RESUMO
We encountered a rare case of appendiceal carcinoma associated with Amyand's hernia, which was difficult to diagnose preoperatively. A 74-year-old man presented to our hospital with right lower abdominal pain. A hard mass was palpable in the right lower abdomen, and blood tests showed a slightly elevated inflammatory response. Computed tomography revealed a 7 × 5 cm mass with indistinct borders and heterogeneous internal density extending from the cecum to the right lower abdominal wall. We diagnosed appendiceal abscess, however, percutaneous biopsy which was performed for differential diagnosis with appendiceal carcinoma showed no malignancy. Thereafter, the patient was followed up. Two months later, a blood test showed insignificant changes in the inflammatory response and a high serum carcinoembryonic antigen level (48.6 ng/mL). An ultrasound showed a mass contiguous to the appendix, extending to the abdominal wall, with abundant blood flow signals. Fluorodeoxyglucose-positron emission tomography showed a high accumulation of fluorodeoxyglucose in the mass. Four months after the initial visit, the patient had an open ileocecal resection combined with an abdominal wall resection based on the preoperative diagnosis of appendiceal carcinoma invading the abdominal wall. During laparotomy, an enlarged appendix tip extended from the internal inguinal ring outside the inferior epigastric artery to the abdominal wall. Histopathological examination of the appendiceal tumor revealed well-differentiated adenocarcinoma, T4b (abdominal wall), N0, Ly0, and V0. When a right lower abdominal mass extends from the cecum to the abdominal wall, appendiceal tumors associated with Amyand's hernia should be considered.
Assuntos
Adenocarcinoma , Neoplasias do Apêndice , Hérnia Inguinal , Humanos , Masculino , Idoso , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/cirurgia , Neoplasias do Apêndice/complicações , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico , Hérnia Inguinal/complicações , Hérnia Inguinal/cirurgia , Hérnia Inguinal/diagnóstico , Hérnia Inguinal/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Queiroz et al. showed that the application of cluster methodology for classifying gastric cancer is suitable and efficient within a Brazilian cohort, which is known for its population heterogeneity. The study highlighted the potential utilization of this method within public health services due to its low-cost, presenting a viable means to improve the diagnosis and prognosis of gastric cancer. BACKGROUND: Our Brazilian cohort with gastric cancer has a distinct distribution between mutated and normal p53. BACKGROUND: New genetic marker-based classifications improve gastric cancer diagnosis accuracy. BACKGROUND: Machine learning integration enhances predictive value in gastric cancer diagnosis. BACKGROUND: Molecular biomarkers complement clinical decisions, advancing personalized medicine. OBJECTIVE: Gastric adenocarcinoma remains an aggressive disease with a poor prognosis, as evidenced by a 5-year survival rate of approximately 31%. The histological classifications already proposed do not accurately reflect the high biological heterogeneity of this neoplasm, particularly in diverse populations, and new classification systems using genetic markers have recently been proposed. Following these newly proposed models, we aimed to assess the cluster distribution in a Brazilian cohort. Furthermore, we evaluated whether the inclusion of other clinical and histological parameters could enhance the predictive value. METHODS: We used a previously described four-immunohistochemistry/EBER-ISH marker to classify a cohort of 30 Brazilian patients with gastric adenocarcinoma into five different clusters and compared the distribution with other genetically diverse populations. Furthermore, we used artificial intelligence methods to evaluate whether other clinical and pathological parameters could improve the results of the methodology. RESULTS: Disclosing the genetic variability between populations, we observed a more balanced distribution of the aberrant/normal p53 ratio (0.6) between patients negative for the other markers tested, unlike previous studies with Asian and North American populations. In addition, decision tree analysis reinforced the efficiency of these new classifications, as the stratification accuracy was not altered with or without additional data. CONCLUSION: Our study underscores the importance of local research in characterizing diverse populations and highlights the complementary role of molecular biomarkers in personalized medicine for gastric adenocarcinoma, enhancing diagnostic accuracy and potentially improving survival rates.
Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Gástricas , Proteína Supressora de Tumor p53 , Neoplasias Gástricas/genética , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Humanos , Brasil , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/análise , Masculino , Feminino , Adenocarcinoma/genética , Adenocarcinoma/classificação , Adenocarcinoma/patologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Estudos de Coortes , Idoso , Análise por Conglomerados , Mutação , Imuno-Histoquímica , Adulto , Prognóstico , Idoso de 80 Anos ou maisRESUMO
To date, there have been no reports on tertiary lymphoid structures (TLS) in primary adenocarcinoma of jejunum and ileum. In this study, we employed digital pathology image analysis software to classify and quantify TLS, and evaluated the maturity of TLS using immunohistochemistry. Molecular genetics and immunotherapy biomarker detection were performed using next-generation sequencing technology, such as tumor mutational burden (TMB) and microsatellite instability (MSI). The aim of this study was to investigate the presence, location, maturity, association with immunotherapy biomarkers, and prognostic value of TLS in primary adenocarcinoma of jejunum and ileum. Compared to secondary follicle-like TLS (SFL-TLS), intra-tumoral TLS (IT-TLS) were more likely to manifest as early TLS (E-TLS) (P = 0.007). Compared to IT-TLS, SFL-TLS had a higher propensity to occur at the invasive margin (IM) (P = 0.032) and showed a trend towards being more prevalent at the tumor periphery (P = 0.057). In terms of immunotherapy biomarkers, there was a higher trend of IM-TLS density in PD-L1(22C3) score CPS < 1 group compared to PD-L1(22C3) score CPS ≥ 1 group (P = 0.071). TMB-H was significantly associated with MSI-H (P = 0.040). Univariate survival analysis demonstrated a correlation between high SFL-TLS group and prolonged disease free survival (DFS) (P = 0.047). There was also a trend towards prolonged DFS in the E-TLS-high group compared to the E-TLS-low group (P = 0.069). The peri-tumoral TLS (PT-TLS)-high group showed a trend of prolonged overall survival (OS) compared to the PT-TLS-low group (P = 0.090). In conclusion, the majority of TLS were located at the invasive margin and tumor periphery, predominantly consisting of mature TLS, while IT-TLS were mainly immature. Notably, TMB was closely associated with MSI and PD-L1, indicating potential predictive value for immunotherapy in primary adenocarcinoma of jejunum and ileum.
Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias do Íleo , Neoplasias do Jejuno , Estruturas Linfoides Terciárias , Humanos , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/imunologia , Prognóstico , Masculino , Feminino , Estruturas Linfoides Terciárias/patologia , Estruturas Linfoides Terciárias/imunologia , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias do Íleo/patologia , Neoplasias do Íleo/mortalidade , Neoplasias do Jejuno/patologia , Taxa de Sobrevida , Seguimentos , Instabilidade de Microssatélites , Adulto , Estudos RetrospectivosRESUMO
Fusobacterium nucleatum (F. nucleatum) is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation, such as periodontitis and gingivitis. In the last 10 years, F. nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression, metastasis and poor disease outcome. While the role of F. nucleatum in colon carcinogenesis has been intensively studied, its role in gastric carcinogenesis is still poorly understood. Although Helicobacter pylori infection has historically been recognized as the strongest risk factor for the development of gastric cancer (GC), with recent advances in DNA sequencing technology, other members of the gastric microbial community, and F. nucleatum in particular, have received increasing attention. In this review, we summarize the existing knowledge on the involvement of F. nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F. nucleatum in GC.
Assuntos
Carcinogênese , Infecções por Fusobacterium , Fusobacterium nucleatum , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Fusobacterium nucleatum/patogenicidade , Infecções por Fusobacterium/microbiologia , Infecções por Fusobacterium/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Helicobacter pylori/genética , Fatores de Risco , Microbioma Gastrointestinal , Animais , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Estômago/microbiologia , Estômago/patologia , Adenocarcinoma/microbiologia , Adenocarcinoma/patologiaRESUMO
Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated SCD expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with SCD promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between SCD expression levels and the abundance of CD8+ T cells and macrophages. Further analyses identified significant associations between SCD expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential SCD expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that SCD enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated SCD expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, SCD overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.
