bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of hepatoma-derived growth factor in early-stage cervical adenocarcinoma
Authors: Tsai C. , Tai M. , Hu T. , Huang S. , Lin J. , Chang H. , ChangChien C. , Lai C. 
Published: March 2020

16002 Background: Hepatoma-derived growth factor (HDGF) is a unique nuclear/growth factor and plays an important role in the progression of different types of cancer. The current study was designed to elucidate the role of HDGF expression during the development of. early-stage cervical adenocarcinoma. Methods: A total of 63 patients with early-stage cervical adenocarcinoma were enrolled in this retrospective study. The HDGF expression in cervical adenocarcinoma was determined by immunohistochemistry. The HDGF immunostaining in the nuclei and cytoplasm of clinical samples was scored and expressed as labeling index to correlate with the clinical parameters of patients with early-stage cervical adenocarcinoma using SPSS software. Results: HDGF immunostaining was detected in both cytoplasm and nucleus of cervical adenocarcinoma. Compared with adjacent non-tumor tissue samples, HDGF expression was significantly increased in either nuclear or cytoplasmic compartment in cervical adenocarcinoma samples (P < 0.001). Moreover, elevated nuclear HDGF levels were correlated with lymph-vascular space invasion (P < 0.05), lymph node metastasis (P < 0.001), recurrence (P < 0.001), advaced grade(P < 0.001). Conclusions: HDGF overexpression is involved in the carcinogenesis of cervical adenocarcinoma. [Table: see text] No significant financial relationships to disclose.
The activity of the synthetic progestin medroxyprogesterone acetate on the invasive phenotype of ovarian cancer cells
Authors: Gogoi R. , Kudla M. , Gill O. , Horwitz K. , Fishman D. 
Published: March 2020

16003 Background: Androgens play an integral role in the physiologic and pathologic processes of the ovary. Yet it has been difficult to study the role of the androgen recptors (AR) separately from the other steroid receptors such as the progesterone receptor (PR) in ovarian cancer. This has been made more complicated because most synthetic progestins such as Medroxyprogesterone acetate (MPA) bind both PR and AR. The objectives of our study were: 1. To create an ovarian cancer cell line constitutively expressing only AR. 2. To compare the role of AR activated by the synthetic progestin MPA vs. the pure androgen dihydrotestosterone (DHT) on the invasiveness of human breast and ovarian cancer cells. 3. To investigate the role of matrix metalloproteases (MMP's) associated with invasion. Methods: ER- and PR- human breast (T47D-Y) and ovarian (OvCa 429) cancer cells were engineered to stably express AR. Immunocytochemistry and western blot analyses confirmed that these breast and ovarian cancer cell lines (called Y-AR and OvCa-AR respectively) are PR-, but AR+. Boyden chamber invasion assays were performed using Y-AR and OvCa-AR cells treated with either vehicle, MPA or DHT. The MMP's associated with invasion were further investigated using zymographic assays. Results: AR activation by either MPA or DHT increased the invasive potential of both breast (p<0.05) and ovarian cancer cells with MPA being significantly more effective than DHT at stimulating invasion. However, regardless of the ligand, activation of AR increases tumor cell invasion. To elucidate the MMP's associated with this activation in OvCa-AR cells, we used zymographic analysis. Interestingly, we found that MPA activation of AR decreases both the total level and activation of MMP-9 compared to DHT and vehicle control. Conclusions: Using our model system we are able to study the role of AR independent of PR on the biology of breast and ovarian cancer cells. Our studies suggest that the use of pharmacological doses of synthetic progestins may actually increase the invasive potential of ovarian cancer cells through AR. We hypothesize that blockade of downstream AR targets or the use of selective AR modulators (SARMS) may be of therapeutic value in the treatment of ovarian cancer. No significant financial relationships to disclose.
Correlation between c-erb-B2 overexpression with disease-free survival and rate of pelvic relapse in patients with advanced cervical cancer treated with chemo-radiotherapy
Authors: Pérez-Regadera J. , Sánchez-Muñoz A. , De-la-Cruz J. , Ballestín C. , Lora D. , García-Martín R. , Alonso-Carrión L. , Mendiola C. , Lanzós E. 
Published: March 2020

