Role of GPX4 inhibition-mediated ferroptosis in the chemoresistance of ovarian cancer to Taxol in vitro.

BACKGROUND: Ovarian cancer remains a common gynecological tumor and the fifth leading cause of death worldwide. Taxol-based chemotherapy is a standard approach to the treatment of ovarian cancer. Glutathione peroxidase 4 (GPX4) is the key regulator of ferroptosis, which is an important form of cell death. Here, we investigate the effect of GPX4 inhibition-mediated ferroptosis on the sensitivity of ovarian cancer cells to Taxol. METHODS AND RESULTS: A2780/PTX and OVCAR-3/PTX Taxol-resistant ovarian cancer cells were established, and stable GPX4 knockout cell lines were generated via lentivirus GPX4-sgRNA. The GPX4 expression level, the apoptosis rate and cell viability were analyzed. The levels of ferroptosis-related factor indicators such as malondialdehyde (MDA) and reactive oxygen species (ROS) were measured. The results showed that the GPX4 protein and mRNA levels were increased in the Taxol-resistant cells. Moreover, GPX4 knockout reduced cell viability and inhibited the colony formation rate. In addition, we found that GPX4 inhibition increased Taxol sensitivity by inducing ferroptosis. CONCLUSIONS: In summary, our studies reveal that GPX4 inhibition promotes ferroptosis and increases the sensitivity of ovarian cancer cells to Taxol in vitro.

The HOXC-AS2/miR-876-5p/HKDC1 axis regulates endometrial cancer progression in a high glucose-related tumor microenvironment.

The tumor microenvironment (TME) is related to chronic inflammation and is currently identified as a risk factor for the occurrence and development of endometrial cancer (EC). Pyroptosis is a new proinflammatory form of programmed cell death that plays a critical role in the progression of multiple diseases. However, the important role of pyroptosis in high-glucose (HG)-related EC and the underlying molecular mechanisms remain elusive. In the present study, transcriptome high-throughput sequencing revealed significantly higher hexokinase domain-containing 1 (HKDC1) expression in EC patients with diabetes than in EC patients with normal glucose. Mechanistically, HKDC1 regulates HG-induced cell pyroptosis by modulating the production of reactive oxygen species and pyroptosis-induced cytokine release in EC. In addition, HKDC1 regulates TME formation by enhancing glycolysis, promoting a metabolic advantage in lactate-rich environments to further accelerate EC progression. Subsequently, miR-876-5p was predicted to target the HKDC1 mRNA, and HOXC-AS2 was identified to potentially inhibit the miR-876-5p/HKDC1 axis in regulating cell pyroptosis in HG-related EC. Collectively, we elucidated the regulatory role of the HOXC-AS2/miR-876-5p/HKDC1 signal transduction axis in EC cell pyroptosis at the molecular level, which may provide an effective therapeutic target for patients with diabetes who are diagnosed with EC.

Inhibition of STAT3 reverses Taxol-resistance in ovarian cancer by down-regulating G6PD expression in vitro.

Ovarian cancer is the eminent gynecological malignancy and chemoresistance remains a major reason for poor in ovarian cancer patients. Taxol has been proved as the most effective chemotherapeutic agent against ovarian cancer. However development of Taxol resistance remains a major problem. Here, we report that STAT3, directly activates pentose-phosphate pathway to exert pro-oncogenic effects on Taxol resistance of ovarian cancer. In addition, we found that STAT3, p-STAT3 and glucose-6-phosphate dehydrogenase (G6PD) protein levels are upregulated in Taxol resistant cell lines compared with Taxol sensitive cell lines. Furthermore, inhibition of STAT3 decreased G6PD mRNA expression level and enhanced the sensitivity of Taxol resistant cell to Taxol. Finally, we found that STAT3 directly binds to the G6PD promoter region and promotes the expression of G6PD at transcriptional level. Taken together, our data indicate that activation of STAT3 promotes ovarian cancer cell proliferation, colony formation, and Taxol resistance via augmenting G6PD expression and pentose-phosphate metabolism flux, which provides a potential therapeutic target that may improve prognosis by decreasing G6PD expression and enhancing Taxol-sensitivity.

