tbuckley/cabot-search huggingface dataset:
Circulating tumour markers and time to progression in the chemotherapy treatment of metastatic breast cancer
Authors: M. Ruiz-Lopez-tejada, L. Tejedor-Cabrera, C. Iradi-Martinez
Journal: Journal of Clinical Oncology (2006)

10674 Background: Monitoring the response to the chemotherapy treatment (CT) in metastatic breast cancer (MBC) by circulating tumour markers (CTM) remains under investigation. We have previosly shown that early lack of biological progression of 4 CTM (1 oncofetal: CEA, 2 mucin related: CA 15.3,CA 549 and cytokeratin 18–19: TPA), predicts anatomic disease control - concordance nearly 100% for every CTM- during CT of MBC (E.J.C. Suppl Oct 2005, Vol 3 Abst 415- ECCO 13). The aim is to evaluate whether the biological behaviour predicts time till progression (TTP), as reliable parameter of the quality of response (QR). Methods: In 106 consecutive courses of different schedules of CT given along 3 years in our Hospital to 55 patients with progressive MBC, we conducted a prospective trial analysing these 4 CTM every 3 weeks before CT infusions and performing CTM concentration / time curves. TTP was calculated by Kaplan Meier method -SPSS 11-. Bio kinetic change has been defined as a lineal slope that includes 2 early and consecutive changes of at least 25% of CTM start value. The analysis covered 604 cycles, 405 curves and 2417 marker determinations. Results: Ninety six per cent of the cases have progressed after their CT courses. In CTM expressing diseases, and sometimes after a no more than 3 weeks paradoxical period, three biological patterns could be detected according to directional possibilities: progressive elevation (Bio P), progressive download (Bio R) and stabilization -without bio kinetic change- (Bio S). Table shows the TTP median values in the different group of cases with the same CTM Bio response patterns; Biological Patterns and TTP Kaplan Meier curves will be shown as a Poster at the meeting. Conclusions: In CTM expressing tumours and taking into account simple kinetics criteria, the dynamic analysis of CTM before infusions can early estimates TTP, adding complemmentary information to the disease control prediction in the evaluation of the QR during the CT of MBC. [Table: see text] No significant financial relationships to disclose.
Initial experience with an innovative pilot program evaluating a multidisciplinary approach to supportive care planning in a survivorship clinic setting.
Authors: Lisa M. Radice, Jeffrey Eagan, Kathleen Y. Michie, Marianne Pearson, Joshua H. Petit
Journal: Journal of Clinical Oncology (2014)

242 Background: The supportive care and rehabilitative needs of cancer patients are highly varied and complex, and optimal care planning often requires the provision and coordination of multiple modalities. To address these needs, an innovative model for multi-disciplinary evaluation and management within a survivorship clinic was piloted. Methods: Between November 2013 and May 2014, 50 patients who had completed cancer therapy with curative intent were seen in a multi-disciplinary survivorship clinic (MDSC) sequentially by an advanced practice practitioner (nurse practitioner or physician assistant), oncology social worker, and oncology rehabilitation therapist. Data regarding specific care planning resulting from this encounter, compliance with recommended therapies, and patient-reported satisfaction were collected. These data were compared against the remaining cohort of patients (N = 402) who completed curative intent cancer therapy in our cancer program during the same period. Results: Rate of referral for rehabilitation services (83.3% vs 13.9%, p &lt; 0.01) and compliance with recommended therapy visits (85.7% vs 44.6%, p &lt; 0.01) were significantly increased among patients seen within the MDSC pilot when compared with similar patients who were not seen in this setting. The number of referred therapy modalities was also increased among patients seen in the MDSC pilot, median 2 (range 1-3 modalities) vs 1 (range 1-2 modalities), respectively. Of patients who completed an assessment following the multi-disciplinary visit, 86% scored their overall experience as excellent which was the highest possible score. Conclusions: Patients seen within an innovative pilot program of multi-disciplinary survivorship care planning appreciated increased rates of referral for rehabilitation services, were referred for a greater number of therapy modalities, and were more compliant with recommended interventions than similar patients who were not seen in this setting. This patient cohort also reported high rates of satisfaction with the pilot program.
Select high risk genetic features predict earlier progression following chemotherapy in chronic lymphocytic leukemia: Prospective randomized trial (Intergroup E2997) to evaluate justification for risk-adapted therapy
Authors: M. R. Grever, G. W. Dewald, D. S. Neuberg, J. C. Reed, S. Kitada, I. W. Flinn, F. R. Appelbaum, R. A. Larson, M. S. Tallman, J. G. Gribben, J. C. Byrd
Journal: Journal of Clinical Oncology (2006)

