Comprehensive copy number and gene expression profiling of the 17q23 amplicon in human breast cancer

The biological significance of DNA amplification in cancer is thought to be due to the selection of increased expression of a single or few important genes. However, systematic surveys of the copy number and expression of all genes within an amplified region of the genome have not been performed. Here we have used a combination of molecular, genomic, and microarray technologies to identify target genes for 17q23, a common region of amplification in breast cancers with poor prognosis. Construction of a 4-Mb genomic contig made it possible to define two common regions of amplification in breast cancer cell lines. Analysis of 184 primary breast tumors by fluorescence in situ hybridization on tissue microarrays validated these results with the highest amplification frequency (12.5%) observed for the distal region. Based on GeneMap'99 information, 17 known genes and 26 expressed sequence tags were localized to the contig. Analysis of genomic sequence identified 77 additional transcripts. A comprehensive analysis of expression levels of these transcripts in six breast cancer cell lines was carried out by using complementary DNA microarrays. The expression patterns varied from one cell line to another, and several overexpressed genes were identified. Of these, RPS6KB1, MUL, APPBP2, and TRAP240 as well as one uncharacterized expressed sequence tag were located in the two common amplified regions. In summary, comprehensive analysis of the 17q23 amplicon revealed a limited number of highly expressed genes that may contribute to the more aggressive clinical course observed in breast cancer patients with 17q23-amplified tumors.

Mutation detection by highly sensitive methods indicates that p53 gene mutations in breast cancer can have important prognostic value.

Human cancer cells with a mutated p53 tumor-suppressor gene have a selective growth advantage and may exhibit resistance to ionizing radiation and certain chemotherapeutic agents. To examine the prognostic value of mutations in the p53 gene, a cohort of 90 Midwestern Caucasian breast cancer patients were analyzed with methodology that detects virtually 100% of all mutations. The presence of a p53 gene mutation was by far the single most predictive indicator for recurrence and death (relative risks of 4.7 and 23.2, respectively). Direct detection of p53 mutations had substantially greater prognostic value than immunohistochemical detection of p53 overexpression. Analysis of p53 gene mutations may permit identification of a subset of breast cancer patients who, despite lack of conventional indicators of poor prognosis, are at high risk of early recurrence and death.

Investigation on Heart Rate Variability (HRV) and psycho-social-affective adjustment in Italian women with ovarian cancer

