RESUMO
OBJECTIVE: This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment. METHODS: This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status. RESULTS: Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively). CONCLUSIONS: EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.
Assuntos
Reparo de Erro de Pareamento de DNA , Hiperplasia Endometrial , Neoplasias do Endométrio , Preservação da Fertilidade , Proteína Supressora de Tumor p53 , Humanos , Feminino , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Adulto , Hiperplasia Endometrial/metabolismo , Hiperplasia Endometrial/patologia , Hiperplasia Endometrial/tratamento farmacológico , Hiperplasia Endometrial/genética , Estudos Retrospectivos , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/genética , Preservação da Fertilidade/métodos , Progesterona , PrognósticoRESUMO
BACKGROUND: Giant ovarian cysts (GOCs)complicated with progressive bulbar paralysis (PBP) are very rare, and no such literature about these cases have been reported. Through the diagnosis and treatment of this case, the perioperative related treatment of such patients was analyzed in detail, and early-stage ovarian mucinous carcinoma was unexpectedly found during the treatment, which provided reference for clinical diagnosis and treatment of this kind of diseases. CASE PRESENTATION: In this article, we reported a 38-year-old female patient. The patient was diagnosed with PBP 2 years ago. Examination revealed a large fluid-dominated cystic solid mass in the pelvis measuring approximately 28.6×14.2×8.0 cm. Carbohydrate antigen19-9(CA19-9) 29.20 IU/mL and no other significant abnormalities were observed. The patient eventually underwent transabdominal right adnexal resection under regional anesthesia, epidural block. Postoperative pathology showed mucinous carcinoma in some areas of the right ovary. The patient was staged as stage IA, and surveillance was chosen. With postoperative follow-up 1 month later, her CA19-9 decreased to 14.50 IU/ml. CONCLUSIONS: GOCs combined with PBP patients require a multi-disciplinary treatment. Preoperative evaluation of the patient's PBP progression, selection of the surgical approach in relation to the patient's fertility requirements, the nature of the ovarian cyst and systemic condition are required. Early mucinous ovarian cancer accidentally discovered after operation and needs individualized treatment according to the guidelines and the patient's situation. The patient's dysphagia and respiratory function should be closely monitored during the perioperative period. In addition, moral support from the family is also very important.
Assuntos
Adenocarcinoma Mucinoso , Neoplasias Ovarianas , Humanos , Feminino , Adulto , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma Mucinoso/complicações , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/diagnóstico , Assistência Perioperatória/métodos , Cistos Ovarianos/cirurgia , Cistos Ovarianos/complicações , Cistos Ovarianos/diagnóstico , Estadiamento de NeoplasiasRESUMO
Ochratoxin A (OTA) is a mycotoxin commonly found in several food commodities worldwide with potential nephrotoxic, hepatotoxic and carcinogenic effects. We previously showed for the first time that OTA treatment enhanced glycolysis in human gastric epithelium (GES-1) cells in vitro. Here, we found that OTA exposure activated inflammatory responses, evidenced by increasing of NF-κB signaling pathway-related protein (p-p65 and p-IκBα) expressions and elevating of inflammatory cytokine (IL-1ß and IL-6) mRNA expressions in GES-1 cells. To elucidate the role of glycolysis in inflammatory effects triggered by OTA, we pretreated GES-1 cells with glycolysis inhibitor (2-deoxy-D-glucose, 2-DG) before OTA exposure. The result showed that 2-DG reduced the protein expressions of p-p65 and p-IκBα and alleviated the mRNA expressions of inflammatory cytokines in OTA-treated GES-1 cells. Furthermore, OTA activated the mTOR/HIF-1α pathway by increasing the protein expressions of p-mTOR, p-eIF4E and HIF-1α, and inhibition of mTOR with rapamycin or silencing HIF-1α with siRNA significantly attenuated OTA-enhanced glycolysis by reducing glycolysis related genes and thereby decreasing inflammatory effects of GES-1 cells. These results demonstrate that OTA activates inflammatory responses in GES-1 cells and this is controlled by mTOR/HIF-1α pathway-mediated glycolysis enhancement. Our findings provide a novel mechanistic view into OTA-induced gastric cytotoxicity.
