tbuckley/cabot-search huggingface dataset:
Assessing clinical response in multiple myeloma (MM) patients treated with monoclonal antibodies (mAbs): Validation of a daratumumab IFE reflex assay (DIRA) to distinguish malignant M-protein from therapeutic antibody.
Authors: Christopher McCudden, Amy Axel, Dominique Slaets, Sandy Frans, Jaime Bald, Jordan Mark Schecter, Tahamtan Ahmadi, Torben Plesner, Kate Sasser
Journal: Journal of Clinical Oncology (2015)

8590 Background: Residual therapeutic mAbs can be detected by assays intended to monitor clonal myeloma protein (M-protein). Daratumumab, a human anti-CD38 IgG1k mAb in MM clinical trials, has been detected on serum protein electrophoresis (SPE) and immunofixation (IFE) gels, interfering with IMWG response criteria requiring negative SPE/IFE for CR/sCR. As new therapeutics emerge that induce very deep responses a method is needed to confirm CR/sCR. Validation and use in clinical studies of an assay that distinguishes daratumumab from M-protein is presented. Methods: Mouse anti-daratumumab antibody is used to shift daratumumab's IFE migration away from M-protein. Commercial and daratumumab-treated MM patient samples were evaluated to assess specificity, reproducibility and concordance. Detection of M-protein depletion by DIRA triggered additional clinical testing to confirm CR/sCR. Results: Daratumumab was identified on IFE in 10/10 samples when added to commercial MM serum in a 1:1 ratio with anti-daratumumab. Reproducibility was tested in 3 independent DIRA runs on 10 samples from daratumumab treated patients (16 mg/kg). 2 independent reviewers assessed daratumumab and M-protein levels and observed 100% concordance. Specificity was evaluated in commercial (n = 16) and daratumumab-treated patient samples (n = 36) by scoring whether the malignant M-protein was shifted with the anti-idiotype antibody. 94.4% (34/36) of samples had no shift in M-protein with anti-daratumumab. 33 daratumumab patient samples (from single-agent or combination studies) were DIRA tested and clinical responses assessed; 13 (39%) had no M-protein (DIRA -ve) and 10 were confirmed as CR. 20 patients had malignant M-protein remaining (DIRA +ve) and monitoring continued. Conclusions: DIRA, a robust and reproducible tool, determines if residual IgGk on IFE is caused by the mAb daratumumab or actual M-protein. DIRA results can trigger further assessments to confirm clinical CR. This first approach to distinguish therapeutic mAb from M-protein in MM will be needed for clinical research and eventually MM treatment.
Efficacy and safety of RAD001 in advanced biliary tract cancer (BTC) patients (pts) progressing after first-line chemotherapy: A phase II study.
Authors: R. Buzzoni, S. Pusceddu, M. Platania, G. Barone, M. Valente, L. Di Guardo, E. Bajetta
Journal: Journal of Clinical Oncology (2010)

e14500 Background: RAD001 (everolimus) is a derivate of rapamycin which acts as a signal transduction inhibitor. Its target is mTOR, a key protein kinase which regulates growth, proliferation and cell survival. Therapeutic effect of mTOR inhibitors on BTC has been evaluated in transgenic mouse models. RAD001 has recently been extensively evaluated in different cancer types. The aim of this study is to assess the disease control rate (DCR) defined as the proportion of patients with CR, PR or SD as a measure of the antitumor effect of RAD001 in cases with BTC progressing after first line chemotherapy. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), ECOG PS ≤ 2, adequate organ function and absence of clinically significant cardiovascular disease. It is planned to enroll a total of 37 pts, from 8 Centres. Patients receive oral RAD001 (10 mg daily dose) continuously from day 1 until progression or discontinuation for any cause. Radiological assessments are performed every 8 weeks. The data presented in the abstract refer subjects only from our Institution. Since February 2009, 18 pts (16 BTC; 2GBC) were enrolled and all are available for efficacy and safety. Median age was 60 years (range 42-75), male/female = 7/11, ECOG 0/1/2 = 7/8/3. Treatment related grade 3/4 toxicities included (number of pts): anemia (2), thrombocytopenia (4), transient SGPT/SGOT elevation (1), fatigue (2). No reactivation of HBV and HCV was observed during the treatment. The DCR was documented in 10 pts (55.5%):1 CR lasted for 9 months, 9 minor responses/SD with a median duration more than six months, and four cases are still in treatment. In 8 pts (44.5%) disease progressed. This preliminary analysis suggests that RAD001 can be safety administrated in chemotreated pts. The achievement of long lasting disease control and antitumor activity is encouraging, but more data needs to be further confirmed after the study is complete with a new trial employing RAD001 as front line therapy. Biological immunohistochemical expression of mTOR in pathological specimens is in progress. No significant financial relationships to disclose.
TMOD-07DIFFERENCES IN TUMOR GRAFT ACCEPTANCE OF 261 GLIOBLASTOMA MULTITFORME (GBM) CELL LINE BETWEEN WILD TYPE C57BL6, CD74 DEFICIENT, AND GAMMA DELTA TCR DEFICIENT MICE
Authors: Sanjib Mukherjee, Long Dao, Richard Tobin, Giuseppina Dusio, Ekokobe Fonkem, M. Karen Newell-Rogers
Journal: Neuro-Oncology (2015)

