tbuckley/cabot-search huggingface dataset:
Battered wife syndrome: overview of dynamics and treatment
Authors: R K Goodstein, A W Page
Journal: American Journal of Psychiatry (1981)

The authors review some pertinent features of the battered wife syndrome, including definitions, incidence, characteristics of wives, injury profiles, setting of the violence, psychodynamics, role of alcohol, family backgrounds, characteristics of husbands, coping responses of wives, seeking help, social support systems, recognition of the battering syndrome, prevention and treatment, and group therapy. Although force has long been used as a resource in family politics, we have just started to understand some of its precipitants, social and clinical consequences, and treatment options. The battering syndrome is not a disease per se because it cuts across socioeconomic and diagnostic categories. Controlled studies and national attention are required in order to understand more about this costly problem, which poses a treatment dilemma to clinical psychiatry.
Does the magnitude of response to initial induction therapy impact plans for immediate autologous stem cell transplant (ASCT) consolidation in the transplant-eligible patient with a new diagnosis of multiple myeloma (MM)?
Authors: J. Willey, K. E. Lemke, M. E. Williams, M. R. Green, S. Lonial
Journal: Journal of Clinical Oncology (2010)

8146 Background: Initial chemotherapy (CT) followed by consolidation with high-dose CT and ASCT is a standard first-line strategy for fit patients with MM. Use of new agents (e.g., bortezomib and lenalidomide) in doublet and triplet combinations appears to produce enhanced cytoreduction during induction. We studied whether magnitude of response during induction impacts plans of American hematology/oncology MDs (AHOMD) to recommend immediate ASCT consolidation as part of initial overall therapy. Methods: Between 7/25 and 8/15/09, we studied >325 AHOMDs using an extensively tested, live, case-based, market research vehicle to anonymously acquire data concerning plans to include ASCT after initial CT. Initial therapy regimen was at the discretion of the physician. Three scenarios were tested: CR/ VGPR/ PR achieved after 4 cycles. (Definitions of VGPR and PR were not specified in the research queries.) Plans for additional therapy/ASCT were quantitated by post 4th cycle status. Results: See Table. Conclusions: When induction × 4 cycles results in a less than a CR, plans for immediate SCT fall [CR 66%; VGPR 61%; PR 41% ] and plans for added induction f/by reconsideration of SCT rise [CR 13%; VGPR 30%; PR 44%]. A magnitude of response adapted paradigm for total induction therapy before ASCT consolidation is operative in patients with a new diagnosis of MM. Outcome after 4 cycles/options for Rx CR VGPR PR ASCT followed by observation 31% 27% 21% ASCT followed by maintenance Rx 29% 30% 15% Tandem ASCT 6% 4% 5% Two more induction cycles followed by consider ASCT 13% 30% 44% Two more cycles induction followed by observation/maintenance CT 12% 16% 5% Maintenance CT 6% 2% 3% Other 3% 1% 3% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcenda Bristol-Myers Squibb, Celgene, Facet Biotech, Millennium, Novartis Bristol-Myers Squibb, Celgene, Facet Biotech, Gloucester Pharmaceuticals, Millennium, Novartis
Biopsychosocial problems identified by women with breast cancer
Authors: M. Loscalzo, K. Clark, J. Mortimer
Journal: Journal of Clinical Oncology (2007)

19514 Background: It is frequently assumed that women with breast cancer have higher levels of distress and psychosocial problems than women with other malignancies. We compared the biopsychosocial needs of breast cancer patients with women with non-breast malignancies. Methods: A biopsychosocial screening tool was developed from clinical practice, focus groups, and the administration of questionnaires to over 3,000 patients. The refined 36-item self-administered questionnaire was completed by all new patients evaluated in the Moores Cancer Center. The severity of each problem was scored from 1 (not a problem) to 5 (the worst problem I could have). Problems scored as 3 or above were identified to be clinically significant. The screening results from women with breast cancer were compared with those of women with non-breast malignancies. Results: Between December 2005 and December 2006, 2063 patients completed screening questionnaires. Complete information, including staging, is available on 299 women, 155 of whom were diagnosed with breast cancer and 144 with non-breast malignancies. The two groups were comparable with respect to age, ethnicity, and the number of significant problems reported. The 5 most common problems identified to be significant by breast cancer patients included: fatigue, sleeping, being dependent on others, feeling depressed, and pain. The non-breast cancer women identified a greater number of significant problems overall with the 5 most significant being: fatigue, sleep, controlling my fear and worry about the future, being dependent on others, and pain. Getting medications and recent weight loss were more commonly identified in the non-breast cancer patients (p&lt;0.05). Conclusions: Our data suggest that breast cancer patients identify similar biopsychosocial needs as women with other primary malignancies. No significant financial relationships to disclose.
5-FU/ folinic acid plus CPT-11 (FOLFIRI.3 regimen) in advanced pancreatic carcinoma (PC): results of an AGEO phase II study
Authors: J. Taieb, T. Lecomte, P. Artru, T. Aparicio, T. Mansourbakht, B. Landi, D. Béchade, N. Germann, T. Poynard, G. Lledo, J. Desrame
Journal: Journal of Clinical Oncology (2005)

