tbuckley/cabot-search huggingface dataset:
Impact in prognosis of residual masses in germ cell tumors.
Authors: Elena Almagro, David Perez, Judit Rubio, Fernando Franco, Magda Palka, Virginia Calvo, Antonio Sánchez, Blanca Cantos, Joaquin Carballido, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2014)

e15617 Background: Residual masses (RM) after treatment with orchiectomy and chemotherapy in patients with germ cell tumors (GCT) may be positive for tumoral cells, necrosis or teratoma and might be implicated in the prognosis of the disease. Methods: We analyzed retrospectively 161 male patients diagnosed of GCT treated between 1974 and 2012 in our hospital with a median follow up of 8.1 years. We compared the evolution of patients with RM with those without. Results: 159 had testicular and 2 extragonadal tumors.41.5% were seminomas and 59.5% non seminomatous.16% of patients diagnosed at stage I had RM, 15% in stage II, whereas 50% in III and 46% in IV (p<0,001). BEP (Cisplatin, etoposide, bleomicine) was the most frecuent chemotherapy scheme used. 89.4% had complete responses, 7.5% parcial responses with negative tumoral markers and 1.9%. with positive markers. 27 (16.8%) of the 161 had RM detected in computed tomography: In 22 were resected, in 5 watchful waiting was decided. In 40% the histology was malignant tumor (MT) , in 32% teratoma, in 27% necrosis or other findings. No histological differences (linfovascular, rete testis or albugineal invasion) were found in those with MT (p=0.13). The finding of teratoma in primary tumor (PT) was not associated with the presence of RM (p=0.31). Median time to diagnosis of PT in the group without RM was 1.2 months, and in the RM group 2.1. (p=0.04). Intermediate or bad prognosis (GCT risk classification), was associated to the presence of RM (55% vs 11.3%, p<0.001). In the group without RM, 27 (20.3%) relapsed whereas 13 (48.1%) did it in the RM group (p=0.001). Progression free survival (PFS) without and with RM after two and ten years was 83% and 57% and 77% and 33% respectively p<0.001 HR:3.1 (CI95% 1.7-5.6). Ten-year overall survival (OS) was 92% and 81% respectively p=0.07 HR:2.5 (CI95% 0.9-6.9). Conclusions: 40% of RM were malignant tumors but we did not find any histological marker that may predict this. Bad or intermediate prognosis and advanced stages as well as elapsed time to diagnosis of PT were associated with the presence of RM. These patients had a raised risk of relapse and a lower rate of PFS but no differences were found in OS. In this serie, the finding of teratoma in primary tumor was not a predictor of residual masses.
Drug-induced apoptosis in mesothelioma cells from chemotherapy-naive versus patients receiving prior chemotherapy.
Authors: Julian R. Molina, Cary A. Presant, Allan Hallquist, Mathieu Perree, James Rutledge, Dennis A. Wigle
Journal: Journal of Clinical Oncology (2014)

e18546 Background: We have previously shown that drug-induced apoptosis (the MiCK assay) can be successfully performed in mesothelioma cells. We studied differences in drug-induced apoptosis between cells from chemo naïve patients (Group 1) compared to patients receiving prior chemotherapy (Group 2). Methods: Tumors from mesothelioma patients were submitted as previously described (Cancer Res 2012; 72: 3901). Cells were purified, put into short-term culture with chemo drugs for 48 hours, and drug-induced apoptosis measured optically using light-scattering. Results from Group 1 were compared to Group 2. Results: 9 Meso specimens were obtained from six patients in Group 1 and 3 patients in Group 2. Prior chemotherapy regimens included cisplatin+pemetrexed, carboplatin+pemetrexed, gemcitabine, vinorelbine, pazopanib, and an experimental vaccine. The mean number of drugs tested was 20 in Group 1 and 31 in Group 2. Mean apoptosis KU values in Group 1 were 1.4 +/- 1.28 KU, and 1.7 +/- 1.11 KU in Group 2 (p=0.57). Percent sensitive drugs were 55% in Group 1 and 66% in Group 2. The most active regimens in Group 1 were dactinomycin, vinorelbine, pemetrexate + doxorubicin and cyclophosphamide associated with KU values of 4.2 to 4.7 KU. The drugs associated with best drug-induced apoptosis in Group 2 were epirubicin, and pemetrexate + doxorubicin (4.9 to 5 KU). Drugs with unexpected apoptotic activity included cyclophosphamide, ifosfamide, certain unusual pemetrexate combinations, and bortezomib amongst others. Conclusions: The MiCK drug-induced apoptosis assay can be performed in mesothelioma. Unexpectedly, there is no difference between sensitivity of cells from chemo naïve mesothelioma patients versus progressing patients, suggesting therapeutic opportunities for individualized treatment regimens. Adaptive trials may be required to show the utility of this approach.