BACKGROUND AND SIGNIFICANCE: Glioblastoma Multiforme (GBM) is a deadly and highly aggressive brain tumor with grim prognosis. At present none of the treatment strategies extend the life of most patients beyond a year. A contribution from the immune system in the control and/or growth of tumors is currently under intense investigation. However, the strategies GBM cells use to hide from the immune system are poorly understood. EXPERIMENTAL APPROACH: To address this issue, we compared the tumor graft acceptance of the mouse GBM 261 neurosphere (mouse glioma cell line/derived from a tumor from a C57Bl6 strain background) into C57Bl6 mice with three genetic modifications (CD74, invariant chain deficient mice; gamma delta knockout mice; and control, wild type C57Bl6 mice). Neurospheres were made from 261 cells by plating 10^5 cells/mL in DMEM/F12 media supplemented with 20 ng/mL EGF and 10 ng/mL bFGF, 0.002% heparin and B27 supplement without retinol. Cells started showing neurosphere morphology at around 6 days. The 261 neurospheres were injected stereotactically in the caudate nucleus and mice were observed for 4-6 weeks after neurosphere injection. RESULTS: The data showed that the tumor acceptance in C57Bl6 mice was higher than acceptance in either CD74 deficient or Gamma Delta TCR deficient mice. In addition, C57Bl6 mice showed rapid tumor growth with robust neurological deficit as early as 4 weeks. No neurological deficit was observed in invariant chain deficient mice or gamma delta knockout mice. CONCLUSIONS: These data suggest a contribution from CD74 as well as gamma delta T cells in tumor graft acceptance. Further experiments are ongoing to determine the potential role of CD74 and/or gamma delta T cells in the progression of GBM.
Familial aggregation of alopecia areata
Authors: Bettina Blaumeiser, Ineke van der Goot, Rolf Fimmers, Sandra Hanneken, Sibylle Ritzmann, Katia Seymons, Regina C. Betz, Thomas Ruzicka, Thomas F. Wienker, Jozef De Weert, Julien Lambert, Roland Kruse, Markus M. Nöthen
Journal: Journal of the American Academy of Dermatology (2006)
Breast Cancer: are Employment and Therapy Compatible, and for Whom?
Authors: E. Antoine, G.M. Ganem, C. Touboul, H. Naman, N. Dohollou, T. Facchini, Y. Coscas, A. Lortholary, S. Catala, S. Jacquot, C. Lhomel, F. Eisinger
Journal: Annals of Oncology (2014)
Patterns of tumor response to trabectedin (ET743) in myxoid liposarcomas
Authors: F. Grosso, G. D. Demetri, J. Y. Blay, I. Judson, A. Le Cesne, C. Spreafico, J. Jimeno, S. Pilotti, M. D’Incalci, P. G. Casali
Journal: Journal of Clinical Oncology (2006)