Drp1 mediates high glucose-induced mitochondrial dysfunction and epithelial-mesenchymal transition in endometrial cancer cells.

This study aims to clarify the role and molecular mechanism of dynamin-related protein 1 (Drp1)-mediated mitochondrial homeostasis in high glucose (HG)-induced endometrial cancer (EC). Normal endometrium and tumor tissues of EC patients with normal and HG levels were collected, and Drp1 and p-Drp1 expression levels were detected by immunohistochemistry. Human EC cells were cultured with different glucose concentrations, and Drp1 and p-Drp1 expression levels were evaluated by Western blotting. Cell models of control and siDrp1 groups under normal and HG conditions were established, and subsequent functional experiments were conducted. Histology and in vitro experiments showed that the HG environment increased Drp1 activation, which could lead to mitochondrial dysfunction. Moreover, the imbalance of mitochondrial homeostasis mediated by Drp1 resulted in cell dysfunction, including altered glucose metabolism and increased epithelial-mesenchymal transition (EMT), migration and invasion. All these changes caused by HG could be partially alleviated by Drp1 knockdown. This study revealed that Drp1 was involved in the progression of EC associated with HG, and Drp1 might be a new potential therapeutic target for EC patients with diabetes.

Physiological functions of Wilms' tumor 1-associating protein and its role in tumourigenesis.

The Wilms' tumor-associated gene WT1 encodes a tumor suppressor gene, which is implicated in renal differentiation and development of adult urogenital system. Wilms' tumor 1-associating protein (WTAP) is initially identified as a nuclear protein that specifically interacts with WT1 in both in vitro and in vivo assays. WTAP is ubiquitously expressed in different tissues and various growth periods, and its expression is involved in cell cycle, RNA splicing and stabilization, N6-methyladenosine RNA modification, cell proliferation, and apoptosis as well as embryonic development. In the present review, we aimed to summarize the functions of WTAP in various physiological and pathological processes, in particular with regard to the current knowledge about the role of WTAP in tumorigenesis of different cancers.

Sevoflurane inhibits the progression of ovarian cancer through down-regulating stanniocalcin 1 (STC1).

BACKGROUND: Ovarian cancer is one of the leading causes of female death worldwide, with a poor prognosis of advanced patients. Sevoflurane, a volatile anesthetic commonly used in clinical operations, has been reported to have anti-cancer activity against some tumors. In the present study, we aimed to investigate the effects of sevoflurane on the progression of ovarian cancer and its potential mechanism. METHODS: The effects of sevoflurane on ovarian cancer cell viability, proliferation, migration, invasion, cell cycle, and apoptosis were determined by functional experiments in vitro. Gelatin zymography assay was performed to examine MMP9 activity. In vivo, sevoflurane was injected into mice of transplantation tumor with SKOV3 cells or with pcDNA-STC1 treated SKOV3 cells. RESULTS: We found that sevoflurane inhibited the viability of SKOV3 and OVCAR3 cells in a dose-dependent manner, and colony formation assay revealed that sevoflurane inhibited ovarian cancer cell colony-formation abilities. Additionally, sevoflurane could induce cell cycle arrest and promote cell apoptosis in SKOV3 and OVCAR3 cells. Moreover, sevoflurane reduced the migration and invasion abilities of SKOV3 and OVCAR3 cells, as well as the MMP-9 activity. Furthermore, sevoflurane down-regulated the expression of stanniocalcin 1 (STC1), and up-regulation of STC1 could reverse the inhibitory effects of sevoflurane on cell proliferation and invasion. In vivo, sevoflurane significantly inhibited the tumor growth, which was be reversed by STC1 overexpression. CONCLUSION: These data reveal an anti-cancer activity of sevoflurane on the growth and invasion of ovarian cancer, which may be through down-regulating STC1. Sevoflurane may serve as a potential anti-cancer agent in ovarian cancer therapy.