Programmed death-1 (PD-1) and EBV-encoded RNA (EBER) expression in Hodgkin lymphoma.
Authors: Semra Paydas, Emine Bagir, Melek Ergin, Berna Bozkurt Duman, Vehbi Ercolak
Journal: Journal of Clinical Oncology (2014)

e19514 Background: PD1 and PD-L1 are new targets in cancer immunotherapy. PD1 protein is an immune check-point expressed in many tumours in response to inflammation and it has two ligands, PD-L1 and PD-L2. EBV is present in malignant Hodgkin/Reed–Sternberg (HRS) cells in approximately 40-50% of Hodgkin lymphoma (HL). The aim of this study is to evaluate the association between PD-1 expression and EBV encoded RNA (EBER). Methods: Formalin-fixed, paraffin-embedded tissue samples from 87 cases with HL were analysed in this study. Immunohistochemical staining was performed on 5-μm sections cut from tissue using antibody to PD-1 (MRQ-22, Ventana). The visualization system used was the BenchMark XT (Ventana) with heat-induced epitope retrieval (CC1 solution, Ventana) and the iView DAB detection kit (Ventana). Chromogenic in situ hybridization for EBER was performed using fluorescein-labeled oligonucleotide probes (INFORM EBER Probe, Ventana). The visualization system used was the BenchMark XT with enzymatic digestion (ISH Protease 2, Ventana) and the iViewBlue detection kit (Ventana). Cases stained with anti-PD1 were scored according to intensity of cytoplasmic and/or membraneous positivity as follows; 0 (no staining), 1+ (weak or equivocal staining), 2+ (moderate staining), or 3+ (strong staining). Tumor cells, HRS cells and peritumoral microenvironment were evaluated separately. Tumor positivity was considered when more than 5% tumor population was stained. Microenvironement was considered positive when more than 20% of all cell population was stained. HRS cells were evaluated as positive or negative, regardless of intensity and rate. EBER was considered as positive in case of dark-blue nuclear staining. Results: PD-1 expression was found in 17 cases and EBER was found in 40 cases. PD-1 expression was detected in 9 cases with EBER expression (9/40) while in 8 cases without EBER expression (8/47) Conclusions: There was no association between PD-1 and EBER expression in HL. In the next step we planned to study PDL-1 expression in these cases
RUNX1 Deficiency Cooperates with SRSF2 Mutation to Further Disrupt RNA Splicing and Exacerbate Myelodysplastic Syndromes in Mouse Models
Authors: Yi-Jou Huang, Ming Yan, Jia-Yu Chen, Liang Chen, Eunhee Kim, Takahiro Shima, Amanda G Davis, Sayuri Miyauchi, Samuel A Stoner, Xiang-Dong Fu, Omar I Abdel-Wahab, Dong-Er Zhang
Journal: Blood (2018)
Durability of Responses on Continuous Therapy and Following Drug Cessation in Deep Responders with Venetoclax and Rituximab
Authors: Danielle M. Brander, John F. Seymour, Shuo Ma, Mary Ann Anderson, Michael Y. Choi, Thomas J. Kipps, Kathryn Humphrey, Abdullah Masud, Ruby Nandam, Su Young Kim, Maria E. Verdugo, Andrew W. Roberts
Journal: Blood (2018)
Early Progression As a Predictor of Survival in Marginal Zone Lymphomas: An Analysis from the Prospective International NF10 Study By Fondazione Italiana Linfomi
