tbuckley/cabot-search huggingface dataset:
Additional primary malignancies in patients with pancreatic cancer.
Authors: Shyam S. Allamaneni, Rohit Sharma, Austin Miller, Saikrishna S. Yendamuri, John F. Gibbs
Journal: Journal of Clinical Oncology (2012)

185 Background: Rates of second primary malignancy have been increasing with increased cancer survivorship. The published literature on second primaries in patients with pancreatic adenocarcinoma is sparse. We addressed this question utilizing the SEER database. Methods: 99,614 patients of primary pancreatic adenocarcinoma diagnosed between 1973-2006 were identified from SEER database. Of these, 8,889 (8.93%) had another primary diagnosed before pancreatic cancer (BPC) and 1813 (1.82%) a second primary diagnosed after pancreatic cancer (APC). SAS was used for statistical analysis and P-value &lt;0.05 was determined to be significant. Results: The most common non-pancreatic primary identified were prostate, breast, lung, colorectal, and urinary bladder. The median age at presentation was 75 and 71 years in the BPC and APC groups respectively. APC patients had higher odds of developing primary cancers of embryonic gut origin (esophagus, stomach, small intestine, hepatobiliary, lung, and thyroid) compared to PBC patients (p&lt;0.05). Patients of BPC compared to APC were more likely to be older than 70 yrs (70.5% vs. 65.3% p=0.01), less likely to undergo surgery for pancreatic cancer (11.2% vs.5.87% p=&lt;0.05) and with decreased median survival (7 vs.3 months). With each passing decade, increasing second primaries were diagnosed, presumably reflecting better overall survival from cancer diagnosis. Conclusions: Approximately 11% of pancreatic adenocarcinoma patients have another cancer in their life time. Identifying common genetic and risk factors in these patients with multiple malignancies may provide the new therapeutic opportunities for patients with pancreatic cancer.
Analysis of Factors Influencing Skin Toxicity after Autologous Hematopoeitic Stem Cell Transplant.
Authors: Anuj Mahindra, Brian Bolwell, Ronald Sobecks, Lisa Rybicki, Stacey Brown, Brad Pohlman, Matt Kalaycio, Robert Dean, Steve Andresen, John Sweetenham, Edward Copelan
Journal: Blood (2007)
Pregnancy-associated breast cancer: Review of the literature.
Authors: V. Bjelic-Radisic, C. P. N. Retussnig
Journal: Journal of Clinical Oncology (2011)

245 Background: Overall, 0.2%-3.8% of all breast cancer cases are diagnosed during the pregnancy. It is to be expected that the incidences of pregnancy-associated breast cancer (PABCS) will likely increase. Therapy of PABCS is the challenge and requests team play of different experts in this area. The aim of this study was to review the actual therapy of PABCS. Methods: Publications relevant to PABCS and their therapy were identified by searching Pubmed database for the period between 1960 and 2010. We used the keywords “cancer”, “pregnancy”, “chemotherapy”, and “systemic treatment”. Search results were adjusted by references from relevant articles. 221 relevant articles and abstracts were found. Articles describing the same patient cohort and articles without data of the kind of drug, trimester of application and without size of patient cohort were excluded from analyses. 79 articles matched the search criteria and were included in analyses. Results: The use of anthracycline-based chemotherapy has been documented in 320 cases, congenital malformation (CM) occurred in 3.75% of the reported cases (similar to the standard population). 14 publications described a methotrexate-containing therapy during pregnancy, CM occurred in 6.67%. Use of taxanes has been documented in 29 cases, CMs were observed in 3.45%. 9 articles (20 cases) published the effects of vinca alkaloids-containing treatment, in 1 cases occur missed abortion. Tamoxifen use during pregnancy is described in 9 publications, 30% of the exposed newborns showed CM. The application of target-agent-trastuzumab during pregnancy is described in 16 case reports with developing of oligo- or anhydramnion, IUGR, pulmonal hypoplasia. Conclusions: Anthracyclines are regarded the safest chemotherapeutic agents during pregnancy and can be given with minimal fetal risk after the first trimester. The routine use of newer agents like taxanes or vinca alkaloids are with high possibility safe in 2. And 3. Trimenom, but because of limited data are not recommended so far. Methotrexate should be avoided during pregnancy. Tamoxifen, aromatase inhibitor and target agents are contraindicated during the pregnancy. Target agents can not be recommended for the use in the pregnancy.
Bone metastases from gastrointestinal stromal tumors (GISTs).
Authors: M. Nannini, M. C. Pallotti, V. Di Scioscio, M. A. Pantaleo, L. Greco, A. Bazzocchi, A. Maleddu, M. Saponara, A. Mandrioli, C. Lolli, M. di Battista, A. Astolfi, S. Formica, M. Zompatori, G. Biasco
Journal: Journal of Clinical Oncology (2011)

