bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysregulation of smoldering multiple myeloma (SMM) progression to multiple myeloma (MM) via modulation of AKT kinase, proinflammatory cytokines, and insulin-like growth factor-1 (IGF-1) in human immunodeficiency virus-1 SMM ( HIVSMM ) patients treated with adjuvant selenomethionine (Se-Met) ritonavir-based HAART.
Authors: McPherson Eugene , Mejia Ervido , Tassy Philippe 
Published: March 2020

e19540 Background: Multiple myeloma is a B-cell malignancy involving germinal center B cells characterized by urinary monoclonal proteins, osteolytic bone lesions and infiltration of bone marrow with plasma cells and pathology involving aberrant chromosomal translocation with increased glucose uptake as glucose transporter (GLUT-4), AKT kinase activation, overexpressed proinflammatory cytokines produced by bone marrow stromal cells (BMSC) in smoldering multiple myeloma and multiple myeloma, These biomarkers are antiapoptotic and control growth, prognosis and survival. Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) are major growth factors in MM. IGF-1 binds to IGF-1 receptor (IGF-1R) as a strong prognostic indicator. Dysregulation and modulation of IGF-1, proinflammatory cytokines, AKT kinase and IL-6 in HIVSMM patients with RTV-based HAART and selenomethionine (Se-Met) adjuvant therapy may suppress NF-kb and abrogate GLUT-4 HIVSMM progression. Methods: We evaluated several HIVSMM patient's biomarkers over four years: CD4, HIVRNA, beta-2-microglobulin, LDH, soluble interleukin -2 receptor (sIL-2R), CRP, SFLC ratio, selenium, bone survey, and bone marrow aspiration/biopsy. Results: CD4 increased to 456/cumm from < 80/cumm, HIVRNA was undetectable from > 1 million copies/ml, beta-2-microglobulin 2.24 mg/L from 14.40 mg/L, LDH 155 IU/L from 432IU/L, sIL-2R 75 pg/ml from 45,752 pg/ml, CRP 1.49 mg/L from 87.4 mg/L, SFLC ratio 0.93 from >2.08, selenium kept >140 mcg/L (high normal level), bone survey negative X 2, and bone marrow aspiration/biopsy plasmacytosis with plasma cells < 5% from > 10% and CD 138 positivity. Conclusions: Dysregulation and modulation of HIVSMM biomarkers with adjuvant Se-Met and RTV-based HAART may suppress AKT kinase and NF-kb activation preventing HIVSMM progression to HIVMM via IGF-1 recruitment of GLUT-4. Overall improved prognosis and survival may be extrapolated to non-HIVSMM patients with concommitant immunomodulary therapy.
A retrospective risk assessment of patients (pts) with high grade upper (UE) and lower extremity (LE) sarcoma: Predictors of survival.
Authors: Kneisl Jeffrey , Crimaldi Anthony Joseph , Symanowski James Thomas , Ahrens Will , Patt Joshua , McCall Bradley , Bates Michael , Ferguson Chad , Livingston Michael B. , Kim Edward S. 
Published: March 2020

e21504 Background: Patient outcomes of high grade extremity soft tissue sarcomas (STS) are dependent upon grade and size of the primary tumor and extent of surgical resection. Poorer overall survival (OS) has been associated with specific anatomic sites (e.g. head and neck, retroperitoneum) but OS has not been evaluated for UE vs LE. We investigated the relationship of tumor size and anatomic sites with OS in our pts with high grade extremity STS. Methods: A retrospective review of all pts diagnosed with a high grade STS of the UE and LE was performed from 1992-2010 via an IRB approved protocol at Levine Cancer Institute. Pts were included if they had sufficient medical records, limb-sparing surgery, age greater than 18 years, no stage IV disease. All cases were centrally reviewed by a single pathologist. Overall survival was analyzed with Cox proportional hazards models and tumor size was analyzed using ANOVA techniques. Results: 93 pts were identified. 61 pts had LE sarcomas and 32 had UE. Demographics: 52% male, 67% Caucasian, 60% >50 years of age. Disease characteristics included 88% deep and 66% >5cm STS. 13% of pts received chemotherapy and 86% received radiation therapy, consistent with NCCN guidelines and institutional protocol. Median baseline tumor size was 7.0 cm with a range of 1.7-40 cm. LE STS were generally larger than UE; medians 8.5 cm (range 1.7-40 cm) vs 5.0 cm (range 2.0-17 cm), p=0.005. When analyzed quantitatively, larger tumor size correlated with an increased risk of death (p=0.001). 28 total deaths occurred (0.3-5.4 yrs). Death rates were 27.9% (17 deaths) with LE STS vs 34.4% (11 deaths) with UE. LE disease had an overall reduced risk of death (HR=0.543). Pts with tumors >5cm had an increased risk of death (HR=3.235 overall) for both LE (HR=3.042) and UE (HR=3.453) sarcomas. Conclusions: To our knowledge, this is the largest reported cohort of high grade STS that stratified on upper and lower extremities. Larger size was associated with higher risk of death. Additionally, we observed a higher risk of death in patients with UE sarcomas vs. LE sarcomas. Strong consideration should be given to UE vs. LE STS when assessing risk and treatment.
Reversal of acquired resistance to pazopanib in soft tissue sarcoma with addition of an mTOR inhibitor: A case report.
Authors: Katz Daniela , Zick Aviad , Cohen Jonathan E. , Sonnenblick Amir , Fridman Evgeniya , Shaham Dorith , Peretz Tamar 
Published: March 2020

