bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of chemotherapy-induced febrile neutropenia in paediatric oncology in developing countries: The Children's Hospital Lahore Pakistan experience.
Authors: Ahmad Alia 
Published: September 2018

e22021 Background: The Oncology Department Of The Children’s Hospital Lahore is a 60 bedded unit providing free treatment to over 1000 new childhood cancer cases each year.The aim of this prospective study was to analyze the burden of chemotherapy induced FN and to assess the leading risk factors . Methods: Prospective review of 100 patients with FN admitted in July to August 2016 was done. Data regarding their age, sex, and clinical features, baseline CBC, course of therapy, hospital stay and understanding of caregivers regarding FN analyzed. Results: Total 100 patients with age ranging from < 1 to 15 years (67% < 5 yrs) were included.M: F Ratio was 1.7:1, 72% of cases had ALL and 28% with solid tumors. 28% had last chemotherapy received in 72 hours, 30% in last week and rest in more than a week time 36% had respiratory tract infections, 18% gastrointestinal infections, 20% mucositis, 10% no focus found and rest 16% had other manifestations Only 2 % presented in < one hour of start of symptoms, 27% < 24 Hours, 61% in < 5 Days and 10% > 5 days duration of symptoms. 45% had Hb < 8 gm%, 33% had platelets < 50000, and 54% had WBC < 1000 and 63% had ANC <100 (p-Value = 0.003- Hospital Stay). 29% presented with first episode while 51 % had 3 or more FN episodes.28% cases stayed 1 hour distance from CHL while 72% had to travel > 1-5 hrs to reach the primary treatment center. 66% received paracetamol at home, 17 had oral antibiotics while 17% had no treatment before reached PTC. Only19% caregivers had adequate awareness regarding FN, 72% had some understanding while 9% had no knowledge about FN (p-value = 0.000). 40% had social issues, 41% were unaware while 13% showed negligence in seeking treatment .46% stayed for 5 days and 48% for more than 5 days. 21% patients had increased doses of oral chemotherapy not adjusted timely according to CBC. Conclusions: Health educationof caregivers and health professionals is of utmost importance to prevent and manage FN effectively. Need of capacity building in pediatric oncology in low income countries along with sustainable social support is essential for provision of standard childhood cancer care and implementation of effective infection control measures.
The open, multicenters, double-arms, randomized, parallel controlled clinical trial of lobaplatin or gemcitabine combined with docetaxel as second-line therapy for advanced osteosarcoma-the effectiveness and safety analysis.
Authors: Sun Yuanjue , Yao Yang , Cai Zhengdong , Yu Xiuchun , Wu Sujia , Ye Zhaoming , Hua Yingqi , Zheng Shui'er , Chen Guojing , Hu Yongcheng , Zhou Yong , Wang Zhen 
Published: September 2018

e22506 Background: to study the progression free survival (PFS), objective response rate (ORR), overall survival (OS) and safety of lobaplatin or gemcitabine combined with docetaxel as second-line therapy for advanced osteosarcoma. Methods: the NO. of clinical trial was HNCA001,a total of 15 cases were enrolled into experiment group adopted lobaplatin combined with docetaxel,and 14 into control group received gemcitabine combined with docetaxel.The trial concluded screening, treatment and follow-up periods.21 dyas as one treatment period,they got drugs at the first day,and were evaluated the effects per two periods, treated at most 6 periods. Results: The baseline characteristics of two groups were no ststistical differences(diastolic blood pressure excluded) (P > 0.05).The PFS rates of 2,4 and 6 periods in experiment group were 87.50%、87.50% and 70.00%,83.33%,27.78% and 0 in control group,middle PFS more than 12 months in experiment group and 3.20 months in control group;while there was no statistical difference of PFS rates(χ2= 2.42,P = 0.1194).The survival rates of 2,4 and 6 periods in experiment group were 100.00%,83.33% and 83.33%,83.33%,83.33% and 0 in control group,the middle OS more than 12 months in the two groups, there was no statistical difference of survival rates (χ2= 0.65,P = 0.4196).The ORR was 6.67% in experiment group and 0 in control group(P = 1.0000).There were no adverse events occurring in the two groups. Conclusions: There is negative results of the trial,most reason may be the samples are greatly less;the next step is samples expanded and follow-up extended for the priority of lobaplatin or gemcitabine combined with docetaxel as second-Line therapy for advanced osteosarcoma. Clinical trial information: NCT02099396.
Real-world outcomes of ponatinib in treatment of advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitor (TKI) failure.
Authors: Heinrich Michael C. , McGarry Lisa , Kerstein David , Huang Hui 
Published: September 2018