e20527 Background: Liver and peritoneum are the most common site of recurrences from gastrointestinal stromal tumors (GISTs). Bone metastases represent a rare finding in clinical practice and their biological significance and clinical management remain unsettled. Methods: We reviewed all patients with advanced/metastatic GIST at our institution and focused on cases with bone metastases, describing the clinical and radiological features of these lesions. Results: Among 71 patients, four had bone metastases. Two were female (82 and 54 years of age) and two were male (62 and 44 years of age). All four of them had an high-risk primary GIST, localized in small intestine in three cases, and in the stomach in the other one. One patient harboured a KIT esone 11 mutation (T>A 69429(p.V559d), one patient had a WT GIST and in the other patients mutational analysis was not assessable. Bone tumour involvement was present at the time of initial diagnosis in two patients, and occurred during the follow-up period after 7 and 2 years in the other two. In all patients bone metastases were associated to other visceral site of relapse. Radiologically, the lesions were diagnosed by CT-scan and had a lytic pattern in all cases, with a widespread skeletal involvement. In no case a single lesion was found. Clinically, bone metastases were symptomatic in three patients and presenting with a pathological fracture in a single case. In only one patient bone lesions were asymptomatic and diagnosed as occasional finding. All patients received zoledronic acid in association with TK inhibitors, obtaining a long stable disease in two cases whereas there was a quick disease progression in the other two cases. Only one patient was also treated with radiotherapy for palliative purpose. Conclusions: Although bone metastases are an infrequent site of recurrence from GISTs, they may become more prevalent due to increased patient life expectancy as well as the improvement in imaging techniques. By now their biological background and prognostic value and their clinical management are unknown. Moreover standard imaging and metabolic criteria for diagnosis and tumor response assessment are still lacking. These data should be collected in large series.
HLADRB3*0101 Combined with DRB4*0101 Are Potential Predictor of Neonatal Alloimmune Thrombocytopenia (NAIT) Development
Authors: Ophira Salomon, Ron Loewenthal, Rivka Kalt, Nurit Rosenberg, Rima Dardik, Vered Yahalom, Ofelia Avishai, Orit Frenkel, Ephraim Gazit, Shlomon Lipitz
Journal: Blood (2011)
Gene expression profile of circulating tumor cells (CTCs) in clear cell metastatic renal cell carcinoma (mRCC).
Authors: R. Iacovelli, C. Nicolazzo, A. Petracca, E. Risi, E. Cortesi
Journal: Journal of Clinical Oncology (2011)

302 Background: The presence of circulating tumor cells (CTCs) is described in 50% of patients affected by mRCC. The detection of CTC seems to be correlated with advanced tumor stage and more aggressive tumor phenotype. In some other solid tumors, such as breast, colorectal and prostate cancer, a growing body of evidence is emerging about the molecular portrait of these cells, whose nature is still largely unknown. The lack of information about CTCs characterization in RCC strongly hampers their application into the clinical practice. Aim of the study was to trace a gene expression profile of CTCs in mRCC patients. Methods: 18 metastatic clear cell mRCC patients were enrolled in the study. All patients provided informed consent. CTCs were isolated from 10cc of peripheral blood by CELLection Dynabeads coated with the monoclonal antibody towards the human Epithelial Cell Adhesion Molecule (EpCam). CELLection Epithelial Enrich is designed to optimally enrich bead-free, viable epithelial tumor cells. Tumor cells were eluted, subjected to RNA extraction and cDNA synthesis. PCR was then performed to investigate the expression of cytokeratin 8 (CK8) and vimentin as markers of clear cell RCC, multidrug resistance (MDR1), multidrug resistance related proteins 1–5–7 (MRP 1, MRP5, MRP 7) as drug resistance markers. Results: According with standard CTCs definition (CK+/CD45-), we found their presence in 9/18 samples (50%). Out of them, vimentin was found in 2/9 (22%), MDR1 in 3/9 (33%), MRP1 in 1/9 (11%), MRP5 in 6/9 (66%) and MRP7 in 9/9 (100%). Conclusions: To our knowledge this is the first attempt to describe a gene expression portrait in CTCs from clear cell mRCC. Of note is that vimentin, classically used as diagnostic marker for clear cell RCC is often lost in CTCs. This seems to further confirm the discrepancy between CTCs and primary tumor phenotype, already demonstrated in breast cancer. The expression profile of genes involved in multidrug resistance in CTCs seems to reflect the well known drug resistance observed in RCC. How these biological information obtainable from a gene expression profile performed on CTCs in clear cell mRCC may be translated into the clinic is currently under investigation. No significant financial relationships to disclose.
First-line bevacizumab (B) plus paclitaxel (P) in HER2-negative (HER2-ve) metastatic breast cancer (mBC): Efficacy and safety in an Italian multicenter retrospective study.
Authors: D. Andreis, G. Scandurra, D. Santini, C. Gucciardino, N. M. La Verde, S. Girelli, I. Alabiso, A. Saetta, F. Atzori, E. Collovà, A. Ferzi, S. Gori, H. Lipari, C. Saggia, I. Marcon, D. G. Generali
Journal: Journal of Clinical Oncology (2011)