9511 Background: Trabectedin (T) is a marine-derived agent found to be active in ovarian cancer and sarcomas. Among sarcomas, activity has been notable in leiomyosarcomas and liposarcomas. Since liposarcomas are a heterogeneous group, including well/de-differentiated, pleomorphic, and myxoid/round cell subtypes, we have noted particularly interesting patterns of responsiveness to T in myxoid liposarcomas, which are associated with t(12;16)(q13;p11) or t(12;22)(q13;q12) chromosomal translocations, resulting in CHOP-TLS or CHOP-EWS fusion products. Methods: 15 cases of myxoid liposarcomas treated with T at the Istituto Nazionale Tumori, Milan, were retrospectively reviewed. In most cases, T was given as a 24-hr continuous infusion every 21 days, at dose levels from 1.0 to 1.5 mg/sqm. 108 courses were delivered, with a median of 5 courses per patient (range 2–20). Observations made in this series were shared with five other institutions having treated myxoid liposarcoma cases with T, all of which also report a significant response rate, for a total of 44 pts. A centralized radiological review of all pts is ongoing. Results: In the Milan series, early tissue alterations in tumors were observed in 14 patients, mainly with a decrease in tumor density on CT scan and/or decrease in contrast enhancement on MRI. These changes were followed by tumor shrinkage amounting to a conventional PR/CR in 8 (pending final review), while 3 others have responses which continue to evolve. Progression followed treatment interruption in one patient, with a minor response occurring at treatment restart. Treatment is continuing in 12 pts (median duration of therapy in excess of 5 months). Further results of the central radiological review from all centres will be reported. Conclusions: Tumor response to T seen in myxoid liposarcoma appears to be marked by early radiological alterations in tumor tissue, often preceding tumor shrinkage, which may be delayed. A selective mechanism of action for this chromosomal translocation-related sarcoma is suggested, and is being actively investigated at the moment. [Table: see text]
Tumor control with PD-1 inhibition in a patient with concurrent metastatic melanoma and renal cell carcinoma
Authors: Melina E. Marmarelis, Meredith R. Davis, Nilay S. Sethi, Katherine M. Krajewksi, Rana R. McKay, Toni K. Choueiri, Patrick A. Ott
Journal: Journal for ImmunoTherapy of Cancer (2016)

Blockade of the immunological checkpoint programmed death 1 (PD-1) using monoclonal antibodies has shown robust anti-tumor activity across a broad range of solid and hematological malignancies including melanoma and renal cell carcinoma (RCC). Characteristic markers such as the presence of tumor infiltrating lymphocytes, PD-L1 status, and mutational load may be equally or even more important in predicting clinical benefit from PD-1 pathway blockade than tumor histology. This case of a patient with concurrent metastatic melanoma and metastatic RCC, both of which were controlled for more than a year after a single dose of the anti-PD-1 antibody pembrolizumab, illustrates the potential to simultaneously treat distinct immunogenic tumors with anti-PD-1 agents.
PD-1:PD-L1(B7-H1) pathway in adaptive resistance: A novel mechanism for tumor immune escape in human papillomavirus-related head and neck cancers.
Authors: Sofia Lyford-Pike, Shiwen Peng, Janis M. Taube, William H. Westra, Belinda Akpeng, Hao Wang, Charles G. Drake, Lieping Chen, Suzanne Louise Topalian, Drew M. Pardoll, Sara I Pai
Journal: Journal of Clinical Oncology (2012)

5506 Background: Human papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) are associated with a strong host immune response. Despite ample tumor infiltrating lymphocytes (TILs), the cancer is able to persist and grow. Here, we provide evidence for an adaptive immune resistance mechanism mediated through the PD-1:PD-L1 pathway. Methods: We evaluated the peripheral blood and tumor infiltrating lymphocytes for PD-1 expression using flow cytometry in HPV-HNSCC patients. We evaluted PD-L1 expression within the tumors using immunohistochemistry. We performed functional assays evaluating IFN-gamma secretion of PD-1+ and PD-1(-) CD8+ T cells isolated from the tumor microenvironment of PD-L1+ and PD-L1(-) HPV-related head and neck cancers. Results: We found the majority of CD8+ TILs in HPV-HNSCC express the PD-1 co-inhibitory receptor. We report a striking association between expression of its ligand PD-L1 on tumor cells and tumor associated macrophages, and the presence of TILs. Interestingly, membranous PD-L1 staining on tumor cells and CD68+ antigen presenting cells was geographically localized to the periphery of tumor nests and juxtaposed to fronts of infiltrating T cells. Functional assays demonstrated that PD-1-dependent T cell inhibition required expression of PD-L1 in the tumor microenvironment. Finally, we report localized expression of PD-L1 in the deep crypts of normal tonsils, the site of HPV infection and origin of HPV-HNSCC. Conclusions: Our findings support the role of the PD-1:PD-L1 interaction in creating an immune-privileged site for initial viral infection and subsequently adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC.
Why, When, and How to Prevent Hepatitis B Virus Reactivation in Cancer Patients Undergoing Chemotherapy
Authors: Bhumsuk Keam, Jeong-Hoon Lee, Seock-Ah Im, Jung-Hwan Yoon
Journal: Journal of the National Comprehensive Cancer Network (2011)