e21508 Background: Pazopanib (P) is a multikinase inhibitor targeting the VEGF and PDGF receptors capable of controlling soft tissue sarcoma for several months. Acquired resistance to P usually leads to chemotherapy resumption. We present a case of reversal of acquired resistance to P by addition of an mTOR inhibitor. Methods: A 46 year old female, completed five cycles of adjuvant treatment with epirubicin and ifosfamide followed by radiotherapy for a fully resected gluteal pleomorphic undifferentiated sarcoma. Ten months later, a single lung metastasis was resected, followed by trabectedin, then switched to gemcitabine and docetaxel after five cycles due to progression. Seven cycles were given with stable disease as best response. Upon progression, P 800mg/d was initiated as part of a compassionate program and continued for six months with a partial response. When disease progressed, treatment was switched to doxorubicin, dacarbazine and cyclophosphamide with rapid progression after two cycles, both complicated by febrile neutropenia. Uncontrolled disease after stopping P, limited response to chemotherapy in the past and worsening myelosupression led us to reintroduce P at 400mg/d in combination with sirolimus 2mg/d with the intention of overcoming acquired resistance to P by inhibiting downstream intracellular mediators. Results: One week after P and sirolimus initiation, pain in a paracostal protruding lesion subsided with softening and a decrease in mass size. After six weeks a CT scan demonstrated a partial response by Choi criteria with an 18% tumor shrinkage and decreased enhancement. Most of the lesions were previously of mixed density and became predominantly necrotic. Treatment was very well tolerated. Conclusions: We report a renewed response to P with addition of an mTOR inhibitor in advanced pleomorphic undifferentiated sarcoma. Crosstalk between pathways, upregulation of PI3K/mTOR signaling along with a rebound effect stirred by cessation of VEGFR blockade may have all contributed to more aggressive disease at the time of progression and may explain reversal of resistance by the addition of a downstream inhibitor such as sirolimus. A study designed to prove this concept is underway.
Adjuvant chemotherapy in patients with malignant fibrous histiocytoma: Single center experience.
Authors: Sekhina Olga , Bulanov Anatoly , Fedyanin Mikhail , Bokhyan Beniamin , Bliznukov Oleg , Aliev Mamed 
Published: March 2020

e21510 Background: There is controversy information about efficacy of adjuvant chemotherapy (ACT) for treatment of Soft Tissue Sarcomas (STS) due to histological heterogeneity of these tumors. Whereas STS are heterogeneous group with different sensitivity to chemotherapy (CT), we conducted retrospective study to assess efficacy of adjuvant chemotherapy in patient with high-grade malignant fibrous histiocytoma (MFH). Methods: From 2000 to 2010, 56 patients with localized malignant fibrous histiocytoma were treated in Russian Cancer Research Center named after N.N. Blokhin. Main features: median age 61 years (range: 16–83 years); III stage 37/56, 66%; II stage 19/56, 34%, median tumor size 10cm (range: 2-25 cm); ACT received 18/56, 32%; ACT not received 36/56, 64%; doxorubicin-based CT 16/18, 88%; ifosfamid-based CT 2/18, 12%. Median follow-up was 59 month. Results: Median disease free survival (DFS) was 30 month. Median overall survival (OS) not reached. Median DFS in patients receiving CT was 30 month versus 10 month in patients without CT (p=0.02, HR=2.5; 95% CI 1.09-5.3). In patients with ACT disease progression was observed statistically significantly less often, then without it (39% versus 69%, p=0.04). Three-year OS in patients with ACT was 95% versus 65% in patients control group (p=0.05). We conducted univariate analysis of features, which influence the risk of disease progression disease. Features of favorable prognosis were T1 (p=0.05) and ACT (p=0.04). In multivariate analysis these features remained statistically significant: T (p=0.01, OR 6.7; 95% CI 1.3-34.1), ACT (p=0.02, OR 0.2; 95% CI 0.05-0.7). Conclusions: ACT improved DFS and OS in patients with high-grade localized resectable MFH. These benefits require confirmation in larger studies.
Interesting antitumor activity of lenalidomide in a patient with hepatic epithelioid hemangioendothelioma (HEH).
Authors: Pallotti Maria Caterina , Pantaleo Maria A. , Lolli Cristian , Nannini Margherita , Saponara Maristella , Mandrioli Anna , Gatto Lidia , Di Scioscio Valerio , Pileri Stefano A , Bolondi Luigi , Biasco Guido 
Published: March 2020