e11502 Background: The combination of B with P as first-line treatment for patients (pts) with HER2-ve mBC showed clinical benefits in terms of progression-free survival (PFS) and objective response rate (ORR) without an effect on overall survival (OS). This Italian multicenter retrospective study wanted to evaluate the first-line B plus P in term of efficacy and safety in routine oncology practice. Methods: A total of 96 female pts with HER2-ve mBC, Eastern Cooperative Oncology Group performance status of 0 to 1, received B 10 mg/Kg every 2 weeks or 15 mg/Kg every 3 weeks combined with P. PFS and OS were estimated using the Kaplan-Meier method and compared with log-rank test. Chi-square test was employed for comparison of proportion. Results: Pts characteristics included: median age 56.8 years; ≥3 sites of lesion 11.5%; previous (neo)adjuvant chemotherapy (CT) 83.4% (taxane-based CT 27.1%). After a median follow-up of 9.6 months, 51 pts progressed and 17 died. 46 pts (48.9% of evaluable pts) attained a disease response: 13 complete responses and 33 partial responses. Median PFS and OS were 9.5 and 22.7 months, respectively. ≥3 sites of lesion were associated with a significant worse PFS (p=0.02) and OS (p=0.03). No associations were found with clinical end-points based on biological variables (ER, Ki-67) stratification. Previous treatment in neo(adjuvant) setting with taxane-based regimens had a significant less chance to obtain disease response (p=0.002), and worse PFS (p=0.009) and OS (p=0.04). The majority of adverse events (AEs) were mild or moderate. Grade ≥3 AEs included hypertension (2.1%), neutropenia (1.0%), thromboembolic events (1.0%) and gastrointestinal perforation (1.0%). The occurrence of hypertension (all grades) was significantly associated with better ORR (76.5% vs 42.8%; p=0.01) and with a trend (not significant) of better PFS (p=0.08). Conclusions: The efficacy and safety data of B plus P collected in this study were consistent with results from first-line trials. Pre-treatment in (neo)adjuvant setting with taxane was associated with a worse prognosis. We also confirmed hypertension as significant predictor of B activity.
Dose-finding and efficacy phase II study of inecalcitol, a new VDR agonist, in combination with docetaxel-prednisone regimen for castration-resistant prostate cancer (CRPC) patients (pts).
Authors: J. Medioni, G. Deplanque, J. Ferrero, T. Maurina, J. P. Rodier, E. Raymond, J. Allyon, S. Renaux, J. Dufour-Lamartinie, S. Oudard
Journal: Journal of Clinical Oncology (2011)

