tbuckley/cabot-search huggingface dataset:
Immunophenotypic profiles of plasma cells and tumor burden in patients with smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS).
Authors: Azam Ghafoor, Katherine R. Calvo, Meghan Corrigan-Cummins, Olga Simakova, Rene Costello, Constance Yuan, Maryalice Stetler-Stevenson, Neha Korde, Mark J. Roschewski, Ola Landgren, Irina Maric
Journal: Journal of Clinical Oncology (2014)

e19589 Background: Classification of MGUS and SMM is based on estimates of plasma cell (PC) burden in bone marrow (BM). This study assessed the best method for the estimation of PC burden in BM and whether differential immunophenotype of PCs correlates with PC burden in MGUS and SMM. Methods: BM biopsies and aspirates were evaluated from patients enrolled in the NIH Natural History Study of MGUS/SMM (n= 94 patients) for the following: PC quantification and immunohistochemical (IHC) expression of CD138, CD56, Cyclin D1, CD117. Results: 55/94 (59%) patients were diagnosed with SMM and 41% (39/94) with MGUS. The percent of PCs estimated on BM core biopsies using CD138 IHC staining yielded on average 57% greater PC burden compared to aspirate differentials (p<.0001). Immunophenotypic expression patterns of different markers were then evaluated with respect to pre-defined plasma cell groups (<10%, 10-19%, and >=20% PCs). Expression profiles for each individual marker demonstrated increase in total composite expression as a function of increasing percentage of PCs (p value =.002). CD56 had the highest coefficient of determination in regression analysis, R²=0.9998. Further, co-expression profiles demonstrated that the set of triple positive expression (CD56+/Cyclin D1+/CD117+) values increased nearly linearly as a function of increasing percentage of PCs (p=0.02). Regression analysis demonstrated a coefficient of determination R²=0.9995. Conversely, PCs triple negative for CD56-/Cyclin D1-/CD117- decreased linearly as a function of increasing percentage of plasma cell groups with coefficient of determination (R²) =0.9856, (P-value =.0006). Conclusions: Plasma cell estimates using biopsy CD138 IHC showed 2-fold difference in the quantification of PC burden compared to aspirate differentials. The presence or lack of co-expression of specific markers (CD56, CyclinD1, CD117) on CD138 positive PCs yielded statistically significant predictors of tumor burden within BMs of SMM/MGUS patients. We conclude that the method used to determine PC burden in BM biopsies has direct implications for diagnosis and prognosis.
Relations of carcinoembryonic antigen (CEA) staining of cancer tissue and serum CEA levels to histologic response in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiotherapy (nCRT).
Authors: Gota Saito, Sotaro Sadahiro, Hiroshi Miyakita, Kazutake Okada, Akira Tanaka, Toshiyuki Suzuki
Journal: Journal of Clinical Oncology (2018)

790 Background: Neoadjuvant chemoradiotherapy (nCRT) is a standard of care for LARC. The serum CEA level is a predictor of the response to nCRT; however, the relation between CEA production immunohistochemically evaluated in cancer tissue and treatment response remains unclear. Methods: The study group comprised 145 patients with clinical Stage II/III rectal cancer who received nCRT followed by surgery from 2005 through 2013. The radiation dose was 40 to 45 Gy. UFT- or S-1-based chemotherapy was given concurrently. Surgery was performed 6 to 8 weeks after the completion of radiotherapy. Immunohistological CEA staining patterns in biopsy tissue obtained before nCRT were evaluated. Specimens in which the luminal cell membrane or the cytoplasm was strongly stained were defined as staining positive. The histologic response was evaluated on the basis of the pathological complete response (ypCR) rate, T downstaging, tumor regression grade (TRG), and tumor shrinkage rate on MRI. Results: CEA staining in biopsy specimens and serum CEA levels were both negative in 17 patients (11.7%) and both positive in 72 patients (49.7%). There was no relation between the groups (p = 0.174). In patients with negative CEA staining, the rates of ypCR, T downstaging, marked regression, and mean tumor shrinkage were 24.3%, 51.4%, 45.9%, and 72.3%, respectively. In patients with positive CEA staining, these rates were 11.1%, 48.1%, 37.0%, and 72.8%, respectively. CEA staining of cancer tissue was not significantly related to the ypCR rate, T downstaging, a marked regression rate, or the tumor shrinkage rate on MRI (p = 0.060, p = 0.849, p = 0.436, and p = 0.874, respectively). Patients with negative serum CEA levels before nCRT had significantly higher rates of ypCR, T downstaging, marked regression, and tumor shrinkage on MRI than did patients with positive serum CEA levels (p = 0.014, p = 0.006, p = 0.002, and p = 0.014, respectively). Conclusions: Serum CEA levels before nCRT were a significant predictor of the histologic response to nCRT; in contrast, tissue CEA staining before nCRT was unrelated to the histologic response to nCRT.
