Insights into inflammation and implications for the pathogenesis and long-term outcomes of endometrial cancer: genome-wide surveys and a clinical cohort study.

BACKGROUND: Despite evidence showing a connection between inflammation and endometrial cancer (EC) risk, the surveys on genetic correlation and cohort studies investigating the impact on long-term outcomes have yet to be refined. We aimed to address the impact of inflammation factors on the pathogenesis, progression and consequences of EC. METHODS: For the genetic correlation analyses, a two-sample of Mendelian randomization (MR) study was applied to investigate inflammation-related single-nucleotide polymorphisms involved with endometrial cancer from GWAS databases. The observational retrospective study included consecutive patients diagnosed with EC (stage I to IV) with surgeries between January 2010 and October 2020 at the Cancer Hospital of Shantou University Medical College. RESULTS: The 2-sample MR surveys indicated no causal relationship between inflammatory cytokines and endometrial cancer. 780 cases (median age, 55.0 years ) diagnosed with EC were included in the cohort and followed up for an average of 6.8 years. Increased inflammatory parameters at baseline were associated with a higher FIGO stage and invasive EC risk (odds ratios [OR] 1.01 to 4.20). Multivariate-cox regression suggested that multiple inflammatory indicators were significantly associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Nomogram models based on inflammatory risk and clinical factors were developed for OS and PFS with C-index of 0.811 and 0.789, respectively. LASSO regression for the validation supported the predictive efficacy of inflammatory and clinical factors on the long-term outcomes of EC. CONCLUSIONS: Despite the fact that the genetic surveys did not show a detrimental impact of inflammatory cytokines on the endometrial cancer risk, our cohort study suggested that inflammatory level was associated with the progression and long-term outcomes of EC. This evidence may contribute to new strategies targeted at decreasing inflammation levels during EC therapy.

Propranolol inhibits the activity of PI3K, AKT, and HIF-1α in infantile hemangiomas.

PURPOSE: We sought to evaluate effect of propranolol in the treatment of infantile hemangiomas by quantifying the amount of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and hypoxia-inducible factor-1α (HIF-1α). METHODS: Hemangioma tissue was isolated from an infant patient and implanted into nude mice to establish a hemangioma model. Twenty-four hemangioma-model nude mice were divided into two groups including a control group (saline, by gastrogavage) and an experimental group (propranolol, by gastrogavage). The hemangioma-model nude mice were euthanized and tumors were removed at 30 and 50 days (before and after treatment). HE staining was used to observe the histopathological changes, and western blot and quantitative real-time PCR were used to describe levels of protein and mRNA expression of PI3K, AKT, and HIF-1α. RESULTS: Propranolol treatment decreased tumor size as compared to the control group. Protein and mRNA expression levels of PI3K, AKT, and HIF-1α were lower in the experimental group at day 50 compared to the control group at day 50 and the experimental group at day 30 (p < 0.05). CONCLUSION: Propranolol can promote regression of infantile hemangiomas, which may be related to the inhibition of PI3K, AKT, and HIF-1α activity.

Promising approach for targeting ROBO1 with CAR NK cells to combat ovarian cancer primary tumor cells and organoids.

Aim: This study aimed to explore using peripheral blood mononuclear cell (PBMC)-derived chimeric antigen receptor (CAR) NK cells targeting ROBO1 as a personalized medicine approach for ovarian cancer. Methods: A two-step strategy generated ROBO1-targeted CAR NK cells from PBMCs of ovarian cancer patients. Efficacy was evaluated using xCELLigence RTCA, CCK-8 and Live/Dead fluorescence assays. Results: ROBO1-NK cells exhibited higher efficiency in eradicating primary ovarian cancer cells and lysing ovarian tumor organoids compared with primary NK cells without ROBO1-CAR modification. Conclusion: These findings highlight the potential of developing ROBO1-targeted CAR-NK cells from patients' PBMCs as a personalized treatment option for ovarian cancer.

Ovarian cancer represents a formidable clinical challenge necessitating the urgent exploration of novel therapeutic approaches. In this study, the focus was directed toward ROBO1, a molecule known to play a pivotal role in cancer angiogenesis and metastasis, while limited investigation in the context of ovarian cancer. Leveraging this knowledge, we sought to construct ROBO1-targeting chimeric antigen receptor natural killer (CAR-NK) cells utilizing peripheral blood mononuclear cells derived from the patients themselves. The overarching goal of this investigation was to harness the potential of immunotherapy using autologous resources to realize personalized treatment strategies for ovarian cancer in clinical settings.

BME-free primary patient-specific organoids obtained with a one-day mimicking method to replicate the corresponding tumor for personalized treatment options.