Authors: Stefano Luminari, Luigi Marcheselli, Irene Defrancesco, Sara Rattotti, Marina Cesaretti, Marco Frigeni, Roberta Sciarra, Federica Cavallo, Marina Deodato, Maria Giuseppina Cabras, Michele Merli, Angela Ferrari, Francesca Re, Michele Spina, Emanuele Cencini, Ombretta Annibali, Alessandro Pulsoni, Marcia Torresan Delamain, Donato Mannina, Gianluca Gaidano, Caterina Stelitano, Daris Ferrari, Carlo Visco, Francesco Angrilli, Vittoria Tarantino, Luca Arcaini
Journal: Blood (2018)
Loss-of-function mutations in PTPRJ cause a new form of inherited thrombocytopenia
Authors: Caterina Marconi, Christian A. Di Buduo, Kellie LeVine, Serena Barozzi, Michela Faleschini, Valeria Bozzi, Flavia Palombo, Spencer McKinstry, Giuseppe Lassandro, Paola Giordano, Patrizia Noris, Carlo L. Balduini, Anna Savoia, Alessandra Balduini, Tommaso Pippucci, Marco Seri, Nicholas Katsanis, Alessandro Pecci
Journal: Blood (2018)
The study of chemotherapeutic substances and combination of melatonin and methotrexate on the cellular culture of prostate cancer and clinical experience.
Authors: Alexandre Tavartkiladze
Journal: Journal of Clinical Oncology (2014)

e22036 Background: Tumor chemosensitivity assay defined by an international group,is an ex vivo means of determining the cytotoxic potential of chemotherapeutic agents on malignant cells isolated from individual fresh cancer tissues. Some recent studies have found that people who work night shifts may be at increased risk for cancer because they have low level melatonin in plasma. Methods: Succession of our research is following: We isolated the malignant cells using from 25ml of whole blood of the patient with prostate Cancer (Stage IV G3). By Oncoquick with a membrane that isolates malignant cells from normal cells after centrifugation and positive selection using epithelial membrane marker Ep-CAM and negative selection using anti-CD45 particles Then we developed cell cultures in a fetal calf serum media and at the same time we developed colony cultures in soft agar. In each culture of the well plate we added a chemotherapeutic substance that is used in clinical application and distinc dose of Combination Melatonin and Methotrexate . Then we developed those cultures and we harvested a sample every 24 hours for 6 days and made the following assays. There was made an isolation of the genomic DNA and mRNA and also the genes many of the oncogenes.The above conclusions were also confirmed by the cell cultures of the tumor and in the diagrams there is a development curve for each category of cytostatics. Results: In this case Melatonin has very good citostatic effect on the prostate cancer cell culture with Methotexate. Conclusions: 1.The specific tumor appears to have resisting populations because of the MDR1 overexpression that can be reversed by the use of verapamil combined with disulfiram. 2.The neoplasmatic cells have the great sensitivity in the alkyliating agent Liposomal Cisplatin and Mitomycin, in the inhibitor of topoisomerase I irinotecan (CPT11); 3. The neoplasmatic cells have the great greatest sensitivity on the Melatonin and Methotrexate combination that confirmed by clinical results of the treatment this patient.
Tumor heterogeneity on a protein level in endometrial cancer.
