tbuckley/cabot-search huggingface dataset:
Cutaneous T-Cell Lymphoma Misdiagnosed as Lipodermatosclerosis
Authors: W. James Tidwell, Janine Malone, Jeffrey P. Callen
Journal: JAMA Dermatology (2016)

k i n u m a b i n fungal pathogenesis remains unknown, though it is l o g i c a l t o a s s u m e t h a t t h r o u g h I L -1 7 i n h i b i t i o n , secukinumab counters IL-17's antifungal properties as well.Individuals with inborn IL-17 pathway deficiencies present with increased susceptibility to Candida and chronic mucocutaneous candidiasis. 1,6 Patients with decreased serum IL-17 levels, such as certain adult patients with T-cell leukemia or lymphoma, have frequent occurrences of superficial dermatophytosis.Because IL-17-producing cells stimulate the keratinocyte-produced antimicrobial p e p t i d e s h u m a n b e t a -d e f e n s i n -2 a n d L L -3 7 a n d neutrophil recruitment, this decrease in IL-17 may reduce cutaneous innate immunity and predispose to superficial dermatophytosis. 6 We report these 2 cases as an observation of a potential adverse effect of secukinumab, in triggering or exacerbating tinea cruris in patients with psoriasis.With increased use of this medication and other treatments targeting IL-17, it may be possible to further elucidate the prevalence of this adverse effect and the role of IL-17 inhibition in the pathogenesis of superficial dermatophytoses.
Suppression of transforming growth factor signalling aborts caerulein induced pancreatitis and eliminates restricted stimulation at high caerulein concentrations
Authors: S. Wildi, J. Kleeff, J. Mayerle, A. Zimmermann, E. P Bottinger, L. Wakefield, M. W Buchler, H. Friess, M. Korc
Journal: Gut (2006)

<b>Background:</b> Transforming growth factors βs (TGF-βs) are implicated in pancreatic tissue repair but their role in acute pancreatitis is not known. To determine whether endogenous TGF-βs modulate the course of caerulein induced acute pancreatitis, caerulein was administered to wild-type (FVB−/−) and transgenic mice that are heterozygous (FVB+/−) for expression of a dominant negative type II TGF-β receptor. <b>Methods:</b> After 7 hourly supramaximal injections of caerulein, the pancreas was evaluated histologically and serum was assayed for amylase and lipase levels. Next, the effects of caerulein on amylase secretion were determined in mouse pancreatic acini, and cholecystokinin (CCK) receptor expression was assessed. <b>Results:</b> The normal mouse pancreas was devoid of inflammatory cells whereas the pancreas from transgenic mice contained lymphocytic infiltrates. Caerulein injection in wild-type mice resulted in 6- and 36-fold increases in serum amylase and lipase levels, respectively, increased serum trypsinogen activation peptide (TAP) levels, gross oedema and a marked inflammatory response in the pancreas that consisted mainly of neutrophils and macrophages. By contrast, FVB+/− mice exhibited minimal alterations in response to caerulein with attenuated neutrophil–macrophage infiltrates. Moreover, acini from FVB+/− mice did not exhibit restricted stimulation at high caerulein concentrations, even though CCK receptor mRNA levels were not decreased. <b>Conclusion:</b> Our findings indicate that a functional TGF-β signalling pathway may be required for caerulein to induce acute pancreatitis and for the CCK receptor to induce acinar cell damage at high ligand concentrations. Our results also support the concept that restricted stimulation at high caerulein concentrations contributes to the ability of caerulein to induce acute pancreatitis.
A phase 1 study of a new therapeutic modality for the local treatment of bladder cancer: Intravesical gemcitabine plus concomitant external radiotherapy
Authors: H. Lopez, P. Foro-Arnalot, G. Gomez de Segura, M. Algara, M. Domenech, I. Garcia-Ribas, J. Palou
Journal: Journal of Clinical Oncology (2008)