e22508 Background: Imatinib is standard front-line treatment for advanced KIT+ GIST. For patients whose tumors progress on imatinib, sunitinib is indicated, followed by regorafenib for those with disease progression on both imatinib and sunitinib. Patients refractory to 2 prior TKIs typically experience rapid progression (median PFS: 4.8 mos for regorafenib; 0.9 mos for placebo [Demetri Lancet 2013]), and with failure of all approved TKIs, unmet need remains high. The oral TKI ponatinib, approved for TKI-refractory CML and Ph+ ALL, has shown activity in heavily-pretreated (76% with ≥4 prior regimens) advanced KIT+ GIST patients in a Phase 2, single-arm study (Heinrich ASCO 2015) at starting dose of 45 mg/day: clinical benefit rate (CBR = CR + PR + SD for ≥16 wks) of 37% and median PFS of 4.3 mos were observed in 30 patients with KIT exon-11-mutant GIST and CBR of 14% and median PFS of 2.0 mos in 15 patients whose GIST lacked a KIT exon 11 mutation. Methods: To examine real-world outcomes, we retrospectively identified patients receiving ponatinib off-label for GIST (ICD-9 171.5x, 171.9x) between 01Jan2014 and 31Dec2016 from sole-source US specialty-pharmacy records. Using patient, physician and pharmacy dispensing data, patient characteristics, treatment setting and dosing were noted, and duration of treatment (DOT) was examined using Kaplan-Meier techniques. Results: We identified 26 probable GIST patients receiving ponatinib over this 2-year period: 58% male; median age 57.5 yrs. Where reported, all received prior TKIs, but data for prior lines of therapy were incomplete. Most (69%) were treated in an academic setting, and the most frequent starting dose was 45 mg (77%). DOT ranged from < 1 to > 19 mos, with an estimated median DOT of 3.8 mos. At 3 mos, 61% of patients were estimated to remain on ponatinib, and at 6 mos, 34%. Conclusions: Available real-world data show that patients treated with ponatinib for TKI-refractory GIST had a median DOT of almost 4 mos, with 1/3 remaining on therapy for > 6 mos. Using DOT as a surrogate for PFS, these results are consistent with Phase 2 study results, and suggest ponatinib may have activity in patients who have exhausted other treatment options.
Various fashions of laparoscopic resection for gastrointestinal stromal tumors in esophagogastric junction.
Authors: Xiong Wenjun , Wang Wei , Wan Jin 
Published: September 2018

e22512 Background: Laparoscopic surgery for small (<5 cm) gastric gastrointestinal stromal tumors (GIST) is now widely performed. However, laparoscopic resection of GIST in esophagogastric junction is technically difficult. Herein, we introduce various fashion of laparoscopic resection for small GIST in esophagogastric junction. Methods: Retrospective review of 40 consecutive patients with small GIST in esophagogastric junction who underwent attempted laparoscopic surgery. GIST in esophagogastric junction was defined as that the distance of the upper border of GIST from esophagogastric line was less than 2 cm. Three fashions of laparoscopic resection were performed: fashion A, laparoscopic wedge resection using linear stapler; fashion B, laparoscopic complete resection by opening the stomach wall and the stomach wall incision was closed with suture; fashion C, laparoscopic proximal gastrectomy with pyloroplasty. The data of clinicopathologic characteristics, operative course and short-term outcomes were analyzed. Results: All procedures were finished successfully and no operative relatively complication was recorded. Tumor in 24/40 (60%) patients was located in greater curvature. 70.1% (17/24) of them received fashion A and others (7/24) underwent fashion B. Tumor in 16/40 (40%) patients was located in lesser curvature. 18.8% (3/16) of them underwent fashion C and others (13/16) underwent fashion B. The mean operative time was 97.4±21.3 min and the mean estimated blood loss was 20.5±10.4 ml. The mean first time of flatus was 39.2±10.0 hours and the time of fluid intake was 40.1±11.7 hours. The mean hospital stay was 4.2±1.3 days. The mean diameter of tumor was 2.7±1.0 cm. Conclusions: Laparoscopic surgery for small GIST in esophagogastric junction is safe and feasible. The selection of various laparoscopic resection fashions was according to the tumor location.
A phase II trial of Q3 week or weekly paclitaxel in combination with bevacizumab for metastatic or unresectable angiosarcoma.
Authors: Bui Nam , Kamat Nikhil , Ravi Vinod , Ganjoo Kristen N. 
Published: September 2018