Authors: Anna Maria Supernat, Sylwia Lapinska-Szumczyk, Hanna Majewska, Jacek Gulczynski, Wojciech Biernat, Dariusz Wydra, Anna Joanna Zaczek
Journal: Journal of Clinical Oncology (2014)

e16539 Background: Endometrial cancer (EC) is the most frequent malignancy of the female genital tract, with approximately 88,068 cases registered each year in the European Union. Discoveries of recent years have pointed to heterogeneous tumor composition. Intratumor heterogeneity may facilitate tumor adaptation leading to therapeutic failure through Darwinian selection. Heterogeneity has been detected in all studied cancers and is associated with more aggressive tumor behaviour and worse prognosis. Data concerning tumor heterogeneity in EC are scarce. The aim of the study was to examine intratumor heterogeneity on a protein level and compare it with clinicopathological data and survival. Methods: The study encompassed 364 formalin-fixed paraffin-embedded primary tumor samples retrospectively collected. Protein expression of ESR1, PGR, ERBB4, PIK3CA, pAKT1, MYC, TOP2A, CDKN2A, RAD21 and RUNX1 was examined by immunohistochemistry. Four 1.5 mm-diameter cores from each tumor were obtained from the most representative areas. Basing on the distribution of the results obtained from at least 3 cores per patient, cut-off point determination of the tumor heterogeneity was performed individually for each protein. Final results were subject to hierarchical clustering. Results: Hierarchical clustering revealed two clusters, one highly heterogenous with 18/355 (5.1%) cases. Strong multi-protein heterogeneity correlated with higher stage of the disease (p=0.01), histology type II (p=0.007), higher grade (p=0.004) and the presence of metastases (p=0.01) as well as shorter overall survival (HR=2.70, 95%CI: 1.44-5.07, p=0.002). Conclusions: Tumor heterogenenity on the protein level is associated with more aggressive tumor behaviour and worse prognosis in endometrial cancer.
Clinical differences and prognostic factors in right and left colon cancer.
Authors: Luis F. Onate-Ocana, Leonora Beltran, Sagrario Gonzalez-Trejo, Jose F. Carrillo, Roberto Herrera-Goepfert, Doris Carmona-Herrera, Vincenzo Aiello-Crocifoglio, Dolores Gallardo-Rincon, Erika Ruiz Garcia
Journal: Journal of Clinical Oncology (2018)

846 Background: Clinical-Pathological and genomic differences between Right-colon cancer (RCC) and Left-colon cancer (LCC) have been reported, but there is not available information from Latin American countries. Methods: A retrospective cohort study was carried out in patients with RCC and LCC treated from January 1989 to December 2016, in a cancer referral center at Mexico City. Patients were assigned into groups according to the location of the neoplasm defined by colonoscopy. Comparison between groups was performed regarding demographic, clinical, histopathology or survival data, using the Student’s T or Squared chi tests, as appropriate. Multivariate analysis was performed employing the logistic regression model. Survival analysis was addressed using the Kaplan-Meier method, and results were compared using the Log rank test. Results: 1,619 patients were included in this analysis; 806 were women (49.8%) and 813 men (50.2%); mean age was 58.1 years old. RCC was registered in 871 cases (53.8%) and LCC in 748 (46.2%). RCC was significantly associated with low socioeconomic status, low body mass index (BMI), low hemoglobin, low serum albumin, and lower lymphocyte count than LCC. Distribution of TNM stages was similar between groups, as well as gender, age of presentation, comorbidities, surgical morbidity and mortality; 72.3% of RCC and 83.2% of LCC were well or moderately differentiated ( p&lt; 0.0001). Mean lymph node retrieval was 19.3 (SD 14.6) for RCC and 15.7 (SD 13.1) for LCC ( p&lt; 0.0001). Mean metastatic lymph node ratio was 0.19 for RCC and 0.21 for LCC ( p= 0.54). Median Overall survival (OS) was 5.55 years (95% CI 4.3–6.8) for RCC, and 3.28 years (95% CI 2.1–4.45) for LCC ( p= 0.052). Conclusions: Striking differences between RCC and LCC were found, mainly represented by anemia and immunonutritional variables. Moreover, OS is substantially better for RCC.
A population-based analysis of patterns of care in stage I testicular seminoma: Updated results from the California Cancer Registry.
