leptin and Uterine-Cervical-Neoplasms

Cervical cancer (CC) is the main malignant tumor of gynecology with high mortality. This study aimed to explore the changes of T lymphocyte subsets in the peripheral blood of patients with intermediate and advanced CC (IACC) treated with nimotuzumab (Nimo) combined with chemoradiotherapy (CRT).. Peripheral blood was extracted before and after treatment, and patients were randomly divided into the CRT group (N = 68) or the Nimo + CRT group (N = 68). The levels of tumor markers squamous cell carcinoma antigen (SCCA), carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA), tumor indexes leptin and insulin-like growth factor-2 (IGF2), and key secretory factors (interferon γ/tumor necrosis factor α/interleukin (IL)-4/IL-13) of Th1 and Th2 cells in the serum were detected. The levels of T lymphocyte subsets CD3+, CD4+, CD8+, and CD4+/CD8+ and the levels of Th1/Th2 and Th17/Treg in CD4+ cell subsets were determined by flow cytometry. The objective remission rate, progression-free survival (PFS), and overall survival (OS) of patients were analyzed, and Kaplan-Meier curves were drawn to show the prognosis of patients.. After treatment, the levels of SCCA, CA125, CEA, leptin, and IGF2 in the serum of patients with IACC were decreased, the level of Th1/Th2 was increased, and the Th17/Treg level was decreased. The treatment effect of Nimo + CRT was more significant than that of CRT alone. Survival curve analysis showed that Nimo + CRT could prolong PFS and OS in patients with IACC. In addition, the follow-up results of patients showed that Nimo did not increase the incidence and severity of adverse reactions caused by CRT.. Nimo combined with CRT can protect the immune function of patients, improve the effective rate, and prolong the survival rate of patients with IACC.

Topics: Carcinoembryonic Antigen; Chemoradiotherapy; Female; Humans; Leptin; T-Lymphocyte Subsets; Th2 Cells; Uterine Cervical Neoplasms

Leptin may be involved in the pathogenesis of numerous cancer types by activation of cellular signal-transduction pathways. In this study, we analyzed the role of leptin and the mechanism(s) underlying its action in cervical carcinoma cells. Firstly, we examined the expression of leptin in 80 cases of cervical carcinoma using immunohistochemical staining. The results showed that the levels of leptin correlated significantly with the grades of cervical carcinoma. At the same time, the expression of leptin correlated positively with c-myc and its downstream gene, bcl-2. The expression of c-myc and bcl-2 was evaluated in leptin-treated HeLa cells by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Recombinant leptin significantly activated the expression of bcl-2 and c-myc in HeLa cells. Finally, the apoptotic index, the proliferative activity and the expression levels of c-myc and bcl-2 were determined in the HeLa cells treated with silencing of leptin. We found that silencing of leptin inhibited the proliferation of HeLa cells and reduced the expression of bcl-2 and c-myc. Our data demonstrated that leptin interferes with the expression of oncogenic c-myc and anti-apoptotic bcl-2, and regulates cell turnover and facilitates the progression of cervical cancer.

Topics: Adult; Aged; Apoptosis; Carcinoma, Squamous Cell; Cell Proliferation; Female; Gene Expression; Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Leptin; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; RNA, Messenger; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

The aim of our investigation was the detection of endocrine-metabolic disorders in patients with hyperplastic processes of endomyometrium, uterine cervix and mammary glands. 88 patients of reproductive age with several gynaecological complaints have been investigated. 72 patients with hyperplastic processes in endomyometrium, uterine cervix (hyperplasia, polyposis, myoma) and mammary glands (fibroadenomatosis, adenomatosis) were selected in main group. Control group consisted of 16 patients without any hyperplastic processes of reproductive organs. Metabolic syndrome in main group was revealed in 28% of cases, in control - 18,8% (chi(2)=3,95, p=0,047); insulin resistance - 37,5% and 18,7% (chi(2)=4,59, p=0,033), respectively; obesity - 52,8% and 25,0% (chi(2)=4,05, p=0,045), respectively; dyslipidemia - 52,8% and 0,0%; hypertension - 26,4% and 12,5% (chi(2)=1,88, p=NS), respectively. Blood leptin level in main group was - 13,7+/-10,9 ng/ml, and in control - 5,0+/-2,9 ng/ml (p=0,005). Our results suggest that metabolic syndrome and its components significantly influences the formation of hyperplastic processes of endomyometrium, uterine cervix and mammary glands. Blood leptin level is significantly increased in patients with hyperplastic pathologies.