Using an EMP2 IgG1 antibody as a novel therapy for therapy-resistant breast cancers.
Authors: Madhuri Wadehra, Meagan Kiyohara, Christen Dillard, Neil A. O'Brien
Journal: Journal of Clinical Oncology (2014)

e22161 Background: Breast cancer is a heterogeneous disease with several subtypes which dictate which course of treatment each patient will receive. However, resistance remains a significant challenge. Nonspecific cytotoxic agents remain the backbone of current therapy, but they are limited by a narrow therapeutic index, significant toxicities and frequently acquired resistance. For example, in triple negative breast cancer (TNBC), an aggressive histological subtype with limited treatment options and very poor prognosis, resistance to current standard therapies such as taxanes severely limits the available options for previously treated patients. This problem also occurs with targeted therapies. Trastuzumab is the standard of care for HER2+ tumors. However, de novo or acquired Trastuzumab resistance isa major limitation of its clinical efficacy. Thus, there remains an urgent unmet need for improved targeted agents for this patient population. Methods: To this end, we define another marker epithelial membrane protein-2 (EMP2) as a novel target for Trastuzumab and taxane resistant tumors. EMP2 expression was determined using standard immunohistochemistry. We have recently developed a novel IgG1 monoclonal antibody to EMP2 termed PG-101. Acquired Trastuzumab and docetaxel resistant tumors were treated with PG-101 using human xenograft models. Results: EMP2 is an oncogenic protein whose expression has been shown to correlate with tumor progression as well as the formation of breast cancer stem cells. In this study, we present evidence that EMP2 is highly expressed in acquired resistant tumor cells both in culture as well as in patient samples. We also tested the efficacy of PG-101 in combination with docetaxel, and we have evidence that the combination significantly improves tumor-free survival. Moreover, preliminary data also strongly suggests that PG-101 can be used as an effective therapy for docetaxel and Trastuzumab resistant tumors whereby PG-101 reduced tumor load in both models in vivo. Conclusions: Given that EMP2 is also overexpressed in endometrial and ovarian cancers, our data collectively suggest that PG-101 therapy has the potential to revolutionize the outcomes for women with cancer.
Patterns of practice in the management of advanced urothelial cancer (UC) in Greece: A retrospective analysis by the hellenic GU Cancer Group (HGUCG).
Authors: Stavros Peroukidis, Maria Likka, Charalampos Andreadis, Vasiliki Bozionelou, Kimon Tzanis, Nikolaos Fragkiskos Pistamaltzian, Ioannis I. Varthalitis, Michalis Karamouzis, Georgia Milaki, Antonios Agorastos, Nikolaos Diamantis, Evangelos Lianos, Nikolaos K. Kentepozidis, Nikos Fytrakis, Iliada Bompolaki, Nikolaos E. M. Androulakis, Ilias Athanasiadis, Haralabos Kalofonos, Dimitrios Mavroudis, Aristotelis Bamias
Journal: Journal of Clinical Oncology (2014)

e15514 Background: Cisplatin based chemotherapy is the tretment of choice in metastatic UC. Worldwide about 50% of patients do not receive this treatment. Available data on this issue are mising for the Greek population. Our purpose was to record everyday clinical practice in UC in our country and to evaluate it in accordance with the existing international guidelines. Methods: Patients with metastatic UC were included in the analysis. Relevant data were collected using an anonymous questionnaire, which focused on fitness-for-cisplatin and 1stline chemotherapy administered. Fitness-for-cisplatin was assessed by recently established criteria (Galsky et al, J Clin Oncol 2011). Results: A total of 253 patients with metastatic urothelial cancer treated with 1st line chemotherapy from 2011-2013 at 8 Greek Oncology Centers have been included in this analysis. 125/253 (50%) patients (M:108, F:17, median age: 74) did not receive cisplatin. All but 3 received a carboplatin/gemcitabine combination. These patients were further analysed for the reasons for not administering cisplatin and possible deviations from the established criteria. 94 patients (75%) had at least one criterion for unfitness-for-cisplatin: CrCl≤60 ml/min: 73 (77%), ECOG PS≥2: 26 (27%), hearing impairment: 8 (8%), neuropathy: 1 (1%), cardiac failure NYHAA III-IV: 6 (6%). The remaining 31 patients (25%) did not fulfill any criterion for unfitness-for-cisplatin. The main reasons for these deviations were comorbidities (17/31 [55%]) and advanced age (17/31 [55%]), while age was the only prohibiting reason for 10 patients (32%). The median age of these 10 pts was 78 years. Deviation from the criteria of fitness-for-cisplatin was independent of gender or treating center. Conclusions: In line with international data, about 50% of Greek patients with metastatic urothelial cancer do not receive cisplatin based chemotherapy. 25% of those did not receive cisplatin although they were suitable for such treatment. Age per se is the main reason for this deviation and represents a promising target to improve the adherence to international guidelines in respect to suitability for cisplatin.