16004 Aims: To determine the impact of the c-erb-B2 overexpression receptor on pelvic relapse and on disease-free survival (DFS) in patients with advanced cervical cancer receiving concurrent chemo-radiotherapy. Methods: One hundred thirty six patients with advanced cervical cancer (stage: 12 IB2-IIA, 34 IIB, 71 IIIB, 19 IVA); histology: 86 epidermoid and 14 adenocarcinoma) were analyzed to detect c-erbB-2 level using an immunohistochemical method (Herceptest Dako). Cases c-erbB-2 (+3) were considered positive. All patients received pelvic radiotherapy, brachitherapy and concurrent chemotherapy with two schedules: 48 patients with tegafur (800 mg/day via oral) and 88 with tegafur (same doses) plus five cycles of weekly cisplatin 40 mg/m2/week iv. Results: Of the 136 biopsies, 32 (23.5%) were c- erbB-2 positive. The disease free survival to 3 and 5 years of the patients were 61% and 58% for c-erb-B2 negative and 36% and 36% for c-erb- B2 positive (p=0.02), respectively.We divided our patients in four groups: c-erb-B2 positive treated with cisplatin; c-erb-B2 positive without cisplatin, c-erb-b2 negative treated with cisplatin and c-erb-b2 negative without cisplatin. The group of patients with c-erb-B2 overexpression that did not received platinum treatment had a higher rate of pelvis relapse (p<0.0001) and with a decreased DFS (p=0.0014). Conclusions: c-erbB-2 overexpression may imply a poor prognosis for patients with advanced cervix cancer, especially if they did not receive concurrent radiochemotherapy with cisplatin. No significant financial relationships to disclose.
Expression of chemokine (C-C motif) ligand-2 (CCL2) is predictive of response to chemotherapy and overall survival in primary ovarian cancer
Authors: Fader A. Nickles , Vaziri S. A. , Rojas-Espaillat L. , Faber P. W. , Elson P. , Biscotti C. V. , Michener C. M. , Rose P. G. , Belinson J. L. , Ganapathi R. 
Published: March 2020

16013 Background: CCL2, a determinant of macrophage infiltration in tumors, is expressed in normal human ovarian surface epithelium but silenced or down-regulated in ovarian adenocarcinomas (Br J Cancer 92:2024, 2005). We determined the association between quantitative expression of CCL2 with platinum-taxane based chemotherapy response and clinical outcome in patients with primary ovarian cancer. Methods: Tumor samples from chemotherapy-naïve patients with advanced serous ovarian adenocarcinoma were obtained at the time of primary cytoreductive surgery. Gene expression profiles using RNA extracted from tissue enriched for >90% tumor from 2 chemotherapy sensitive (CS) and 8 chemotherapy resistant (CR) patients were performed using the Illumina Sentrix Human-6 Expression Bead-Chip microarray. Gene expression was quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in a larger patient cohort. Statistics were generated using Wilcoxon rank sum tests and Kaplan-Meier survival curves. Results: Clustering analysis of gene expression profiles identified several genes, including CCL2, that were differentially expressed between the CS and CR tumor specimens. Levels of CCL2 were significantly (p<.001) under-expressed in all 8 CR patient tumors as compared to the 2 CS tumors. Quantification of CCL2 gene expression in 9 CS and 16 CR tumors by RT-PCR demonstrated that CCL2 was significantly down-regulated in the CR tumors when compared to the CS tumors (p<.001). Using normalized PCR cycle threshold scores, 22 of the 25 tumors were correctly classified, i.e., 8/9 CS had low CCL2 expression (sensitivity = 89%) and 14/16 CR had high expression (specificity = 88%). For patients with low CCL2 expression, progression free survival was 12 months versus 18.6 months for those with high CCL2 expression (p=.05). Median overall survival (OS) was 20.8 months for patients with low CCL2 expression, while OS was not yet reached for those with high CCL2 levels (p=.01). Conclusions: Results demonstrate that expression of CCL2 correlates with response to chemotherapy and survival in patients with primary ovarian cancer. Expression of CCL2 may be a useful independent biomarker of response to treatment and clinical outcome. No significant financial relationships to disclose.
Weekly association of gemcitabine and topotecan in early recurrent ovarian cancer patients: A French multicenter phase II study
Authors: Joly F. , Petit T. , Pautier P. , Guardiola E. , Mayer F. , Chevalier-Place A. , Delva R. , Sevin E. , Henry-Amar M. , Bourgeois H. 
Published: March 2020