4116 Background: New therapies are clearly needed to improve the prognosis of patients (pts) with advanced PC. The rationale to develop the FOLFIRI.3 regimen is based on pre-clinical experiments on cell cultures and human tumor xenografts indicating optimal synergy between CPT-11 and fluorouracil when CPT-11 is given before and after 5-FU. Methods: 30 pts with non pre-treated locally advanced (LA) or metastatic (M) PC were prospectively enrolled. They received a FOLFIRI.3 regimen : CPT-11 90 mg/m2 d1 and d3, folinic acid 400 mg/m2 on a 2h00 infusion and continuous 5-FU 2000 mg/m2 from d1 to d3 (on a 46h00 infusion). Treatment was repeated every two weeks until disease progression or limiting toxicity. Eligibility criteria were: pathologically proven PC, PS (ECOG) 0–2, age ≥ 18, measurable disease, serum bilirubin < 1.5 UNL, adequate hematological and renal functions. Results: Twenty-five pts are currently evaluable for toxicity and efficacy. Patient’s characteristics, treatment toxicity and clinical activity are summarized in the following table. No Toxic death occurred. Hematological grade 3–4 toxicities consisted in neutropenia (24%) and thrombocytopenia (4%), without any febrile neutropenia or bleeding event. Grade 3–4 non hematological toxicities were nausea vomiting (24%) and diarrhea (24%). Grade 2 alopecia was observed in 12 pts (48%). Six objective responses were observed, one leading to a surgical resection of the tumor. Conclusion: The FOLFIRI.3 regimen seems to be an active regimen with manageable toxicity in non pre-treated advanced PC pts. Updated results of this ongoing study will be presented at the meeting. No significant financial relationships to disclose.
Evaluation of sensitivity to change of the MPAC scale, validated in Spanish, in pain measurement in cancer patients
Authors: Y. Escobar, M. Domine, F. Valcarcel, J. Contreras, F. Lobo
Journal: Journal of Clinical Oncology (2007)

19567 Background: The Memorial Pain Assessment Card (MPAC) allows an easy measurement of oncologic pain in the clinical practice. In 2004, a Spanish version of the MPAC scale was validated in cancer pain. The goal of the present work was to evaluate the sensitivity to change of the validated Spanish version by oncologic patients. Methods: Epidemiological, prospective, 2-months multicenter study, conducted at 4 services of oncology. The included patients suffered continuous chronic cancer pain and were in a susceptible situation of change (pain intensity ≥ 3 in a Visual Analogue Scale). The MPAC card was administered at baseline and at 1 and 2 months, including the 4 subscales (pain relief [VASPR], pain intensity measured by VAS [VASPI] and by an 8-items descriptors subscale [Tursky], and psychological distress [VASMOOD]). Data about clinical situation and satisfaction of the patient and the health care professionals with the MPAC card was also collected. Sensitivity to change was evaluated by comparing 2-months versus baseline results in the MPAC subscales. Results: Fifty-four patients with oncologic pain (76% men) with a mean (SD) age of 57(11) years were included. 74% of patients presented metastasis, and in 80% of cases the treatment was palliative. All the MPAC VAS subscales showed sensitivity to change across the 2-months period: mean VASPI at baseline 6.6(1.7) vs 3.5(2.0) at 2 months (p&lt;0.0001, Wilcoxon test [WX]); VASPR 4.5(1.9) vs 6.3(2.3) (p&lt;0.0001 [WX]); VASMOOD 5.5(2.1) vs 4.0(2.1) (p=0.0008 [WX]). Furthermore, 90.5% of patients showed changes in Tursky subscale (78.6% less pain, 11.9% increased pain), being these changes significantly associated with VASPI scores (p=0.0006, Kruskal-Wallis test). Both patients and medical personnel agreed in the card use facility (63% and 71% of cases, respectively). Conclusions: The Spanish MPAC version has demonstrated sensitivity to change in all the MPAC subscales (pain relief, pain intensity and psychological distress). Its facility of administration may allow a useful and quick evaluation of the cancer pain in the clinical practice. No significant financial relationships to disclose.
Modulation of Murine Neuroblastoma in Nude Mice by Opioid Antagonists2
Authors: Ian S. Zagon, Patricia J. McLaughlin
Journal: JNCI Journal of the National Cancer Institute (1987)