Hepatitis B virus (HBV) reactivation is a serious clinical problem in HBV carriers undergoing chemotherapy. The clinical course of HBV reactivation can be separated into 2 phases: 1) an increase in HBV replication and 2) hepatic injury. Patients with resolved HBV infections (negative for hepatitis B surface antigen [HBsAg], and positive for both hepatitis B core antibody [anti-HBc] and/or hepatitis B surface antibody) can experience HBV reactivation, and Western guidelines recommend that not only HBsAg but also anti-HBc be screened before initiation of chemotherapy or immunosuppressive therapy. Several meta-analyses have repeatedly confirmed the prophylactic role of lamivudine in preventing HBV reactivation. In conclusion, screening for HBV is required before chemotherapy, and prophylactic antiviral therapy can reduce not only the incidence of HBV reactivation but also HBV-related morbidity and mortality.
Case 23-1999
Authors: Robert N. Husson, Eugene J. Mark
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 10-month-old girl was admitted to the hospital because of fever and a rash.She had apparently been well until one month earlier, when she was examined because of fever and an erythematous rash suggestive of scarlet fever. A throat culture was negative. The rash improved after a 10-day course of amoxicillin. A diagnosis of roseola was made. A few days later, the skin on the arms and legs began to peel. Eleven days before admission, the patient's temperature rose to 40°C, and she became irritable, ate poorly, and had a nonproductive cough, coryza, swollen lips, and . . .
Streptozocin–Doxorubicin, Streptozocin–Fluorouracil, or Chlorozotocin in the Treatment of Advanced Islet-Cell Carcinoma
Authors: Charles G. Moertel, Myrto Lefkopoulo, Stuart Lipsitz, Richard G. Hahn, David Klaassen
Journal: New England Journal of Medicine (1992)

The combination of streptozocin and fluorouracil has become the standard therapy for advanced islet-cell carcinoma. However, doxorubicin has also been shown to be active against this type of tumor, as has chlorozotocin, a drug that is structurally similar to streptozocin but less frequently causes vomiting.
PTU-219 Use of antegrade colonic enema for the treatment of faecal incontinence and functional constipation in adults: a systematic review
Authors: A Patel, R Arasaradnam, C Harmston
Journal: Gut (2015)

<h3>Introduction</h3> Antegrade continence enema (ACE) is a proximal colonic stoma that allows antegrade lavage of the colon for the treatment of faecal incontinence (FI) and functional constipation (FC). Since its first description,<sup>1</sup>it has become widely accepted in the paediatric population. However, its role in the treatment of these conditions in adults has not been established. This review aims to evaluate the clinical response and complications of ACE in the adult population. <h3>Method</h3> The Medline and EMBASE databases were searched using the following criteria: (antegrade AND (continent OR continence OR colonic) AND enema).ti, ab [Limit to: Humans and (Age Groups All Adult 19 plus years)]. The Cochrane Central Register of Controlled trials (CENTRAL) was searched using the term “antegrade continence enema” in the Title, Abstract or Keywords section. Two independent reviewers screened abstracts and selected studies for inclusion. Only studies with participants aged 16 years and above were selected and quality of study was assessed using the MINORS score.<sup>2</sup> <h3>Results</h3> In all, 381 articles were retrieved, of which, 90 were duplicates. After review of the 291 abstracts, 32 full text publications were scrutinised and 18 were found to meet the inclusion criteria. Four studies were from the same institution, hence, 15 studies describing outcomes in 384 patients were included in the final analysis. All reports were observational cross sectional studies, four were prospective. Six studies included patients with either FC or FI, four with FI alone and five with FC alone. There was considerable heterogeneity within and across studies, hence, meta-analysis was not possible. Most studies were of poor quality as reflected in the low MINORS score. The number of participants still using ACE ranged from 47% to 100% over a follow up period of 6 to 55 months. Eleven studies reported achievement of full continence in 33% to 100% patients. Four studies described functional outcomes and seven studies reported a wide range of patient satisfaction. The rate of stoma stenosis varied from 8% to 50% and the rate of end stoma varied from 0–24%. <h3>Conclusion</h3> ACE has been reported as an acceptable treatment of FI or FC in adults across several analyses. There is wide variation regarding outcome measures. Larger prospective studies are required to assess the role of ACE in the adult population. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Malone PS, Ransley PG, Kiely EM. Preliminary report: the antegrade continence enema. Lancet 1990;336:1217–8 Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003;73:712–6
High-Dose Chemotherapy and Autologous Bone Marrow Transplantation Compared with MACOP-B in Aggressive B-Cell Lymphoma
Authors: Alessandro M. Gianni, Marco Bregni, Salvatore Siena, Cristina Brambilla, Massimo Di Nicola, Fabrizio Lombardi, Lorenza Gandola, Corrado Tarella, Alessandro Pileri, Fernando Ravagnani, Pinuccia Valagussa, Gianni Bonadonna
Journal: New England Journal of Medicine (1997)