Topics: Adult; Breast Neoplasms; Cervix Uteri; Endocrine System Diseases; Female; Humans; Hyperplasia; Leptin; Mammary Glands, Human; Metabolic Syndrome; Reproduction; Uterine Cervical Neoplasms

Serum levels of vascular endothelial growth factor (VEGF) can be seen as surrogate markers of angiogenesis. Recently, leptin, which is involved in the control of satiety and energy expenditure, was also shown to modulate angiogenesis. As angiogenesis plays an abundant role in cervical carcinogenesis, we evaluated serum VEGF and leptin in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer.. Serum VEGF and leptin were measured in 84 patients with cervical cancer, in 28 patients with CIN I-III, and in 35 healthy women, using a commercially available enzyme-linked immunosorbent assay and radioimmunoassay, respectively.. Serum VEGF was significantly elevated in patients with cervical cancer and in patients with CIN I-III compared to healthy women. In patients with cervical cancer serum VEGF was significantly correlated with tumor stage, but not with lymph node involvement and histological grade. Univariate and multivariate analyses showed that elevated pretreatment serum VEGF was not associated with the duration of disease-free and overall survival. Serum leptin did not differ among patients with cervical cancer, patients with CIN I-III, and healthy women. Serum leptin was significantly correlated with body mass index (BMI). All further analyses were performed with absolute and serum leptin corrected by BMI. No differences in serum leptin could be ascertained between patients with cervical cancer and patients with CIN I-III. Serum leptin was not associated with any clinicopathological parameter and patients' survival. No correlation between serum VEGF and leptin was found.. It can be speculated that serum VEGF might be used as a surrogate marker of angiogenesis in patients with cervical cancer. Our data support the concept that VEGF plays a role in malignant transformation and tumor growth, but not in the lymphatic spread of cervical cancer. This is the first report on leptin in a gynecological malignancy. Our results show that serum leptin falls short of being a useful marker in patients with cervical cancer.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Disease-Free Survival; Endothelial Growth Factors; Female; Humans; Leptin; Lymphokines; Middle Aged; Neoplasm Staging; Neovascularization, Pathologic; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

To investigate the effects of total abdominal hysterectomy on circulating leptin levels, 16 pre- and 8 postmenopausal patients with uterine leiomyoma or carcinoma in situ of the uterine cervix were enrolled. Serum levels of leptin and fasting blood sugar (FBS) were determined before (day -7) and after surgery (day +1 and +7). Body mass index (BMI) was recorded at day -7 and +7. Anesthesia duration, surgical duration, hematology, and blood loss during surgery were recorded. Relations of these variables to serum leptin levels were investigated. Serum leptin levels rose from 7.3+/-4.7 ng/mL to 9.3+/-5.8 ng/mL at day +1 (P < 0.01), then decreased to 4.9+/-3.0 ng/mL at day +7 (P < 0.05 vs. values at day -7 and +1). FBS levels also rose from 89.4+/-7.5 mg/dL to 119.3+/-24.0 mg/dL (P < 0.01), then returned to normal at day +7 (96.2+/-9.0 mg/dL). However, there was no significant correlation observed between FBS and leptin levels at each time point (r < or = 0.22). BMI decreased from 22.7+/-3.0 kg/m2 to 21.7+/-2.9 kg/m2 at day +7 (P < 0.001). At day -7 and +7, leptin levels were positively correlatd with BMI (r = 0.79, P < 0.001 and r = 0.71, P < 0.001, respectively). Circulating leptin levels were increased on day one after total abdominal hysterectomy.

Topics: Adult; Blood Glucose; Body Mass Index; Carcinoma in Situ; Female; Humans; Hysterectomy; Leiomyoma; Leptin; Middle Aged; Postmenopause; Premenopause; Uterine Cervical Neoplasms; Uterine Neoplasms