16016 Background: A weekly association of gemcitabine and topotecan was tested with the aim of evaluating its efficacy and tolerance in patients recurring after first line platinum and taxane-based chemotherapy. Methods: From December 2004 to April 2006, 77 patients whose disease has progressed within 12 months (time-free interval, TFI) after first line chemotherapy were enrolled in a multicenter phase II study. Primary endpoint was overall response rate (ORR). Gemcitabine (1000 mg/m2) and topotecan (2.5 mg/m2) were given day 1, 8 and 15 (q 28 d) for 6 to 9 cycles. Tumor response was assessed according to RECIST or Rustin criteria. Clinical response was assessed using symptoms improvement in responders and patients with stable disease. Follow-up was updated December 2006. Results: Initial characteristics were: median age 63 years (38 to 80), WHO PS 0–1 93%, serous histology 85%, TFI < 6 months 45%, measurable disease 71%. Four cycles (1 to 8) were administered in average. The only major toxicity was neutropenia (Grade 3 and 4 in 17% and 6% of patients) with one febrile neutropenia; one toxic death (pneumopathy) was observed. 34% of cycles were incomplete (d8 and/or d15 not administered) because of grade 1–2 thrombopenia or grade 1–4 neutropenia. Lenograstim and erythropoietin were administered in 14% and 34% of patients, respectively. Sixty-six (86%) patients were evaluable for response (2 cycles administered). The ORR was 14% (CR=3%, PR=11%); there were 53% of stable disease. ORR was 7% and 20% in patients with TFI < 6 months and = 6 months, respectively. Symptoms were improved in 18 (64%) of 28 patients and pain in 11 (39%) of 28 patients. Median event-free survival time was 3.7 months. Median overall survival time was 12.3 months (7.5 and 15.6 months in patients with TFI < 6 months and = 6 months, respectively; p=0.0244). Conclusions: In resistant/refractory ovarian cancer, weekly gemcitabine and topotecan is associated with low objective response rate but with a high proportion of stable disease and symptoms control leading to acceptable quality of life. No significant financial relationships to disclose.
Pelvic node control in patients with locally advanced uterine cervical cancer treated with concurrent chemoradiotherapy
Authors: Toita T. , Nagai Y. , Tamaki W. , Ogawa K. , Gibo S. , Kakinohana Y. , Kamiyama K. , Inamine M. , Aoki Y. , Murayama S. 
Published: March 2020

16018 Background: To evaluate pelvic node control in cervical cancer patients treated with concurrent chemoradiotherapy (CCRT) without surgical resection. Methods: Ninety-six patients (stage IB2, 3; IIA, 2; IIB, 49; IIIA, 1; IIIB, 40; IVA, 1) with uterine cervical squamous cell carcinoma treated with CCRT were analyzed. Cervical tumor diameter and pelvic node status were assessed by MRI. The median maximum tumor diameter was 58 mm (range, 36–86 mm). Thirty-four patients had positive pelvic nodes (= 10 mm in shortest diameter). The largest diameter of the positive nodes ranged from 10–50 mm (median, 18 mm). All patients received CDDP (20 mg/m2 for 5 days every 21 days), pelvic external beam RT (PERT), and high-dose-rate intracavitary brachytherapy (HDR-ICBT). The planned RT schedule consisted of PERT with 40 Gy/20 fractions (frs) followed by HDR-ICBT with 18–24 Gy/3–4 frs and PERT with 10 Gy/5 frs using a midline block. Thirty of thirty-four node-positive patients received boost RT (6–10 Gy/3–5 frs) to involved nodes. The dose from HDR-ICBT to the pelvic nodes was estimated at a point 6 cm lateral to the midline at the level of the vaginal fornix. Doses of ERT and HDR-ICBT were simply summed and used for pelvic node dose-response analysis. The median total dose was 60 Gy (range, 52–64 Gy) for positive nodes and 54 Gy (range, 51–55 Gy) for negative nodes. Median follow-up of the surviving 79 patients was 41 months (range, 8–98 months). Results: Four-year overall survival (OAS), pelvic control (PC), and distant metastasis-free (DMF) rates for all 96 patients were 79%, 90%, and 79%, respectively. Four-year OAS, PC, and DMF rates for node-positive/node-negative patients were 60%/89% (P=0.002), 82%/95% (P=0.08), and 66%/86% (P=0.008), respectively. Pelvic nodal recurrence was observed in 4 patients. One patient developed isolated pelvic node recurrence while the other 3 had concurrent recurrences at other sites, including 1 with a cervical tumor and 2 with cervical tumor and distant metastases. Nodal recurrence rates by largest diameter were 1/62 for node-negative patients, 1/14 for nodes 10–14 mm, 0/13 for nodes 15–29 mm, and 2/7 for nodes = 30 mm. Conclusions: Pelvic nodal metastases < 30 mm were well controlled by CCRT without surgical resections using RT dose delivered. No significant financial relationships to disclose.
Validation of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) Symptom Index (FOSI) in a phase II clinical trial of pertuzumab in patients with advanced ovarian cancer
Authors: Beaumont J. , Yount S. , Lalla D. , Lubeck D. , Derynck M. , Karlan B. , Cella D. 
Published: March 2020