Naltrexone, an opioid antagonist, had an inhibitory effect on the growth of murine S20Y neuroblastoma in BALB/c nude mice. Daily injections of 0.1 mg naltrexone/kg, which invoked a receptor blockade for 6-8 hours/day, resulted in 31-92% delay in latency time prior to tumor expression and a 27-49% increase in mean survival time; the magnitude of antitumor response was governed by tumor burden. Inoculation of neuroblastoma (10(6)-2.5 X 10(4) cells) resulted in measurable tumors in 10-13 days and mean survival times of 30-34 days. Immunoreactive beta-endorphin was detected in tumor tissue (39.7 pg/mg protein). Receptor binding assays revealed specific saturable binding of ligands related to delta- and kappa-binding sites, but not for the mu-binding site. These results demonstrate that opioid antagonist modulation of neuro-oncogenesis is not dependent on the integrity of T-cell-mediated immunity and suggest the feasibility of utilizing the nude mouse model in exploring the role of endogenous opioids in human cancers.
Treatment of mantle-cell lymphomas with intermittent two-hour infusion of cladribine as first-line therapy or in first relapse
Authors: M.J. Rummel, K.U. Chow, E. Jäger, D.K. Hossfeld, L. Bergmann, H.-D. Peter, M.-L. Hansmann, A. Meyer, D. Hoelzer, P.S. Mitrou
Journal: Annals of Oncology (1999)
Synergistic benefit in inflammatory arthritis by targeting IκB kinase ϵ and interferon β
Authors: M Corr, D L Boyle, L Ronacher, N Flores, G S Firestein
Journal: Annals of the Rheumatic Diseases (2008)

The I kappaB kinase (IKK)-related kinase IKKepsilon regulates type I interferon expression and responses as well as proinflammatory mediator production. We examined the role of IKKepsilon in arthritis and its ability to enhance the therapeutic response to systemic interferon (IFN) beta therapy in passive murine K/BxN arthritis.IKKepsilon(-/-), IFN alpha(approximately)beta R(-/-) and wild type mice were given K/BxN serum and treated with polyinosinic polycytidylic acid (poly(I:C)), IFN beta, or normal saline. Clinical response and histological scores were assessed. Gene expression in the paws was measured by quantitative PCR. Serum interleukin 1a receptor agonist (IL1Ra) and IL10 were measured by ELISA and multiplex bead array.Arthritis was almost completely blocked in wild type mice if arthritogenic K/BxN serum and the Toll-like receptor (TLR)3 ligand, poly(I:C), were coadministered at the onset of the model, but not in established disease. Mice deficient in IFN alpha(approximately)beta R had an accelerated course of arthritis, and did not respond to poly(I:C). IKKepsilon null mice had a modest decrease in clinical arthritis compared with heterozygous mice. Low doses of IFN beta that were ineffective in wild type mice significantly decreased clinical arthritis in IKKepsilon null mice. Articular chemokine gene expression was reduced in the IKKepsilon(-/-) mice with arthritis and secreted IL1Ra (sIL1Ra) mRNA was significantly increased. Serum levels of IL1Ra were increased in low dose IFN beta-treated IKKepsilon(-/-) mice.Subtherapeutic doses of IFN beta enhance the anti-inflammatory effects of IKKepsilon deficiency, possibly by increasing production of IL1Ra and unmasking the antichemokine effects. Combination therapy with low dose IFN beta and an IKKepsilon inhibitor might improve efficacy of either agent alone and offers a novel approach to RA.
Screening lung Tumour tissue for whole genome sequencing
Authors: F. Goh, M. Daniels, J. G. Shaw, D. Courtney, L. Passmore, L. McCaul, E. Duhig, B. Clarke, K. Parsonson, J. Brady, D. Butler, M. Martins, M. Davidson, C. M. Wright, J. Martin, L. Morrison, Relan, F. S. M. Savarimuthu, M. N. Windsor, K. S. Matar, R. Naidoo, R. Tam, M. Colosimo, I. A. Yang, R. Bowman, K. M. Fong
Journal: Journal of Thoracic Oncology (2012)
Impact of radiofrequency ablation therapy for breast cancer in nipple-areolar complex
Authors: M. Kusama, Y. Imamura
Journal: Journal of Clinical Oncology (2009)

