tbuckley/cabot-search huggingface dataset:
Carbon dioxide laser ablation of basal cell carcinoma with visual guidance by reflectance confocal microscopy: a proof‐of‐principle pilot study
Authors: B.P. Hibler, H. Sierra, M. Cordova, W. Phillips, M. Rajadhyaksha, K.S. Nehal, A.M. Rossi
Journal: British Journal of Dermatology (2016)

Laser ablation is an alternative, nonsurgical treatment modality for low‐risk basal cell carcinoma (BCC). However, lack of confirmative tumour destruction or residual tumour presence has been a limiting factor to its adoption. Reflectance confocal microscopy (RCM) provides noninvasive, cellular‐level resolution imaging of the skin and is capable of identifying tumour. To evaluate the use of RCM to guide carbon dioxide (CO2) laser ablation of BCC, confirm destruction and correlate findings with histology. RCM was used preablation to evaluate for features of BCC. Ablation was performed with a CO2 laser, and the response rapidly assessed using handheld RCM to evaluate for residual tumour. Confirmative pathology was used to verify confocal imaging. Preablation RCM imaging identified tumour with features not identified on normal, surrounding skin. Postablation, RCM documented complete removal of tumour in six cases and residual tumour in two. Histological examination identified the ablated area and confirmed clearance of tumour in the six aforementioned cases and corroborated confocal findings for residual tumour in the other two cases. We report successful treatment of superficial and nodular BCC using CO2 laser ablation augmented by RCM imaging for preablation guidance and verification of tumour removal postablation. Akin to complete circumferential and deep margin control techniques, using RCM helps to map peripheral and deep BCC margins to hone in on areas exhibiting persistent tumour after ablation. CO2 laser ablation visually guided by RCM can help circumvent previously cited limiting factors of laser ablation for tumour destruction by providing cellular‐level resolution imaging of tumour and margin assessment in between each laser pass and postablation.
Abstract 18993: High Prevalence of Cognitive Impairment in Older Heart Failure Patients at Hospital Discharge
Authors: Catherine Demers, Karen Harkness, George A Heckman, Peter Prior, Robert S McKelvie, Lehana Thabane, Nancy Dafoe, Gary Foster, Anne Pizzacalla, Sindy Virk, Cara Morris, Koon K Teo, Christopher Patterson
Journal: Circulation (2012)

Background: Evidence suggests that HF patients do not consistently engage in self-care. One possible reason may be the presence of undetected mild cognitive deficits (MCD). The primary objective of this study was to prospectively evaluate whether MCD measured with the Montreal Cognitive Assessment (MoCA) test in HF patients aged ≥60 years at hospital discharge is associated with impaired ability to self-care (measured with the Self-Care Heart Failure Index (SCHFI), patient is considered adequate if score ≥70/100). Methods / Results: We prospectively recruited HF patients within 48 hours from hospital discharge. In addition to the assessment of cognitive function, we measured baseline intelligence (NAART35), depression (Geriatric Depression Scale, GDS15 ), caregiver burden (modified Oberst Caregiver Burden Scale), activities of daily living (Barthel index), and frailty (Clinical Frailty Scale, CFS). We have recruited 51 patients (mean age 78, SD 7 years, 51% male) in this study. Sixty eight percent of patients have a high school education or less, 45% are married, 42% widowed, and 64% of patients have a total household income of &lt;$40,000. Fifty three percent of patients have a left ventricular ejection fraction &gt;45%. The mean number of medications at hospital discharge is 10 (SD 4). The mean MoCA score at baseline was 22 (SD 4) and 87% of patients had a MoCA score &lt;26 (indicating cognitive impairment). The SCHFI at baseline was 64 for self-maintenance, 46 for self-management, and 63 for self-confidence. Caregiver burden was low for the 2 subscales (Demand: 1.9, Difficulty: 1.3). The mean score for the GDS15 was 4/15 (no depression: 0-4/15), Barthel index was 82/100 indicating that the patients are not fully independent for ADLs. The mean CFS score was 4/7 indicating that these individuals are limited by symptoms during their activities. Conclusion: To our knowledge, this is the first prospective study at hospital discharge indicating a high prevalence of cognitive impairment. These results suggest that older HF patients have significant undetected cognitive deficits which may impact on their ability to self-care, which may in turn potentially lead to re-hospitalization early after hospital discharge.
Monoclonal Antibodies Specific to the Acute Lymphoblastic Leukemia t(1; 19)-Associated E2A/pbx1 Chimeric Protein: Characterization and Diagnostic Utility
Authors: Bi-Ching Sang, Liangru Shi, Peter Dias, Li Liu, Jia Wei, Zhi-Xue Wang, Craig R. Monell, Fred Behm, Stefan Gruenwald
Journal: Blood (1997)
Multicellular Spheroids: A New Model Target for In Vitro Studies of Immunity to Solid Tumor Allografts: Brief Communication
Authors: Robert M. Sutherland, H. Robson MacDonald, Robert L. Howell
Journal: JNCI Journal of the National Cancer Institute (1977)