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Ocratoxinas , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Inibidor de NF-kappaB alfa , Linhagem Celular , Serina-Treonina Quinases TOR/genética , Glicólise , RNA Mensageiro , EpitélioRESUMO
BACKGROUND: Cesarean scar defect (CSD) presents as a cystic defect that connects the uterine cavity at the site of the previous cesarean section (CS). Endometriosis refers to the discovery of endometrial glands and stroma outside the uterine cavity. Cases of endometriosis cysts at CSD have not been reported. CASE PRESENTATION: In this article, we will present a patient with an endometriosis cyst at CSD with symptoms of a prolonged menstrual cycle, periods without cyclic abdominal pain, and a history of cesarean delivery. The gynecologic ultrasound showed a CSD and a mixed mass in the right front of the uterus. After about 1 month, the tumor grew from a diameter of 4.75 cm to 8.06 × 6.23 × 3.66 cm. The patient eventually had an operation, which revealed a mass protruding from the incision in the anterior uterine wall, which was attached to the anterior uterine wall by a thin tip with a smooth surface. Intraoperative rapid cytopathology suggested that endometrial glands were seen within the smooth muscle tissue, similar to endometriosis. Subsequently, the patient underwent resection of the endometriotic cyst. Final paraffin pathology showed smooth muscle with visible endometrial glands and old hemorrhage, and a one-year follow-up showed no recurrence of endometriosis cysts at CSD. CONCLUSIONS: Endometriosis cysts at CSD are very rare. The clinical symptoms may be less obvious, and the diagnosis relies mainly on the patient's previous surgical history and imaging. A finding of a pelvic mass in the location of the CSD, with or without symptoms of menstrual changes and intermittent abdominal pain, should be considered an endometriotic cyst at CSD. Surgical treatment is a good choice for this disease. Further studies are needed regarding the etiological mechanism of this case and why the mass enlarged rapidly in one mouth.
Assuntos
Cistos , Endometriose , Feminino , Gravidez , Humanos , Endometriose/complicações , Endometriose/cirurgia , Endometriose/diagnóstico , Cicatriz/complicações , Cicatriz/diagnóstico por imagem , Cesárea/efeitos adversos , Dor Abdominal , Cistos/diagnóstico por imagem , Cistos/etiologia , Cistos/cirurgiaRESUMO
OBJECTIVE: Gene mutations in tumor cells can lead to several unique metabolic phenotypes, which are crucial for the proliferation of cancer cells. EGFR mutation (EGFR-mt) is the main oncogenic driving mutation in lung adenocarcinoma (LUAD). HIF-1 α and PKM2 are two key metabolic regulatory proteins that can form a feedback loop and promote cancer growth by promoting glycolysis. Here, the linkage between EGFR mutational status and HIF-1α/PKM2 feedback loop in LUAD were evaluated. METHODS: Retrospective study were performed on LUAD patients (n = 89) undergoing first-time therapeutic surgical resection. EGFR mutation was analyzed by real-time PCR. Immunohistochemistry was used to measure the expressions of HIF-1α and PKM2. RESULTS: We found that the protein expressions of HIF-1α and PKM2 were significantly higher in LUAD than normal lung tissues. In adenocarcinomas, the two protein expressions were both correlated with worse pTNM stage. Moreover, the correlation between the proteins of HIF-1α/PKM2 feedback loop and the EGFR mutational status were also analyzed. We found that EGFR-mt tumors showed higher HIF-1α and PKM2 proteins compared to tumors with EGFR wild-type. Meanwhile, HIF-1α expression was significantly correlated with higher pTNM stage, and PKM2 showed a similar trend, only in EGFR-mutated tumors. The expression of HIF-1α was positively correlated with PKM2 in LUAD, furthermore, this correlation was mainly in patients with EGFR-mt. CONCLUSION: Different expression and clinical features of HIF-1α/PKM2 feedback loop was existed between LUAD and normal lung tissues, especially in EGFR mutational tumors, supporting the relationship between EGFR mutation and the key related proteins of aerobic glycolysis (HIF-1α and PKM2) in lung adenocarcinomas.