e22513 Background: Paclitaxel (P) and bevacizumab (B) are both agents that provide clinical benefit in advanced angiosarcoma. The objective of this study was to assess the efficacy and safety of P-B in two regimens: Q3 week or weekly P with B for patients with advanced AS. Methods: We conducted a multicenter phase II trial. Patients were to receive P 200mg/m2 IV with B 15mg/kg IV every 21 days (Regimen A) or P 90mg/m2 IV weekly D1, 8, 15 with B 15mg/kg IV D1 of a 28 day cycle (Regimen B) x6 cycles. Maintenance B followed at a dose of 15 mg/kg intravenously once every 21 days. The primary end point was 4 month non-progression rate (NPR, RECIST 1.1). Results: A total of 16 patients were entered in the study between June 2010 through September 2013. Sites of disease included soft tissue (n = 5), skin/scalp (n = 5), breast (n = 4), and viscera (n = 2). All four breast patients were radiation induced after treatment for breast adenocarcinoma. 11 were chemotherapy naïve while 5 had received prior systemic chemotherapy. Results are reported as both an aggregate as well as per regimen (Table 1). 4 month NPR was 62.5% with median overall survival 16 months and median progression free survival 5.06 months. Of the 16 patients, 11 made it to cycle 3 and thus were evaluable for response. There were 1 CR, 4 PR, 2 SD, and 6 PD. There were no grade 5 toxicities, ten grade 3 toxicities and four grade 4 toxicities. The most common grade 3 toxicity was neutropenia (3/10) with other notable toxicities including peripheral neuropathy, hypertension, and heart failure. Grade 4 toxicities included neutropenia, bowel perforation, atrial flutter, and acute coronary syndrome. The breakdown between the two regimens revealed comparable efficacy and safety with similar ORR, 4mNPR, mOS, mPFS, and G3/4 toxicities. Conclusions: P and B followed by maintenance B is active and has a tolerable safety profile. Q3 week and weekly paclitaxel appear similar in efficacy and safety. Clinical trial information: NCT01055028. [Table: see text]
Single-center experience with intimal sarcoma, an ultra-orphan, commonly fatal mesenchymal malignancy.
Authors: Van Dievel Julie , Sciot Raf , Delcroix Marion , Vandeweyer Raf , Debiec-Rychter Maria , Dewaele Barbara , Cornillie Jasmien , Van Cann Thomas , Meyns Bart , Schöffski Patrick 
Published: September 2018

e22532 Background: Intimal sarcoma is a rare malignancy that, clinically and radiographically, often mimics pulmonary embolism. The intravascular tumor tends to disseminate rapidly and metastases can be present at first diagnosis. Methods: We reviewed all cases of intimal sarcoma which were diagnosed, treated and followed at the University Hospitals Leuven between April 2006 and April 2016. Results: We identified 13 patients with a median age of 51. In 6 patients initial findings were suggestive of thromboembolic disease. PDGFRA amplification was the most prevalent molecular finding, present in 11 patients. The MDM2 gene was amplified in 9 cases, the EGFR gene in three patients. The median overall survival was 13 months. Eleven patients underwent surgery. In 5 cases with inoperable and/or metastatic disease chemotherapy was given. Treatment with imatinib was initiated in 4 patients. Conclusions: Intimal sarcoma is an extremely rare and aggressive malignancy that has a very poor prognosis. Mimicking thromboembolic disease, diagnosis and treatment can be delayed. Surgery is the mainstay of treatment but is seldom curative. The disease is highly resistant to cytotoxic and targeted treatment. Given the fact that intimal sarcoma commonly expresses more than one molecular target, combination therapy might be an option, though toxicity may be a limitation.
Complex approach in the treatment of retroperitoneal fibrosarcoma.
Authors: Ulmasov Firdavs , Djuraev Mirjalol , Yusupbekov Abrorjon , Egamberdiev Dilshod Makhmudovich 
Published: September 2018