We compared a regimen of six chemotherapeutic agents administered sequentially at high doses, followed by myeloablative treatment and bone marrow transplantation, with a regimen of methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as initial or salvage treatment for adults with diffuse large-cell lymphoma.
Survivorship: Tools for Transitioning Patients With Cancer
Authors: Mary Ann Morgan, Crystal S. Denlinger
Journal: Journal of the National Comprehensive Cancer Network (2014)

The number of cancer survivors will be increasing over the next decade. Caring for this burgeoning population will place demands on oncologists and primary care providers to meet the needs of the expected large numbers of new patients as the baby-boom generation ages. Many will live beyond 5 years and possibly for decades after diagnosis. Patients experience many transitions depending on the type and stage of cancer, its treatment, and the long-term or late effects they have from the disease and its treatment. The Institute of Medicine's report, "From Cancer Patient to Cancer Survivor: Lost in Transition," recommends that patients be provided with a summary of their cancer treatment and follow-up care plan (ie, survivorship care plan [SCP]), including recommendations on healthy lifestyle behaviors and resources to promote self-care. This plan should be shared with the patient's other health care providers, including the primary care provider. This will facilitate communication among providers and with the patient, which is a key component to quality care. The American College of Surgeons Commission on Cancer has also made providing SCPs to patients at completion of treatment a quality standard. Barriers to providing SCPs have been identified and include lack of time, reimbursement, and knowledge of late treatment effects and current guidelines. Survivorship guidelines are being developed by professional organizations that may be useful for providers. This article provides some practical tools that address these recommendations to help providers and patients with transitions along the cancer trajectory.
Use of Prednisone in the Management of Some Hemorrhagic States
Authors: Mario Stefanini, Nancy B. Martino
Journal: New England Journal of Medicine (1956)

PREVIOUS work has indicated the value of ACTH and cortisone in the management of thrombocytopenic purpura (idiopathic and secondary), anaphylactoid purpura, vascular pseudohemophilia and similar conditions.1 2 3 4 5 6 7 8 9 10 11 12 13 The therapeutic efficacy of these drugs seems to depend on a complex series of specific as well as nonspecific effects.14 Bleeding manifestations are strikingly decreased. For full therapeutic efficacy, however, doses of these hormones are required that often cause unpleasant side effects (such as salt retention, hypertension and potassium depletion).The introduction of prednisone§ has supplied a corticosteroid hormone apparently free of some side effects of ACTH and cortisone. It was believed that this . . .
Case 19-2000
Authors: Aubrey J. Katz, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 17-year-old boy was admitted to the hospital because of obstructive jaundice and weight loss.The patient had been well until two months earlier, when he consulted a physician because of pruritus. Topical antibiotic preparations were prescribed for excoriations, without improvement. Laboratory studies were performed a week later and were repeated after seven days (Table 1). An abdominal ultrasonographic examination showed distention of the gallbladder and common bile duct, with two large cysts in the left upper quadrant. Three days before admission, the patient came to this hospital.The patient had been born in the United States; . . .
Immunohistologic Abnormalities of the Microfibrillar-Fiber System in the Marfan Syndrome
Authors: David W. Hollister, Maurice Godfrey, Lynn Y. Sakai, Reed E. Pyeritz
Journal: New England Journal of Medicine (1990)

Indirect-immunofluorescence studies of skin and cultured dermal fibroblasts from patients with the Marian syndrome demonstrate apparent deficiency of one element of connective tissue — the microfibrillar-fiber system — in assays using specific antibodies against fibrillin, a major microfibrillar protein. This study was designed to test whether these immunostaining abnormalities are consistent and diagnostic features of the disease.