bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective study of chemotherapy-induced clostridium difficile infection in lung cancer patients.
Authors: Toi Yukihiro , Sugawara Shunichi , Kobayashi Takao , Kawashima Yousuke , Koizumi Tatsuhiko , Okazaki Keito , Takahara Masatoshi , Kuda Tomoya , Tanaka Akiko , Ishimoto Osamu , Honda Yoshihiro 
Published: March 2020

e19521 Background: Diarrhea after antibiotic treatment is primarily ascribed to the development of mucosal lesion for which Clostridium difficile infection (CDI) is held responsible. Evidence on CDI in patients on chemotherapy without antibiotic treatment prior to chemotherapy is on the rise. However there have been few reports describing diarrhea in relation to regimens of chemotherapy. The aim of our study was to find out whether the incidence of CDI in patients on cancer chemotherapy increases even in the absence of prior antibiotic treatment. Methods: From March 2010 through September 2011, we investigated the presence of Clostridium difficile (C.difficile) and its toxin in any patients undergoing diarrhea while receiving cytotoxic anticancer agents or epidermal growth factor receptor tyrosine kinase inhibitors. Whenever Grade2 or worse diarrhea defined by the Common Terminology Criteria for Adverse Events version4 occurred, we examined their stool samples for anaerobic culture and simultaneously tested for toxins A and B. A case of CDI is defined by the presence of symptoms (usually diarrhea) and either a stool test positive for C.difficile toxins or toxigenic C.difficile according to criteria of the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. Results: A total of 345 consecutive patients (492 in terms of chemotherapy -regimens) were enrolled in this study. 36 of 492 regimens (7.3%) showed Grade2 or worse diarrhea. CDIs without prior antibiotic exposure were confirmed in as many as 8 out of these 36 regimens (22.2%). CDI was more frequently observed in patients of the regimens including S-1 or irinotecan than other anticancer drugs. Conclusions: CDI may remain undetected among patients who had diarrhea defined as above unless due attention is paid to this possibility. It is highly recommended to perform tests for the detection of C.difficile toxins so that necessary measures can be instituted without delay in the treatment of diarrhea of patients on chemotherapy. Further analysis for drugs specificity and prevention against CDI is necessary.
Paulinia cupana (Guaraná) purified dry extract (PC-18) for chemotherapy related fatigue in patients solid tumors.
Authors: Del Giglio Adriana Braz , Lerner Tatiana Goberstein , Lera Andrea Thaumaturgo , Paiva Henrique Soares , Carelli Bruno , Azevedo Renata Guise Soares , Goldman Cecilia , Schindler Fernanda , Pianowski Luiz F , Latorre Claudia Grandino , Santi Patricia , Cruz Felipe Melo , Cubero Daniel Iracema , Del Giglio Auro 
Published: March 2020

e19552 Background: Paulinia cupana (guaraná) is an amazonic plant with stimulant proprieties which was shown previously to be effective for chemotherapy related fatigue in patients with breast cancer in a randomized double blind placebo controlled trial conducted by our group (J Altern Complement Med. 2011;17(6):505-12). Purpose: Extend our study to patients with different tumor types receiving various regimens of chemotherapy, treated with a purified dry extract of Paulinia cupana (PC-18). Methods: We included patients with solid tumors older than 18 years of age who were scheduled to receive systemic chemotherapy. We excluded patients with fibromyalgia and uncontrolled hypothyroidism, depression, anemia, hypertension or cardiac disease. We evaluated basal fatigue with the BFI questionnaire before chemotherapy, and included only patients who had an increase in their BFI score after one week. PC-18 was given at 50 mg PO bid, starting after one week of chemotherapy. We employed the FACIT-F, BFI, Chalder, HADS and PSQI questionnaires to evaluate fatigue, anxiety, depression and sleep quality at one week and after 4 weeks of chemotherapy. Results: 36 patients with a mean age of 54 years, 61 % female, 28% with breast, 22% colorectal, 8.3% lung , 8.3% head/neck, 5.6% ovarian and 27% of other carcinomas were included. Fatigue scores improved significantly when we compared scores of the BFI (mean difference = 19.39; 95%CI 12.4 – 26.37, p < 0.0001), FACIT-F (mean difference = -11.51; 95%CI -19.25 - -3.76, p = 0.0049) and Chalder (mean difference = 4.571; 95% CI 1.86 – 7.28, p = 0.0018) questionnaires. HADS subscales scores of anxiety (p = 0.025) and depression (p = 0.0095) also improved significantly after 3 weeks of PC-18 therapy. PSQI scores did not change significantly (p = 0.26) after 3 weeks of PC-18 treatment. Conclusions: We conclude that Paulinia cupana (Guaraná) PC-18 extract is active for treatment of chemotherapy related fatigue in patients with a variety of solid tumors and also improves their anxiety and depression scores without worsening the quality of their sleep.