Postoperative adjuvant chemotherapy combined with intracavitary brachytherapy achieved the equivalent survival compared with concurrent chemoradiotherapy in cervical cancer patients with intermediate-risk.

OBJECTIVES: The current study was aimed to evaluate the efficacy and toxicity of postoperative adjuvant chemotherapy (CT) combined with intracavitary brachytherapy (ICRT) in cervical cancer patients with intermediate-risk. METHODS: We analyzed the medical records of 558 patients who were submitted to radical surgery for Stage IB-IIA cervical cancer. A total of 172 of those 558 patients were considered intermediate-risk according to the GOG criteria. Among those 172 patients, 102 were subjected to CT combined with ICRT (CT+ICRT) and the remaining 70 patients were treated with concurrent chemoradiation (CCRT). The 3-year disease free survival (DFS), overall survival (OS), and complications of each group were evaluated and analyzed. RESULTS: No significant difference was observed in 3-year DFS or OS of the patients submitted to CT+ICRT and CCRT. Importantly, the frequencies of grade III to IV acute complications were significantly higher in patients submitted to CCRT than in those treated with CT+ICRT (Hematologic, P = 0.016; Gastrointestinal, P = 0.041; Genitourinary, P = 0.019). Moreover, the frequencies of grade III-IV late complications in patients treated with CCRT were significantly higher compared with CT+ICRT-treated patients (Gastrointestinal, P = 0.026; Genitourinary, P = 0.026; Lower extremity edema, P = 0.008). CONCLUSIONS: Postoperative adjuvant CT+ICRT treatment achieved equivalent 3-year DFS and OS but low complication rate compared to CCRT treatment in early stage cervical cancer patients with intermediate-risk.

Derlin1 functions as an oncogene in cervical cancer via AKT/mTOR signaling pathway.

BACKGROUND: Cervical cancer (CC) ranks third in the morbidity and mortality of female cancer around the world. Derlin1 has been found to be overexpressed in several human cancers. However, it is still unclear about its roles in CC. The research aims to explore the relationship between Derlin1 and CC. METHODS: We purchased a human CC tissues microarray, which contained CC tissues and corresponding para-cancerous tissues from 93 patients with primary cervical squamous cell carcinoma. Immunohistochemical staining was used to confirm the expression of Derlin1 in these tissues. And we detected the differential expression of Derlin1 in cervical cancer cell lines and normal cervical epithelial cells (H8). Further, the cervical cancer cell lines SiHa and C33A were used as an in vitro model, which was down-regulated the expression of Derlin1 using siRNA interference technology. The effects of Derlin1 down-regulating in CC cell lines on cell proliferation and migration were detected by CCK8 assay and transwell assay, respectively. The effect of Derlin1 down-regulating on apoptosis was analyzed by flow cytometry, and apoptosis-related proteins were detected using western blotting. In-depth mechanisms were studied using western blotting. In addition, the effects of Derlin1 up-regulating in normal cervical epithelial cells also were exposed. RESULTS: Derlin1 was significantly elevated in CC tissues (81.7%, 76/93), and the expression of Derlin1 was positively correlated with the tumor size, pathological grade, and lymph node metastasis in CC patients. And Derlin1 was high expressed in cervical cancer cell lines compared to H8 cells. Knockdown of Derlin1 in cervical cancer cell lines inhibited cell proliferation and migration. Moreover, knockdown of Derlin1 induced apoptosis and affected the expression of apoptosis-related proteins, including Bcl-2, Bax, Bim, caspase3 and caspase9. Further experiments showed that AKT/mTOR signal pathway might be involve in this processes that knockdown of Derlin1 inhibited the expression of p-AKT and p-mTOR. Over-expression of Derlin1 in H8 cells promoted cell proliferation and migration via up-regulated the expression of p-AKT and p-mTOR. CONCLUSION: Derlin1 is an oncogene in CC via AKT/mTOR pathway. It might be a potential therapeutic target for CC.

Surgical and Oncologic Outcomes of Radical Abdominal Trachelectomy Versus Hysterectomy for Stage IA2-IB1 Cervical Cancer.