Multicellular spheroids of EMT6 mammary sarcoma cells of BALB/c origin were incubated with normal spleen cells or alloimmune spleen cells generated in vitro in mixed leukocyte cultures (MLC). After 24 hours, spheroids were trypsinized and assayed for surviving tumor cells by use of a cloning technique. Under these conditions a 60-80% reduction in clone-forming tumor cells was observed after incubation of spheroids with immune lymphocytes as compared to normal lymphocyte controls. This cytotoxic effect occurred in situ, and alloimmune cells sensitized against unrelated antigens were much less cytotoxic than were specifically sensitized cells. In parallel autoradiographic studies, some immune lymphoid cells that had been labeled with tritiated thymidine during the proliferative phase of the MLC could be demonstrated within spheroids after 24 hours. These results suggested that multicellular spheroids will be a useful in vitro model for more detailed analysis of the factors controlling infiltration in in situ destruction of solid tumor grafts.
Ocular Fluid Analysis in Children Reveals Interleukin‐29/Interferon‐λ1 as a Biomarker for Juvenile Idiopathic Arthritis–Associated Uveitis
Authors: Anne‐Mieke J. W. Haasnoot, Jonas J. W. Kuiper, Sanne Hiddingh, Peter A. W. J. F. Schellekens, Wilco de Jager, Saskia M. Imhof, Timothy R. D. J. Radstake, Joke H. de Boer
Journal: Arthritis & Rheumatology (2016)

Childhood uveitis is a vision-threatening inflammatory eye disease commonly attributed to juvenile idiopathic arthritis (JIA). The pathogenesis is poorly understood, which makes clinical management challenging. We analyzed soluble mediators in ocular fluid (aqueous humor [AqH]) and serum from children with JIA-associated uveitis and common childhood uveitis to identify potential biomarkers and investigate the ocular microenvironment of this sight-threatening eye disease.AqH (n = 73) and paired serum (n = 66) samples were analyzed for 51 soluble mediators of inflammation by multiplex immunoassay. Twenty-one children with JIA-associated uveitis were compared to 15 children with chronic anterior uveitis without arthritis, 29 children with noninfectious idiopathic uveitis, and 8 children with noninflammatory conditions (controls). For visualization of the joint effect of multiple mediators, we used the radial coordinate visualization (Radviz) method. Optimal biomarker level cutoffs were also determined.The levels of interleukin-29 (IL-29)/interferon-λ1 (IFNλ1) were decreased (P < 0.001) and the levels of latency-associated peptide and osteoprotegerin were increased (P = 0.002 and P = 0.001, respectively) in samples of AqH, but not serum, from patients with JIA-associated uveitis. Multivariate analysis correcting for disease activity and treatment revealed that intraocular levels of IL-29/IFNλ1 were specifically decreased in patients with JIA-associated uveitis as compared to those with idiopathic uveitis. Indeed, JIA-associated uveitis patients and idiopathic uveitis patients showed distinct profiles of intraocular soluble mediators. IL-29/IFNλ1 showed a high area under the curve value (0.954), with 23.5 pg/ml as the optimal cutoff value.We identified IL-29/IFNλ1 as an intraocular biomarker for JIA-associated uveitis, which suggests that aberrant IFNλ signaling might be important in JIA-associated uveitis and distinct from other forms of childhood uveitis.
Distribution of T-Lymphocytes and B-Lymphocytes in Peripheral Blood and Effusions of Patients With Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W. Domagala, E. E. Emeson
 5, L. G. Koss
Journal: JNCI Journal of the National Cancer Institute (1978)

