Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.

Aptamer-Based Recognition of Breast Tumor Cells: A New Era for Breast Cancer Diagnosis.

Breast cancer is one of the leading causes of death among women worldwide and can be classified into four major distinct molecular subtypes based on the expression of specific receptors. Despite significant advances, the lack of biomarkers for detailed diagnosis and prognosis remains a major challenge in the field of oncology. This study aimed to identify short single-stranded oligonucleotides known as aptamers to improve breast cancer diagnosis. The Cell-SELEX technique was used to select aptamers specific to the MDA-MB-231 tumor cell line. After selection, five aptamers demonstrated specific recognition for tumor breast cell lines and no binding to non-tumor breast cells. Validation of aptamer specificity revealed recognition of primary and metastatic tumors of all subtypes. In particular, AptaB4 and AptaB5 showed greater recognition of primary tumors and metastatic tissue, respectively. Finally, a computational biology approach was used to identify potential aptamer targets, which indicated that CSKP could interact with AptaB4. These results suggest that aptamers are promising in breast cancer diagnosis and treatment due to their specificity and selectivity.

Exploring biomarkers and prognostic factors in uterine carcinosarcoma: An insight into L1CAM, CDX2, p53, and MSI status.

BACKGROUND: Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers. METHODS AND FINDINGS: The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively). CONCLUSION: The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival.

Avaliação do papel dos Corpúsculos Lipídicos na Carcinogênes Esofágica / [Evaluation of the role of Lipid Corpuscles in Esophageal Carcinogens]

O câncer de esôfago (CE) é a sexta causa mais freqüente de morte por câncer. Existem dois tipos principais de CE: Carcinoma Epidermóide (CEE) e Adenocarcinoma (ADE). Para o desenvolvimento do CEE os principais fatores de risco são o consumo de tabaco e álcool, e para o ADE podemos citar o refluxo esôfago-gástrico, obesidade e o esôfago de Barrett (EB), uma condição onde o epitélio estratificado do esôfago é substituído por um epitélio colunar metaplásico intestinal. Corpúsculos lipídicos (CL) são inclusões citoplasmáticas envolvidas na produção de eicosanóides e são mais abundantes em células associadas a reações inflamatórias e neoplasias. Sabendo que o processo inflamatório desempenha um papel importante no CE, o objetivo deste trabalho foi avaliar o papel dos CLs no CE. Primeiramente foi avaliada a presença de CL em amostras humanas de esôfago. Não houve marcação para ADRP nas amostras de esôfago normal, entretanto, houve um aumento gradativo na marcação dessa proteína na evolução do ADE e a marcação em CEE foi positiva em apenas poucos casos. Avaliamos também linhagens celulares de CE e observamos um aumento no número de CL na linhagem de ADE (OE33), quando comparada à linhagem de esôfago normal (Het1A) e a linhagem de CEE (OE21), corroborando os resultados anteriores. Para entender como os CLs eram formados já nos estágios iniciais de desenvolvimento do ADE, a linhagem Het1a, foi submetida a insultos que mimetizam os principais fatores de risco associados ao ADE e foi observadoum aumento no número de CL quando incubada com pH ácido, ácidos biliares, nicotina e ácido oleico. Além disso, esses estímulos foram capazes de induzir aumento na expressão de genes associados à resposta inflamatória e também de gene envolvido no desenvolvimento do EB...