6521 Background: Genomic features including lack of IgV H mutations, del(11q), del(17p), and p53 mutations have been reported to predict clinical course and overall survival in CLL patients (pts). Bcl-2 family proteins and ZAP-70 have also been explored as predictors in CLL. Methods: We prospectively evaluated the prognostic significance of clinical features and laboratory variables on response and progression-free survival (PFS) following treatment with fludarabine (F, n=132) or fludarabine plus cyclophosphamide (FC, n=137) as part of the US Intergroup Trial E2997 for previously untreated CLL. Results: FC therapy had higher complete response (CR) (23.4% versus 4.6%), overall response (OR) (74.3% versus 59%), and median PFS (31.6 mos versus 19.2 mos) compared to F. CR and OR were not significantly different based on interphase cytogenetics, IgV H status, or p53 mutation. IgV H status or levels of ZAP-70, Bcl-2, Bax, Mcl-1, XIAP, Caspase-3, and Traf-1 proteins were not associated with clinical response or PFS. IgV H status and ZAP-70 levels were associated with time from diagnosis to treatment. Using a model including treatment arm, pts with del(17p) or (11q) had significantly shorter PFS (hazard ratios 3.54 and 2.05 respectively). In pts with a p53 mutation without del(17p) there was no enhancement of the model predicting poorer outcome, nor did IgV H status enter the model for predicting PFS. Conclusions: Combination chemotherapy is associated with a higher CR, OR, and PFS. Also, initiation of therapy for pts with Rai stages 0/1 resulted in a higher response rate. Del(17p) and del(11q) are highly predictive of shortened PFS with fludarabine-based chemotherapy. IgV H and p53 mutational status, as well as expression of ZAP-70, Bcl-2 family proteins, and CD38, did not predict response or PFS. ZAP-70 expression is associated with cytogenetic subsets predicted to have a worse overall prognosis, but did not identify pts who will do poorly with therapy. A combination of clinical staging and cytogenetics provide support for future risk-stratified treatment of CLL. Pts with a projected short response duration can be identified for future investigational strategies. No significant financial relationships to disclose.
Progression-free survival in metastatic, BRAF-mutated colorectal cancer.
Authors: Van Karlyle Morris, Michael J. Overman, Dipen M Maru, Scott Kopetz
Journal: Journal of Clinical Oncology (2013)

458 Background: BRAF mutations occur in 5-8% of metastatic colorectal cancers and are associated with a significantly worse overall prognosis relative to patients with BRAF wild-type tumors. However, the outcomes with standard chemotherapy of a large cohort of patients with BRAF mutant tumors have not been described. Methods: We searched the MD Anderson Cancer Center databases for colorectal cancer patients with identified BRAF mutations between December 2003 and May 2012. Patients were analyzed for clinical characteristics, progression-free survival, and chemotherapeutic agents used. Survival was estimated according to the Kaplan-Meier method. Results: Among the 1567 patients tested for BRAF mutations at our institution, 127 (8.1%) had tumors with BRAF mutations. The average age was 59.6 years at the time of diagnosis, and 65/127 patients (51.2%) were male. The 71 patients who presented with metastatic disease received a median of 2 lines of chemotherapy. For the first three lines of chemotherapy, median progression-free survival was 5.6 months (n=69 patients), 3.9 months (n=58), and 3.4 months (n=31), respectively. Median PFS was not affected by the backbone chemotherapeutic agent in the first-line setting, whether oxaliplatin-based or irinotecan-based (6.1 months vs. 5.1 months, respectively, p-value = 0.78). Conclusions: Progression-free survival is expectedly poor for patients with BRAF-mutated metastatic colorectal cancer. Despite the ascertainment bias present in this cohort (with testing preferentially performed in patients suitable for clinical trials in refractory disease), fewer than half of patients with metastatic disease received more than 2 lines of therapy. This data not only provides historic controls suitable for future study design in this population but also supports the idea that novel therapeutic options are essential for this group of patients.
Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function
Authors: Min Chul Park, Hyobin Jeong, Sung Hwa Son, YounHa Kim, Daeyoung Han, Peter C. Goughnour, Taehee Kang, Nam Hoon Kwon, Hyo Eun Moon, Sun Ha Paek, Daehee Hwang, Ho Jun Seol, Do-Hyun Nam, Sunghoon Kim
Journal: Cancer Research (2015)