Abstract 19119: Oxidative Damage in the Gastrocnemius Predicts Mortality Rates in Patients With Peripheral Artery Disease
Authors: Panagiotis Koutakis, Hernan Hernandez, Jonathan R Thompson, Evlampia Papoutsi, Holly K DeSpiegelaere, Dimitrios Miserlis, Gleb Haynatzki, Duy M Ha, Constance J Mietus, Julian Kyung-Soo Kim, Zhen Zhu, George P Casale, Iraklis I Pipinos
Journal: Circulation (2016)

Introduction: Patients with peripheral artery disease (PAD) experience advancing myopathy in their ischemic legs along with increased functional impairment and increased mortality rates. Myofiber oxidative damage is a central mechanism in the development of PAD myopathy and correlates with degree of functional impairment and decline. Hypothesis: This study evaluated the hypothesis that myofiber oxidative damage in gastrocnemius biopsies from patients with PAD predicts mortality rates. Methods: Oxidative damage was quantified as levels of protein carbonyl groups in the myofibers of gastrocnemius samples obtained from PAD patients. Carbonyl data were grouped into tertiles and the 5-year, all-cause mortality for each tertile was determined by Kaplan-Meier curves and compared by the Modified Peto test. A Cox-regression model was used to control for the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidi...
OP0170 Human il-38 reduces joint inflammation in a mouse model of gouty arthritis
Authors: D.M. De Graaf, F.L. Van de Veerdonk, E.Z. Eisenmesser, L.A.B. Joosten, C.A. Dinarello
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Interleukin-38 (IL-38) is the last member of the IL-1 family of cytokines to be fully investigated for its functions. IL-38 is proposed as an anti-inflammatory cytokine in various auto-inflammatory diseases, such as psoriasis and rheumatoid arthritis. For example, IL-38 knockout mice have exacerbated autoantibody-induced arthritis. Current understanding of the capacity of IL-38 in gout, a prototype IL-1β driven auto-inflammatory disease, is unknown. <h3>Objectives</h3> We hypothesised that <i>in vivo</i> treatment with human recombinant IL-38 results in a reduction in join inflammation in a mouse model of gouty arthritis. <h3>Methods</h3> We treated C57/Bl6 mice with 1 µg recombinant IL-38 (3–152 AA) intraperitoneally at 24, 12 and 2 hours before induction of gouty arthritis with intra-articular injection of albumin-opsonized monosodium urate crystals (300 µg) and palmitic acid (200 µM) in 10 µL PBS. Joint inflammation was scored after 4 hours. The synovial lining was cultured in RPMI for 2 hours to allow cytokines to be secreted, and cytokines in the synovium were extracted with Triton-X 100 to obtain total cytokines (membrane and intracellular). In the synovial culture fluid and extract, IL-1β, IL-6 and KC were measured by ELISA. Data <h3>Results</h3> Mice treated with recombinant IL-38 exhibited significantly reduced joint swelling and redness on a three-point macroscopic inflammation scale: Vehicle-treated 1.5±0.25 vs IL-38 Treated 0.75+0.25 (n=10, p&lt;0.0001, Mann Whitney-U test). The 2 hour synovial membrane culture fluid contained significantly lower levels of IL–1β (1207±480 vs 379±184 pg/mL, p&lt;0.05), IL-6 (10783±2490 vs 5321±2935 pg/mL, p&lt;0.05) and KC (4390±931 vs 1081±750 pg/mL, p&lt;0.05). In extract of the synovial membrane, there is a reduction in IL–1β (1505±397 vs 624±509 pg/mL, p&lt;0.05), IL-6 (11059±2299 vs 3597±2509 pg/mL, p&lt;0.01) and KC (1505±397 vs 624±509 pg/mL, p&lt;0.05). <h3>Conclusions</h3> Human recombinant IL-38 reduces swelling and redness of the joint, and pro-inflammatory cytokines secreted by and contained in the synovial membrane in a mouse model of gouty arthritis. These data reveal that recombinant IL-38 has therapeutic benefit in an IL–1β mediated model of inflammation. <h3>Disclosure of Interest</h3> None declared