e21511 Background: Epithelioid hemangioendothelioma (HEH) is a rare malignant vascular soft tissue tumor occurring mostly in the liver. The molecular background is still unkonwn and therefore the medical treatment has not been established. Some case reports treated with angiogenesis inhibitors are described. Lenalidomide has anti-proliferative and cytotoxic effects, immunomodulatory properties but also anti-angiogenic activity. In literature there are few case of patient with solid tumors treated with lenalidomide.We report a patient affected by HEH treated with lenalidomide for long time. Methods: In 2010, a 73 year old man arrived our attention with multiple hepatic lesions diagnosed with contrast computed tomography (CT), abdominal magnetic resonance (MR) imaging and contrast enhanced ultrasound (CEUS) of the liver. An ultrasound guided biopsy of an hepatic lesion was made and histopathology exam deposed for the diagnosis of HEH. We decided to treat the patient with lenalidomide 25 mg daily on 1- 21 every 28 days, because a liver transplantation was not inidcated for the age of the patient. The follow up of disease was made by abdominal ultrasound and MR every three/four months. Results: The patient was treated with lenalidomaide for thirty months totally. After six months the imaging showed a stable disease and after ten months MR also demonstrated an intralesional structure modification as colliquative necrosis. In February 2012, after 24 months of continuos therapy, we decide to stop the treatment for fatigue and for other comorbidity of the patient. After five months of suspension, the ultrasound showed a dimensional increase of a target hepatic lesion & so we restarted lenalidomide for other six months. MR imaging demonstrated a stable disease and abdominal ultrasound showed a decrease of the dimension of a target hepatic lesion. The patient is still under treatemnt with a control of disease. Conclusions: HEH is a rare tumors with probably an indolent natural history but this case report suggests an interesting activity of lenalidomide and antiangiogentic drugs in the treatment of this solid tumor. More patients treated with lenalidomide are encouraged and a small phase II study should be proposed.
Effects of temozolomide combined with bevacizumab in patients with relapsed uterine sarcoma.
Authors: Sasaki Naoki , Kouta Hiroko , Ikeda Yuji , Takano Masashi , Kikuchi Ryoko , Kudoh Kazuya , Kita Tsunekazu , Furuya Kenichi , Kikuchi Yoshihiro 
Published: March 2020

e21520 Background: Common treatment for patients with unresectable relapsed uterine sarcoma is anthracycline-based combination chemothersapy, but the response is not satisfactory. We evaluated the effects of temozolomide combined with bevacizumab in patients with relapsed uterine sarcoma. Methods: From 2009 to 2012, nine patients with relapsed uterine sarcoma were treated with weekly bevacizumab (2mg/kg; days1,8, and 15, q4 weeks) and temozolamide (80mg/body, daily), and treatment continued until disease progression. The response and adverse effects were evaluated using the response evaluation criteria in solid tumors (RECIST), and common terminology criteria for adverse events (CTCAE) version 3.0. Results: In RECIST evaluation, 1 (11%) of 9 patients had complete response (CR) and 1 (11%) had partial response (PR). Four patients (44%) had stable disease (SD) for at least three months. The response rate (RR; CR+PR) and clinical benefit rate (CBR; CR+PR+SD) were 22% and 66%, respectively. The median progression-free survival was 9.8 months (range from 3 to 32 months). There were no treatment-related deaths or CTCAE grade 4 toxicities, and no patients were dose-reduced due to toxicity. Conclusions: Temozolomide combined with bevacizumab provided disease stabilization in some patients with relapsed uterine sarcoma with tolerable toxicities. These results suggested that this combination would offer another option in the treatment of unresectable relapsed uterine sarcoma.
Oxidative modification of proteins of blood plasma in the development of ovarian cancer relapse.
Authors: Surikova Ekaterina Igorevna , Nerodo Galina , Goroshinskaya Irina Aleksandrovna , Kachesova Polina Sergeevna 
Published: March 2020