Assuntos
Adenocarcinoma de Pulmão , Subunidade alfa do Fator 1 Induzível por Hipóxia , Neoplasias Pulmonares , Piruvato Quinase , Humanos , Adenocarcinoma de Pulmão/genética , Linhagem Celular Tumoral , Receptores ErbB/genética , Retroalimentação , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Piruvato Quinase/genéticaRESUMO
BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, the coexistence of PTC and medullary thyroid carcinoma (MTC) is uncommon. While the simultaneous occurrence of both cancers with small lymphocytic lymphoma (SLL) in lymph nodes with PTC metastasis is very rare. This study presents a unique case of concurrent PTC, MTC, and SLL, highlighting the exceptional rarity of these coexisting tumors. METHODS: A 75-year-old female with a thyroid tumor underwent total thyroidectomy, bilateral central neck lymph node dissection, and right radical neck lymph node dissection. Histopathological examination revealed a low-grade medullary thyroid carcinoma (MTC) in the left lobe and classical papillary thyroid carcinoma (PTC) in the right lobe, with PTC metastasis in the cervical lymph nodes and concurrent SLL in the affected lymph nodes. RESULTS: Coexistence of PTC, MTC and SLL in the same patient is rare, there are currently no standardized treatment guidelines due to the limited literature. However, it is essential to consider not only the treatment for each type of tumor but also the potential risks or conflicts associated with the treatments. In the case reported in this paper, the papillary carcinoma invaded the capsule of the right lobe of the thyroid and metastasized to the cervical lymph nodes, warranting radioactive iodine therapy. However, considering the potential negative impact of radioactive iodine on the pre-existing lymphoma, the radioactive iodine therapy was postponed. Meanwhile, constant monitoring of calcitonin and thyroid globulin should be performed to monitor tumor recurrence as was performed in the present case. CONCLUSION: Since MTC, PTC, and SLL may coexist, patients with PTC deserve careful surveillance for the other disease entities. This case underscores the need for heightened awareness among clinicians, radiologists, and pathologists regarding the possibility of concurrent thyroid tumors and abnormal lymph nodes, guiding comprehensive pre-operative evaluations and postoperative monitoring strategies. This study aims to provide a warning for routine pathological diagnosis and contribute data for related research.
Assuntos
Carcinoma Neuroendócrino , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Feminino , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Idoso , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/complicações , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/complicações , Tireoidectomia , Neoplasias Primárias Múltiplas/patologia , Metástase Linfática , Excisão de Linfonodo , Esvaziamento CervicalRESUMO
hypoxia inducible factor-1α (HIF-1α) and pyruvate kinase M2 (PKM2) are 2 key metabolic regulatory proteins, they could engage in a positive feedback loop and drive cancer growth by enhancing glycolysis. This study aimed to investigate the expression of HIF-1α and PKM2 in papillary thyroid carcinoma (PTC) and its correlation with the patients clinicopathological features and with tumor invasion and metastasis. Surgically resected PTC specimens from 60 patients were collected. The expression levels of HIF-1α and PKM2 in PTC tissues were examined by immunohistochemical staining. The full clinical records of all patients were collected to analyze the relevance between HIF-1α and PKM2 expressions and the clinical pathological features of PTC. The results showed that the positive expressions of HIF-1α, PKM2, and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all significantly higher in PTC than those in normal thyroid follicular epithelium, and a positive correlation was found between HIF-1α and PKM2 in PTC. Further analysis showed that in PTC, the positive expression of HIF-1α and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were significantly associated with bigger tumor size, moreover, the positive expressions of HIF-1α, PKM2 and HIF-1α/PKM2 axis (HIF-1α+/PKM2+) were all correlated with capsular invasion and lymph node metastasis, while they were all not correlated with gender, sex and multicentricity of tumor. This study identified HIF-1a/PKM2 axis as potential molecular marker for predicting the invasion and progression of papillary thyroid carcinoma.