Randomized trial effect of an oral nutritional supplement with eicosapentaenoic acid on nutritional and inflammatory parameters, response and toxicity to chemotherapy, quality of life, and survival in treatment-naive patients with advanced non-small lung cancer.
Authors: Sanchez-Lara Karla , Turcott Jenny , Juarez Eva , de la Torre Martha , Villanueva Geraldine , Green Dan , Arrieta Oscar 
Published: March 2020

e19594 Background: Nutritional interventions have shown increased of energy intake but the effect of improvement in health related quality of life (HRQL) in non small cell lung cancer (NSCLC) patients is controversial. Eicosapentaenoic acid has been proposed to have anti-inflammatory, anticachectic and possibly could have antitumoral effects. Methods: Patients with advanced NSCLC naive to treatment were included and randomly assigned to receive diet and oral nutritional supplement enriched with EPA or only isocaloric diet. All patients received paclitaxel and cisplatin-carboplatin treatment. Weight, body composition measured with bioelectrical impedance analysis, dietary ingestion, inflammatory parameters and HRQL were assessed at baseline and after 1st and 2nd cycle. Response to chemotherapy and survival were evaluated. Results: Ninety-two patients were analyzed, (46 EPA, 46 control group). No basal differences between groups were found. Experimental group present significantly increased albumin levels, energy, proteins, lipids and carbohydrate intake, and reduced serum CPR, TNF-α and Neutrophyls/Lymphocytes index. Patients in experimental group presented minor prevalence of weight loss and increased 1.6 kg of lean body mass (LBM) compared with controls. In HRQL, experimental group presented an improvement in global and physical scale and anorexia, and regarding toxicity, fatigue and neuropathy diminished. There was no difference in response rate, progression free survival and overall survival between groups. Conclusions: EPA enriched supplementation provided a therapeutic advantage by increasing LBM and nutrients intake, improving HRQL, and reduce several toxicity parameters in NSCLC patients under chemotherapy. The study was registered with ClinicalTrials.gov, number NCT01048970.
Resection of esophageal gastrointestinal stromal tumors.