Authors: Stanley A Yap, Lindsay M Yuh, Rosemary Donaldson Cress, Rebecca Rankin Wagenaar, Marc A. Dall'Era, Christopher P. Evans, Primo Lara
Journal: Journal of Clinical Oncology (2014)

e15533 Background: Recent data have shown the feasibility of surveillance strategies and adjuvant chemotherapy, as well as adjuvant radiotherapy, in the management of stage I testicular seminoma. However, few studies have assessed the impact of these data on population-level practice patterns. In this study, we assess shifting practice patterns across a 20 year timespan in the management of stage I seminoma. Methods: Using the California Cancer Registry, we reviewed all patients diagnosed with stage I seminoma in California between 1988 and 2010. We determined whether primary treatment consisted of radiotherapy, chemotherapy, or surveillance. Overall rates of the various treatments were assessed across the study period. Other analyzed variables included patient age, socioeconomic status, race, and year of diagnosis. Predictors of treatment selection were assessed using logistic regression analysis. Results: A total of7,235 patients with stage I seminoma were identified. The most common primary treatment was radiotherapy (62%), followed by surveillance (29%) and chemotherapy (6.5%). Significant changes in the rate of various treatment strategies were noted across the study period (p<0.01). Rates of surveillance increased from 23% prior to 2000 to 51% in 2010. Similarly, rates of chemotherapy increased from 3.6% prior to 2000 to 20% in 2010. Conversely, rates of radiotherapy decreased from 73% prior to 2000 to 30% in 2010. Significant predictors of undergoing surveillance on multivariable analysis included diagnosis after 2001 (OR 1.41, CI 1.21-1.65), lower socioeconomic status (OR 1.58, CI 1.32-1.90), and age at diagnosis >60 (OR 1.58, CI 1.19-2.09). With a median follow-up of 96 months, 5-year overall survival (OS) rate among those undergoing radiotherapy, chemotherapy, or surveillance was 98%, 95%, and 96% respectively. Conclusions: In this large registry analysis, we found that treatment patterns in the management of stage I seminoma have shifted with active surveillance now the dominant management strategy. This perhaps reflects temporal changes in the perception of differential morbidity risk amongst adjuvant therapy options.
Abstract 19439: Melatonin Blunts Pressure-overload Left Ventricular Hypertrophy and Improves Cardiac Performance in Pathologic and PPhysiologic Cardiac Hypertrophy
Authors: Joost Offerhaus, Dong Lee, Djahida Bedja, Oscar Cingolani
Journal: Circulation (2015)

Introduction: Reactive oxygen species (ROS) has been established as key mediators in cardiac hypertrophy and function through activation of redox-sensitive kinases, by stimulating NADPH oxidase. Melatonin has been described as having potent antioxidant properties in different tissues. Hypothesis: The hormone melatonin, would prevent pressure-overload (pathologic) hypertrophy, Methods: Mice (C57Bl6) were subjected to transverse aortic constriction (TAC), and treated with melatonin (MEL, 10 mg/Kg/day) in water (“TAC+MEL”) or placebo (TAC). A second group underwent intense treadmill exercise for 8 weeks and also received melatonin (EX-MEL) or water (EX). A sham operated group served as control (“sham”). After 7 weeks of TAC and 8 weeks of exercise, cardiac function was assessed by echocardiography and pressure –volumetric analysis. Cardiac ROS activity (TBARS, NRF2, Keap-1) was determined. Results: TAC promoted LVH in mice (LVMI: 6.38±0.38 mg/mm tibia length (sham), 8.11±0.63 (TAC) which was blunted by melatonin (LVMI: 6.34±0.31 (TAC+MEL) mg/mm, P&lt;0.05). Increased LVH was associated with decreased endocardial shortening measured by echocardiography, from 61±2 (sham) to 54±1.8 % (TAC + placebo), P &lt;0.05. This decrease in fractional shortening was less pronounced in the TAC+ MEL group (58±2.9%) as well as in PV loop analysis. The antioxidant action of MEL was evidenced by the decrease in myocardial lipid peroxidation (TBARS) from 0.35±0.02 (TAC) to 0.25±0.02 (TAC+MEL) nmol/mg of protein, P&lt;0.05. Adult mice isolated myocyte studies revealed that Ang 2 (20nM) increased sarcomere shortening and calcium transient, both of which were blunted when cells were pre-incubated with melatonin (p&lt; 0.005, Ang2 vs MEL + Ang2). In the exercise group, melatonin had only a small, non-significant reduction in LVMI, but a marked improvement in cardiac performance (PV loop analysis). Conclusion: Melatonin prevents pressure-overload LVH and improves contractility due to its antioxidant action. In physiologic LVH (exercise), melatonin does not affect hypertrophy, but exerts a positive effect on cardiac performance. These effects seem to be, at least in part, mediated through melatonin interfering with the Keap-1- Nrf2 antioxidant pathway.