STUDY OBJECTIVE: To compare the surgical and oncologic outcomes between abdominal radical trachelectomy (ART) and radical hysterectomy (RH) for stage IA2-IB1 cervical cancer. DESIGN: A retrospective cohort study (Canadian Task Force classification II-2). SETTING: Shandong Cancer Hospital, Shandong, China. PATIENTS: Three hundred twenty-nine patients with IA2-IB1 cervical cancer. INTERVENTIONS: All patients underwent ART or RH. MEASUREMENTS AND MAIN RESULTS: All patients were divided into ART (n = 143) and RH (n = 186) groups according to the surgical approach. Additionally, oncologic and fertility outcomes were compared for different tumor pathologies and sizes in ART patients. The ART group had similar case characteristics as the RH group, except that the ART group had a longer surgical time. During a similar follow-up period, there were 4 (2.9%) recurrences and 3 (2.2%) patients who died from recurrence in the ART group compared with 8 (4.6%) recurrences and 4 (2.3%) patients who died from recurrence in the RH group (p = .444 and p = .999, respectively). In the ART group, squamous cell carcinoma (SCC) patients had a 5-year overall survival and pregnancy rate similar to those of non-SCC patients (98.1% vs 96.8%, p = .999; 33.3% vs 26.7%, p = .873), and patients with tumors ≤2 cm and 2 to 4 cm experienced a similar 5-year overall survival rate (97.0% vs 98.6%, p = .999), except patients with tumors ≤2 cm had a higher pregnancy rate (45.2% vs 17.2%, p = .020). CONCLUSION: ART seems to have similar surgical and oncologic outcomes to RH, except ART has a longer surgical time. Both non-SCC patients and stage IA2-IB1 patients with 2- to 4-cm tumors can undergo ART safely. Patients with tumors ≤2 cm have a higher pregnancy rate than patients with 2- to 4-cm tumors.

A genetic variant of miR-335 binding site in the ERBB4 3'-UTR is associated with prognosis of ovary cancer.

Ovarian cancer is one of the leading gynecologic malignancies globally, the 5-year survival rate for patients with advanced stage ovarian cancer is very low. Our objective was to test the hypothesis that miR-335 was associated with the survival of patients with ovarian cancer. Bioinformatics tools and luciferase report assay were used to select the target of miR-335, and real-time PCR was used to detect the expression of miR-335 and ERBB4 in different genotype groups. Finally, Cox regression and Kaplan-Meier analyses were used to assess the relationship of ERBB4 genotype and survival of ovary cancer. Firstly, individuals carried ERBB4 rs186724 GG genotype had poorer overall survival compared with those carried CC/CT genotypes in ovarian cancer, while the participants with rs1836724 GA genotype had the same overall survival with that in participants with rs1836724 AA genotype in accordance with the result of Cox regression and Kaplan-Meier analyses. Then according to result of the in-silicon analysis, ERBB4 was the target of miR-335, and rs1836724 was located on 3'UTR of ERBB4, the binding site of miR-335, and miR-335 inhibited the expression of ERBB4 and this regulation was more suppressed when the G allele replaced by the variant A allele. Finally, miR-335 was similar among GG, GA, and AA groups, and ERBB4 level was higher in GG group. Finally, malignant grade is apparently higher in GG group than the other group. The data indicated that the ERBB4 rs1836724 polymorphism was associated with the survival of ovarian cancer.

miR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA hypermethylation.