Authors: Trifanov Vladimir , Kit Oleg I , Vladimirova Liubov Yu , Trifanov Dmitriy , Kasatkin Vadim 
Published: March 2020

e20503 Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of gastrointestinal tract. GISTs account for 0,1% to 0,3% of all tumors in the gastrointestinal tract. Two thirds of these tumors arise from the stomach, 25% arise from the small intestine and less than 5% arise from esophagus. Use of tyrosine kinase inhibitors has revolutionized therapy for GISTs but complete resection remains the treatment of choice. Methods: We report our experience (from 2005 to 2011) with five patients who underwent resection of esophageal GIST. Reviewed consensus management guidelines and performed a literature review for reported cases. Results: All five patients underwent surgery intervention at our institute. Four patients had no metastasis and they underwent tumor enucleation. Due to submucosal location only one of them was diagnosed with GIST by endoscopic biopsy before surgery. One patient had a giant liver metastasis invading totally all segments of right lobe of liver. He underwent transhiatal extirpation simultaneously combined with extended right-sided hemihepatectomy. That patient suffered from total dysphagia, 15 kg weight loss, gastrointestinal bleeding and a big lump in his right hypochondrium. After laparotomy we diagnosed big metastatic nodule invading the whole right lobe of liver 25 cm in diameter. After diaphragmotomy we diagnosed tumor of the lower third of esophagus. Consequently, we performed extended right-sided hemihepatectomy and transhiatal esophagus extirpation. Two months later esophageal plastics by means of ileocaecal segment of colon was performed. The pathological diagnosis was confirmed in all five cases by microscopic examination (KIT+; CD17+, mitotic rate). In adjuvant regime imatinib (400 mg/body/day) was administered for a year for all five patients. The patients are alive now, they were followed up every six months with CT for two years. Fortunately, no new tumors were observed during this period of time. Conclusions: Esophagectomy is the treatment of choice for esophageal GISTs but requires attention to operative details that emphasize complete en block excision of surrounding tissue and metastatic nodules.
Dose escalation of doxorubicin hydrochloride and ifosfamide in previously untreated Ewing sarcoma.
Authors: Memon Muhammad , Raja Madras A. , Ahmad Javed , Pant Rajive , Shaheen Mahmoud , Al-Dayel Fouad 
Published: March 2020

e20508 Background: Ewing’s sarcoma is a primary malignant tumour of the bone. Ifosfamide and doxorubicin hydrochloride are two active drugs. Administration of the maximum feasible doses may help achieve the best result. In this study we proposed to use the combination of vincristine, actinomycin D, doxorubicin hydrochloride, ifosfamide (VAAI) for total of 12 cycles. Methods: All eligible patients will receive initially four cycles of VAAI. Doses include: vincristine maximum 2 mg IV doxorubicin hydrochloride 25 mg/m2 IVpush for 3 days ifosfamide 3 Gm/m2 as an intravenous infusion over 2 hours for 3 days. Each cycle will be repeated every 21 days. Patient will then undergo response evaluation, and subjected to surgical resection when posible. If surgery is incomplete, not possible or refused, radical radiation therapy to a dose of 55 Gy was given. Post operatively patient will recice two cycle of adriamycin base chemotherapy and than will continue with actinomycin d to complete 12 cycles. Results: 16 patients were enroll, mean age 19 years range 15-35, male/female 9/7, tumor location pelvis 3 femur 5 tibia 1 humrus 2 foot 2 maxilla 1 radius 1 extra skeletal at thigh 1. After the enrolment of three patients, there was frequent incidence of febrile neutropenia and mucositis, dose of ifofamide was reduce to 2.25 gm/m2 and GCSF was added. Out of 16 patients enrolled, 5 patients withdrew (1 recurrent febrile neutropenia, 2 disease progression, 1 delay of chemotherapy more than 3 weeks and 1 was rediagnosed post 4 cyles and surgert as synovial sarcoma). 9 patients received all 12 cycles of chemotherapy (5 patients needed further dose reduction of ifofamide by 20% as per protocol, and 2 patients received 11 cycles. There was no toxic death. 8 patients had mild to moderate mucositis, nausea and vomiting grade 2 in 4 patients and in 3 grade 3.10 patients underwent surgical resection of tumor and 8 patient received radiation therapy. 8 patient achieve complete remission. Conclusions: This is a unique study that all the patient enrolls were more than 14 years, this combination of chemotherapy was well tolerated, had good feasibility and easily manageable toxicity and can be administered as a outpatient. To the best of our knowledge this is the first study using this chemotherapy as outpatient.
Effect of zeb1 and zeb2 on pancreatic fibrobast-induced epithelial-to-mesenchymal transition (EMT) in pancreatic cancer.