The relative distribution of T- and B-lymphocytes in the blood and in pleural or abdominal effusions was compared among 24 patients with fluid accumulation due to metastatic cancer and 8 patients without evidence of cancer. The data obtained indicated that the mean percentage of T-lymphocytes in malignant effusions was significantly greater than that in the peripheral blood of the same patients. At the same time, the mean eprcentage of B-lymphocytes was decreased in malignant effusions when compared with peripheral blood. Neither of these differences was observed when effusions and blood of patients with nonmalignant effusions were compared. In addition, patients with both types of effusions had fewer total lymphocytes in their blood than did normal control patients, whereas those with cancer-associated effusions had an increased proportion of active T-lymphocytes in their blood.
Fixed infusion rate (FIR) gemcitabine (G) based treatment for advanced renal cell carcinoma (ARCC): Efficacy and toxicity data from a phase II study
Authors: F. Zustovich, G. Cartei, R. Ceravolo, F. Salmaso, S. Zovato, G. Artioli, S. Cingarlini, S. Binato, D. Pastorelli
Journal: Journal of Clinical Oncology (2006)

14632 Background: ARCC is still an untreatable disease because high dose IL2 therapy is feasible and effective only in a small percentage of patients (pts). Standard dose IL2 is palliative as well as every other treatment. G is a well tolerated agent, even in aged pts and is moderately effective in ARCC. FIR of 10 mg/m 2 /min increases intracellular G active metabolites and may enhance therapeutic and toxic effect. Aim of study was to evaluate the FIR-G effectiveness in ARCC. Methods: G was administered IV at 10 mg/m 2 /min FIR for 50 to 1250 min according to age and PS on day 1,8,15 every 28. Immunotherapy (IT) was IL2 3MU subcutaneously daily for 5 days a week or Alfa-INF 3MU three days a week, chronically given. Results: We enrolled 23 pts; 5 female; median age 59 years (29–75), all stage IV disease, all nephrectomized with histologically confirmed clear cell carcinoma; median Fhurman’s grade was 3 (1–4); median PS was 2 (0–3); 9 pts had bone mets; prior treatments: IT, mostly low doses IL2, in 12 pts; chemotherapy in 7 pts and palliative radiotherapy in 9 pts. 125 cycles (median of 5, range 1–35) were administered with a median G dose of 1050 mg/m 2 over 105’. 13 Pts received IT (11 pts were IT naïve and received IL2 and 2 pts previously treated with IL2 received Alfa-INF). In the 22 pts valuable for toxicity grade 1–2/#pts was: granulocytopenia/5, anemia/2, nausea/5, vomiting/2, constipation/1, mucositis/1, fever/1, infection/1, fatigue/2, cutaneous/5, peripheral edema/4; grade 3–4 was: anemia/3, nausea/1, fatigue/3, cutaneous/1, vascular venous/1, peripheral edema/1. 26 cycles had to be delayed due to side effects. In the 22 valuable pts we reported 3 PR with a RR of 14% and 11 pts (50%) had SD. All pts were valuable for TTP with a median of 5.6 months (1–35). Data on OS are still immature with a median of 15+ (3–55+). Conclusions: FIR-G ± IT is safe and moderately effective against ARCC. Due to the small number of pts no separate analysis is possible between G ± IT or prognostic factors groups. Nevertheless our TTP and OS data are promising considering the detrimental prognostic factors in the treated population. Present work was part of studies program of, and partly supported by, AOI (Associazione Oncologia Italiana), Padova, Italy. No significant financial relationships to disclose.
RISK OF LUNG CANCER IN PATIENTS WITH PREINVASIVE BRONCHIAL LESIONS FOLLOWED BY AUTOFLUORESCENCE BRONCHOSCOPY AND CHEST COMPUTED TOMOGRAPHY
Authors: Alaa Mohamed, Shibuya Kiyoshi, T. Fujiwara, W. Hironobu, H. Hoshino, S. Yoshida, M. Suzuki, K. Hiroshima, Y. Nakatani, Aliae Mohamed-Hussein, Maha Elkouly, Tarek Mahfouz, I. Yochino
Journal: European Respiratory Journal (2011)