Clinical outcome and prognosis of metastatic colorectal cancer (mCRC) patients (pts) on phase 1 trials: A single institution experience from 1999 to 2016.
Authors: Audrey E. Kam, Gopichand Pendurti, Umang H. Shah, Mohammad Haroon Ghalib, Imran Chaudhary, Sengottuvel Viswanathan, Ioannis Mantzaris, Sanjay Goel
Journal: Journal of Clinical Oncology (2018)

828 Background: Pts with mCRC who progress on all standard therapies have a poor prognosis and limited therapy options. Phase 1 trials represent a valuable treatment option. Herein we report the characteristics and outcomes of mCRC patients treated at our institution. Methods: We reviewed records of pts with mCRC enrolled on phase I trials at our institution from January 1999 to December 2016. Treatment-related response, toxicity, and deaths were recorded. Prognostic factors for overall survival (OS) were calculated using univariate (UVA) and multivariable Cox PH analysis (MVA). Results: We observed 187 enrollments with 152 unique patients accrued on 37 phase I trials. Median age was 59 years (range 29-83) and median number of prior therapies was 3 (range 0-8). 144 patients were evaluable for response. The clinical benefit rate (SD+response, CBR) was 33.2% and the ORR was 4.3%. Grade 3/4 non-hematological and hematological AE were seen in 25.5% and 17.3% of patients, respectively. Treatment-related mortality was 0.5%. Median PFS was 1.7 mos and OS was 8.2 mos. In UVA, the following variables predicted a shorter OS: age (p = 0.049); PS &gt; 1 (p &lt; 0.01); sites of metastases &gt; 2 (p = 0.04); LDH &gt; ULN (p &lt; 0.001); albumin &lt; 3.5 (p &lt; 0.001); direct bilirubin &gt; ULN (p = 0.02); WBC &gt; 5.2 (p = 0.001); anemia (p = 0.046). In MVA, age &gt; 60 (HR 1.63, p &lt; 0.004), albumin &lt; 3.5 (HR 3.69, p &lt; 0.001), direct bilirubin &gt; ULN (HR1.69, p &lt; 0.01), and WBC &gt; 5.2 (HR 1.97, p &lt; 0.001) were negative prognostic factors for OS, adjusted for race and sex. A risk score based on MVA revealed that patients with a score of 0-1 had an improved OS (12.5mos) compared to a score of 2 (9.1mos, p-value &lt; 0.005) and 3 (3.2 mos, p-value &lt; 0.001). Conclusions: Patients with mCRC enrolled on phase 1 trials had a CBR of 33.2% and median OS of 8.2 mos, which exceeds third line therapies including regorafenib and trifluridine/tipiracil. Negative prognostic factors for OS were: age &gt; 60, albumin &lt; 3.5, direct bilirubin &gt; ULN, and WBC &gt; 5.2. A risk score based on these parameters showed that patients with a higher score had a significantly shorter OS, which may be useful in selecting patients for phase 1 trials.