16129 Background: Gemcitabine (G) has emerged recently as a safe and potentially active treatment for superficial bladder cancer. Gemcitabine is also considered a very potent radiosensitizing agent. The safety of the concomitant administration of intravesical gemcitabine with external radiotherapy (RT) has been tested in patients with bladder cancer. Methods: Patients with transitional carcinoma of the bladder, either superficial or invasive, not candidates or refusing cystectomy and without nodal or systemic spread were eligible for this trial. Patients entered after complete or incompleteTUR. CIS or multifocal tumors were allowed. Two G dose levels (DL) were tested. In DL1 patients received 1000 mg of G in 50 mL of saline for 1 hour at the beginning of weeks 1, 3, 5 and 7. In DL2 patients received the same dose of G once a week during RT. Radiotherapy was administered in 1.8 Gy/day fractions, 5 days a week. Planned dose was 55.8 Gy for those with superficial tumors only. Patients with ≥T2 also received 45 Gy on pelvis. Patients with residual tumor after TUR received 59.4 Gy on the bladder. Results: Nine patients were screened and 7 treated. One patient was withdrawn from the trial because was not able to retain G for the scheduled time from the first instillation. Three patients were treated at DL 1 and 3 at DL2, 5 males and 1 female. Age range 73 -84 yr. One patient had a T1 G3, the remaining 5 were T2. All but one entered the trial after complete TUR. The 6 patients received the intended doses of G (4 instillations for DL1 and 7 for DL2). All patients received the planned doses of RT. None of the treated patients presented a dose limiting toxicity (DLT). The 5 patients who entered with complete TUR did not recur in the bladder (follow up 8+ to 35+ months). Anyhow during the follow up, 1 patient presented pelvic nodal recurrence, another patient died from pneumonia and a third patient presented NSCLC stage IIIB; all of them without evidence of local recurrence. The only patient with residual disease after TUR was evaluated as stable disease after treatment. Conclusion: weekly intravesical gemcitabine concurrently with standard bladder radiotherapy has been show to be a feasible new therapeutic modality which deserves to be tested in Phase 2. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Lilly Oncology
Reply to A. Fiorentino et al
Authors: Jennifer R. Bellon
Journal: Journal of Clinical Oncology (2015)

I would like to address the following points in response to the letter by Fiorentino et al. First, the authors claim that quality of life is “undoubtedly” improved with a reduction in local recurrence. Although this may be the case, data from Liu et al suggest that a subset of patients may have such a low rate of local recurrence that they have no appreciable benefit from radiation therapy. If this is borne out in future prospective studies, then for these patients the toxicity of radiation can be avoided without sacrificing cancer-related outcomes. Second, the authors argue that intensive and costly follow-up will be necessary to monitor patients who do not receive adjuvant radiation. However, if the local recurrence in this select group of patients proves to be low, as these preliminary data suggest, follow-up will not need to be any different from that of standard-risk patients who have been treated with adjuvant radiation. Third, although it is true that modern radiation techniques have resulted in low rates of acute and chronic toxicity, all interventions have some potential morbidity. If there exists a subset of patients that has no meaningful benefit from radiation, then any adverse effects are unjustified. Fourth, given the possibility that radiation may contribute to the low rate of axillary recurrence in the sentinel node–only arm in the American College of Surgeons Oncology Group study Z0011, I agree that excluding radiation in patients with a positive sentinel node who receive breast conservation could potentially increase axillary recurrences. Such patients were not permitted in the randomized trial conducted by Fyles et al, nor will they be included in the prospective studies in Canada (ClinicalTrials.gov identifier NCT01791829), Michigan (ClinicalTrials.gov identifier NCT02400190), or Boston. Radiation has been an important component of breastconserving therapy for several decades. However, it is not without cost, both in terms of potential adverse effects for the patients, as well as financial effects. With our improved understanding of the biologic heterogeneity of breast cancer, we are now in a position to more precisely tailor treatment to each individual patient. Hopefully, this will allow us to omit radiation for patients who are unlikely to benefit.
Treatment and survival of non-Hodgkin lymphoma patients over the age of 8
Authors: F. O. Nascimento, H. P. Soares, A. Ruiz, G. B. Weinberg, M. Cusnir
Journal: Journal of Clinical Oncology (2008)