INTRODUZIONE: L’integrazione mente-corpo applicata ad un ambito patologico predominante in questi tempi, come il cancro, è il nucleo di questa tesi. Il background teorico entro cui è inserita, è quello della Psiconeuroendocrinoimmunologia (Bottaccioli, 1995) e Psico-Oncologia. Sono state identificate, nella letteratura scientifica, le connessioni tra stati psicologici (mente) e condizioni fisiologiche (corpo). Le variabili emerse come potenzialmente protettive in pazienti che si trovano ad affrontare il cancro sono: il supporto sociale, l’immagine corporea, il coping e la Qualità della Vita, insieme all’indice fisiologico Heart Rate Variability (HRV; Shaffer & Venner, 2013). Il potenziale meccanismo della connessione tra queste variabili potrebbe essere spiegato dall’azione del Nervo Vago, come esposto nella Teoria Polivagale di Stephen Porges (2007; 2009). OBIETTIVI: Gli obiettivi principali di questo studio sono: 1. Valutare l’adattamento psicologico alla patologia in termini di supporto sociale percepito, immagine corporea, coping prevalente e qualità della vita in donne con cancro ovarico; 2. Valutare i valori di base HRV in queste donne; 3. Osservare se livelli più elevati di HRV sono associati ad un migliore adattamento psicologico alla patologia; 4. Osservare se una peggiore percezione dell’immagine corporea e l’utilizzo di strategie di coping disadattive sono associate ad una Qualità della Vita più scarsa. METODO: 38 donne affette da cancro ovarico, al momento della valutazione libere da patologia, sono state reclutate presso la clinica oncologica del reparto di Ginecologia dell’Azienda Ospedaliero-Universitaria di Parma, Italia. Ad ogni partecipante è stato chiesto di compilare una batteria di test composta da: MSPSS, per la valutazione del supporto sociale percepito; DAS-59, per la valutazione dell’immagine corporea; MAC, per la valutazione delle strategie di coping prevalenti utilizzate verso il cancro; EORTC-QLQ30, per la valutazione della Qualità della Vita. Per ogni partecipante è stato registrato HRV di base utilizzando lo strumento emWave (HeartMath). RISULTATI PRINCIPALI: Rispondendo agli obiettivi 1 e 2, in queste donne si è rilevato una alto tasso di supporto sociale percepito, in particolare ricevuto dalla persona di riferimento. L’area rivelatasi più critica nel supporto sociale è quella degli amici. Per quanto riguarda l’immagine corporea, la porzione di campione dai 30 ai 61 anni, ha delle preoccupazioni globali legate all’immagine corporea paragonabili ai dati provenienti dalla popolazione generale con preoccupazioni riguardo l’aspetto corporeo. Invece, nella porzione di campione dai 61 anni in su, il pattern di disagio verso l’aspetto fisico sembra decisamente peggiorare. Inoltre, in questo campione, si è rilevato un disagio globale verso l’immagine corporea significativamente più alto rispetto ai valori normativi presenti in letteratura riferiti a donne con cancro al seno con o senza mastectomia (rispettivamente t(94)= -4.78; p<0.000001; t(110)= -6.81;p<0.000001). La strategia di coping più utilizzata da queste donne è lo spirito combattivo, seguito dal fatalismo. Questo campione riporta, inoltre, una Qualità della Vita complessivamente soddisfacente, con un buon livello di funzionamento sociale. L’area di funzionalità più critica risulta essere il funzionamento emotivo. Considerando i sintomi prevalenti, i più riferiti sono affaticamento, disturbi del sonno e dolore. Per definire, invece, il pattern HRV, sono stati confrontati i dati del campione con quelli presenti in letteratura, riguardanti donne con cancro ovarico. Il campione valutato in questo studio, ha un HRV SDNN (Me=28.2ms) significativamente più alto dell’altro gruppo. Tuttavia, confrontando il valore medio di questo campione con i dati normativi sulla popolazione sana (Me=50ms), i nostri valori risultano drasticamente più bassi. In ultimo, donne che hanno ricevuto diagnosi di cancro ovarico in età fertile, sembrano avere maggiore HRV, migliore funzionamento emotivo e minore sintomatologia rispetto alle donne che hanno ricevuto diagnosi non in età fertile. Focalizzando l’attenzione sulla ricerca di relazioni significative tra le variabili in esame (obiettivo 3 e 4) sono state trovate numerose correlazioni significative tra: l’età e HRV, supporto percepito , Qualità della Vita; Qualità della Vita e immagine corporea, supporto sociale, strategie di coping; strategie di coping e immagine corporea, supporto sociale; immagine corporea e supporto sociale; HRV e supporto sociale, Qualità della Vita. Per verificare la possibile connessione causale tra le variabili considerate, sono state applicate regressioni lineari semplici e multiple per verificare la bontà del modello teorico. Si è rilevato che HRV è significativamente positivamente influenzata dal supporto percepito dalla figura di riferimento, dal funzionamento di ruolo, dall’immagine corporea totale. Invece risulta negativamente influenzata dal supporto percepito dagli amici e dall’uso di strategie di coping evitanti . La qualità della vita è positivamente influenzata da: l’immagine corporea globale e l’utilizzo del fatalismo come strategia di coping prevalente. Il funzionamento emotivo è influenzato dal supporto percepito dalla figura di riferimento e dal fatalismo. DISCUSSIONI E CONCLUSIONI: Il campione Italiano valutato, sembra essere a metà strada nell’adattamento dello stato psicologico e dell’equilibrio neurovegetativo al cancro. Sicuramente queste donne vivono una vita accettabile, in quanto sopravvissute al cancro, ma sembra anche che portino con sé preoccupazioni e difficoltà, in particolare legate all’accettazione della loro condizione di sopravvissute. Infatti, il migliore adattamento si riscontra nelle donne che hanno avuto peggiori condizioni in partenza: stadio del cancro avanzato, più giovani, con diagnosi ricevuta in età fertile. Pertanto, è possibile suggerire che queste condizioni critiche forzino queste donne ad affrontare apertamente il cancro e la loro situazione di sopravvissute al cancro, portandole ad “andare avanti” piuttosto che “tornare indietro”. Facendo riferimento alle connessioni tra variabili psicologiche e fisiologiche in queste donne, si è evidenziato che HRV è influenzata dalla presenza di figure significative ma, in particolare, è presumibile che sia influenzata da un’appropriata condivisione emotiva con queste figure. Si è anche evidenziato che poter continuare ad essere efficaci nel proprio contesto personale si riflette in un maggiore HRV, probabilmente in quanto permette di preservare il senso di sé, riducendo in questo modo lo stress derivante dall’esperienza cancro. Pertanto, HRV in queste donne risulta associato con un migliore adattamento psicologico. Inoltre, si è evidenziato che in queste donne la Qualità della Vita è profondamente influenzata dalla percezione dell’immagine corporea. Si tratta di un aspetto innovativo che è stato rilevato in questo campione e che, invece, nei precedenti studi non è stato indagato. In ultimo, la strategia di coping fatalismo sembra essere protettiva e sembra facilitare il processo di accettazione del cancro. Si spera sinceramente che le ricerche future possano superare i limiti del presente studio, come la scarsa numerosità e l’uso di strumenti di valutazione che, per alcuni aspetti come la scala Evitamento nel MAC, non centrano totalmente il target di indagine. Le traiettorie future di questo studio sono: aumentare il numero di osservazioni, reclutando donne in diversi centri specialistici in diverse zone d’Italia; utilizzare strumenti più specifici per valutare i costrutti in esame; valutare se un intervento di supporto centrato sul miglioramento di HRV (come HRV Biofeedback) può avere una ricaduta positiva sull’adattamento emotivo e la Qualità della Vita.

