Gene expression dependent and independent enrichment analyses were performed with GSEA and ShinyGO, respectively, followed by quantification of cellular reprogramming, extent of differentiation and pleiotropy using three unique metrics. Stage-specific gene regulatory networks using Bayesian Network Splitting Average were generated, followed by network topology analysis. MEME, STREME and Tomtom were employed to identify transcription factors and miRNAs that play a regulatory role downstream of pseudogenes to initiate cellular reprogramming and further promote oncogenic transformation. The patient samples were stratified based on the expression pattern of pseudogenes, followed by GSEA, mutation analysis and survival analysis using GSEA, MAF and 'survminer', respectively. RESULTS: Pseudogenes display a unique stage-wise expression pattern that characterizes stage II (SII) ESCA with a high rate of cellular reprogramming, degree of differentiation and pleiotropy. Gene regulatory network and associated topology indicate high robustness, thus validating high pleiotropy observed for SII. Pseudogene-regulated expression of SOX2, FEV, PRRX1 and TFAP2A in SII may modulate cellular reprogramming and promote oncogenesis. Additionally, patient stratification-based mutational analysis in SII signifies APOBEC3A (A3A) as a potential hallmark of homeostatic mutational events of reprogrammed cells which in addition to de-regulated APOBEC3G leads to distinct events of hypermutations. Further enrichment analysis for both cohorts revealed the critical role of combinatorial expression of pseudogenes in cellular reprogramming. Finally, survival analysis reveals distinct genes that promote poor prognosis in SII ESCA and patient-stratified cohorts, thus providing valuable prognostic bio-markers along with markers of differentiation and oncogenesis for distinct landscapes of pseudogene expression. CONCLUSION: Pseudogenes associated with the events of differentiation potentially aid in the initiation of cellular reprogramming to facilitate oncogenic transformation, especially during SII ESCA. Despite a better overall survival of SII, patient stratification reveals combinatorial de-regulation of pseudogenes as a notable marker for a high degree of cellular differentiation with a unique mutational landscape.


Assuntos
Carcinoma , Citidina Desaminase , Neoplasias Esofágicas , Proteínas , Humanos , Pseudogenes , Teorema de Bayes , Carcinogênese/genética , Neoplasias Esofágicas/genética , Reprogramação Celular , Carcinoma/genética , Proteínas de Homeodomínio/genética
16.
BMJ Case Rep ; 17(2)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355211

RESUMO

A woman in her 70s with a medical history of recurrent ovarian carcinoma was referred to the gastroenterologist because of rectal blood loss. Colonoscopy revealed a spontaneously bleeding lesion, which was not a typical colorectal carcinoma by optical diagnosis. Biopsies confirmed the diagnosis of recurrence of the former ovarian carcinoma. The patient was not eligible for surgical resection due to former abdominal surgery and she declined chemotherapy due to severe side effects earlier. After a multidisciplinary team consultation, she was treated with endoscopic full-thickness resection (eFTR). This is a minimally invasive resection technique for removal of challenging colorectal lesions. The patient has recovered well and 2 years after the metastasis resection with eFTR there still have been no signs of recurrent malignancy.


Assuntos
Carcinoma , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Neoplasias Ovarianas , Feminino , Humanos , Resultado do Tratamento , Recidiva Local de Neoplasia , Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Carcinoma/cirurgia , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Estudos Retrospectivos
18.
J Med Case Rep ; 18(1): 78, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38311786

RESUMO

BACKGROUND: Secretory carcinoma (SC) has been described as a distinct salivary gland tumor in the fourth edition of the World Health Organization (WHO) classification of head and neck tumors. SC is generally considered as a slow-growing low-grade malignant tumor, while several cases have been reported with high-grade features, and even metastases in the literature up until now. In this article, a soft tissue SC case is discussed with high-grade microscopic features and neural invasion. A review of the salivary gland SC cases with aggressive behavior is also debated. CASE PRESENTATION: A 65-year-old Caucasian man presented with a left neck mass for the past six months. The imaging studies demonstrated a very large cystic cervical mass (46 × 23 mm) with papillary projections in the anterolateral aspect of the left neck zone Vb. He underwent left radical neck dissection (level I-V) and was followed up for 12 months with the diagnosis of Secretory carcinoma. CONCLUSION: Although SC generally has a good outcome, multiple recurrences and unusual metastases may occur, which should be considered by either the pathologists or clinicians.


Assuntos
Adenocarcinoma , Neoplasias da Mama , Carcinoma , Neoplasias das Glândulas Salivares , Masculino , Humanos , Idoso , Carcinoma/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico por imagem , Neoplasias das Glândulas Salivares/cirurgia , Glândulas Salivares/patologia
20.
J Investig Med High Impact Case Rep ; 12: 23247096241231641, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344974

RESUMO

The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift and sustained response, underscoring the potential role of belzutifan as a viable option in second or subsequent lines of therapy for individuals with somatic VHL mutations. Despite both patients experiencing a pulmonary crisis with respiratory compromise, their rapid response to belzutifan further emphasizes its potential utility in cases involving pulmonary or visceral crises. This report contributes valuable insights into the treatment landscape for advanced ccRCC with somatic VHL mutations.


Assuntos
Carcinoma de Células Renais , Carcinoma , Indenos , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Mutação
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