Assuntos
Adenocarcinoma , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , Estearoil-CoA Dessaturase , Microambiente Tumoral , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Humanos , Masculino , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Metilação de DNARESUMO
BACKGROUND: Gastric cancer (GC) is the fourth leading cause of cancer mortality worldwide. Peritoneal metastasis (PM) is a significant cause of death in patients with GC, and presents a major challenge in clinical diagnosis and treatment. Predicting the occurrence of PM in high-risk patients, and diagnosing and treating PM in advance to improve patient survival, remains an unsolved problem in clinical practice. Given the low positive rate of cytology and difficulty in diagnosing occult PM, new molecular markers and detection technologies for early diagnosis require urgent validation. The primary objective of this study is to observe and evaluate the predictive effect of intraoperative peritoneal lavage fluid (PLF) circulating tumour cells (CTC) and circulating tumour DNA (ctDNA) levels in patients with pT4NxM0/pT1-3N+M0 GC on metachronous PM after R0 resection. METHODS AND ANALYSIS: This prospective single-centre clinical study is conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine. In this study, 200 cases of patients with pT4NxM0/pT1-3N+M0 gastric adenocarcinoma older than 18 years will be screened. Participants will undergo intraoperative PLF CTC and ctDNA testing and will be followed up for 2 years, with imaging assessments performed every 3-6 months until PM occurrs. The primary outcome is the incidence of PM 1 year after surgery, which will be estimated using Clopper-Pearson method, with 95% CIs calculated and compared between groups. Secondary outcome include the incidence of PM 2 years after surgery, overall survival and disease progression. Data will be analysed using the Kaplan-Meier method and the log-rank test. ETHICS AND COMMUNICATION: Informed consent has been obtained from all subjects. This protocol has been approved by the Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine (LY2023-142-B). The findings will be disseminated through peer-reviewed manuscripts, reports and presentations. TRIAL REGISTRATION NUMBER: ChiCTR2300074910.
Assuntos
DNA Tumoral Circulante , Células Neoplásicas Circulantes , Lavagem Peritoneal , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirurgia , Estudos Prospectivos , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Masculino , Feminino , Líquido Ascítico/metabolismo , China , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Adenocarcinoma/cirurgia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Valor Preditivo dos Testes , Gastrectomia/métodos , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEGJ) is most common in men and the elderly, but the disease is becoming more common in female and young adult persons. We have investigated the clinicoepidemiological characteristics of female and young adult patients with AEGJ and the 12-year trends in the Kurashiki area for young adult patients with AEGJ. METHODS: Patients diagnosed with AEGJ in 12 hospitals between January 2008 and December 2019 were included in this study. Patients were divided into three groups by age (young adult [≤50 years], middle-aged [51 to 70 years], and elderly [>70 years]). Factors associated with AEGJ such as obesity, smoking, hiatal hernia and male, which were reported in our previous study, were identified. RESULTS: One hundred and eighty-eight AEGJ patients, including 36 females and 20 young adults, were characterized. There was no significant change in the annual incidence of AEGJ among female (p=0.078) and young adult patients (p=0.89). Female patients without any associated factors, accounting for 53% (19/36) of the female patients and young adult patients, had significantly more histologically undifferentiated cancers than patients with at least one associated factor (58% [11/19] vs. 30% [50/169], p=0.025) and middle-aged and elderly patients (60% [12/20] vs. 30% [25/83] vs. 28% [24/85], p =0.026). Smoking was significantly less common in women than in men (8% [3/36] vs. 57% [87/152], p < 0.01). There were no significant differences between ages in the proportions of these associated factors. CONCLUSIONS: Histologically undifferentiated AEGJ cancers were more frequent in female patients without any associated factors and in young adult patients. Factors associated with AEGJ may differ between women and men, but they are similar in young adults and older adults. No increase in young adult patients with AEGJ was observed in the 12-year study.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Humanos , Feminino , Junção Esofagogástrica/patologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Adulto , Estudos Retrospectivos , Estudos Prospectivos , Incidência , Fatores de Risco , Fatores Sexuais , Fatores Etários , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Fumar/epidemiologia , Adulto Jovem , Hérnia Hiatal/epidemiologiaRESUMO