e22002 Background: Comparative analysis of oxidative modification of proteins of blood plasma level in patients with ovarian cancer in a state of remission and during the formation of tumor relapse with various intensity of bloodstream in it. Methods: The research includes 61 patients with ovarian cancer, from whom 11 women were in a state of remission, and 50 had local relapse in the cavity of the lesser pelvis. With the help of ultra-sonic scanner we evaluated the intensity of vascularization and the speed of bloodstream in relapsing tumors. We also studied the level of blood plasma spontaneous metal catalyzed oxidative modification of proteins (OMP), spectrophotometrically registering 2, 4-dinitrophenylhydrazines. Results: In remission there was noted the increase of OMP products level by 74.4% under 530 nm (p<0.05) in blood plasma as compared with the its level in healthy women. During the progress of avascular relapse there was noted the increase of OMP products level by 63.3% under 370 nm (p<0.001) and decrease of OMP products level by 32.2% under 530 nm as compared with the level in remission. In the group with hyper intensive bloodstream in relapse tumor the level of OMP products increased by 37.4% under 370nm (p<0.05) and the level of products decreased by 24% under 530 nm as compared with the group with avascular relapse. In case with metal catalyzed OMP the low level of OMP products under 370 nm (by 18-28% lower than the level of OMP of healthy women, p<0.01), the high level of OMP products under 530 nm (by 24-47% higher than the level of OMP of healthy women, p<0.01) remained, and the level of OMP under 430 nm was increasing as compared with healthy women. Conclusions: The increase of OMP products of neutral character registered under 370 nm, and the decrease of the products of the basic character registered under 530 nm take place during the progress of cancerous process and intensification of the bloodstream in a tumor. The dynamics metal catalyzed OMP products shows the heightened formation of the products of the basic character (430 and 530 nm), being the markers of proteins fragmentation.
RACGAP1 overexpression in uterine carcinosarcomas.
Authors: Mi Shijun , Lin Mingyan , Heim Jennifer , Isani Sara , Brouwer-Visser Jurriaan , Cossio-Poblete Maria , Smotkin David , Gunter Marc J. , Zheng Deyou , Huang Gloria S. 
Published: March 2020

e22009 Background: Uterine carcinosarcomas, also known as malignant mixed mullerian tumors (MMMT), are rare and highly aggressive neoplasms that carry a poor prognosis even when diagnosed at an early stage. A better understanding of the molecular mechanisms underlying the development of uterine carcinosarcoma may lead to specific targeted therapies for these refractory tumors. Methods: Using a next generation sequencing approach and bioinformatic analysis, we compared the whole transcriptomes of 6 histologically normal endometrial tissues and 6 uterine carcinosarcoma tissues from patients. Quantitative real-time PCR and immunoblotting were done to validate the differentially expressed genes. Lentiviral transfection with short hairpin RNAs was performed to achieve targeted gene silencing in a carcinosarcoma cell line. p53 and survivin levels were monitored by immunoblotting. Results: We identified 27 dramatically differentially expressed genes between normal endometrial tissues and uterine carcinosarcoma tissues from patients. We confirmed the differential expression of these genes between normal tissues and uterine carcinosarcoma tissues by qRT-PCR. Of these, we found that RACGAP1 is significantly overexpressed in all of the uterine carcinosarcoma tissues at the mRNA level and at the protein level, compared to normal endometrial tissues. Silencing of RACGAP1 by shRNA in a carcinosarcoma cell line remarkably reduces cancer cell proliferation and leads to p53 upregulation and survivin downregulation. Conclusions: Our data demonstrate that RACGAP1 may represent a novel biomarker and therapeutic target for uterine carcinosarcomas.
Salmonella typhimurium A1-R prolongs survival of aggressive pancreatic cancer in orthotopic nude mouse models.
Authors: Maawy Ali , Zhang Yong , Bouvet Michael , Hoffman Robert M. , Zhao Ming 
Published: March 2020