Psychosocial Distress Screening in a Community Cancer Center: An Examination of Gender Differences

Objective: The aim of this study was to gain a better understanding of the needs of male and female oncology patients within a community cancer setting to inform the provision of psychosocial services. Data obtained from 835 single-page measures of oncology patient distress were collected and analyzed to examine the relationship between gender and reported level of distress, the source of this distress, and requests for follow-up from psychosocial service providers.Method: Patients in medical and radiation oncology were given a distress screener tool that included a distress thermometer, a problem checklist, and a list of psychosocial service providers with whom the patient could request to speak.Results: Women reported higher levels of distress than men (p=.003). Women were also more likely than men to endorse practical problems as the cause of their distress (p=.003). A marginally significant relationship between gender and requesting the cancer resource navigator was also found (p=. 059)Conclusion: Gender is a salient factor in reported distress among cancer patients. Although no single variable can entirely explain an individual's response to cancer, male and female patients do appear to have distinctive, gender-specific needs. Psychosocial interventions that account for differences related to gender-role may be particularly beneficial. These results also illustrate the utility of consistent screening practices to better understand and meet the psychosocial needs of oncology

Psychosocial Distress Screening in a Community Cancer Center: An Exploratory Study of Distress Screening Across the Cancer Treatment Continuum

Purpose: The primary goal of this exploratory study is to demonstrate that distress screening across the course of cancer treatment is possible and provides valuable information about patient needs over time. Distress screening is aligned with guidelines from national accrediting organizations and may lead to improved health-related quality of life, satisfaction with medical care, and possibly survival.Methods: Medical, surgical, and radiation oncology patients completed a screening instrument before their appointments during a six-month period. Patients indicated their level of distress on four domains (practical, emotional, health and social concerns). De-identified data was collected, aggregated and descriptive statistics were analyzed.Results: Approximately 3000 screens were collected and 1500 cancer patients were screened. Of patients who indicated distress, 54% demonstrated a distress level of five or greater. Distress level eight was the most frequent level of distress indicated. The Cancer Dietitian was the most commonly requested healthcare team provider. The Health Concern domain was most frequently endorsed.Conclusion: NCCN, IOM and COC guidelines recommend distress screening in all cancer treatment centers, however implementation has proven difficult. This study adds to the literature about distress in cancer patients, demonstrates the feasibility of repeated distress screening and provides a model program demonstrating the implementation of repeated distress screening at a community cancer center. Findings highlight the importance of supportive oncology services due to the prevalence of high levels of distress. Findings demonstrate the importance of the Cancer Dietitian in supportive cancer care. Additionally, the research reveals a potential perceived stigma in seeking psychosocial oncology services.