e22537 Background: to improve the efficiency of the treatment of retroperitoneal fibrosarcomas by developing complex approach with using neoadjuvant endoarterial chemotherapy, surgical intervention followed by radiotherapy. Methods: For material of the study we analyzed treatment results of 34 patients with retroperitoneal giant fibrosarcoma. Depending on the method of treatment patients were divided into 2 groups: 1 main group n = 16, underwent neoadjuvant chemotherapy + surgery + radiotherapy 2 control group n = 18 who underwent surgery + adjuvant chemotherapy. There was performed endoarterial catheter into the close blood vessels feeding the tumor at the preoperative period. Chemotherapy was conducted 3 cycles by CAP regimen. Drugs were administered endoarterially with 48 hours infusion. After receiving chemotherapy for all patients there was performed radical surgery. Postoperatively patients received radiotherapy to the tumor bed with single dose 1.8-2 Gr and up to total dose - 60 Gr. Results: Therewere selected the following criteria: - The effect of chemotherapy on tumor size, extension and traumatizing of surgical treatment, and the duration of relapse-free and metastases-free period. - The effectiveness of postoperative radiotherapy for the duration of disease-free period. Chemotherapy in the preoperative period, led to partial regression of tumors in 9 (58.3%) patients. In 4 (25.0%) patients the process was stabilized, in 3 (16.7% 5 + 15%) observed progression of the process. Study of patients’ survival, which is the main determining factor showed an increase of survival in the main group up to 18.2 +0.4 months, and in the control group 12.4 +0.3 months. (P < 0.05). Recurrence free survival in the main group was 10,2 +0,4 months, and in the control group 7,3 +0,3months (P < 0.05), metastases-free survival consisted 11,4+0,5 months and 9,1+0,4 month, respectively.(P < 0.05). Conclusions: Complex approach in the treatment of retroperitoneal fibrosarcomas significantly increased the overall survival and as well as the relapse-free and metastases-free survival. Using adjuvant continuously endoarterial chemotherapy gives partial effect in 58.3% cases, and thereby leads to more favorable conditions for surgery.
Comparative analysis of cell cycle parameters in primary and recurrent soft tissue sarcomas.
Authors: Novikova Inna Arnoldovna , Nepomnyashchaya Evgeniya M. , Aliev Timur , Zlatnik Elena Yurievna , Selyutina Olesya N. , Ulianova Elena Petrovna , Vashchenko Larisa Nikolaevna , Ausheva Tatiana Valeryevna Ausheva , Andreyko Elena A. 
Published: September 2018

e22538 Background: The purpose of the study was to determine DNA content and distribution of cells in cell cycle phases by flow cytometry in patients with primary and recurrent soft tissue sarcomas. Methods: 60 patients with soft tissue sarcomas (STS) were recruited: 30 with primary tumors and 30 with recurrent ones. Mean age of patients with primary STS was 56±5.4 years, with recurrent STS – 55±6.7 years. DNA content was determined using the BD Facs Cantoo II flow cytometer with CycleTEST PLUS DNA Reagent Kit (Becton Dickinson). The data were processed using ModFit LT program. Results: Comparative analysis of the cell cycle kinetics showed an increase in the percentage of cells in G2+M phase by 2 times in diploid and by 2.1 times in aneuploid recurrent tumors in comparison with primary ones (1.8±0.5% vs. 0.9±0.1% for diploid tumors; 5.4±2.2% vs. 2.6±0.7% for aneuploid tumors). An increase in the percentage of aneuploid tumors was found in recurrent G2 and G3 tumors (from 50% in primary to 66.7% in recurrent G2 tumors and from 63.25% in primary to 85% in recurrent G3 tumors). Mean content of aneuploid cells in recurrent G2 tumors was 2.2 times higher (p≤0.05), while the differences in primary and recurrent G3 tumors were not significant. The percentage of aneuploid tumors depended on the disease stage and increased in stages IIb and III in recurrent tumors, compared to primary ones (from 37.5% to 71.4% in recurrent st. IIb; and from 65% in primary st. III to 72.7% in recurrences) (p≤0.05). Conclusions: DNA analysis by flow cytometry demonstrated a high biologic potential of both primary and recurrent tumors. Some values in the mitotic cycle in recurrent tumors were probably associated with adjuvant therapy, as well as influenced by the coefficient of two parameters – the percentage of cells in G2+M phase and the cell loss factor determining a high malignant potential of these tumors.
GGNBP2 to suppress tumor growth and cancer stem cell load of triple negative breast cancer by controlling STAT3 pathway.
Authors: Zhang Jin , Hu Yunhui , Lei Zhenmin 
Published: September 2018