Introduction and aim of the work: To assess risk of lung cancer (LC) in patients with preinvasive bronchial lesions and to identify factors associated with higher risk.  Patients and methods: 124 patients with one or more preinvasive bronchial lesions and normal chest computed tomography (CT) (mean age 66.7 years, 121 males and 3 females), followed-up by white light and autofluorescence bronchoscopy (AFB) every 4-6 mo and chest CT every 6-12 mo, end points were development of carcinoma in situ (CIS) or LC.  Results: Among 124 patients with 240 preinvasive bronchial lesions, 20 CIS or LC lesions were detected during follow-up in 20 (16%) patients, 7 were detected as new endobronchial lesions, 10 as new peripheral lesions and 3 as local progression from severe dysplasia to CIS. Median time to progression was 24 months (range: 6-54 mo). The Cumulative risk of progression was 7% at one year, 20% at three years and 44% at 5 years. Among detected lung cancers, 80% were stage 0 or stage1 and underwent treatment with curative intent. Diagnosis of new SD during follow-up (p=0.0001), chronic obstructive pulmonary disease (COPD) (p = 0.001) or smoking index >52 packyear (p = 0.042) was associated with higher risk. Even after controlling for other risk factors,COPD was associated with risk of progression. Baseline lesion grade was not predictive of patient outcome (p = 0.146).  Conclusions: Patients with preinvasive bronchial lesions, especially those with new SD during follow-up, COPD or smoking >52 pack-year are at high risk of LC, AFB and CT follow-up facilitated early detection and treatment with curative intent.
Phase I study of sunitinib with irinotecan/5-fluorouracil/ leucovorin (FOLFIRI) for advanced gastroesophageal cancers.
Authors: N. I. Khushalani, G. J. Fetterly, R. V. Iyer, A. Litwin, W. Brady, M. M. Javle
Journal: Journal of Clinical Oncology (2010)