142 Background: Inecalcitol is a novel vitamin D receptor (VDR) agonist which shows high antiproliferative effects in human cancer cell lines and a 100-fold lower hypercalcemic activity than calcitriol the natural ligand of VDR. Methods: Escalating dosages of inecalcitol were combined to chemotherapy in naive metastatic CRPC patients. Safety and efficacy were evaluated in groups of 3-6 pts receiving inecalcitol every other day, daily or twice a day on a 21-day cycle in combination with docetaxel (75mg/m 2 q3w) and oral prednisone (5mg bid). Pts received up to six cycles unless unacceptable toxicity or disease progression. Primary endpoint was dose limiting toxicity (DLT) defined as G3 hypercalcemia within the first cycle. Efficacy endpoint was PSA response defined as ≥30% decline within 3 months. Results: Eight dose levels from 40 to 8,000 μg have been evaluated in 54 pts; 83 % had bone metastases, 13% had visceral disease only. Median age was 71 years (range, 49-87), median Gleason score (Gs) 7 and median PSA 28.5 ng/mL (range, 0.8-962.4). DLT occurred in 2/4 patients receiving 8,000 μg/day after 1 and 2 weeks of treatment. Calcemia normalized in few days after interruption of treatment. The 2 other experienced only G2 and were stepped down to 4,000 μg. After dose reduction, calcemia remained within normal ranges and G1.The maximum tolerated dose is defined at 4,000 μg qd. Most of adverse events reported were grade 2. G3-4 were mainly hematological toxicity. Frequency of AEs related to docetaxel did not seem to be modified.82% of the patients had ≥30% PSA decline within 3 months of treatment whereas in historical data around 65% are responder with docetaxel as a single agent. PSA response was observed after 1 cycle of treatment in 43% of the patients. Time to biochemical relapse defined as an increase of 25% over nadir was 169 days. Conclusions: High antiproliferative daily dose of inecalcitol, a new VDR, agonist has been safely used in combination with docetaxel in CRPC patients. This combination treatment shows encouraging PSA response (&gt; 30% PSA response: 82%). A multicenter randomized double blind phase III study is forecasted to confirm these results. [Table: see text]
Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome
Authors: Lisa C. Burnett, Charles A. LeDuc, Carlos R. Sulsona, Daniel Paull, Richard Rausch, Sanaa Eddiry, Jayne F. Martin Carli, Michael V. Morabito, Alicja A. Skowronski, Gabriela Hubner, Matthew Zimmer, Liheng Wang, Robert Day, Brynn Levy, Ilene Fennoy, Beatrice Dubern, Christine Poitou, Karine Clement, Merlin G. Butler, Michael Rosenbaum, Jean Pierre Salles, Maithe Tauber, Daniel J. Driscoll, Dieter Egli, Rudolph L. Leibel
Journal: Journal of Clinical Investigation (2016)

Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum critical deletion region encompassing 3 genes, including the noncoding RNA gene SNORD116. Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell–derived (iPSC-derived) neurons. Moreover, Nhlh2 and Pcsk1 expression were reduced in hypothalami of fasted Snord116 paternal knockout (Snord116p–/m+) mice. Hypothalamic Agrp and Npy remained elevated following refeeding in association with relative hyperphagia in Snord116p–/m+ mice. Nhlh2-deficient mice display growth deficiencies as adolescents and hypogonadism, hyperphagia, and obesity as adults. Nhlh2 has also been shown to promote Pcsk1 expression. Humans and mice deficient in PC1 display hyperphagic obesity, hypogonadism, decreased GH, and hypoinsulinemic diabetes due to impaired prohormone processing. Here, we found that Snord116p–/m+ mice displayed in vivo functional defects in prohormone processing of proinsulin, pro-GH–releasing hormone, and proghrelin in association with reductions in islet, hypothalamic, and stomach PC1 content. Our findings suggest that the major neuroendocrine features of PWS are due to PC1 deficiency.
Definition, discrimination, diagnosis and treatment of central breathing disturbances during sleep
Authors: Winfried Randerath, Johan Verbraecken, Stefan Andreas, Michael Arzt, Konrad E. Bloch, Thomas Brack, Bertien Buyse, Wilfried De Backer, Danny Joel Eckert, Ludger Grote, Lars Hagmeyer, Jan Hedner, Poul Jennum, Maria Teresa La Rovere, Carla Miltz, Walter T. McNicholas, Josep Montserrat, Matthew Naughton, Jean-Louis Pepin, Dirk Pevernagie, Bernd Sanner, Dries Testelmans, Thomy Tonia, Bart Vrijsen, Peter Wijkstra, Patrick Levy
Journal: European Respiratory Journal (2016)

The complexity of central breathing disturbances during sleep has become increasingly obvious. They present as central sleep apnoeas (CSAs) and hypopnoeas, periodic breathing with apnoeas, or irregular breathing in patients with cardiovascular, other internal or neurological disorders, and can emerge under positive airway pressure treatment or opioid use, or at high altitude. As yet, there is insufficient knowledge on the clinical features, pathophysiological background and consecutive algorithms for stepped-care treatment. Most recently, it has been discussed intensively if CSA in heart failure is a "marker" of disease severity or a "mediator" of disease progression, and if and which type of positive airway pressure therapy is indicated. In addition, disturbances of respiratory drive or the translation of central impulses may result in hypoventilation, associated with cerebral or neuromuscular diseases, or severe diseases of lung or thorax. These statements report the results of an European Respiratory Society Task Force addressing actual diagnostic and therapeutic standards. The statements are based on a systematic review of the literature and a systematic two-step decision process. Although the Task Force does not make recommendations, it describes its current practice of treatment of CSA in heart failure and hypoventilation.
Abstract 15623: Transplantation of Adipose-derived Stem Cells Sheet for Accelerated Neovascularization and Engraftment in Acute Myocardial Infarction Rats
Authors: Jong-Ho Kim, Hyung Joon Joo, Mina Kim, Seung-Cheol Choi, Chi-Yeon Park, Jeong Ik Lee, Soon Jun Hong, Do-Sun Lim
Journal: Circulation (2015)