BACKGROUND: With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma. METHODS: This retrospective study analyzed the clinicopathological data from 6,585 AJCC stage I-III rectal adenocarcinoma in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Kaplan-Meier survival analysis and multivariate Cox proportional were used to assess the impact of PR on survival. Propensity score matching (PSM) was employed to balance the baseline covariates between the PR and non-PR groups and to compare postoperative pathological differences. RESULTS: After PSM, PR did not improve overall survival (OS) in stages I (p = 0.33), II (p = 0.37), and III (p = 0.14) patients. Multivariate Cox analysis indicated that PR was not an independent prognostic factor for patients. Restricted cubic spline (RCS) analysis demonstrated a nonlinear negative correlation between OS hazard ratios and both circumferential resection margin (CRM) and lymph node evaluation (LNE). Compared to the non-PR group, patients in the PR group had lower tumor deposits (TD) (p < 0.001), positive CRM (p = 0.191), and perineural invasion (PNI) (p = 0.001). CONCLUSION: PR is not an independent prognostic factor for rectal adenocarcinoma patients. However, PR can reduce the likelihood of TD, CRM, and PNI, thereby potentially influencing the quality of surgery.
Assuntos
Adenocarcinoma , Estadiamento de Neoplasias , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Neoplasias Retais/radioterapia , Neoplasias Retais/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/radioterapia , Adenocarcinoma/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Programa de SEER , Terapia Neoadjuvante , Cuidados Pré-Operatórios/métodos , Pontuação de Propensão , Radioterapia Adjuvante , AdultoRESUMO
BACKGROUND: Giant bullous emphysema is characterized by large bullae occupying at least one-third of the hemithorax and leading to compression of the surrounding lung parenchyma. Overdiagnosis can occur because of the atypical appearance of hyperplastic type II pneumocytes, which may be mistaken for malignant cells. CASE PRESENTATION: A 48-year-old male with a history of smoking and occupational exposure presented with dyspnea and drowsiness. Initial chest X-ray revealed a tension pneumothorax, and subsequent chest CT revealed extensive bullous emphysema and lung cancer in the right middle lobe (RML). Pathologic examination initially indicated resected bullae to metastatic adenocarcinoma, but upon review, it was determined that the reactive alveolar cells were misdiagnosed as malignant. CONCLUSIONS: This case emphasizes the need for thorough histopathological assessment and prudent interpretation of atypical cellular morphology.
Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Enfisema Pulmonar , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/secundário , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Enfisema Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Erros de Diagnóstico , Diagnóstico Diferencial , Vesícula/diagnósticoRESUMO
BACKGROUND: Brain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy. DESIGN: A retrospective search spanning 20 years (2003-2022) was conducted on our archives and identified 21 cases diagnosed as "metastatic prostate adenocarcinoma (mPCa)" in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa. RESULT: The mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis. CONCLUSION: mPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.
Assuntos
Adenocarcinoma , Neoplasias Encefálicas , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/patologia , Idoso , Adenocarcinoma/secundário , Adenocarcinoma/patologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Diagnóstico DiferencialRESUMO
BACKGROUND: In this paper, a rare case is reported, where the patient is a 74-year-old man. He suffered from recurrent pneumothorax within half a year and experienced a relapse after receiving conservative treatments. CASE PRESENTATION: Diagnostic workup revealed a cystic lesion in the right middle lobe, which has been interpreted as a bulla during the initial chest CT scan. Due to recurrent pneumothorax and poor response to the conservative treatments, the patient underwent bullectomy and pleurodesis. The pathology showed that the wall of the cystic lesion was invasive adenocarcinoma. CONCLUSIONS: This case highlights the importance of monitoring cystic lesions in the lungs, especially in patients with a history of smoking and emphysema.
Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Pneumotórax , Tomografia Computadorizada por Raios X , Humanos , Masculino , Pneumotórax/etiologia , Idoso , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Recidiva , Cistos/cirurgia , Cistos/diagnóstico por imagem , Cistos/diagnóstico , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , PleurodeseRESUMO
BACKGROUND: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. METHODS: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. RESULTS: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. CONCLUSIONS: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.
Assuntos
Adenocarcinoma , Células-Tronco Neoplásicas , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Animais , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Camundongos , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/genética , Nitrilas/farmacologia , Feniltioidantoína/farmacologiaRESUMO
NLRP1, the first identified inflammasome-forming sensor, is thought to be involved in cancer, yet its definite function in lung adenocarcinoma (LUAD) remains unclear. Herein, we explored the expression and function of NLRP1 in LUAD. Decreased NLRP1 expression was identified in LUAD, which was associated with a poor prognosis. Overexpression of NLRP1 inhibited tumor growth in vitro and in vivo. Mechanically, this effect was observed regardless of inflammasome activation. Further studies revealed that overexpression of NLRP1 downregulated the phosphorylation of DRP1 and promoted mitochondrial fusion, which was mediated by inhibition of NF-κB activity. NF-κB agonist could neutralize the effect of NLRP1 on mitochondrial dynamics. In addition, LUAD sensitivity to cisplatin was enhanced by decreased mitochondrial fission resulting from up-regulated NLRP1. In conclusion, our findings demonstrated an unexpected role of NLRP1 in LUAD by modulating mitochondrial activities, which provides strong evidence for its potential in LUAD treatment.
Assuntos
Adenocarcinoma de Pulmão , Inflamassomos , Neoplasias Pulmonares , Mitocôndrias , Proteínas NLR , Humanos , Inflamassomos/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Proteínas NLR/metabolismo , Animais , Mitocôndrias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Dinâmica Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/fisiologia , Camundongos , Masculino , Proliferação de Células/efeitos dos fármacos , FemininoRESUMO
The SLC7A11/xCT cystine transporter is intricately linked with ferroptosis. By mediating intracellular cystine flux, it regulates oxidative stress within neoplastic cells, thereby curtailing ferroptosis and influencing the emergence of colorectal cancer. This study aimed to gauge the SLC7A11/xCT expression across various tumorigenic stages in early colorectal adenocarcinoma tissues, shedding light on its specific role in the genesis of these early malignancies. Sixty specimens that underwent endoscopic submucosal dissection (ESD) resection with pathologic diagnosis of colorectal adenocarcinoma were collected. SLC7A11/xCT expression was pinpointed using immunohistochemistry, and correlations with the patients' clinical-pathological features were drawn. Additionally, a comprehensive bioinformatics assessment was undertaken to discern differential SLC7A11/xCT expressions across a spectrum of cancers. Immunohistochemical assessments unveiled a pronounced cytoplasmic SLC7A11/xCT expression, manifesting as a brownish-yellow hue, particularly in nascent colorectal cancer samples. Its expression was discernibly correlated with both patient gender and adenocarcinoma differentiation grade (P<0.05). Nevertheless, factors such as patient age, tumor localization, infiltration depth, diameter, adjacent adenoma histology, its major axis, and dysplasia degree bore no statistical significance with SLC7A11/xCT levels (P>0.05). Bioinformatics insights pointed to an upregulated SLC7A11/xCT expression across diverse malignancies, inclusive of colon adenocarcinoma, esophageal cancer, acute myeloid leukemia, lung squamous cell carcinoma, colorectal cancer, and endometrial cancer (P<0.05). Elevated SLC7A11/xCT expression marks early colorectal adenocarcinoma, with the intensity of this expression being intertwined with the patient's gender and the tumor's differentiation grade. It is postulated that colorectal cancer cells might amplify SLC7A11/xCT to stymie ferroptosis, thus fostering neoplastic proliferation, metastasis, and cellular stemness.