Introduction: In cancer treatment, every minute counts. Due to the unpredictable behavior of cancer cells caused by continuous mutations, each cancer patient has a unique situation and may or may not respond to a specific drug or treatment. The process of finding an effective therapy can be time-consuming, but cancer patients do not have the luxury of time for trial and error. Therefore, a novel technology to fast generate a patient relevant organoid for the therapies selecting is urgently needed. Methods: Utilizing the new organoid technology by specially dissolving the mesenchyme in tumor tissues acquired from cancer patients, we realized the work of creating patient-specific organoids (PSO) within one day. Results: PSO properties reflect those of its respective original in vivo tumor tissue and can be utilized to perform various in vitro drug sensitivity tests to identify the most effective clinical treatment for patients. Additionally, PSO can aid in assessing the efficacy of immune cell therapies. Discussion: Organoid technology has advanced significantly in recent years. However, current cancer organoid methods involve creating 3D tumor tissue from 2D cancer cells or cell clusters, primarily for cancer research purposes aimed at investigating related molecular and cellular mechanisms of tumor development. These methods are research-driven, not tailored towards clinical applications, and cannot provide personalized information for individual patients. PSO filled the gap of clinic-driven and time-saving method for the personalized therapies selecting to the cancer patients.

Reduced stress-associated FKBP5 DNA methylation together with gut microbiota dysbiosis is linked with the progression of obese PCOS patients.

Polycystic ovary syndrome (PCOS) is a common endocrine disease in females that is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovaries. However, the exact etiology and pathogenesis of PCOS are still unknown. The aim of this study was to clarify the bacterial, stress status, and metabolic differences in the gut microbiomes of healthy individuals and patients with high body mass index (BMI) PCOS (PCOS-HB) and normal BMI PCOS (PCOS-LB), respectively. Here, we compared the gut microbiota characteristics of PCOS-HB, PCOS-LB, and healthy controls by 16S rRNA gene sequencing, FK506-binding protein 5 (FKBP5) DNA methylation and plasma metabolite determination. Clinical parameter comparisons indicated that PCOS patients had higher concentrations of total testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone, and HOMA-IR while lower FKBP5 DNA methylation. Significant differences in bacterial diversity and community were observed between the PCOS and healthy groups but not between the PCOS-HB and PCOS-LB groups. Bacterial species number was negatively correlated with insulin concentrations (both under fasting status and 120 min after glucose load) and HOMA-IR but positively related to FKBP5 DNA methylation. Compared to the healthy group, both PCOS groups had significant changes in bacterial genera, including Prevotella_9, Dorea, Maihella, and Slackia, and plasma metabolites, including estrone sulfate, lysophosphatidyl choline 18:2, and phosphatidylcholine (22:6e/19:1). The correlation network revealed the complicated interaction of the clinical index, bacterial genus, stress indices, and metabolites. Our work links the stress responses and gut microbiota characteristics of PCOS disease, which might afford perspectives to understand the progression of PCOS.

Use of clinical nomograms for predicting survival outcomes in young women with breast cancer.

Early-onset breast cancer (BC) has been recognized to be more aggressive compared with its later counterparts. Survival models of BC in young patients have rarely been reported in previous studies. The current study aimed to establish and validate prediction models with clinicopathological variables for visceral metastasis-free survival (VFS), disease-free-survival (DFS) and overall survival (OS) time in young patients with BC. Clinicopathological data were obtained for 351 patients with primary breast tumors who were ≤40 years old. Univariate and multivariate analyses were performed and nomograms were established to screen and illustrate the prognostic factors. Risk scores were calculated based on coefficients from the Cox regression analysis. Internal validation of the prediction models was conducted by predicting the prognosis of cases randomly sampled from the cohort used in the current study. Multivariate analysis demonstrated that N stage (P=0.004), molecular subtype (P=0.007) and age (P=0.005) were significant independent prognostic factors for VFS. Similarly, N stage (P=0.002) and molecular subtype (P=0.001) were significantly associated with DFS. In addition, N stage (P=0.006), molecular subtype (P=0.006) and the presence of an initially inoperable tumor (P=0.005) were significant independent prognostic factors for OS. According to the Cox regression analysis, nomograms were generated to illustrate the effect of independent prognostic factors on VFS, DFS and OS. Risk scores were calculated and internal validation demonstrated the reliability of the prediction models. In conclusion, N stage and molecular subtype were identified as predictors for VFS, DFS and OS in early-onset BC. Furthermore, an age of <35 years at diagnosis was revealed to be unfavorable for VFS and the presence of an initially inoperable tumor was identified to reduce OS time.

Intralesional injection of triamcinolone acetonide for cavernous hemangiomas: A case report.

RATIONALE: Cavernous hemangiomas referred to as venous malformations (VMs), are not true vascular tumors. The treatment of cavernous hemangiomas is controversial. PATIENT CONCERNS: A five-year-old girl with a cavernous hemangioma on her right buttock had undergone surgery but recurred 1 month after the operation. DIAGNOSES: Cavernous hemangioma was diagnosed on the basis of physical examination, magnetic resonance imaging (MRI) and postoperative pathologic examination. INTERVENTIONS: We treated her with intralesional injection of triamcinolone acetonide (TCA) for 8 times. OUTCOMES: She was cured and had no recurrence during the 3-month follow-up. LESSONS: This prompts that TCA may provide a more effective and safer choice for the treatment of cavernous hemangiomas.