Authors: Visa Laura , Samper Esther , Rickmann Mariana , Postigo Antonio , Sanchez-Tillo Esther , Fernandez-cruz Laureano , Balsells Josep , Maurel Joan , Molero Xavier , Vaquero Eva Cristina 
Published: March 2020

e21035 Background: EMT renders neoplastic cancer cells the ability to migrate and to invade distant organs. The hallmark of EMT is the loss of E-cadherin, which is a prerequisite for epithelial tumor cell invasion. In pancreatic cancer, loss of tumor E-cadherin is an independent predictor of poor outcome. Aims: To analyze the effect of pancreatic fibroblasts (PF) on inducing EMT in pancreatic cancer cells and to identify the transcription factors (Snail, Slug, ZEB1, ZEB2) that mediate EMT process. Methods: Human PFs were isolated from human pancreatic specimens obtained from chronic pancreatitis and from unaffected margins of pancreatic adenocarcinoma and serous cistoadenoma. PF were cultured until complete cellular activation, as assessed by expression of α-smooth muscle actin, vimentin and fibronectin. Human pancreatic cancer cells Panc-1 were exposed to PF conditioned medium (PF-CM) and EMT analyzed by cell morphology, migration, and E-cadherin expression (quantitative RT-PCR and immunoblot). Gene expression of Snail, Slug, ZEB1, and ZEB2 was analyzed by quantitative RT-PCR, and their activity modulated by siRNA Results: Conditioned media from all types of activated PFs induced EMT changes in Panc-1 cells, as shown by 1) morphological transition from cobblestone shaped to fibroblast-like cells, 2) stimulation of cell migration, and 3) E-cadherin down–regulation; mRNA expression of Snail transiently increased at 30 min after exposure to PF returning to basal levels afterwards; mRNA levels of ZEB1 were not up-regulated upon exposure to PF-CM. However, ZEB1 protein greatly accumulated after 48h incubation with PF-CM, suggesting that PF prevent ZEB1 degradation in Panc-1 cells. Combined RNA downregulation of ZEB1 and ZEB2, but not of Snail and/or Slug, suppressed E-cadherin repression induced by PF. Conclusions: Activated PFs promote the invasive phenotype of pancreatic cancer cells through ZEB1 and ZEB2 activation.
Interleukin-15 expression in lung cancer.
Authors: Adhami Faisal , Steel Jason C , Morris John Charles 
Published: March 2020

e21064 Background: Interleukin-15 (IL-15) is a pro-inflammatory cytokine that stimulates the differentiation and proliferation of T, B, and NK cells. IL-15 is normally tightly bound by its receptor, IL-15Rα. Dendritic cells and monocytes/macrophages primarily express both IL-15 and IL-15-Rα; however, expression has been detected on epithelial cells including those of the lung. In the lung, IL-15 is thought to play a role in the induction of immune responses to infection. Over expression of IL-15 has been shown to induce NK cell activation and cytotoxic T-lymphocyte (CTL) responses leading to tumor regression. Little is known about IL-15 or IL-15Rα expression in lung cancer. Methods: mRNA from 146 primary lung cancers were analyzed by multiplex qPCR for expression of IL-15, IL-15Rα and b-actin (internal control) and compared to expression in normal lung tissue from 45 patients. Of the 146 patients, 50 were stage I (IA=20, IB=30), 49 stage II (IIA=9, IIB=40), 36 stage III (IIIA=18, IIIB=18), and 11 stage IV. Results: Comparing the expression of IL-15 between normal lung and tumor, we found tumors expressed significantly less IL-15 than normal lung (P<0.001). Lung cancers at any given stage, expressed significantly less IL-15 than that seen in normal lung. When comparing stages, stage IV tumors expressed significantly less IL-15 than tumors of stages I (P=0.021), II (P=0.020), or III (P=0.024). There was no difference in expression between stages I, II or III (P>0.05). When examining the expression of IL-15Rα we found no differences between normal lung and tumor. No differences were seen between normal lung and stages I-IIIA; however, significantly less IL-15Rα expression was noted in stages IIIB and IV compared to normal lung. Between stages, stages I and II had significantly more IL-15Rα expression than stage IV tumors. There were no differences between stages I, II and III. Conclusions: Pro-inflammatory cytokines such as IL-15 may be important for the induction of lung immunity. IL-15 expression is down regulated in lung cancers and this down regulation increases with stage. We posit that the down regulation of IL-15 by lung cancers may aid in their evasion of immune responses allowing progression and dissemination of tumor.