Assuntos
Sistema y+ de Transporte de Aminoácidos , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/genética , Feminino , Masculino , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Pessoa de Meia-Idade , Idoso , Ressecção Endoscópica de Mucosa , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Adenocarcinoma/cirurgia , Adenocarcinoma/genética , Imuno-Histoquímica , Regulação Neoplásica da Expressão Gênica , AdultoRESUMO
In esophageal adenocarcinoma, the presence of lymph node metastases predicts patients' survival even after curative resection. Currently, there is no highly accurate marker for detecting the presence of lymph node metastasis. The SEMA3F/NRP2 axis was initially characterized in axon guidance and recent evidence has revealed its significant involvement in lymphangiogenesis, angiogenesis, and carcinogenesis. Hence, the objective of this study was to elucidate the roles of SEMA3F and its receptor NRP2 in esophageal adenocarcinoma. We conducted an immunohistochemical evaluation of SEMA3F and NRP2 protein expression in 776 patients with esophageal adenocarcinoma who underwent Ivor-Lewis esophagectomy at the University Hospital of Cologne. Total and positive cancer cell counts were digitally analyzed using QuPath and verified by experienced pathologists to ensure accuracy. Positive expression was determined as a cell percentage exceeding the 50th percentile threshold. In our cohort, patients exhibiting SEMA3F positive expression experience significantly lower pT- and pN-stages. In contrast, positive NRP2 expression is associated with the presence of lymph node metastases. Survival analyses showed that the expression status of NRP2 had no impact on patient survival. However, SEMA3F positivity was associated with a favorable patient survival outcome (median OS: 38.9 vs. 26.5 months). Furthermore, SEMA3F could be confirmed as an independent factor for better patient survival in patients with early tumor stage (pT1N0-3: HR = 0.505, p = 0.014, pT1-4N0: HR = 0.664, p = 0.024, pT1N0: HR = 0.483, p = 0.040). In summary, SEMA3F emerges as an independent predictor for a favorable prognosis in patients with early-stage esophageal adenocarcinoma. Additionally, NRP2 expression is linked to a higher risk of lymph node metastases occurrence. We hypothesize that low SEMA3F expression could identify patients with early-stage tumors who might benefit from more aggressive treatment options or intensified follow-up. Furthermore, SEMA3F and its associated pathways should be explored as potential tumor-suppressing agents.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Metástase Linfática , Proteínas de Membrana , Proteínas do Tecido Nervoso , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Esofagectomia , Proteínas de Membrana/metabolismo , Estadiamento de Neoplasias , Proteínas do Tecido Nervoso/metabolismo , Neuropilina-2/metabolismo , Neuropilina-2/genética , PrognósticoRESUMO
OBJECTIVE: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy. DESIGN: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed. RESULTS: A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity. CONCLUSION: Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.
Assuntos
Adenocarcinoma , Antígenos CD , Apirase , Linfócitos T CD8-Positivos , Neoplasias Esofágicas , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1 , Humanos , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Receptor de Morte Celular Programada 1/metabolismo , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Apirase/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Masculino , Feminino , Antígenos CD/metabolismo , Pessoa de Meia-Idade , Idoso , Prognóstico , Biomarcadores Tumorais , Cadeias alfa de Integrinas/metabolismoRESUMO
5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. ß-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins-Cyclin D1, and CDK4 as well as PCNA and GSK-3ß were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3ß protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3ß signaling pathway.