Abstract Tumor permeability is a critical determinant of drug delivery and sensitivity, but systematic methods to identify factors that perform permeability barrier functions in the tumor microenvironment are not yet available. Multicellular tumor spheroids have become tractable in vitro models to study the impact of a three-dimensional (3D) environment on cellular behavior. In this study, we characterized the spheroid-forming potential of cancer cells and correlated the resulting spheroid morphologies with genetic information to identify conserved cellular processes associated with spheroid structure. Spheroids generated from 100 different cancer cell lines were classified into four distinct groups based on morphology. In particular, round and compact spheroids exhibited highly hypoxic inner cores and permeability barriers against anticancer drugs. Through systematic and correlative analysis, we reveal JAK–STAT signaling as one of the signature pathways activated in round spheroids. Accordingly, STAT3 inhibition in spheroids generated from the established cancer cells and primary glioblastoma patient–derived cells altered the rounded morphology and increased drug sensitivity. Furthermore, combined administration of the STAT3 inhibitor and 5-fluorouracil to a mouse xenograft model markedly reduced tumor growth compared with monotherapy. Collectively, our findings demonstrate the ability to integrate 3D culture and genetic profiling to determine the factors underlying the integrity of the permeability barrier in the tumor microenvironment, and may help to identify and exploit novel mechanisms of drug resistance. Cancer Res; 76(5); 1044–54. ©2015 AACR.
PWE-398 Cold hands warm heart: does hand rubbing really make a difference?
Authors: C Gunner, M Lee, A Bhakta, H Casserly, K Chapple
Journal: Gut (2015)

<h3>Introduction</h3> Abdominal examination by a physician with cold hands may produce patient discomfort. Traditionally, the examining hands are rubbed together to alleviate this discomfort. However, abdominal skin is only sensitive to changes in temperature greater than 0.8°C. Therefore, we investigated whether a traditionally-performed ‘hand rub’ results in a clinically-relevant change in hand temperature. <h3>Method</h3> 39 female and 32 male test subjects were recruited at random on multiple days in summer. All were members of staff. Inclusion criteria were willingness to partake, possession of two hands and no injuries which may hinder full participation. Participant age ranged from 20 to 55. An infrared thermometer was used to measure baseline subject hand temperature in degrees centigrade on the right hand at a distance of 2 cm. Subjects were instructed to rub their hands together vigorously for 2 and 10 s with repeat palm temperature recordings taken 2 s after each rub, simulating the time taken in clinical practice between hand rubbing and patient contact. This process was repeated 3 times with an interval time of 1 min. <h3>Results</h3> Baseline palm temperature was 30.9 ± 1.4°C. After 2 s of hand rubbing palmar temperature rose to 31.1 ± 1.2°C (P = 0.11) and after 10 s of hand rubbing palmar temperature rose to 31.3 ± 1.3°C (P = 0.02). <h3>Conclusion</h3> Vigorous hand rubbing prior to abdominal examination produces no clinically meaningful rise in hand temperature. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Williams LE, Bargh JA. Experiencing Physical Warmth Promotes Interpersonal Warmth. <i>Science</i>. 2008 October 24; 322(5901):606-607 Stevens J, Choo K. Temperature Sensitivity of the Body Surface Over the Life Span. Somatosensory and Motor Research. 1998;15(1):13-28
The cyclophilin-inhibitor alisporivir stimulates antigen presentation thereby promoting antigen-specific CD8+ T cell activation
Authors: Katharina Esser-Nobis, Julia Schmidt, Katja Nitschke, Christoph Neumann-Haefelin, Robert Thimme, Volker Lohmann
Journal: Journal of Hepatology (2016)