Residential Lead-Hazard Interventions, Childhood Anxiety, and Cognitive Impairment
Authors: Consuelo M. Beck-Sagué, Tomás R. Guilarte
Journal: JAMA Pediatrics (2018)

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REGN5458, a Bispecific BCMAxCD3 T Cell Engaging Antibody, Demonstrates Robust In Vitro and In Vivo Anti-Tumor Efficacy in Multiple Myeloma Models, Comparable to That of BCMA CAR T Cells
Authors: David J Dilillo, Kara Olson, Katja Mohrs, T. Craig Meagher, Kevin Bray, Olga Sineshchekova, Thomas Startz, Marc Retter, Stephen Godin, Frank Delfino, John Lin, Eric Smith, Olin Gavin Thurston, Jessica R. Kirshner
Journal: Blood (2018)
Detection of <i>MDM2 </i>gene amplification in soft tissue sarcoma by FISH.
Authors: Hiroaki Kimura, Norio Yamamoto, Toshiharu Shirai, Hideji Nishida, Katsuhiro Hayashi, Akihiko Takeuchi, Yoshikazu Tanzawa, Kentaro Igarashi, Shingo Shimozaki, Takashi Kato, Yu Aoki, Takashi Higuchi, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2014)

10562 Background: The MDM2 (murine double minute-2) gene is an oncogene whose expression plays important roles in controlling the cell cycle and tumorigenesis. The MDM2 is located on chromosome 12, and has been reported to be amplified in a subset of malignant tumors. In this study, we examined soft tissue sarcomas (STS) specimens for MDM2 gene amplification by fluorescent in situ hybridization (FISH). Methods: 137 cases of formalin-fixed and paraffin-embedded specimens were used for this study. Surgical pathology reports, HE sections, and previous immunohistochemical slides were carefully reviewed. The pathological diagnoses were shown in the Table. The FISH probe for MDM2 was co-hybridized with CEP12 probe that is specific for chromosome 12. The average number of MDM2 and CEP12 ratio was calculated and a ratio>2.0 was considered amplified. Results: Of 137 STS, MDM2 amplification was detected in 33 cases (24%). Of the WDLS/ALT, 93% (26/28) showed amplification of MDM2. A total of 4 of 4 (100%) DDLS showed amplification of MDM2. Two of 10 MPNST and 1 of 7 myxofibrosarcoma also showed amplification of MDM2. Conclusions: WDLS/ATL are often difficult to distinguish morphologically from benign lipomatous tumors, while DDLS may be challenging to distinguish from other high-grade sarcomas, especially on needle biopsy specimens that lack areas of WDLS. With the increased use of small needle core biopsy in which only limited tissue is available for histologic evaluation, increased utilization of molecular studies to identify the characteristic molecular aberrations of WDLS and DDLS may prove useful in clinical practice. MDM2 amplification by FISH was a useful adjunct in the diagnostic approach for WDLS vs benignlipomatous tumors and DDLS vs pleomorphic or spindle cell sarcomas. Diagnosis FISH-positive Liposarcomas ALT/WDLS 28 26 MXLS 28 0 DDLS 4 4 MFH 19 0 Leiomyosarcoma 18 0 Synovial sarcoma 12 0 MPNST 10 2 Myxofibrosarcoma 7 1 Rhabdomyosarcoma 7 0 Low-grade fibromyxoid sarcoma 4 0 137 33 Abbreviations: ATL, atypical lipomatous tumor; WDLS, well-differentiated liposarcoma; DDLS, dedifferentiated liposarcomas; MFH, malignant fibrous histiocytoma; MPNST, malignant peripheral nerve sheath tumor.