8569 Background: The incidence of Non-Hodgkin Lymphoma (NHL) has been increasing by 1–2% annually; the rise is most dramatic in patients over 80, in whom the rate rose 500% in the last 2 decades. Elderly are usually excluded from clinical trials, and often from treatment; thus, optimal treatment for elderly patients is unknown. The objective of this study was to review the characteristics, management and outcomes of NHL patients older than 80 years at diagnosis. Methods: The records of all patients over age 80 diagnosed with NHL from 2000 to 2005 were reviewed. A total of 107 patients were found and categorized as per the WHO classification. For statistical analysis, the patients were divided into subgroups: (I) type of tumor (a. aggressive, b. indolent), (II) international prognostic index (IPI) (1–2: low, 3–5: high), and (III) chemotherapy protocol (a. standard, b. non-anthracycline, c. no treatment). Overall survival rates were compared among subgroups of patients. Results: Thirty patients (28%) received standard chemotherapy (CHOP or CHOP-Rituximab). Forty-five (42%) received non-anthracycline chemotherapy and 32 (30%) were not treated. Overall 1-year and 3-year survival rates were 61.1±11.8% and 22.3±8.4%. The median survival time was 21±6 months. The indolent subgroup had better 1 and 3-year survival than the aggressive subgroup (70.5% and 28% versus 47.1% and 9.1% respectively, p=0.01). Similar results were seen in patients with low grade IPI when compared with high grade IPI (62.2% and 43% versus 41% and 8.1% respectively, p=0.002). The CHOP subgroup was compared with the non-anthracycline and “no treatment” subgroups in the different subtypes. In the aggressive subgroup, patients treated with CHOP had significantly longer 1-year and 3-year survival rates than those treated with non-anthracycline (76% and 42% versus 35.8% and 17% respectively, p=0.014) or those receiving no treatment (28.5% and zero, p=0.001). Conclusions: Very elderly patients with aggressive NHL (large B-cell) have significantly better survival rates at 1 and 3 years when treated with CHOP or CHOP-R. Age alone should not be a contraindication to treatment. Chemotherapy, howerver, did not affect outcome in patients with indolent NHL. No significant financial relationships to disclose.
Paclitaxel injectable emulsion: Phase 2a study of weekly administration in patients with platinum-resistant ovarian cancer
Authors: A. Lissianskaya, M. Gershanovich, N. Ognerubov, O. Golubeva, J. Pratt
Journal: Journal of Clinical Oncology (2004)

5047 Background: Paclitaxel Injectable Emulsion (PIE; TOCOSOL Paclitaxel) is a convenient, ready-to-use, Cremophor-free, unmodified paclitaxel product administered over 15 minutes. Methods: As part of a Phase 2A program, a multicenter study of PIE was conducted in taxane-naive patients (pts) with Stage III/IV platinum-resistant ovarian cancer (ov ca) pts receiving 2nd line therapy. Pts were either refractory to induction chemotherapy or had recurrent disease within 6 months of 1st line therapy. PIE was given IV over 15 min weekly. Dose cohorts were 80, 100, and 120 mg/m2. Results: 52 women, median age = 52 yrs, median ECOG PS = 1, 30/21 Stage III/IV were enrolled (one Stage I pt is included in safety but not efficacy analysis). Prior chemo: platinum in all pts, with cyclophosphamide in 49 pts (plus doxorubicin in 10) or gemcitabine in 3. By study design, 7 pts received 80, 6 received 100, and 39 received 120 mg/m2/wk. Accrual is complete; 5 pts are still on therapy; follow-up for progression and survival continues. Grade 3–4 toxicities in more than 5% of pts across the entire Phase 2A program (n=145) included neutropenia (G3 17%; G4 16%; febrile 2%), anemia (G3 11%; G4 1%), peripheral neuropathy (G3 9%; G4 0%) and dyspnea (G3 4%; G4 1%). . Infusion-related symptoms were infrequent and generally resolved without treatment if the infusion was interrupted for several minutes. In the ov ca study, pts received PIE for 1 to 47 (median 9) weeks. PIE was discontinued for adverse events in 5 pts, investigator decision in 6, unspecified reasons in 13, and progressive disease in 23 pts. Objective responses by RECIST are summarized in the table. Conclusion: PIE is well tolerated and shows promising efficacy given on a weekly schedule by 15 minute infusion in pts with refractory or resistant ov ca who have progressed after platinum-based therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PSI Pharma Support Intl; Sonus Pharmaceuticals Sonus Pharmaceuticals Sonus Pharmaceuticals Sonus Pharmaceuticals
Association of Pharmacokinetics or Pharmacogenomics with Toxicity of Erlotinib in Patients with Recurrent Advanced Non-Small Cell Lung Cancer
Authors: T. Hirose, K. Fujita, S. Kusumoto, Y. Oki, Y. Murata, T. Sugiyama, H. Ishida, T. Shirai, M. Nakashima, T. Yamaoka, K. Okuda, T. Ohnishi, T. Ohmori, Y. Sasaki, A. Tamura, K. Ohta
Journal: Annals of Oncology (2014)
Health literacy screening prior to education for patients with cancer.
Authors: Donna Lynn Berry, Barbara Halpenny, Peter Chang, Julia H. Hayes, Jon Noel, Srik Vedachalam, Erica Fox, Erica Sorrentino
Journal: Journal of Clinical Oncology (2013)