e23003 Background: Gametogenetin binding protein 2 (GGNBP2) is encoded in human chromosome 17q12-q23, a region known as a breast and ovarian cancer susceptibility locus. GGNBP2 has a single C2H2 zinc finger and a consensus LxxLL nuclear receptor (NR) binding motif. We have reported that GGNBP2 suppresses ERα-positive breast tumorigenesis by acting as a nuclear receptor co-repressor to restrain ERα activity. However, the detailed molecular mechanisms of GGNBP2 and its role in triple negative breast cancer (TNBC) remain largely unclear. Methods: A human breast cancer tissue array containing 138 human breast tumor tissues were utilized to examine GGNBP2 expression in breast cancer samples by IHC. To address the potential anti-breast tumor activity of GGNBP2 in vitro, we expressed exogenous GGNBP2 in TNBC cells, including MDA-MB-231 and Cal51 cell lines. Cell proliferation and cell cycle were assessed by cell growth curve/EdU assays and flow cytometry after propidium Iodide staining. Apoptosis was determined by flow cytometry after annexin V staining, by caspase 3/7 and caspase 9 activity assays. Cancer stem cell properties were determined by expression of CD44/CD24/ALDH1 markers. The levels of phosphorylated STAT3 and total STAT3 were determined by western blot. Quantitative PCR and Western blot were carried out to evaluate the effects of GGNBP2 overexpression on STAT3 target genes, CCND1, Mcl-1, survivin, bax and bim expression. Results: GGNBP2 expression is down-regulated in TNBC cells and patient tumors. GGNBP2 down-regulated expression is associated with poor patient survival. Overexpression of GGNBP2 significanly induces cell cycle G0/G1 phase arrest and apoptosis in TNBC cell lines. Expression of cancer stem cell markers also decreased in GGNBP2-overexpressed TNBC cells. GGNBP2 reduces the expression levels of CCND1, Mcl-1 and survivin, promotes the expression levels of bax and bim proteins. Importantly, overexpression of GGNBP2 inhibits STAT3 phosphorylation and STAT3 downstream target gene expression, including CCND1, Mcl-1 and survivin. Conclusions: GGNBP2 serves as a critical nuclear negative regulator of STAT3-mediated gene expression and tumorigenesis in TNBC.
NIDOGEN1 as a novel regulator of endothelial control over breast cancer invasion and metastasis.
Authors: Buess Martin , Ferraro Daniela A. , Patella Francesca , Zanivan Sara , Christofori Gerhard 
Published: September 2018

e23005 Background: The microenvironment is a central regulator of cancer biology. While the contribution of fibroblasts has been largely studied, the role of endothelial cells as regulators of cancer cell behavior is still poorly understood. As in a diverse spectrum of physiological processes in normal tissue, endothelial cells may exert a similar regulatory control in cancer progression and metastasis. Methods: To characterize the functional effects of endothelial-cancer interaction we focused on an in vitro co-culture model. Results: Co-culturing human umbilical venous endothelial cells (HUVEC) with SKBR-3 breast cancer cells induced morphological changes with epithelial-mesenchymal transition traits (EMT) and a significantly increased migratory and invasive potential. This activity leading to an elongated phenotype, expression of mesenchymal markers and pro-migratory gene sets in SKBR-3 was contained in HUVEC conditioned medium. The pro-migratory effect on SKBR-3 was significantly more pronounced when the supernatant was obtained from a sub-confluent and highly proliferative endothelial cell culture than from a confluent and resting endothelial cell layer. To identify the secreted regulatory molecules, we analyzed the supernatant of sub-confluent and confluent endothelial cells by quantitative MS proteomics (SILAC analysis). Eight candidate proteins significantly more secreted in conditioned medium from confluent HUVEC represented potential inhibitors of migration. Among them NIDOGEN1 was found to be necessary and sufficient for the inhibition of EMT and migration in SKBR-3. Stimulation of SKBR-3 with supernatant from sub-confluent HUVEC increased p-STAT3 levels in SKBR-3. Silencing nidogen1 in confluent HUVEC re-activated phosphorylation of STAT3 indicating that NIDOGEN1 inhibits the promigratory STAT3 pathway. The STAT3 pathway and migration were also inhibited by overexpression of nidogen1 in MDA-MB-231 LM2 cells.When injected in the mammary fat pad of nude mice these cells formed significantly less lung metastases than controls (p < 0.01). Conclusions: We identified NIDOGEN1 as a novel regulator of endothelial control over cancer cell migration, invasion and metastasis.