e11511 Background: Preservation of the safety surgical margin is difficult in BCT of a breast cancer in the vicinity of the nipple-areola complex, and mastectomy is required even for tiny tumors, with consequent poor cosmetic efects. Radiofrequency ablation (RFA) is an advanced, minimally invasive technique for breast cancer. Its application for the tumor in the nipple-areola region has recieved considerable interest. Methods: RFA of 32 malignant lesion was performed in 30 patients with nipple-areolar breast cancer (Tis: 4, T1: 18; T2: 8). One of the patients had received preoperative chemotherapy. And one patient was male breast cancer(T2).Surgery was performed on an outpatient basis.A 19-gauge cooled-tip needle was used in all cases. About 10–20ml of 5% glucose solutions was injected between the nipple-areola and the tumor before RFA to maintain a space to avoid heat damage that can occur due to diffusion of RF waves. RFA was continued until the moisture of the tumor was vaporized. This required an average of 4.3 sessions. Irradiation of radiofrequency with a boost was conducted in 23 patients. All patients were reviewd at, one month and every three monthe thereafter with US.The follow-up was complete and the median follow-up was 13months(6–30). Results: In one patient, who had undergone preoperative chemotherapy was observed a recurrence in the nipple on 9 months later, but disappeared after a second ablation of RF. Cosmetic features were maintained after surgery, except in the case that received preoperative chemotherapy, in which a mild deformity in the nipple was evident. There has been no recurrence in the 29 primary cases over a relatively short observation period. Conclusions: RFA enables treatment of breast cancer in the nipple-areolar region without damage to the surrounding tissues and degradation of cosmetic features. No significant financial relationships to disclose.
Phosphorylation and nuclear localisation of Akt is induced by hypoxia and associated with a poor prognosis in malignant pleural mesothelioma
Authors: K. A. Gately, D. Stewart, D. Waller, A. Davies, K. J. O'Byrne
Journal: Journal of Clinical Oncology (2008)

22034 Background: The phosphatidylinositol-3 kinase (PI3K)/Akt (PKB) pathway is activated in many solid tumours, and plays a central role in cell survival. Recent evidence indicates that hypoxia induces upregulation and activation of the PI3K/Akt pathway. Once activated, Akt phosphorylates a variety of downstream substrates, including the pro-apoptotic transcription factor FOXO3a, facilitating cell survival by blocking apoptosis. This study examined the interaction between phosphorylated Akt (pAkt) and hypoxia in mesothelioma cell lines and patient tumour samples. Methods: Western blot analysis was used to examine the effect of hypoxia on Akt and pAkt expression in 4 MPM cell lines (JU77; ONE58; CRL5915; CRL5820) in the presence or absence of the PI3K inhibitor, LY294002. High-content screening (HCS) analyses, using the Incell 1000 analyser, was used to quantify changes in subcellular localisation of pAkt and FOXO3a in the cells. FACs and HCS were used to quantify levels of apoptosis. Tumour samples from 187 patients with MPM were stained using pAkt and carbonic anhydrase (CA)-IX (a surrogate marker of hypoxia) specific antibodies. Results: Hypoxia induced the activation of Akt in the MPM cell lines with an increase in nuclear pAkt expression. This correlated with a reduction in nuclear FOXO3a expression. An increase in the level of apoptosis was seen under hypoxic conditions when Akt phosphorylation was blocked by LY294002. This correlated with an increase in nuclear FOXO3a. A positive association between pAkt and CA-IX immunostaining was observed in the tumour samples, supporting the in vitro findings that intra-tumoural hypoxia is a stimulus for Akt phosphorylation. On multivariate analysis increased expression of nuclear pAkt, sarcomatoid histology, weight loss >5% and increasing CALGB score emerged as independent prognostic variables predicting a poor survival. Conclusions: The in vitro and tumour sample work demonstrates that hypoxia induces activation of Akt in MPM. The association between increased nuclear pAkt and reduced nuclear FOXO3a, reversed by LY294002, indicates that pAkt plays a central role in the inhibiton of apoptosis under hypoxic conditions and therefore may represent a novel therapeutic target in MPM. No significant financial relationships to disclose.
Outcome of patients with recurrent Ewing's sarcoma family of tumors (ESFT)
Authors: D. S. Hawkins, L. Barker, J. E. Sanders, T. Pendergrass
Journal: Journal of Clinical Oncology (2004)