Analysis of the mutation rate in lymphocytes derived from patients with cutaneous T-cell neoplasms using the PIG-a gene.
Authors: Doratotaj Behzad , Zamechek Leah B. , Hymes Kenneth B. , Araten David J. 
Published: March 2020

e21082 Background: It has been proposed that genomic instability may account for the high number of mutations observed in cancer. Inherited mutations in repair genes might play a role; alternatively, hypermutability may be the result of mutagens, or may be limited to a specific pre-malignant population. Here we have investigated the hypothesis that cutaneous T cell neoplasms might be associated with constitutional hypermutability, using an assay based on the PIG-A gene. A broad spectrum of mutations can inactivate PIG-A, which is X-linked; thus, only one mutation is required to produce the PIG-A-null phenotype, which entails a loss of all GPI-linked membrane proteins (e.g. CD48, CD55, CD59, CD52). Methods: We have isolated peripheral blood lymphocytes from normal donors and patients with cutaneous T cell neoplasms, which are initially stimulated with phytohemagglutinin. After 1 week, cells are stained with an anti-CD59 antibody and sorted to eliminate pre-existing mutants. The collected GPI (+) cells are then counted, returned to culture with IL-2 and IL-15, and re-stimulated with beads bearing anti-CD2, anti-CD3, and anti-CD28. After 3 weeks in culture the cells are re-counted, and the frequency (f) of new mutants arising in vitro is determined by flow cytometry, by staining sequentially with a mixture of mouse antibodies specific for 4 GPI-linked proteins, followed by a secondary PE-conjugate, followed by a FITC conjugated antibody specific for a non-GPI linked protein, e.g., CD4, CD8, or CD45. The number of cell divisions (d) in culture is determined by live cell counts before and after expansion, and the mutation rate (μ) is calculated as μ = f / d. Results: Amongst 15 normal donors (mean age 54), μ in proliferating CD45 + T cells ranged from 10 to 183 x 10-7 mutations per cell division (median 35 x 10-7). Amongst 10 patients with cutaneous T cell neoplasms (mean age 60) μ ranged from 7 to 116 x 10-7 (median 23 x 10-7) in proliferating CD4+ cells, and μ ranged from 10 to 363 x 10-7 (median 26 x 10-7) in proliferating CD8 + cells. Conclusions: We conclude that a constitutional increase in the mutation rate, as detected by this assay, is not a common feature of cutaneous T cell malignancies.
Gene expression combined with gene set enrichment analysis to identify markers of vinorelbine efficacy in breast cancer patients.