Assuntos
Adenocarcinoma , Apoptose , Proliferação de Células , Fluoruracila , Glicogênio Sintase Quinase 3 beta , Camundongos Nus , Norisoprenoides , Transdução de Sinais , Neoplasias Gástricas , Animais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Fluoruracila/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Norisoprenoides/farmacologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Camundongos , Apoptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Sinergismo Farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Quinase 3 da Glicogênio Sintase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/metabolismoRESUMO
Recent advancements have elucidated the multifaceted roles of the Schlafen (SLFN) family, including SLFN5, SLFN11, SLFN12, SLFN13, and SLFN14, which are implicated in immunological responses. However, little is known about the roles of this gene family in relation to malignancy development. The current study aimed to explore the diagnostic and prognostic potential of Schlafen family genes in colorectal adenocarcinoma (COAD) through bioinformatics analysis. Leveraging advanced bioinformatics tools of bulk RNA-sequencing and single-cell sequencing, we conducted in-depth analyses of gene expressions, functional enrichment, and survival patterns of patients with colorectal cancer compared to normal tissue. Among Schlafen family genes, the transcription levels of SLFN5 in COAD tissues were significantly elevated and correlated with poor survival outcomes. Furthermore, SLFN5 regulated the immune response via Janus kinase (JAK)/signal transduction and activator of transcription (STAT)/interferon (IFN)-alpha/beta signaling. These chemokines in inflammation are associated with diabetes and metabolism, suggesting their involvement in altered cellular energetics for COAD progress. In addition, an immune cell deconvolution analysis indicated a correlation between SLFN5 expression and immune-related cell populations, such as regulatory T cells (Tregs). These findings highlighted the potential clinical significance of SLFN5 in COAD and provided insights into its involvement in the tumor microenvironment and immune regulation. Meanwhile, the drug discovery data of SFLN5 with potential targeted small molecules suggested its therapeutic potential for COAD. Collectively, the current research demonstrated that SFLN5 play crucial roles in tumor development and serve as a prospective biomarker for COAD.
Assuntos
Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Análise de Célula Única , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Análise de Célula Única/métodos , Prognóstico , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Análise de Sequência de RNA , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Perfilação da Expressão Gênica , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Proteínas de Ciclo CelularRESUMO
The incidence of esophagogastric junction adenocarcinoma is increasing gradually. The surgical procedures mainly include radical resection of the primary tumor, lymph node dissection, and digestive tract reconstruction. Due to the special anatomical location of esophagogastric junction adenocarcinoma, the pattern of lymph node metastasis is not clear, and regional lymph nodes dissection especially in the lower mediastinum is still controversial, and awaits further high-quality evidence. Meanwhile, due to the special anatomical location of the lower mediastinum, it is often difficult to perform lower mediastinal lymph node dissection. How to complete the lower mediastinal lymph nodes dissection more safely and effectively is the key point for gastric cancer surgeons. In this paper, the progress, consensus, and controversy on the extent of lower mediastinal lymph nodes dissection in patients with esophagogastric junction adenocarcinoma were discussed. Based on our own experience, the current clinically techniques for lower mediastinal lymph nodes dissection were summarized to further improve the quality control of lower mediastinal lymph nodes dissection in patients with esophagogastric junction adenocarcinoma.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Junção Esofagogástrica , Excisão de Linfonodo , Mediastino , Neoplasias Gástricas , Humanos , Excisão de Linfonodo/métodos , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Mediastino/cirurgia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Linfonodos/patologia , Metástase LinfáticaRESUMO
PURPOSE: Therapeutic management of colorectal cancer (CRC) does not yet yield promising long-term results. Therefore, there is a need for further investigation of possible therapeutic options. Various experiments have studied the effects of apigenin on CRC and have shown conflicting results. This systematic review and meta-analysis investigates the currently existing evidence on the effect of apigenin on CRC. METHODS: Medline, Embase, Scopus, and Web of Science databases were searched for articles related to apigenin and its effect on CRC in the preclinical setting. Cell viability, growth inhibition, apoptosis, and cell cycle arrest for in-vitro, and body weight, tumor size, and mortality in in-vivo studies were extracted as outcomes. RESULTS: Thirty-nine articles investigating colorectal adenocarcinoma were included in this meta-analysis. Thirty-seven of these studies had data for in vitro experiments, with eight studies having data for in vivo experiments. Six articles had both in vitro and in vivo assessments. Our analysis showed apigenin reduces cell viability and induces growth inhibition, apoptosis, and cell cycle arrest in in vitro studies. The few in vivo studies indicate that apigenin decreases tumor size while showing no effects on the body weight of animal colorectal adenocarcinoma models. CONCLUSION: Our results demonstrated that apigenin, through reducing cell viability, inducing growth inhibition, apoptosis, and cell cycle arrest, and also by decreasing the tumor size, can be considered as a possible adjuvant agent in the management of colorectal adenocarcinoma. However, further in vivo studies are needed before any efforts to translate the current evidence into clinical studies.