Endometrial cancer is the most common gynecological cancer in the United States. We wanted to identify epigenetic aberrations involving microRNAs (miRNAs), whose genes become hypermethylated in endometrial primary tumors. By integrating known miRNA sequences from the miRNA database (miRBase) with DNA methylation data from methyl-CpG-capture sequencing, we identified 111 differentially methylated regions (DMRs) associated with CpG islands (CGIs) and miRNAs. Among them, 22 DMRs related to 29 miRNAs and within 8 kb of CGIs were hypermethylated in endometrial tumors but not in normal endometrium. miR-137 was further validated in additional endometrial primary tumors. Hypermethylation of miR-137 was found in both endometrioid and serous endometrial cancer (P < 0.01), and it led to the loss of miR-137 expression. Treating hypermethylated endometrial cancer cells with epigenetic inhibitors reactivated miR-137. Moreover, genetic overexpression of miR-137 suppressed cancer cell proliferation and colony formation in vitro. When transfected cancer cells were implanted into nude mice, the cells that overexpressed miR-137 grew more slowly and formed smaller tumors (P < 0.05) than vector transfectants. Histologically, xenograft tumors from cancer cells expressing miR-137 were less proliferative (P < 0.05), partly due to inhibition of EZH2 and LSD1 expression (P < 0.01) in both the transfected cancer cells and tumors. Reporter assays indicated that miR-137 targets EZH2 and LSD1. These results suggest that miR-137 is a tumor suppressor that is repressed in endometrial cancer because the promoter of its gene becomes hypermethylated.

MicroRNA-138 is a potential biomarker and tumor suppressor in human cervical carcinoma by reversely correlated with TCF3 gene.

BACKGROUND: The aim of our work is to identify the functional mechanism of microRNA-138 (miR-138) in human cervical cancer. METHODS: MiR-138 expression was investigated by qRT-PCR in cervical cancer cell lines and human tumors. Correlations of patients' clinicopathological factors and overall survival with miR-138 expression were analyzed. In SiHa and HeLa cells, miR-138 was either upregulated or downregulated to evaluate its regulations on cervical cancer in vitro proliferation, invasion and in vivo xenograft growth. Downstream target gene of miR-138, TCF3, was analyzed by dual-luciferase reporter assay, and by qRT-PCR to evaluate its expression in cervical tumors and cervical cancer cell lines. TCF3 was either upregulated or downregulated in SiHa and HeLa cells to further evaluate its role in regulating cervical cancer proliferation and invasion. RESULTS: MiR-138 is downregulated in both cervical tumors and cervical cancer cell lines. Low expression of miR-138 in cervical tumors is closely correlated with patients' clinicopathological factors and poor survival. In SiHa and HeLa cells, lentivirus-induced miR-138 upregulation inhibited cancer proliferation and invasion in vitro, and xenograft growth in vivo, whereas miR-138 downregulation had little effect. TCF3 was confirmed to be regulated by miR-138, and upregulated in cervical cancer tumors and cell lines. In vitro cervical cancer proliferation and invasion were significantly inhibited by SiRNA-mediated TCF3 downregulation, but unaffected by TCF3 overexpression. CONCLUSION: MiR-138 may be a tumor suppressor and potential prognostic biomarker in cervical cancer. Its downstream target, TCF3, may also regulate cancer development in a reverse manner as miR-138.

Successful en bloc venous resection with reconstruction and subsequent radiotherapy for 2 consecutive recurrences of intravenous leiomyoma--a case report.

BACKGROUND: Intravenous leiomyomas are a rare variant of uterine leiomyoma. Although histologically benign, these tumors are associated with a poor prognosis due to propensity for metastasis, high recurrence rate, difficulty of obtaining complete resection, and frequent extension into and along major veins. CASE PRESENTATION: We describe a 43-year-old patient initially presenting with lower abdominal pain. Clinical examination revealed a large right pelvic mass that was shown by computed tomography (CT) to surround the right external iliac vein, right common iliac vein and distal inferior vena cava. The patient had a history of total abdominal hysterectomy with bilateral ovarian cystectomies for uterine leiomyoma approximately 3 years prior to her presentation. Her past surgical history also included removal of an ovarian endometriosis cyst and right hydrosalpinx. The patient underwent an exploratory laparotomy. Operative findings included complete occlusion of the right iliac vessels and distal vena cava by a large tumor that filled the pelvis and extended to the level of the right kidney. The mass was resected en bloc with the involved veins and synthetic vascular grafts were placed. This highly technical procedure was complicated by hemorrhage requiring a total of 32 units of red blood cells and 2.0 L of plasma. Pathologic examination confirmed intravenous leiomyoma. On Immunohistochemical staining, the tumor cells were positive for CD32, CD34, Vimentin and smooth muscle actin. Eight months after this procedure, the patient again presented with an abdominal mass. She was diagnosed with a pelvic recurrence and noted to have intravascular extension into the left iliac vein and inferior vena cava. For this tumor she underwent radiation treatment with three-dimensional conformal radiation therapy (total dose 4500 cGy). The tumor gradually decreased in size during follow-up and became undetectable by CT. CONCLUSIONS: Surgical excision is the mainstay of treatment of intravenous leiomyoma. Radiation therapy may be an effective alternative in patients with unresectable disease or poor surgical candidates.