e22013 Background: Salmonella typhimurium A1-R has been previously shown to target multiple tumor types in various mouse models. The aim of this study was to test the efficacy of S. typhimurium A1-R against a high aggressive pancreatic cell line in an orthotopic nude mouse model. Methods: Human MiaPaCa2 pancreatic cancer cells, expressing red fluorescent protein (RFP), were implanted subcutaneously in nude mice. After tumor engraftment, the mice were subjected to intravenous therapy with S. typhimurium A1-R (5×107 CFU) once a week for 3 weeks. The tumors were harvested and weighed after the treatment period. MiaPaCA2-RFP was subsequently surgically implanted orthotopically and S. typhimurium A1-R treatment was initiated 2 weeks later. Mice were treated with intravenous A1-R (5×107CFU) once a week for 6 weeks, after which survival and tumor growth were recorded. Results: In the subcutaneous tumor model, significant decreases in the rate of tumor growth (p = 0.049) and tumor size (p = 0.004) were observed upon termination. In the orthotopic model, a significant decrease in the rate of tumor growth (p = 0.01) and increased survival was observed (p = 0.014). None of the mice showed any adverse events or weight loss from bacterial therapy. Conclusions: The results suggest further investigation S. typhimurium A1-R, including in combination with chemotherapy, with the goal of cure of pancreatic cancer.
Transcriptional gene expression profile in hepatocarcinoma cells induced by acetylsalicylic acid (ASA) in hepatitis C virus (HCV)-subgenomic replicon system.
Authors: Rios Ibarra Clara Patricia , Verduzco Garza Barbara , Ortiz Lopez Rocio , Grondin Yohann , Lozano Sepulveda Sonia , Quintanilla Guzman Arturo , Rivas Estilla Ana Maria 
Published: March 2020

e22016 Background: It has been demonstrated that ASA treatment could down-regulate in vitro HCV expression in hepatocarcinoma cells (~50%, p 0.05). However, the signaling pathway induced during ASA antiviral effect has not been elucidated. We analyzed the transcriptional expression profile of Huh-7-HCV-subgenomic replicon cells in presence or absence of ASA in order to identify the signaling pathway and the molecular mechanisms involved in the antiviral effect induced by ASA on HCV expression. Methods: Huh-7-HCV-replicon cells (hepatocarcinoma) were exposed to 4 mM ASA from 24 to 72 hours. Total RNA was isolated, quantified and validated by capillary electrophoresis. After that, we performed a retrotranscription in vitro. Synthesized transcripts were marked with biotin, purified, fragmentized and hybridized in HG-U133 Plus 2 Gene Expression. Hybridization signals were captured with Gen Chip 3000 7G Scanner and analyzed by Expression Console and Dchit Software. Results: After normalization, we obtained hierarchical maps with differentially-expressed genes. Among genetic targets over-expressed, the following stood out CCAAT-enhancer-binding proteins (C/EBP), interleukine-8 (IL-8), cytochrome P450 (CyP450) and methallothioneins (MT) genes were found. Among down-regulated genes we identified ribonucleotide reductase (RR) and superoxide dismutase (SOD) genes. Some of these genes have been previously associated with oxidative stress regulation. All results were validated by real time PCR. Conclusions: We observed that ASA modulates the expression of genes associated with antioxidant role as SOD and methallothioneins. Antioxidant agents can inhibit virus proliferation. HCV decreased antioxidant defense, which promotes the development of hepatic complications caused by HCV infection, including liver cancer. Therefore, ASA could be inducing an antioxidant environment regulating HCV replication. This study provides a tool for identifying novel host factors in hepatocarcinoma cells involved in the antiviral effect regulated by ASA against HCV and improves our understanding of the regulatory mechanism of HCV replication.
Using certain indices of fibrinolytic system for forecasting the efficiency of neoajuvant chemotherapy in ovarian cancer.
Authors: Frantsiyants Yelena , Moiseyenko Tatiana , Komarova Yekaterina , Kozlova Larisa 
Published: March 2020

e22022 Background: Using cell markers that characterize biological properties of a tumor, the relevance of treatment used can be determined for each patient, further ways of surveillance of the patients can be selected, and individual forecasts of the illness can be made. Methods: After 1 course of neoajuvant chemoterapy according to the scheme CAP, in the malign tumor tissue of 21 patients (T3a-c N0-1M0-1), the activity of plasminogen and plasmin was determined by ELISA. Then the ratio K of plasminogen (PG) and plasmin (P) was calculated. As a blank, tumor tissue of 18 patients having ovarian cancer without chemotherapy administered has been studied. On all patients, operations in full or cytoreductive surgery were performed. Results: With efficient treatment, ratio K increased (К=1,4±0,2) relative to indices in patients without neoajuvant chemotherapy (К=0,3±0,17), while it remained the same (К=0,2±0,09) or decreased relative to initial data if there was no clinical effect, which is confirmed by further development of ovarian cancer. Conclusions: Thus, determining of plasminogen and plasmin – fibrinolytic system indices – in the tumor tissue and calculating of their ratio allows detecting the patients who have effect from treatment and good forecast and ones without effect, having bad forecast, who need aggressive ajuvant treatment. It also allows determining individual sensitivity or resistance of malign tumors in patients to certain regimens of chemotherapy. At the same time, there is an opportunity to objectify the results of specific therapy.