[Analysis of recurrence pattern and prognosis of patients with cervical carcinoma and pelvic lymph node metastasis].

OBJECTIVE: To investigate the pattern of disease relapse and prognostic risk factor of patients with cervical carcinoma and pelvic lymph node metastasis. METHODS: A total of 124 cases of International Federation of Gynecology and Obstetrics (FIGO) Ib1-IIa cervical carcinoma with pelvic node metastasis who were treated at the Cancer Center of Sun Yat-sen University during January 1994 to December 2001 were selected for this study. Prognosis and recurrence were retrospectively analyzed using the clinico-pathological data RESULTS: The overall 5 year survival and 5 year disease-free survival were 63.3% and 61.4%, respectively. Overall recurrence rate was 39.5% (49/124), among which intra-pelvic relapse (61.0%, 25/41) was significantly more common than extra-pelvic relapse (31.7%,13/41; P=0.008). Multivariate analysis identified involvement of common iliac node as an independent prognostic factor (P=0.035). According to this factor, node-positive patients could be divided into low risk group (without common iliac node involvement, 104 cases) and high risk group (with common iliac node involvement, 20 cases). The 5 year disease-free survival were 69.4% and 24.5% respectively, with a significant difference (P=0.003). Intra-pelvic relapse was observed in 22.1% (23/104) of low risk and 25.0% (5/20) of high risk group respectively, with no significant difference (P>0.05). However extra-pelvic relapse was seen in 7.7% (8/104) of low risk and 40.0% (8/20) of high risk group, with a significant difference (P<0.01). CONCLUSIONS: Common iliac node involvement is a significant factor influencing the prognosis of patients with cervical carcinoma and pelvic lymph node metastasis. Patients with positive common iliac nodes have significantly decreased 5 year disease-free survival and higher extra-pelvic disease recurrence rates compared with those whose common iliac nodes are negative. These findings provide important data for design of individualized treatment mode.

[Diagnostic value of multiple tumor marker detection for mature and immature teratoma of the ovary].

BACKGROUND & OBJECTIVE: It is difficult to differentially diagnose mature cystic teratoma (MCT) and immature teratoma (IT) of the ovary before operation. This study was to evaluate the value of multiple tumor marker detection in differential diagnosis of ovarian MCT and IT. METHODS: Clinical data of 272 patients with ovarian teratoma, diagnosed pathologically and treated at Cancer Center of Sun Yat-Sen University from Jan. 1995 to Dec. 2005, were reviewed. Of the 272 patients, 254 had MCT and 18 had IT. The serum levels of carbohydrate antigen 125 (CA125), CA153, CA199, neuron-specific enolase (NSE), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) in MCT and IT were compared. RESULTS: Of the 254 patients with MCT, the median age was 30, the mean serum levels of CA125, CA153, CA199, NSE, AFP and CEA were 25.5 x 103 u/L, 11.8 x 103 u/L, 106.6 x 103 u/L, 12.6 microg/L, 2.7 microg/L and 2.5 microg/L. Of the 18 patients with IT, the median age was 23, the mean serum levels of these tumor markers were 140.3 x 103 u/L, 16.8 x 103 u/L, 112.0 x 103 u/L, 18.0 microg/L, 369.5 microg/L and 3.2 microg/L. Both the serum levels and positive rates of CA125, CA153 and AFP were significantly higher in IT than in MCT (P<0.05). When detected alone to differentially diagnose MCT and IT, the specificity of CA125, CA153, AFP were high, and the sensitivity of CA125 was the best (50.0%). The sensitivity was elevated to 71.4% by combined detection of CA125, CA153 and AFP. CONCLUSION: Combined detection of tumor markers, especially CA125, CA153 and AFP, may be helpful for differential diagnosis of ovarian MCT and IT.

[Clinical analysis of 12 cases of uterine carcinosarcoma].

BACKGROUND & OBJECTIVE: Uterine carcinosarcoma, also known as malignant mixed mullerian tumors, is an uncommon neoplasm that carries a poor prognosis. This study was to analyze the clinical manifestation, diagnosis, treatment and prognosis of this disease. METHODS: Clinical data of 12 uterine carcinosarcoma patients, diagnosed in Cancer Center of Sun Yat-sen University from 1978 to 2004, were analyzed. RESULTS: Of the 12 cases of uterine carcinosarcoma, 2 were in the cervix, 10 in the corpus uteri. The main clinical manifestation of cervical carcinosarcoma was contact vaginal bleeding. Carcinosarcoma in the corpus uteri manifested abnormal vaginal bleeding and postmenstrual bleeding. Diagnosis depended on pathology. Twelve patients undergone operation. Eight patients received chemotherapy and 2 received radiotherapy after operation. One cervical carcinosarcoma patient died within 2 year. The 1-, 3-, and 5-year survival rates of the 12 patients were 80.0%, 50.0%, and 50.0%,respectively. CONCLUSIONS: Primary surgery is the main treatment for uterine carcinosarcoma. The prognosis of uterine carcinosarcoma is associated with surgicopathologic stage and treatment modalities.