TPS201 Background: The incidence of gastroesophageal junction (GEJ) adenocarcinoma (AC) has dramatically increased in the Western world. Chemotherapy (CT) options have reached a plateau with median survival for advanced GEJ cancer rarely exceeding 12 months. VEGF and PDGF are strong angiogenic promoters in gastric cancer increasing proliferation, invasion and survival of the neoplastic cell. Disrupting this pathway may serve as a new therapeutic strategy in GEJ cancer. Sunitinib (S) is an oral receptor tyrosine kinase inhibitor of VEGFR, PDGRF, KIT, FLT-3, and RET. S is synergistic with CT, including 5FU in preclinical models (Mol Cancer Ther 2:471-478, 2003). We hypothesized that the addition of S to FOLFIRI in advanced GEJ AC would augment therapeutic efficacy. Methods: Primary aim is to determine the MTD of S in combination with FOLFIRI in advanced GEJ cancer. Secondary end-pts include response, overall and progression-free survival, and pharmacokinetics (PKs) of irinotecan (I), SN-38, and S (steady-state) to determine any interactions. Therapy-naïve advanced gastric and GEJ AC patients (pts) with adequate organ function, performance status (ECOG 0-1) are eligible. UGT1A1*28 7/7 homozygous polymorphism is an exclusion. Treatment consists of standard FOLFIRI (I 180 mg/m2, leucovorin 400 mg/m2, 5FU 400 mg/m2 followed by 46-hr infusion 5FU 2,400 mg/m2 q2w) with escalating doses of S given orally daily starting on day 2 (dose range 25 mg–67.5 mg, increments of 12.5 mg per cohort). Per prespecified design, initial intra- and inter-patient dose escalation was permitted, but then changed to a standard 3+3 design after observed toxicities. Initial experience also mandated amendments to an intermittent S dosing schedule of 14 days in a 28-day cycle, with decrease in I dose to 150 mg/m2, 5FU bolus to 320 mg/m2 and 5FU infusion to 2,000 mg/m2 q2w. Dose- limiting toxicities are assessed in the 1st 4 wks of treatment (febrile neutropenia, G4 neutropenia > 7d, G4 thrombocytopenia or anemia, ≥ G3 non- heme toxicity, dose delay > 14d). PKs for I/SN-38 assessed without and with S; PKs for S assessed on days 14 and 15 of cycle 1. Current accrual is at 12 pts. This study is supported by an IISP research grant from Pfizer, Inc. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Randomized phase II study of gefitinib alone or with simvastatin in previously treated advanced non-small cell lung cancer (NSCLC)
Authors: J. Han, S. Lee, T. Yun, Y. Moon, I. Park, H. Kim, J. Lee
Journal: Journal of Clinical Oncology (2009)

8057 Background: Statins reduce not only serum cholesterol levels but also mevalonate synthesis by inhibiting HMG-CoA reductase. Mevalonate is a precursor of several cellular major products including dolichol, geranylpyrophosphate (GPP) and farnesyl-pyrophosphate (FPP). Dolichol has a stimulatory effect on DNA synthesis and is linked to several tumor cell proteins. GPP and FPP cause isoprenylation of Ras and Rho those regulate signal transduction of several membrane receptors crucial for cell proliferation, differentiation, and apoptosis, which result in resistance to gefitinib. Thus depletion of mevalonate metabolites may enhance gefitinib activity in NSCLC. This study compared gefitinib alone with gefitinib plus simvastatin in patients with recurrent NSCLC after at least one chemotherapy. Methods: Between May 2006 and September 2008, 107 patients (51% male, 74% adenocarcinoma, 50% never-smoker, 54% more than two prior regimens) were randomly assigned to gefitinib alone (250 mg/d orally, n=53) or gefitinib plus simvastatin (250mg/d and 40 mg/d orally, respectively, n=54). A cycle was considered as 4 weeks of treatment. Therapy was continued until disease progression or intolerable toxicities. The primary end point was to assess response rate. Secondary end points included time to progression and survival. Median follow-up was 10.1 months. Results: Efficacy was similar for gefitinib and gefitinib plus simvastatin groups. Objective tumor response rates (RR) were 31.5% (95% CI, 19.1 to 43.9) and 32.1% (95% CI, 19.5 to 44.7); median PFS were 1.9 and 2.0 months; and median OS were 9.5 and 12.7 months, respectively. In subgroup analysis, gefitinib plus simvastatin showed a trend for higher RR than gefitinib alone in non-adenocarcinoma group (38.5% vs. 7.7%, p=0.08). Adverse events at both arms were generally mild (grade 1 or 2) and consisted mainly of skin reactions. Conclusions: Gefitinib combined with simvastatin did not improved efficacy compared to gefitinib alone in this unselected patient population, but showed a trend for higher efficacy in non-adenocarcinoma patients. Although it is preliminary, gefitinib combined with simvastatin showed slightly increased OS. Updated survival data will be presented. No significant financial relationships to disclose.
Clinical and pharmacokinetic study of oral etoposide in patients with AIDS-related Kaposi's sarcoma with no prior exposure to cytotoxic therapy.
Authors: G Schwartsmann, E Sprinz, M Kromfield, L Kalakun, E Sander, G Prolla, L Di Leone, L Gerhardt, D R Mans
Journal: Journal of Clinical Oncology (1997)