Background: Transplantation of adipose-derived stem cell (ADSCs) has been suggested to improve cardiac function after acute myocardial infarction (AMI). Poor retention rate and differentiation ability of the implanted ADSCs limited their therapeutic potential. This study investigated the application of cell sheet technology for ADSC to improve engraftment and functional recovery in rat AMI model. Methods: Mouse ADSC (mADSC) sheets were successfully obtained by using the thermo-responsive dishes. Three groups of sham (n=10), suspended mADSC myocardial injection (n=10) and mADSC sheet transplantation (n=10) were compared in rat AMI model of left anterior descending coronary artery ligation. Final analyses were performed at day 28 after cell implantation. Results: In rat AMI model, mADSC sheet showed higher cellular engraftment in the infarcted heart compared to suspended mADSCs and sham control (signal unit; 227.3±18.3, 2.0±2.0 and 0; p&lt;0.05). Cytokine analysis of the cell-implanted myocardial tissues showed that higher expression of IGF-1, bFGF, TGF-β1, and EGF in mADSC sheet compared to suspended mADSCs and sham control (p&lt;0.05). Microvascular density of the peri-infarct zone was also higher in mADSC sheet compared to suspended mADSCs and sham. Interestingly, the transplanted cell-derived microvessels determined by mouse specific anti-vWF antibody were detected only in mADSC sheet. Echocardiography showed the significant improvement of ejection fraction (EF) in both suspended mADSCs and mADSC sheet compared to sham control (ΔEF; 15.60±0.44%, 15.24±0.62% and 3.53±%0.18; p&lt;0.05). Conclusions: Although the functional recovery was comparable between ADSC sheet transplantation and suspended ADSC injection, ADSC sheet transplantation improved the cellular engraftment, paracrine effect of growth factor and cytokine secretion, and in-vivo neovascularization compared to suspended ADSC injection.
Risk Factors for Inhibitor Development in Mild and Moderate Hemophilia A: A Case-Control Study.
Authors: Christine L Kempton, J. Michael Soucie, Connie H. Miller, Craig Hooper, Miguel A. Escobar, Mark T. Reding, Alice J. Cohen, Nigel S. Key, Arthur R. Thompson, Marilyn J. Manco-Johnson, Thomas C. Abshire
Journal: Blood (2009)
Association of KRAS G12D mutation with outcome in patients with pancreatic cancer after surgery.
Authors: Yo Mikayama, Soichiro Morinaga, Takuo Watanabe, Masakatsu Numata, Hiroshi Tamagawa, Naoto Yamamoto, Manabu Shiozawa, Makoto Akaike, Kameda Yoichi, Shoichi Matsukuma, Yohei Miyagi
Journal: Journal of Clinical Oncology (2012)

221 Background: The frequency of KRAS gene mutations in pancreatic adenocarcinoma is high and most mutations occur in codon 12 and 13. However, the association of KRAS mutation status with clinical outcome of pancreatic cancer patients after surgery is not clearly understood. The aim of present study was to clarify whether presence of mutation in KRAS is of prognostic significance, and to determine whether the different type of KRAS mutation have different impact on clinical outcome in pancreatic cancer. Methods: A total of 62 pancreatic adenocarcinoma tissues from patients underwent curative surgery were analyzed for KRAS mutation. DNA was extracted from the tissue microarray. The domain containing the KRAS gene codons 12 and 13 was amplified by PCR, and KRAS mutation was detected by loop hybrid mobility shift assay (LH-MSA). Results: KRAS mutation was detected in 41 of 62 tumors (66.1%). Mutations of KRAS codon 12 and codon 13 were detected in 37 of 62 tumors (59.7%) and in 4 of 62 tumors (6.5%), respectively. G12D mutation were detected in 35.5% (22/62) and G12V mutation in 19.4% (12/62) of all. The patients with KRAS mutations had a significantly shorter overall survival (OS) (log rank, p=0.0375) and disease free survival (DFS) (p=0.0175). When the type of mutation were evaluated, G12D mutation was significantly associated with both shorter OS (p=0.0410) and DFS (p=0.0214), whereas G12V mutation was associated with neither OS (p=0.6727) nor DFS (p=0.9854). Conclusions: The presence of KRAS mutation was significantly associated with poor outcome of pancreatic cancer patients after surgery. A specific mutation G12D demonstrated significant association with shorter OS and DFS in pancreatic cancer. The different type of KRAS mutation might have different impact on clinical outcome in pancreatic cancer.