Esophageal cancer (EC) is the sixth most frequent cause of cancer death. There are two main types of EC: Epidermoid Carcinoma (EEC) and Adenocarcinoma (ADE). For the development of CEE, the main risk factors are tobacco and alcohol consumption, and for ADE we can mention esophagogastric reflux, obesity and Barrett's esophagus (BE), a condition where the stratifiedepithelium of the esophagus is replaced by an intestinal metaplastic columnar epithelium. Lipid droplets (LD) are cytoplasmic inclusions involved in the production of eicosanoids and are moreabundant in cells associated with inflammatory reactions and neoplasms. As the inflammatory process plays an important role in EC, the objective of this work was to evaluate the role of LDs in EC. First, the presence of LD was evaluated in human esophageal samples. There was no ADRP staining in the normal esophagus samples, however, there was a gradual increase in staining score of this protein inthe evolution of the ADE and in EEC cases ADRP staining was positive in only a few cases. We also evaluated EC cell lines and observed an increase in the number of LD in the ADE cell line (OE33) when compared to the normal esophagus cell line (Het1A) and the EEC cell line (OE21), corroborating the previous results. To understand how LDs were formed in the early stages of ADE development, the Het1a cell line was subjected to insults that mimic the major risk factors associated with ADE and an increase in the number of LD was observed when incubated with acidic pH, bile acids, Nicotine and oleic acid. In addition, these stimuli were able to induce an increase in theexpression of genes associated with the inflammatory response and gene involved in the development of BE. We also evaluated this stimulus in tumor cells and found that only the OE33 cell line showed increased LD number and increased expression of IL-8 and COX-2...

Papel do fator NFAT1 na regulação do ciclo celular e na expressão de ciclinas

A família de fatores de transcrição NFAT (Nuclear Factor of Activated T cells) apresenta um papel central na regulação de diversos genes relacionados com a resposta imune e recentemente foram implicados na proliferação e diferenciação de diversos tipos celulares. Nossos resultados mostram que os linfócitos B deficientes para NFAT1, quando estimulados pelo BCR, proliferavam mais, apresentavam um aumento do número de células na fase G1 do ciclo celular e um aumento na expressão dos genes das ciclinas A2, E1 e E2. Além disso, o silenciamento do NFAT1 aumentou a proliferação de uma linhagem celular de células B. Análises adicionais demonstraram que a expressão ectópica de NFAT1 em células CHO inibiu a proliferação celular, a expressão das ciclinas A2, E1 e E2, a formação de colônias in vitro e o crescimento tumoral in vivo. Juntos estes resultados indicam que o NFAT1 apresenta um papel de regulador negativo do ciclo celular.

The NFAT (Nuclear Factor of Activated T cells) family of transcription factors plays a central role in the regulation of several genes related to the immune response and has been recently implicated in the proliferation and differentiation of numerous cell types. Our results show that NFAT1-deficient Blymphocytes stimulated through BCR proliferate more, present an increase in the number of cells in the G1 phase of the cell cycle and an up regulated expression of cyclins A2, E1 and E2 when compared to wild type. Also, silencing of NFAT1 increased the proliferation rate of a B cell line. Further analyses demonstrated that ectopic expression of NFAT1 in CHO cells inhibited cellular proliferation, cyclins A2, E1 and E2 expression, colony formation in vitro and tumor growth in vivo. Together, these results indicate NFAT1 as a negative regulator of the cell cycle.

Papel do fator de transcrição NFAT1 na regulação do ciclo celular e na expressão de ciclinas / [Role of the transcription factor NFAT1 in the regulation of the cell cycle and in the expression of cyclins]

A família de fatores de transcrição NFAT (Nuclear Factor of Activated T cells) apresenta um papel central na regulação de diversos genes relacionados com a resposta imune e recentemente foram implicados na proliferação e diferenciação de diversos tipos celulares. Nossos resultados mostram que os linfócitos B deficientes para NFAT1, quando estimulados pelo BCR, proliferavam mais, apresentavam um aumento do número de células na fase G1 do ciclo celular e um aumento na expressão dos genes das ciclinas A2, E1 e E2. Além disso, o silenciamento do NFAT1 aumentou a proliferação de uma linhagem celular de células B. Análises adicionais demonstraram que a expressão ectópica de NFAT1 em células CHO inibiu a proliferação celular, a expressão das ciclinas A2, E1 e E2, a formação de colônias in vitro e o crescimento tumoral in vivo. Juntos estes resultados indicam que o NFAT1 apresenta um papel de regulador negativo do ciclo celular