Authors: Audet Robert , Shen Changyu , Willis Scooter , Duchnowska Renata , Adamowicz Krzysztof , Zok Jolanta , Rogowski Wojciech , Litwiniuk Maria Malgorzata , Debska Sylwia , Jaworska Magdalena , Foszczynska-Kloda Malgorzata , Kulma-Kreft Monika , Zabkowska Katarzyna , Jassem Jacek , Edgerton Susan , Thor Ann D. , Miller Kathy , Sledge George W. , Leyland-Jones Brian 
Published: March 2020

e21099 Background: Vinorelbine (V) induces mitotic arrest and apoptosis but there are limited data on its effect on gene expression in breast cancer clinical setting. Methods: 43 adult female patients with pathologically confirmed breast cancer and locally advanced or metastatic disease were treated with V 25 mg/m2 days 1, 8, 15 of a 28-day cycle. Gene expression was assessed in archival FFPE tissue using the microarray-based DASL assay (cDNA-mediated Annealing, Selection extension and Ligation) and correlated with time-to-progression (TTP). Using a Gene Set Enrichment Analysis (GSEA), groups of genes that share a common molecular function, chromosomal location, or regulation were identified in patients classified as having either a short (S) (n=25) or a long (L) (n=18) time to progression (TTP) divided by the median (72 days). The GSEA software ( http://www.broadinstitute.org/gsea/index.jsp ) was used for the analysis. Results: GSEA focusing on genes grouped according to similar a) molecular function: 16 out of a set of 43 genes involved in histone binding were enriched in group S (p = 0.002), consistent with higher expression in group S of HIST3H2BB and HIST1H3I as well as a nuclear transcription factor promoting their expression. b) transcription factors: 14 out of 47 genes were enriched in group S (p = 0.004) and corresponds to genes with promoter regions that match c-fos serum response element-binding transcription factor that modulates, for example, ABCC1 and ABCB1 (P-gp/MDR1) solute carriers. c) chromosomal location: in group S, genes were enriched on chromosome 11q21 (20 out of 45 genes p = 0.004) and on chromosome 12p12 (14 out of 22 genes p = 0.002). Conclusions: a) the up-regulation of histone binding genes is consonant with recent discovery of high affinity V binding to histones b) the role of P-gp/MDR1 in V transport is well known c) our observations on chromosome 11q21 and12p12 are novel. DASL expression combined with GSEA highlights gene sets that correlate with clinical outcome and may lead to predictive markers of V efficacy. Further confirmatory analysis is needed due to the limitation of small sample size and multiple comparisons.
Expression of prostate-specific membrane antigen (PSMA) in the neovasculature of nonprostate human tumors of epithelial and nonepithelial origin.
Authors: Magargal Wells Wrisley , Qian Dapeng , Olson William C. 
Published: March 2020

e21131 Background: PSMA is a transmembrane glycoprotein present not only in prostate cancer epithelial cells but also in the neovasculature of many other solid tumors. This expression profile makes it an attractive target for tumor-specific delivery of chemotherapeutic agents to the neovasculature of non-prostate solid tumors. We generated an antibody-drug conjugate (ADC) comprised of a fully human anti-PSMA monoclonal antibody (mAb), conjugated to monomethylauristatin E, a potent cytotoxic agent. PSMA ADC is currently undergoing Phase I clinical testing in men with advanced prostate cancer. Previously, we reported high level PSMA expression in the neovasculature of carcinomas from kidney, colon, non-small cell lung, breast and liver. Here we extend our study to additional carcinomas as well as tumors of non-epithelial origin. Methods: Expression of PSMA protein was evaluated by immunohistochemical analysis of frozen tissues using biotinylated mAb that specifically recognizes the native dimeric form of PSMA. The semi-quantitative scheme of 0 to 3+ was used to indicate the amount of epitope based on the intensity of the color reaction. The strongest possible staining was scored 3+ while 2+ staining was considered moderate and 1+ was considered weak. Endothelial cells were detected by morphology and staining of selected slides with an anti-CD 34 mAb. Results: Moderate to strong (2+ to 3+) neovasculature staining was seen in over 80% of specimens from, bladder (10/10), ovarian (9/10) and pancreatic (8/10) carcinomas. Moderate to strong neovascular staining was seen in 40-80% of specimens from several non-carcinoma tumors, including glioblastoma (4/5), melanoma (7/10), non-Hodgkins lymphoma (6/10), osteosarcoma (3/7) and myeloma (2/5). Only weak (1+) staining was seen in angiosarcoma (2/3) and no staining was observed in the testicular cancers tested (0/5). Conclusions: Robust neovascular expression of PSMA dimer was observed across all eight non-prostatic carcinomas. Significant neovascular expression was also observed in several non-epithelial tumors. These findings may be relevant to the development of novel anti-neovascular therapies that target PSMA.