Prognostic factors and genes associated with endometrial cancer based on gene expression profiling by bioinformatics analysis.

BACKGROUND: Endometrial cancer (EC) is the most prevalent malignancy worldwide. Although several efforts had been made to explore the molecular mechanism responsible for EC progression, it is still not fully understood. AIM OF THE STUDY: To evaluate the clinical characteristics and prognostic factors of patients with EC, and further to search for novel genes associated with EC progression. METHODS: We recruited 328 patients with EC and analyzed prognostic factors using Cox proportional hazard regression model. Further, a gene expression profile of EC was used to identify the differentially expressed genes (DEGs) between normal samples and tumor samples. Subsequently, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis ( http://www.genome.jp/kegg/ ) for DEGs were performed, and then protein-protein interaction (PPI) network of DEGs as well as the subnetwork of PPI were constructed with plug-in, MCODE by mapping DEGs into the Search Tool for the Retrieval of Interacting Genes database. RESULTS: Our results showed that body mass index (BMI), hypertension, myometrial invasion, pathological type, and Glut4 positive expression were prognostic factors in EC (P < 0.05). Bioinformatics analysis showed that upregulated DEGs were associated with cell cycle, and downregulated DEGs were related to MAPK pathway. Meanwhile, PPI network analysis revealed that upregulated CDK1 and CCNA2 as well as downregulated JUN and FOS were listed in top two nodes with high degrees. CONCLUSIONS: Patients with EC should be given more focused attentions in respect of pathological type, BMI, hypertension, and Glut4-positive expression. In addition, CDK1, CCNA2, JUN, and FOS might play important roles in EC development.

Glucose promotes cell proliferation, glucose uptake and invasion in endometrial cancer cells via AMPK/mTOR/S6 and MAPK signaling.

OBJECTIVES: Obesity and diabetes are well-known risk factors for the development of endometrial cancer. A high rate of aerobic glycolysis represents a key mechanism by which endometrial cancer cells consume glucose as its primary energy source. The up-regulated glycolytic pathway is a common therapeutic target whose inhibition has implications for anti-tumor activity in cancer cells. This study aimed to investigate the effect of various concentrations of glucose on cell proliferation in endometrial cancer. METHODS: ECC-1 and Ishikawa cells were treated with low glucose (1mM), normal glucose (5mM) and high glucose (25mM), and cytotoxicity, apoptosis, cell cycle, adhesion/invasion, and changes of AMPK/mTOR/S6 and MAPK pathways were evaluated. RESULTS: Our results revealed that high glucose increased cell growth and clonogenicity in two endometrial cancer cell lines in a dose dependent manner. Low glucose induced the activity of cleaved caspase 3 and caused cell cycle G1 arrest. High glucose increased the ability of adhesion and invasion by decreasing E-cadherin and increasing Snail expression. In addition, high glucose increased glucose uptake and glycolytic activity through modulating the AMPK/mTOR/S6 and MAPK pathways. CONCLUSIONS: Our findings suggest that glucose stimulated cell proliferation through multiple complex signaling pathways. Targeting glucose metabolism may be a promising therapeutic strategy in the treatment of endometrial cancer.

The Treatment of Pelvic Locoregional Recurrence of Cervical Cancer After Radical Surgery With Intensity-Modulated Radiation Therapy Compared With Conventional Radiotherapy: A Retrospective Study.