PURPOSE In this phase II and pharmacokinetic study, chronic, low-dose, oral etoposide was evaluated for its efficacy in patients with AIDS-related Kaposi's sarcoma who were not previously exposed to cytotoxic therapy. PATIENTS AND METHODS Of 28 patients accrued for the study, 25 were assessable for toxicity and response. Twenty-four patients were male (homosexual or bisexual cases) and one patient was female (partner of a bisexual male). All patients were human immunodeficiency virus (HIV)-positive, New York University (NYU) disease stage IIB to IVB, and most exhibiting skin and lymph node and/or visceral disease. Median age was 33 years (range, 21 to 50), and median World Health Organization (WHO) performance status was 2 (range, 0 to 3). The patients received a mean number of six treatment courses (range, four to 27). Prior therapy included local/regional irradiation, immunotherapy (interferon-alpha), local resection, and/or cryotherapy. No prior cytotoxic therapy was allowed. Etoposide was administered at a schedule of 25 mg/m2 orally, twice a day for 7 days, every 2 weeks. Plasma concentrations of the drug were measured in six patients by a high-performance liquid chromatography (HPLC) method, after chloroform extraction using teniposide as internal standard. RESULTS The overall response rate was 32% (two complete and six partial responses), and the median progression-free survival was 8 weeks (range, 4 to 27). Five patients (20%) had stable disease, while 12 cases (48%) did not respond. Patients without a history of opportunistic infections seemed to respond better. The regimen was well tolerated. The main toxic effects consisted of mild to moderate nausea and vomiting in approximately half of the cases, and WHO grodes 3 to 4 leukopenia and thrombocytopenia in eight of 25 (36%) and five of 25 (20%) of cases, respectively. However, only two patients had to discontinue treatment because of prolonged and severe neutropenia. No toxic deaths were documented. The pharmacokinetic analyses revealed the achievement of potentially therapeutic and lowly myelosuppressive plasma etoposide concentrations (2.1 micrograms/mL; range, 1.3 to 2.6) for a significant period of time, ie, for approximately 4.6 hours postdosing. CONCLUSION At the schedule applied, etoposide shows significant objective antitumor activity in advanced AIDS-related Kaposi's sarcoma, and induces acceptable clinical toxicity. This apparent efficacy of the regimen could be a result of the prolonged maintenance of cytotoxic plasma concentrations of etoposide during each treatment course, and the absence of toxic peak levels of the drug. These results, together with the appreciable bioavailability of oral etoposide, make the regimen feasible for outpatient treatment of patients with advanced AIDS-related Kaposi's sarcoma. Further studies using the above-mentioned approach are warranted.
Ips Cell Lines From Members Of a Family With Variable Penetrance Of An RPS19 Mutation Recapitulate The Diamond Blackfan Anemia (DBA) Phenotype and Show Differences In Ribosome Biogenesis and TGF Beta Signaling
Authors: Jingping Ge, Marisa Apicella, Shwetha Manjunath, Jason A. Mills, Loïc Garçon, Gregory M. Podsakoff, Deborah L. French, Mitchell J. Weiss, Monica Bessler, Philip J. Mason
Journal: Blood (2013)
Cell-Mediated Cytotoxic Response to Cells Bearing Marek's Disease Tumor-Associated Surface Antigen in Chickens Infected With Marek's Disease Virus
Authors: J. M. Sharma, B. D. Coulson
Journal: JNCI Journal of the National Cancer Institute (1977)

In a microcytotoxicity test in which 51Cr-labeled cells of a Marek's disease (MD) lymphoblastoid line (MSB-1 line) were used, cell-mediated cytotoxicity of spleen cell suspensions prepared from chickens inoculated with MD virus was demonstrated. This cytotoxic response, presumably directed against MD tumor-associated surface antigen, was detectable briefly after virus infection and paralleled the appearance of early lymphoproliferative lesions characteristic of MD.