16021 Background: The FOSI is a very brief(8-item) index derived from the FACT-O to measure symptom response to treatment for ovarian cancer(OC). We evaluated its performance in a single arm Phase II clinical trial. Methods: The FOSI was administered to patients with advanced OC participating in a single arm Ph II clinical trial of pertuzumab(Gordon et al, JCO (2006) v24:4324;2006)). Pertuzumab, a humanized HER2 antibody is the first in a new class of investigational agents known as HER dimerization inhibitors(HDIs). Patients completed the FOSI at D1 of each 3 week cycle, up to 17 cycles. Validation analyses focused on data from the first 4 cycles and included Cronbach's alpha coefficients plus cross-sectional and longitudinal comparisons of groups defined by ECOG performance status (PS). Results: 62 patients completed the FOSI at baseline (B), 54 at cycle 2, 44 at cycle 3 and 27 at cycle 4. The FOSI showed acceptable internal consistency reliability with alphas of 0.73 to 0.80. The FOSI differentiated patients with PS 0 from those with PS =1 at each cycle (Table). There was a difference in FOSI scores in patients with worsened PS from those whose PS improved or was unchanged at cycle 2 only (p<0.001). The ES (mean change/ SD of change scores) for the group with worsened PS was -0.77. The minimally important difference was estimated to be 2–3 points. Conclusions: The FOSI is a valid symptom measure in this population of OC patients, demonstrating acceptable reliability, validity and responsiveness to clinical change. [Table: see text] No significant financial relationships to disclose.
A pilot study of sentinel lymph nodes identification in patients with endometrial cancer
Authors: Li B. , Wu L. , Li X. , Zhang W. , Li S. , Gao J. 
Published: March 2020

16022 Background: The sentinel lymph node (SLN) biopsy has showed the feasibility to limit the extent of lymphadenectomy in vulvar and cervical cancer, but few studies have examined this procedure in endometrial cancer. The aim of this study is to examine the feasibility of SLN identification for the patients with endometrial cancer. Methods: Twenty patients with endometrial cancer undergoing hysterectomy and lymphadenectomy were included in the study. At laparotomy, methylene blue dye was injected into the subserosal myometrium of corpus uteri at multiple sites. Dye uptake into lymphatic channels was observed and blue nodes were identified as SLNs. The SLNs were biopsied before lymphadenectomy performed. The samples of SLNs and non-SLNs were recorded separately and correlated with the final pathological results. Results: Dye uptake into lymphatic channels was seen in all 20 cases. Among them, SLN was identified in 15 (75%) cases. A total of 71 SLNs with a mean number of 4.7 (range, 1–10) were identified from all pelvic sites. The most frequent locations of SLNs included obturator in 29 (41%), interiliac in 16 (26%). No dye-containing paraaortic node was found. Two patients (10%) had nodal metastases, and they all had at least one SLN found to be positive, the false-negative-rate was 0. No adverse reactions or injures were attributed to the study. Conclusions: This study shows the feasibility and safety of SLN identification with blue dye in patients with endometrial cancer undergoing staging surgery. The SLNs accuratly predicted the nodal metastases in the study.This approach might provide an alternative to limit the extent of nodal sampling. No significant financial relationships to disclose.
Surgical management and prognostic indicators of uterine leiomyosarcoma
Authors: Gagua I. R. , Kuznetsov V. V. , Lazareva N. I. , Nechushkina V. M. , Zavolskaya Z. A. 
Published: March 2020