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Relevância Clínica , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide , Fatores de Transcrição , Neoplasias da Glândula Tireoide/patologia , Subunidade alfa do Fator 1 Induzível por HipóxiaRESUMO
Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium species that greatly threatens human health. We previously showed that OTA induced cycle arrest, apoptosis and autophagy in human gastric epithelium cells (GES-1). However, the mechanism underlying these effects is still unclear. Here, we showed that OTA exposure increased the expression of endoplasmic reticulum (ER) stress indicators (GRP78, PERK, ATF6, eIF2α, and CHOP), suggesting the activation of the unfolded protein response pathway. 4-phenylbutyric acid (4-PBA), an ER stress-specific inhibitor, attenuated OTA-induced loss of cell viability and apoptosis in GES-1 cells. It also attenuated the G2 phase arrest and autophagy induced by OTA, as evidenced by upregulated G2 phase-related proteins (Cdc2, Cdc25C, and cyclinB1) and downregulated autophagy markers (LC3B and Beclin-1). Moreover, OTA was found to increase ROS generation, and the inhibition of ROS formation by N-acetylcysteine (NAC), an ROS inhibitor, attenuated OTA-induced ER stress and subsequent apoptosis, cell cycle arrest, and autophagy. Collectively, these results suggest that the ROS-mediated ER stress pathway contributes to the OTA toxin-induced cytotoxicity in GES-1 cells. This study offers new insights into the molecular mechanisms underlying OTA toxicity in gastric cells.
Assuntos
Estresse do Retículo Endoplasmático , Ocratoxinas , Acetilcisteína/farmacologia , Apoptose , Proteína Beclina-1 , Epitélio , Humanos , Ocratoxinas/toxicidade , Espécies Reativas de Oxigênio/metabolismoRESUMO
Pyriform sinus fistula is uncommon and easily misdiagnosed. Most reported cases occur in children and are associated with either acute suppurative thyroiditis or deep neck infection. Asymptomatic pyriform sinus fistula is difficult to diagnose because it can manifest as an incidental thyroid nodule with highly suspicious malignant features on ultrasonography. The patient was a 41-year-old man with asymptomatic thyroid nodules incidentally detected on ultrasonography. Surgery was performed under the suspicion of thyroid cancer. Pathology findings revealed multiple cystic walls lined by ciliated columnar cells with stratified squamous epithelial cysts in a background of inflammatory and lymphoid cells. Barium swallow examination performed 2 weeks later revealed a sinus tract measuring 1.8 cm that arose from the apex of the left pyriform sinus. The diagnosis and management of pyriform sinus anomalies are challenging. The majority of physicians, including some otolaryngologists, lack an understanding of the disease, which should be considered one of the important differential diagnoses of neck masses. Barium swallow examination, ultrasonography, computed tomography, and laryngoscopy are useful to diagnose this condition.
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Fístula , Seio Piriforme , Tireoidite Supurativa , Adulto , Erros de Diagnóstico , Fístula/diagnóstico por imagem , Humanos , Masculino , Pescoço , Seio Piriforme/diagnóstico por imagemRESUMO
Esophageal squamous cell carcinoma (ESCC) is generally known to be a highly fatal cancer, and thus novel molecular targets are needed to improve its diagnosis and treatment. AJUBA has been shown to regulate cell cycle, adhesion, proliferation, apoptosis, and migration in many malignant tumors. However, the clinical significance of AJUBA in ESCC tumor metastasis remains unclear. In this study, we explored the role of AJUBA, Yes-associated protein 1 (YAP1), and matrix metalloproteinase 14 (MMP14) in the clinical presentation and survival of ESCC. Immunohistochemical staining showed higher expression of these proteins in cancer tissues than in paired adjacent tissues, and this upregulation was differently related to lymph node metastasis and TNM stage. AJUBA expression was positively correlated with that of YAP1. High expression of MMP14 was associated with reduced survival. In general, our findings reveal that AJUBA, YAP1, and MMP14 might function as oncoproteins and contribute to novel targeted therapy in ESCC.