8517 Background: The overall survival (OS) of relapsed ESFT is poor, and the relative benefit of high-dose therapy (HDT) is controversial. To determine the factors associated with outcome for relapsed ESFT, we performed the following analysis. Methods: We retrospectively identified 52 consecutive ESFT patients initially diagnosed before December 31, 2000, with disease recurrence between 1985 and 2002, who were treated at CHRMC and had adequate medical records for review. Results: All patients initially received multi-agent chemotherapy, most frequently vincristine, doxorubicin, cyclophospamide (C), etoposide (E), and ifosfamide (I) (27 patients). Twenty-five patients had metastatic disease at presentation. The median relapse-free interval (RFI) was 17 months (range 5–90 months). Most recurrences were metastatic only (36 patients) or local and metastatic (10 patients). Forty patients received second-line treatment with systemic chemotherapy, most frequently IE (23 patients), IE with carboplatin (6 patients), or topotecan and C (5 patients), with or without additional surgery and/or radiotherapy. Twenty-six (50%) patients achieved a partial or complete response to second-line treatment, with a median duration of response of 30 months (range 5–119 months). The 5-year OS for all relapsed patients was 23% (95% CI, 11–35%). By univariate analysis, improved OS was associated with response to second-line treatment (47% vs. 0%, p <0.0001), RFI > 24 months (51% vs. 12%, p = 0.0001), and no metastases at initial diagnosis (34% vs. 12%, p = 0.03). Because all 13 patients who received HDT also had responsive relapse, we performed a multivariate analysis. Reduced risk of death was associated with response to second-line therapy (odds ratio 0.16, 95% CI 0.05–0.48), RFI > 24 months (odds ratio 0.28, 95% CI 0.12–0.66) and receiving HDT (odds ratio 0.29, 95% CI 0.09–0.93), but not metastases at initial diagnosis (odds ratio 1.0, 95% CI 0.4–2.4). Nine of the 12 surviving patients received HDT. Conclusions: HDT as consolidation therapy for relapsed ESFT is associated with improved OS, even after adjusting for RFI and response to second-line treatment. No significant financial relationships to disclose.
<i>BRAF</i> mutations in patients with well-differentiated pancreatic neuroendocrine tumors (WD pNETs).
Authors: Nitya Prabhakar Raj, Paul A. Meyers, Leonard Saltz, Diane Lauren Reidy
Journal: Journal of Clinical Oncology (2015)

321 Background: Whole exome sequencing in WD pNETs demonstrated an increased number of mutations in genes implicated in chromatin remodeling and in the PI3K/Akt/mTOR pathway. Next-generation sequencing (NGS) allows us to bring this technology to the clinic to better characterize WD pNETs and potentially offer tailored therapies. Methods: A NGS platform developed at Memorial Sloan Kettering Cancer Center (MSKCC) termed MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets) was used. This platform screens for 341 cancer genes commonly altered across tumor types. Thus far, 14 patients with WD pNETs have consented to MSK-IMPACT. Results: To date, mostpatients harbor no clinically validated or actionable mutations. Two patients, however, harbor different and potentially actionable BRAF mutations. The first patient is a 39 year-old woman with a BRAF V600E mutation. She presented with somatostatin receptor-negative, aggressive disease involving the liver, lymph nodes, adnexa, and peritoneum. She was initially diagnosed elsewhere as having a signet ring cell adenocarcinoma, and responded to FOLFOX and bevacizumab. Pathology review at MSKCC, however, identified the tumor as metastatic WD pNET. Upon disease progression, a repeat biopsy confirmed metastatic WD pNET. She is currently on capecitabine and temozolomide with clinical improvement. The second patient is a 22 year-old woman with metastatic WD pNET with a BRAF K601E mutation. Her tumor also has an aggressive behavior; she has progressed on all conventional and nonconventional therapies. Given the finding of a BRAF K601E mutation, she received trametinib and dabrafenib, but developed disease progression after 3 months. Conclusions: Two potentially actionable BRAF mutations were identified from NGS of WD pNETs. BRAF mutations have not been previously reported in pNETs. It is unclear whether BRAF mutations are oncogenic drivers, and whether BRAF-targeted treatments would be beneficial. Both patients show an atypical, aggressive presentation and course. Further testing is warranted to determine the role and clinical significance of BRAF in pNETs. Evaluation using pNET tissue microarrays is ongoing and will be reported at the meeting.