16024 Background: Uterine leiomyosarcoma (LMS) is a rare malignant tumor. Preoperative diagnosis is established only in 13.5% patients at our center. Currently, the main method of treatment of LMS is surgery. The efficacy of chemotherapy and radiotherapy are questionable. So, the aim of our study is to establish the optimal treatment modalities and prognostic indicators for this tumor. Methods: A retrospective chart review was done to 163 patients with LMS treated at the NNBRCRC from 1970 to 2002. Multivariate statistical analysis was performed to determine the most important prognostic indicators for LMS. Surgical treatment, as independent method, was performed to 108 patients (66.3 %). Combined treatment, including surgery and postoperative chemotherapy was performed to 30 patients (18.4 %), surgery + radiotherapy - 12 (7.4 %) patients. Complex treatment (surgery + chemotherapy + radiotherapy) was performed to 11 (6.7 %) patients. Results: Histologically, LMS is the most common (41,4%) among all sarcomas of female genital tract. Immunohistochemistry and electronmicroscopy play a major role in establishing the diagnosis. 5 year overall and disease - free survival of patients with LMS is 48.5± 4.2% and 44.3 ± 4.3 %, respectively. We observed association between ovarian preservation and improved survival: overall 5 year survival in patients with ovarian preservation and those who underwent oophorectomy is 87.3 ± 8.4 % and 49.0 ± 5.3 %, respectively (p<0,05). On the basis of multivariate analysis we determined the following prognostic indicators, affecting the outcome of patients with LMS: disease stage, mitotic index, tumor cell necrosis, depth of tumor invasion in myometrium, tumor size, age, menstrual status of the patients and optimal surgery. Conclusions: According to our data, the optimal surgery for LMS is total abdominal hysterectomy in the reproductive age and total abdominal hysterectomy with bilateral salpingo-oophorectomy in the postmenopausal period. The most favorable prognostic indicators are: patient age younger than 30, I stage of disease, tumor size less than 10 cm, less than 10 mitotic figures per 10 high - power fields, submucosal or subserosal location of well-differentiated tumor. No significant financial relationships to disclose.
Effects of PKC beta inhibitor enzastaurin on chemoresistant ovarian cancer cell lines
Authors: Meinhold-Heerlein I. , Bräutigam K. , Bauerschlag D. , Maass N. , Mundhenke C. , von Kaisenberg C. , Schollmeyer T. , Jonat W. , Arnold N. , Bauknecht T. 
Published: March 2020

16030 Background: Enzastaurin (LY317615.HCl), a selective inhibitor of protein kinase C beta II (PKCβII), leads to apoptosis and suppression of angiogenesis and represents a promising drug for clinical development. The effects of Enzastaurin were investigated utilizing the ovarian cancer cell line HEY and several chemoresistant subclones. Methods: The cell line HEY was used to develop subclones with selective resistance against cisplatin, etoposide, docetaxel, paclitaxel, gemcitabine, and pemetrexed. PKCβII expression was determined by immunoblotting and RT-PCR analyses. The platin-sensitive ovarian cell line IGROV1 with high expression of PKCβII served as control. All cell lines were exposed to 5 μM Enzastaurin for up to three hours. Immunoblotting analyses determined the expression of Enzastaurin targets PKCβII and glycogen synthase kinase 3β (GSK3β). Proliferation and apoptosis induction after Enzastaurin treatment was evaluated using MTT assay and DAPI staining. Results: All resistant cells showed a significantly higher expression of phosphorylated GSK3β than the parental cells. The highest expression level was detected in cisplatin- and paclitaxel-resistant cells. A decrease of phosphorylation occurred after exposure to Enzastaurin for 30 minutes, most obvious in parental, cisplatin- and gemcitabine-resistant cells. Proliferation and apoptosis assays demonstrated the paclitaxel and docetaxel resistant cells as the most sensitive cells. In contrast, cisplatin-resistant cells exhibited the highest resistance. Enzastaurin resistance also correlated with elevated PKCβII expression. Conclusion: The results indicate that ovarian cell lines with high expression of phosphorylated GSK3β display also a strong dephosphorylation. Though in these cell lines the inhibitory effect of Enzastaurin is most prominent, cell proliferation is hardly affected, nor apoptosis is accelerated. There is cross-resistance between platinum and Enzastaurin in some cell lines; however Enzastaurin demonstrated promising activity against taxane resistant cell lines. [Table: see text]