OBJECTIVE: The aim of this study was to investigate the therapeutic response and toxicity of intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (c-RT) as adjuvant therapy in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. METHODS: This retrospective study included 161 patients with unresectable pelvic locoregional recurrence of cervical cancer after radical surgery between March 2003 and May 2012. All patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer and received radical hysterectomy and pelvic lymphadenectomy. A total of 82 patients were treated with c-RT, whereas the remaining 79 patients underwent IMRT. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation. RESULTS: The mean dose delivered to the planning target volume was significantly higher in the IMRT group than in the c-RT group (61.8 vs 50.3 Gy, P = 0.029). Intensity-modulated radiation therapy plans yielded better dose sparing of small bowel, bladder, and rectum than did c-RT (P < 0.05). Moreover, the IMRT patients experienced less acute and chronic toxicities (P < 0.05) and better short-term effects (complete response + partial response) than did those treated with c-RT (89.9% vs 63.4%, P = 0.03). Three- and 5-year overall survival rates were significantly higher in the IMRT group than in the c-RT group (3-year: 58.4% vs 39.1%, P = 0.012; 5-year: 35.4% vs 21.4%, P = 0.007). Furthermore, 5-year progression-free survival rates were significantly higher in the IMRT group than in the c-RT group (26.1% vs 15.1%, P = 0.031). CONCLUSIONS: Intensity-modulated radiation therapy achieved outcomes superior to c-RT in patients with pelvic locoregional recurrence of cervical cancer after radical surgery. The acute and chronic toxicities were acceptable, and the adjacent organs at risk were well protected.

Distribution pattern of circumflex iliac node distal to the external iliac node metastasis in stage IA to IIA cervical carcinoma.

OBJECTIVES: This study aimed to investigate the metastatic rate of circumflex iliac node distal to the external iliac node (CINDEIN) and its associations with clinicopathological factors in patients with stage IA to IIA cervical cancer to determine whether dissection of CINDEIN had a role in surgery of these patients. METHODS: Six hundred thirty-three patients with the International Federation of Gynecology and Obstetrics stage IA to IIA cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were retrospectively reviewed. The metastatic rate and distribution of the pelvic lymph nodes (PLNs) and CINDEINs were analyzed. RESULTS: The PLN metastatic rate was 25.6% (162 of 633 patients). Sixteen of 162 node-positive patients had CINDEIN metastases. Only 1 patient without PLN metastases had positive CINDEIN nodes. Univariate analysis revealed that other PLNs (including lymph nodes collected from obturator, external iliac, and internal iliac regions) and lymph vascular space involvement were the risk factors of CINDEIN metastases (P < 0.05). Other PLN metastasis (odds ratio, 50.6; 95% confidence interval, 6.6-386.7) was an independent risk factor for metastasis to CINDEIN by binary logistic regression analysis. CONCLUSIONS: Circumflex iliac node distal to the external iliac node metastases seemed to occur secondarily to widespread PLN metastases. In early stage cervical cancer, removal of the CINDEIN as a routine surgical procedure might be omitted to reduce operation time and minimize surgical morbidity.

Gene expression changes after ionizing radiation in endothelial cells derived from human endometrial cancer-preliminary outcomes.

BACKGROUND: Accumulating evidence has demonstrated that death of microvascular endothelial cells plays a decisive role in the tumor response against radiotherapy. Nevertheless, radiation-induced gene alterations on cancer-associated endothelial cells of human endometrial carcinoma remain poorly understood. The purpose of this study was to elucidate the gene expression changes after X-ray radiation in human endometrial carcinoma vascular endothelial cells and to provide new targets for combined treatment of radiation and anti-angiogenesis in human endometrial carcinoma. MATERIALS AND METHODS: Endometrial cancer-derived endothelial cells, which obtained before and 4 h after 400 cGy X-ray radiation from four endometrial carcinomas, were analyzed by gene expression profile. The selected meaningful genes from gene microarray experiments were validated by real-time quantitative PCR. RESULTS: Microarray analyses showed 49 significantly changed genes which were common to all the microarray experiments. There into, 14 genes were found to be in persistent up-regulation and 14 in persistent down-regulation 4 h after X-ray radiation when compared with the control group. These genes were involved in cell cycle and growth regulation, cell-apoptosis, chemokine, cell signaling, cellular stress response, angiogenesis, DNA synthesis and repair and cell adhesion. Eight randomly selected genes were validated by real-time PCR. DISCUSSION: The genes of cancer-derived endothelial cells regulated by X-ray radiation as well as their related signal pathways, which obtained from gene expression profiling data, were relevant to radiosensitivity of endometrial cancer. This study shows that the identified genes and their related signaling pathways are candidated biomarkers for radiation and anti-angiogenesis of human endometrial carcinoma.