Implicating the mechanisms of ADP-ribosylation factor activation in the resistance of invasive breast cancer cells to EGFR tyrosine kinase inhibitors

ADP-ribosylation factor-1 (ARF1) est une petite GTPase principalement connue pour son rôle dans la formation de vésicules au niveau de l’appareil de Golgi. Récemment, dans des cellules de cancer du sein, nous avons démontré qu’ARF1 est aussi un médiateur important de la signalisation du récepteur du facteur de croissance épidermique (EGFR) contrôlant la prolifération, la migration et l'invasion cellulaire. Cependant, le mécanisme par lequel l’EGFR active la GTPase ainsi que le rôle de cette dernière dans la régulation de la fonction du récepteur demeure inconnue. Dans cette thèse, nous avions comme objectifs de définir le mécanisme d'activation de ARF1 dans les cellules de cancer du sein hautement invasif et démontrer que l’activation de cette isoforme de ARF joue un rôle essentiel dans la résistance de ces cellules aux inhibiteurs de l'EGFR. Nos études démontrent que les protéines d’adaptatrices Grb2 et p66Shc jouent un rôle important dans l'activation de ARF1. Alors que Grb2 favorise le recrutement d’ARF1 à l'EGFR ainsi que l'activation de cette petite GTPase, p66Shc inhibe le recrutement du complexe Grb2-ARF1 au récepteur et donc contribue à limiter l’activation d’ARF1. De plus, nous démontrons que ARF1 favorise la résistance aux inhibiteurs des tyrosines kinases dans les cellules de cancer du sein hautement invasif. En effet, une diminution de l’expression de ARF1 a augmenté la sensibilité descellules aux inhibiteurs de l'EGFR. Nous montrons également que de hauts niveaux de ARF1 contribuent à la résistance des cellules à ces médicaments en améliorant la survie et les signaux prolifératifs à travers ERK1/2, Src et AKT, tout en bloquant les voies apoptotiques (p38MAPK et JNK). Enfin, nous mettons en évidence le rôle de la protéine ARF1 dans l’apoptose en réponse aux traitements des inhibiteurs de l’EGFR. Nos résultats indiquent que la dépletion d’ARF1 promeut la mort cellulaire induite par gefitinib, en augmentant l'expression de facteurs pro-apoptotiques (p66shc, Bax), en altérant le potentiel de la membrane mitochondriale et la libération du cytochrome C. Ensemble, nos résultats délimitent un nouveau mécanisme d'activation de ARF1 dans les cellules du cancer du sein hautement invasif et impliquent l’activité d’ARF1 comme un médiateur important de la résistance aux inhibiteurs EGFR.

Endothelial Progenitor Cells in Breast Cancer

Editorial

Investigational cancer treatments coverage report /

To comply with 20 ILCS 1405/56.3, the Illinois Dept. of Insurance was required to conduct a three year report (2000-2002), which included an analysis of the effect of the coverage requirements on the cost of insurance and health care; the results of the treatments to patients; the mortality rate among cancer patients; any improvements in care of patients; and any imporvements in the quality of life of patients.

Social Support Networks and Self-Efficacy of Peruvian Women Diagnosed with Cancer: A Biocultural Analysis of Health Behavior Constructs

Thesis (Ph.D.)--University of Washington, 2016-06

Information extraction from clinical and radiology notes for liver cancer staging

Thesis (Ph.D.)--University of Washington, 2016-06

Approaches and Strategy for Cancer Research and Surveillance Data: Integration, Information Pipeline, Data Models, and Informatics Opportunities

Thesis (Ph.D.)--University of Washington, 2016-04

A randomized controlled trial of a nurse-administered educational intervention for improving cancer pain management in ambulatory settings