Cyclophilin-inhibitors have potent antiviral activity against Hepatitis C virus (HCV) and are promising candidates for broad-spectrum antiviral therapy. Cyclosporine A (CsA) acts immunosuppressive by blocking T cell activation and antigen presentation. Alisporivir, a non-immunosuppressive CsA analog in clinical development, does not inhibit T cell activation. In this study we explored the impact of alisporivir on antigen presentation.Hepatoma cells endogenously expressing the epitope-restricting major histocompatibility complex-class I (MHC-I) allele HLA-A2 and constitutively expressing a viral antigen were established to study the impact of cyclophilin-inhibitors on antigen presentation. Antigen-specific CD8(+) T cell activation and MHC-I surface expression were measured to quantify antigen presentation.Our work establishes a novel cell culture model to study antigen presentation in liver-derived cells. Authentic regulation of antigen presentation was ensured by the action of pro- and anti-inflammatory cytokines. Alisporivir pretreatment stimulated antigen presentation by hepatoma target cells, leading to enhancement of antigen-specific CD8(+) T cell activation by 40%. Alisporivir, as well as a panel of other cyclophilin-inhibitors, induced an increase of MHC-I and beta-2 microglobulin on the surface of several cell lines. The drug neither enhanced MHC-I transcript or protein levels nor affected surface expression of other proteins or protein trafficking in general. Proteasome-inhibitors completely blocked the alisporivir-directed enhancement of surface MHC-I, suggesting an influence of the drug on peptide-availability.Alisporivir stimulates antigen presentation by inducing enhanced MHC-I surface expression, thereby promoting antigen-specific CD8(+) T cell activation. This immunostimulatory function might further contribute to the antiviral activity of non-immunosuppressive cyclophilin-inhibitors.
Two Phenomena Associated With Skin Grafting From Tumor-Bearing Syngeneic Donors
Authors: George J. Svet-Moldavsky, M.D., Demuri M. Mkheidze, Alexander L. Liozner
Journal: JNCI Journal of the National Cancer Institute (1967)

Syngeneic skin grafting from mice with transplantable solid tumors was often accompanied by the development of tumors originating from the skin grafts. These tumors appeared at intervals corresponding to the time of their development when pieces of tumors were transplanted. Syngeneic grafting of skin from mice with transplantable sarcoma resulted in the regular rejection of transplants. The presence of some tumors may cause the donor's tissues to become incompatible in the syngeneic system. The characteristics of this phenomenon, designated as “heterogenization” of skin by means of tumor, are presented. Skin grafts taken from mice that had rejected a skin transplant derived from a tumor-bearing donor were also rejected in the syngeneic transplantation. Possible mechanisms of the described phenomena are briefly discussed.
P0199 : Acute kidney injury in cirrhosis: Baseline serum creatinine predicts patient outcomes
Authors: F. Wong, J.G. O’Leary, K.R. Reddy, G. Garcia-Tsao, M.B. Fallon, S.W. Biggins, R. Subramanian, P. Thuluvath, P.S. Kamath, H. Patton, B. Maliakkal, P. Tandon, H. Vargas, L.R. Thacker, J.S. Bajaj
Journal: Journal of Hepatology (2015)
Cyclic Mechanical Stretch In Two And Three Dimensions Activates YAP/TAZ To Regulate Surfactant Expression In Type 2 Alveolar Cells And Distal Airway Progenitor Cells
Authors: Wagner Darcy, Bonenfant Nick, D. Borg Zachary, Sokocevic Dino, Zhou Beiyun, Borok Zea, R. Stripp Barry, R Loi, J. Weiss and Daniel
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Multicenter phase II trial of mitoxantrone in patients with advanced nasopharyngeal carcinoma in Southeast Asia: an Asian-Oceanian Clinical Oncology Association Group study.
Authors: M Dugan, D Choy, A Ngai, J Sham, P Choi, W Shiu, T Leung, P Teo, U Prasad, S Lee
Journal: Journal of Clinical Oncology (1993)