155 Background: We have developed and tested the Personal Patient Profile-Prostate (P3P), an efficacious decision intervention for men with localized prostate cancer (LPC). Usability evaluations in minority men of varying education levels suggested additional development needs for this web-based intervention. Establishing the link between health literacy and comprehension and use of education materials is important as we develop interventions for all patients with cancer and is critical to assuring informed consent to treatment and adherence to therapeutic regimens. Appropriate methods of literacy assessment are infrequently used in clinical settings. Methods: The purpose of this analysis was to explore feasibility of health literacy testing prior to P3P use in minority men with a new diagnosis of LPC. Black and Hispanic men were recruited at 3 Boston hospitals. Prior to using the P3P, patients completed the Short Assessment of Health Literacy-English (SAHL-E), an 18-item measure of an adult’s ability to read and understand medical terms. Scores &gt;14 indicate adequate health literacy. Assessment duration was recorded and demographic information collected. Results: Nine men participated in the first 3 months of the study. All identified as Black/African-American, and three also identified as Hispanic/Latino (Dominican, Central American, Cape Verdean). Participants’ median age was 68 (range 52-77), and education level ranged from less than high school diploma to post-graduate degree. Administration of the SAHL-E took from 4 to 12 minutes (median=5). Data completeness was high. Scores ranged from 5 to 18 (median=16), with two patients scoring below 14; these two with low health literacy were the only two without any college education and also required at least 10 minutes to complete the screening. Conclusions: The SAHL-E was a feasible approach to screening for health literacy in a sample of minority men prior to providing a patient decision support intervention. Preliminary results suggest some ability to identify those patients who will require greater support during use of educational interventions or understanding written documents.
Brief communication: exogenous estrogens and breast cancer in women with natural menopause.
Authors: Casagrande J, Gerkins, Henderson Be, Mack T, Pike Mc
Journal: JNCI Journal of the National Cancer Institute (1976)

90 breast cancer patients aged 50-64 were compared with 83 controls matched for age race and socioeconomic class to determine the relationship between administration of exogenous estrogens and breast cancer when the factors of age age at  menopause and calendar year were controlled.  No harmful effect of estrogen administration was demonstrat ed but a previous finding by the authors of a beneficial effect was neg ated.  It is suggested however that there are still too many confounding factors in a study of this type for a harmful association to be revealed and it is recommended that a case-control study be carried out in a large prepaid medical care  system.
Phase I/II study of the combination of sorafenib and temsirolimus in patients with metastatic melanoma
Authors: K. B. Kim, M. A. Davies, N. E. Papadopoulos, A. Y. Bedikian, W. Hwu, K. Woodard, E. W. Washington, J. E. Dancey, J. Wright, P. Hwu
Journal: Journal of Clinical Oncology (2009)