Prognostic Impact of the Interaction between DNMT3A mutation and Internal Tandem Duplication of the FLT3 Gene (FLT3-ITD) in Patients with De Novo Mutated NPM1 (NPM1mut) acute Myeloid Leukemia
Authors: Guadalupe Oñate, Ana Garrido, Jordi Esteve, Rosa Coll, Montserrat Arnan Sangerman, Susana Vives, Antonia Sampol, Mar Tormo, Lourdes Escoda, Maria Paz Queipo De Llano, Antoni Garcia-Guiñon, Joan Bargay, Olga Salamero, Alba Aljarilla, Salut Brunet, Jorge Sierra, Josep Nomdedeu, Marta Pratcorona
Journal: Blood (2018)
Trends in the Risk of Second Primary Malignancies (SPMs) Among Survivors of Chronic Lymphocytic Leukemia(CLL)
Authors: Vivek Kumar, Sikander Ailawadhi, Leyla Bojanini, Aditya Mehta, Anshika Singh, Taimur Sher, Vivek Roy, Prakash Vishnu, Julian A Marin-Acevedo, Victoria R. Alegria, Aneel Paulus, Sonikpreet Aulakh, Madiha Iqbal, Rami Manochakian, Winston Tan, Asher A. Chanan-Khan, Meghna Ailawadhi
Journal: Blood (2018)
Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) for advanced nonseminomatous germ cell tumor (NSGCT): Correlation of teratoma in the primary tumor and RPLND histology.
Authors: Donato Callegaro Filho, Oren Smaletz, Taciana Sousa Mutao, Luiz Victor Maia Loureiro, Ricardo Silvestre e Silva Macarenco, Charles Rosenblatt, Wladimir Alfer Jr.
Journal: Journal of Clinical Oncology (2014)

e15537 Background: PC-RPLND plays an important role in the management of residual masses of advanced NSGCT of the testis. Teratomatous elements in the primary tumor is a risk factor for teratoma in the retroperitoneum, but there is still some controversies whether the absence of teratoma in the primary tumor does correlate with the absence of teratoma in the retroperitoneum, and if surgery is required in all patients with residual mass. Methods: A retrospective analysis of all patients with advanced NSGCT treated with 3-4 cycles of cisplatin based chemotherapy with residual masses (> 1.0 cm) and serum tumor markers normalization that underwent PC-RPLND at our institution between January 2003 and July 2013. Confidence intervals were built using a normal distribution and a binomial exact test. Results: We identified 12 male patients with primary NSGCT in the testis/retroperitoneum, Median age 27 y/o (range, 18-39) presenting with initial tumor staging II (9 pts) and III (3 pts). Teratoma was present in the primary tumor in 5 patients. Primary chemotherapy regimen was BEP in eleven patients and unknown in one. Two patients underwent conventional dose salvage chemotherapy before RPLND. The median size of retroperitoneal metastasis by computerized tomography was 2.75 cm (range, 1.1 – 16). Pathological findings yielded necrosis in 3/12 (25%, 95% CI 5%-49%) and teratoma in 9/12 (75%, 95% CI 50%-99%) patients. No patient with viable tumor cells in the residual masses was identified in this group (0%, 95% CI 0%-22%). Of the 7 patients without teratoma in the primary tumor, five had actually teratoma revealed in the retroperitoneal pathology (71%, 95% CI 38%-100%). The median follow-up is 12 months (range, 0-76) and all patients are currently NED. Conclusions: PC-RPLND remains a standard of care for all patients with > 1.0 cm residual mass. Lack of teratoma in the primary tumor does not predict the absence of teratoma in the retroperitoneum for men treated with chemotherapy for metastatic NSGCT.
Changes in Imaging Surveillance of Diffuse Large B-Cell Lymphoma Survivors after Publication of the American Society of Hematology Choosing Wisely® Recommendations
Authors: Urshila Durani, Dennis Asante, Herbert C Heien, Carrie A. Thompson, Thorvardur R. Halfdanarson, Prema Peethambaram, J. Fernando Quevedo, Jose C Villasboas, Ronald S. Go
Journal: Blood (2018)