PURPOSE Patients with advanced nasopharyngeal carcinoma (NPC) have a high incidence of recurrence and often develop distant metastases despite local control. This prospective multicenter phase II trial was conducted to evaluate the safety and efficacy of Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ) in the therapy of patients with advanced NPC. PATIENTS AND METHODS One hundred eight patients with advanced NPC, namely, those with recurrent or persistent disease following primary radiotherapy, or newly diagnosed metastatic disease, were treated with mitoxantrone. Mitoxantrone was administered intravenously at an initial dose of 12 mg/m2 and repeated every 3 weeks, with dose escalation to a maximum of 14 mg/m2. The distribution of histologic subtypes was representative of NPC, with the majority being (61%) undifferentiated (or anaplastic) carcinoma. RESULTS The overall response rate (complete response [CR] and partial response [PR]) was 25% (95% confidence interval, 17% to 33%). The median response duration, time to treatment failure, and survival duration were 140, 82, and 394 days, respectively. Histology (poorly differentiated squamous cell) was found to be the only important factor in predicting response (P = .04) based on a multivariate analysis of nine pretreatment characteristics. The major dose-limiting toxicity was leukopenia. The incidences of nausea/vomiting, alopecia, and stomatitis/mucositis were 34%, 6%, and 3%, respectively. None were severe. Two patients had asymptomatic, moderate Alexander-grade cardiotoxicity. CONCLUSION This study represents a large, controlled multicenter trial of single-agent mitoxantrone in the treatment of advanced NPC. Mitoxantrone was well tolerated and produced an overall response rate comparable to that of other single-agent therapies used in the treatment of advanced head and neck cancer. Combination trials with mitoxantrone for advanced disease should be considered.
Comparison of two adjuvant chemotherapy regimens for locally advanced gastric cancer with long term follow-up
Authors: S. Jeong, J. Choi, S. Kang, H. Lee, J. Jung, Y. Choi, Y. Cho, S. Han, H. Lim
Journal: Journal of Clinical Oncology (2008)

4644 Background: Although adjuvant chemotherapy (CTX) has demonstrated small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, optimal chemotherapy regimen remains to be determined. Methods: We retrospectively analyzed the survival of 313 locally advanced gastric cancer patients (pts) (stage IB: 28, II: 95, IIIA: 89, IIIB: 46, IV: 55) who underwent adjuvant CTX after curative resection (≥D2 dissection). One hundred and six pts received 5-FU, doxorubicin (DOX) CTX (5-FU 500 mg/m2 weekly for 36 wks, DOX 40 mg/m2 q 3 weeks x 12) with or without OK432 (FA group), while 207 pts underwent 5-FU, mitomycin-C (MMC), and polysaccharide-K (PSK) CTX (5-FU 500 mg/m2 weekly for 24 wks, MMC 8 mg/m2 q 6 wks x 4, PSK 3 g/day for 16 wks) (FM group). Results: The median follow-up durations of survivors in the two groups were 147 (134–160) months (FA group) and 113 (93–134) months (FM group), respectively. The stage distribution and mean age in the two groups were almost identical. There was no significant difference in 8-year overall survival (OS) between FA and FM groups (52.8% vs. 55.6%, p=0.783). FM group showed superior 8-year OS (80.0% vs. 64.1%, p=0.036) compared with FA group in stage IB or II patients, while there was no statistically significant difference in 8-year OS (39.0% vs. 46.3%, p=0.168) in stage IIIA to IV patients Conclusions: 5-FU, MMC, and PSK CTX for 24 wks is as effective as 5-FU and DOX-based CTX with longer treatment duration and even superior in stage IB and II pts. No significant financial relationships to disclose.
Clinical Trial of Oral Nelfinavir before and during Radiation Therapy for Advanced Rectal Cancer
Authors: Esme J. Hill, Corran Roberts, Jamie M. Franklin, Monica Enescu, Nicholas West, Thomas P. MacGregor, Kwun-Ye Chu, Lucy Boyle, Claire Blesing, Lai-Mun Wang, Somnath Mukherjee, Ewan M. Anderson, Gina Brown, Susan Dutton, Sharon B. Love, Julia A. Schnabel, Phil Quirke, Ruth Muschel, William G. McKenna, Michael Partridge, Ricky A. Sharma
Journal: Clinical Cancer Research (2016)

Nelfinavir, a PI3K pathway inhibitor, is a radiosensitizer that increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach.
Crime and violence among mental patients reconsidered in view of the new legal relationship between the state and the mentally ill
Authors: L Sosowsky
Journal: American Journal of Psychiatry (1978)

The author compared the arrest rates of 301 former state mental hospital patients with those of the local county population and selected U.S. cities. He found that the patients had a markedly higher incidence of arrests for criminal behavior, including violent offenses, than either of the comparison groups. Patients who were female, aged 20-30, and nonwhite had higher arrest rates for violent offenses than the rest of the study group. These findings are at variance with those of earlier studies but are in general agreement with more recent studies. The author suggests the need for further research in order to more completely identify those factors which explain the high crime rate among the mentally ill.