The persistence of negative attitudes towards cancer pain and its treatment suggests there is scope for identifying more effective pain education strategies. This randomized controlled trial involving 189 ambulatory cancer patients evaluated an educational intervention that aimed to optimize patients' ability to manage pain. One week post-intervention, patients receiving the pain management intervention (PMI) had a significantly greater increase in self-reported pain knowledge, perceived control over pain, and number of pain treatments recommended. Intervention group patients also demonstrated a greater reduction in willingness to tolerate pain, concerns about addiction and side effects, being a "good" patient, and tolerance to pain relieving medication. The results suggest that targeted educational interventions that utilize individualized instructional techniques may alter cancer patient attitudes, which can potentially act as barriers to effective pain management. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Risk factors for development of delirium among oncology patients

To determine the occurrence of delirium in oncology inpatients and to identify and evaluate admission characteristics associated with the development of delirium during inpatient admission, a prospective observational study was conducted of H 3 patients with a total of 145 admissions with histological diagnosis of cancer admitted to the oncology unit over a period of ten weeks. At the point of inpatient admission, all patients were assessed for the presence of potential risk factors for development of delirium. During the index admission patients were assessed daily for the presence of delirium using the Confusion Assessment Method. Delirium was confirmed by clinician assessment. Delirium developed in 26 of 145 admissions (18%) and 32 episodes of delirium were recorded with 6 patients having 2 episodes of delirium during the index admission. Delirium occurred on average 3.3 days into the admission. The average duration of an episode of delirium was 2.1 day. Four patients with delirium (15%) died. All other cases of delirium were reversed. Factors significantly associated with development of delirium on multivariate analysis were: advanced age, cognitive impairment, low albumin level, bone metastases, and the presence of hematological malignancy. Hospital inpatient admission was significantly longer in delirium group (mean: 8.8 days vs 4.5 days in nondelirium group, P

Factors associated with the wish to hasten death: a study of patients with terminal illness

Background. There is considerable debate regarding the clinical issues surrounding the wish to hasten death (WTHD) in the terminally ill. The clinical factors contributing to the WTHD need further investigation among the terminally ill in order to enhance understanding of the clinical assessment and treatment needs that underlie this problem. A more detailed understanding may assist with the development of appropriate therapeutic interventions. Method. A sample of terminally ill cancer patients (N=256) recruited from an in-patient hospice unit, home palliative care service and a general hospital palliative care consulting service from Brisbane Australia between 1998-2001 completed a questionnaire assessing psychological (depression and anxiety), social (family relationship, social support, level of burden on others) and the impact of physical symptoms. The association between these factors and the WTHD was investigated. Results. A high WTHD was reported by 14% of patients. A discriminant function analysis revealed that the following variables were associated with a high WTHD (P

Doctors and their patients: A context for understanding the wish to hasten death

There is a paucity of research that has directly examined the role of the health professional in dealing with a terminally ill patient's wish to hasten death (WTHD) and the implications of this for the support and services needed in the care for a dying patient. Themes to emerge from a qualitative analysis of interviews conducted on doctors (n = 24) involved in the treatment and care of terminally ill patients were (i) the doctors' experiences in caring for their patients (including themes of emotional demands/expectations, the duration of illness, and the availability of palliative care services); (ii) the doctors' perception of the care provided to their respective patients (comprising themes concerning satisfaction with the care for physical symptoms, for emotional symptoms, or overall care); (iii) the doctors' attitudes to euthanasia and (iv) the doctors' perception of their patients' views/beliefs 'regarding euthanasia and hastened death. When responses were categorised according to the patients' level of a WTHD, the theme concerning the prolonged nature of the patients' illnesses was prominent in the doctor group who had patients with the highest WTHD, whereas there was only a minority of responses concerning support from palliative care services and satisfaction with the level of emotional care in this group. This exploratory study presents a set of descriptive findings identifying themes among a small group of doctors who have been involved in the care of terminally ill cancer patients, to investigate factors that may be associated with the WTHD among these patients. The pattern of findings suggest that research investigating the doctor-patient interaction in this setting may add to our understanding of the problems (for patients and their doctors) that underpins the wish to hasten death in the terminally ill. Copyright (C) 2003 John Wiley Sons, Ltd.