[Incidence and influencing factors of distal external iliac lymph node metastasis in early cervical cancer].

OBJECTIVE: The distal external iliac lymph nodes are located along the external iliac artery between the deep circumflex iliac vein and the inguinal canal. Our study aimed to investigate the incidence of metastasis in distal external iliac lymph nodes and its association with clinicopathological factors in patients with early stage cervical cancer, and to determine the role of distal external iliac lymph nodes dissection in the surgery. METHODS: Five hundred and twenty-four patients with early stage cervical cancer underwent radical hysterectomy and bilateral pelvic lymphadenectomy in the Shandong Province Cancer Hospital between June 1995 and December 2011, and their clinicopathological features were analyzed retrospectively. RESULTS: Of the 524 patients, 124 (23.7%) had pelvic lymph node metastasis. The metastasis rates were 16.2% (85 of 524 patients) in the obturator lymph nodes, 12.2% (64 of 524 patients) in the internal and external iliac lymph nodes, 2.9% (15 of 524 patients) in the common iliac lymph nodes, 2.1% (11 of 524 patients) in the distal external iliac lymph nodes, and 1.7% (9 of 524 patients) in the para-aortic nodes. The incidence of isolated positive distal external iliac lymph nodes was 0.2%. Univariate analysis showed that lymphovascular space invasion, pelvic lymph node metastases (excluding distal external iliac lymph nodes) were significantly associated with distal external iliac lymph node metastasis (P < 0.05). Logistic regression analysis showed that pelvic lymph node metastasis (excluding distal external iliac lymph nodes) was the independent risk factor for metastasis to distal external iliac lymph nodes. CONCLUSIONS: In early stage cervical cancer, distal external iliac lymph node metastasis is rare, especially in cases with stage IA or without pelvic lymph node metastasis. Less extensive pelvic lymphadenectomy may be considered in these patients in order to reduce operative complications and improve patients' quality of life. The deep circumflex iliac vein may be an appropriate landmark for the caudal limit of external iliac lymphadenectomy. However, if pelvic lymph node metastasis (excluding distal external iliac lymph nodes) is found by intraoperative rapid pathological diagnosis, systematic pelvic lymphadenectomy including removal of the distal external iliac lymph nodes should be performed in order to reduce the risk of distant metastasis.

Myelopreservation with Trilaciclib in recurrent advanced ovarian cancer: a case report.

Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment protocol includes cytoreductive surgery for ovarian cancer plus postoperative consolidation chemotherapy and maintenance therapy, although it carries a high recurrence rate. During the treatment period, chemotherapy can lead to bone marrow suppression, a condition known as Chemotherapy-Induced Myelosuppression (CIM). This suppression may necessitate dose reduction or chemotherapy treatment cycle delay. In severe cases, CIM can result in infection, fever, and potential harm to the patient's life. Here, we report a case of a female patient with ovarian malignant tumor of biochemical recurrence who treated with chemotherapy combined with Trilaciclib, following previous perioperative chemotherapy with occurrence of severe CIM. It involves an intravenous injection of Trilaciclib before chemotherapy, which significantly abates the side effects of chemotherapy, reduces the occurrence of severe CIM, improves the patients' quality of life, and decreases the economic burden of hospitalization. We hope that this retrospective analysis of the case may serve as a reference in preventing and treating severe CIM during chemotherapy in some patients with malignant tumors, ultimately benefiting more patients with tumors.