9026 Background: Inhibition of Signal transduction pathways at multiple levels may be a more effective therapeutic cancer strategy for advanced cancer patients. Sorafenib, a multikinase inhibitor and temsirolimus, an inhibitor of critical survival pathways, are targeted compounds with single agent anti-tumor activity in several solid tumors. Inhibition of mutant B-Raf and the AKT signaling pathway has been effective in vitro with melanoma cell lines. Therefore, we designed a phase I/II study of the combination of sorafenib and temsirolimus to inhibit multiple pathways for greater clinical efficacy.Methods: Patients (pts) with stage IV or unresectable or recurrent stage III melanoma and ECOG performance status of 0 to 1 were eligible. Pts with treated brain metastases were eligible if they had not progressed for 3 months. Sorafenib was given orally twice daily and temsirolimus was given intravenously once a week, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per RECIST. Results: To date, 22 pts have been enrolled and treated. Median age was 56.5, and 17 were male. Median ECOG PS was 1. The MTD doses were sorafenib 400 mg in AM / 200 mg in PM daily and temsirolimus 25 mg IV weekly. The dose-limiting toxicity (DLT) included thrombocytopenia, hand-foot syndrome (HFS), serum transaminase elevation and hypertriglyceridemia. Other common adverse events were dry skin, fatigue, taste alteration, anorexia, flatulence, diarrhea, skin rash, insomnia, neuropathy, myalgia, and headaches, anemia, hypercholesterolemia, hyperglycemia and hypophosphatemia. There were 9 pts with stable disease among 21 evaluable pts for response. Conclusions: Sorafenib and temsirolimus can be administered concomitantly although with significant toxicity at higher dose levels. Currently, pts are enrolled in a dose expansion cohort. Pharmacokinetic data will be presented. Supported in part by NCI grant UO1 CA062461 and N01 CM17003. [Table: see text] No significant financial relationships to disclose.
OP0110 Assessment and Determinants of Aesthetic Discomfort in Hand Osteoarthritis: The Liège Hand Osteoarthritis Cohort (LIHOC)
Authors: A. Neuprez, O. Bruyère, N. Dardenne, S. Disteche, E. Maheu, N. Burlet, J.-Y. Reginster
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Whereas hand osteoarthritis (OA) is a frequent disease, which may lead to considerable pain and physical limitations, limited research has been performed, compared to lower limbs OA. The primary complaint of patients is frequently related to the disgracious appearance of their hand joints. However, few studies have been conducted to identify the magnitude and the determinants of aesthetic discomfort in hand OA. <h3>Objectives</h3> The LIège Hand Osteoarthritis Cohort (LIHOC) is a prospective cohort of 203 patients diagnosed with hand OA which are prospectively followed to better understand the impact of hand OA on quality of life and health resources utilization. <h3>Methods</h3> At baseline, these patients were asked to rate their aesthetic discomfort related to hand OA on a 100 mm Visual Analog Scale and also use a seven-point Likert scale (0-7), commonly used in forensic medicine, to quantify the magnitude of their aesthetic damage. <h3>Results</h3> The median value of the aesthetic discomfort VAS was 35.0 (Q1: 6.0-Q3: 59.0). Correlation analyses were performed between these scorings and clinical hand parameters. The median damage was rated at 3.0 (1.0-4.0), corresponding to a "moderate" level. Aesthetic discomfort (VAS) and the magnitude of the aesthetic damage (Likert) were significantly (p&lt;0.02) correlated with the gender of the patients, the duration since the diagnosis of hand OA, the radiological assessment using the Verbruggen and Kellgren-Lawrence scales, the Australian Canadian Osteoarthritis Hand Index (AUSCAN), assessing the three dimensions of pain, disability and joint stiffness, of hand function based on the Functional Index for Hand Osteoarthritis (FIHOA), the spontaneously recorded global pain (VAS) and the number of joints presenting with erosive or severe lesions, bony deformations or the number of articulations, spontaneously reported as painful (Likert only) or painful at pressure. However, when a stepwise analysis procedure was applied, the only parameters which remained significantly correlated to the aesthetic discomfort were the number of erosive joints (p&lt;0.0001) the total AUSCAN score (p&lt;0.0001) and the gender of the patients (p=0.0026). For the assessment of aesthetic damage, the parameters which remained significantly associated were the AUSCAN total score (p&lt;0.0001), a duration of hand OA above the 10 years (p=0.01) and the number of erosive joints (p&lt;0.0001). <h3>Conclusions</h3> Aesthetic discomfort and aesthetic damage are significant complaints in patients presenting with hand OA. The major determinants of their impact are gender, duration of hand OA, number of erosive joints and the Australian Canadian Osteoarthritis Hand Index. <h3>Disclosure of Interest</h3> None declared
Loss of MKP3 is associated with cisplatin-resistance and tumorigenicity of ovarian cancer
Authors: David Chan, Vincent Liu, Hextan Ngan
Journal: Cancer Research (2007)

3687  The Ras-Raf-MEK-ERK1/2 (ERK) pathway plays a pivotal role in various cellular responses, including cellular growth, differentiation, survival and motility. Constitutive activation of ERK pathway due to increased exposure to growth factors, overexpression or mutation of receptor tyrosine kinases, Ras and Raf has been linked to many cancers. On the other hand, recent studies have found that the ERK activity is also modulated by a number of negative regulators. In this study, we identified Dual specificity MAPK phophatase 3 (MKP3), one of the negative regulators, was frequently downregulated and correlated with high ERK1/2 activity in human ovarian cancer. Intriguingly, we found that the loss of MKP3 was associated with high intracellular reactive oxygen species (ROS) accumulation such as H2O2. Mild treatment of ovarian cancer cells by hydrogen peroxide H2O2 resulted in MKP3 degradation through proteasome/ubiquitination pathway. Furthermore, enforced expression of MKP3 in MKP3-deficient ovarian cancer cells significantly reduced ERK1/2 activity, sensitized ovarian cancer cells to cisplatin-induced apoptosis, and inhibited cell proliferation and anchorage-independent growth ability in soft agar. These results suggest a molecular mechanism that the accumulation of ROS during ovarian cancer progression may cause the degradation of MKP3, which in turn leads to aberrant ERK1/2 activation and contributes to cisplatin-resistance and tumorigenicity of human ovarian cancer.