Using a rhabdomyosarcoma patient-derived xenograft to examine precision medicine approaches and model acquired resistance.

Background: Precision (Personalized) medicine has the potential to revolutionize patient health care especially for many cancers where the fundamental disease etiology remains either elusive or has no available therapy. Here we outline a study in alveolar rhabdomyosarcoma, in which we use gene expression profiling and a series of drug prediction algorithms combined with a matched patient-derived xenograft (PDX) model to test bioinformatically predicted therapies.

Procedure: A PDX model was developed from a patient biopsy and a number of drugs identified using gene expression analysis in combination with drug prediction algorithms.

Epidermal growth factor receptor inhibitor gefitinib added to chemoradiotherapy in locally advanced head and neck cancer.

Purpose: Assess efficacy and toxicity of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, added to, and in maintenance after, concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer (LA-HNC) and correlate outcomes with EGFR gene copy number alterations.

Patients And Methods: Patients with stage III to IV LA-HNC received two cycles of carboplatin/paclitaxel induction chemotherapy (IC) followed by split-course CCRT with fluorouracil, hydroxyurea, twice daily radiotherapy (FHX), and gefitinib (250 mg daily) followed by continued gefitinib for 2 years total. The primary end point was complete response (CR) rate after CCRT.

Prospective evaluation of the relationship of patient age and paclitaxel clinical pharmacology: Cancer and Leukemia Group B (CALGB 9762).

Purpose: To prospectively evaluate the pharmacokinetics and toxicity profile of paclitaxel in relation to patient age in adults > or = 55 years old.

Patients And Methods: Paclitaxel was administered at 175 mg/m2 for 3 hours to 153 patients, 46 of whom were > or = 75 years of age. Pharmacokinetic and toxicity assessments were performed.

A randomized controlled trial of darbepoetin alfa administered as a fixed or weight-based dose using a front-loading schedule in patients with anemia who have nonmyeloid malignancies.

Background: The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading).

Methods: During the correction phase, patients with anemia (hemoglobin < 11.

Cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) for advanced-stage Hodgkin's disease: CALGB 8856.

Successful treatment of advanced-stage Hodgkin's disease (HD) may critically depend on dose intensity. Because mechlorethamine, Oncovin, procarbazine, and prednisone (MOPP), and Adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) are not suitable for major dose escalation, we evaluated the activity and toxicity of combined cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOPE) in advanced HD, here used at conventional dose intensity, as a preparatory study prior to using this regimen at higher dose intensity. Ninety-two patients were treated with CHOPE (cyclophosphamide, 750 mg/m2, day 1; doxorubicin, 50 mg/m2, day 1; vincristine, 1.

A Comparison of Oral Ondansetron and Intravenous Granisetron for the Prevention of Nausea and Emesis Associated with Cisplatin-Based Chemotherapy.

PURPOSE: To compare the efficacy and safety of oral ondansetron with i.v. granisetron each given as a single dose prior to administration of highly emetogenic cisplatin chemotherapy.

Phase II study of induction and adjuvant chemotherapy for squamous cell carcinoma of the head and neck. A long-term analysis for the Illinois Cancer Center.

Background: In 1982, the Illinois Cancer Center initiated a Phase II trial in which the following treatment was administered: Induction chemotherapy (cisplatin and infusional 5-fluorouracil [5-FU]) was administered before definitive local therapy. Definitive local therapy, consisting of surgery, radiation, or both, was followed by three cycles of the same chemotherapy program.

Methods: Eligible patients had Stage III or IV squamous cell carcinoma of the head and neck with no distant metastases.

A surrogate carries a fertilised ovum: multiple crossings in ego boundaries.

Recent advances in reproductive technologies have created situations in which early psychoanalytic thinking with regard to the procreative wish, infertility, and the significance of pregnancy in mothering, calls for reconsideration. The paper addresses briefly issues related to psychological infertility; it focuses specifically on possible psychological implications during full surrogacy, as this procedure is now practised in many fertility clinics in North America. The analysis of a young woman whose infertility was related to her exposure, during intra-uterinary life, to her mother's hormonal treatment (DES), presented us with the opportunity to observe the many psychological issues developing during in vitro fertilisation (IVF) and other similar procedures and, ultimately, to address the far more complex interpersonal states evolving between the biological (genetic) mother and the surrogate during full surrogacy.

Early sexual abuse and nightmares in the analysis of adults.

An examination of the nightmares of four adults in analysis who had been sexually abused as children revealed a characteristic distortion of the body representation as it appeared in the manifest content of the dream. The authors believe that childhood sexual trauma has profound and pervasive effects on the development and consolidation of the body image. Experienced as a grave assault on body integrity and function, it mobilizes primitive anxieties and specific genital anxieties, resulting in distortion, fragmentation, or disintegration of the body representation.

Randomized double-blind comparison of three dose levels of intravenous ondansetron in the prevention of cisplatin-induced emesis.

The selective 5-hydroxytryptamine3 (5HT3) antagonist ondansetron has been shown to be an effective antiemetic in patients receiving cisplatin chemotherapy. This double-blind study compared the efficacy and safety of three doses of intravenous ondansetron in the prevention of nausea and vomiting associated with high-dose (> or = 100 mg/m2) cisplatin chemotherapy. A total of 125 patients were randomized (1:1:1) to receive 0.

Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting.

Purpose: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis.

Patients And Methods: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.

Concomitant cisplatin and hyperfractionated external beam irradiation for advanced malignancy of the head and neck.

The combination of cisplatin and hyperfractionated external beam irradiation (HEBI), followed by salvage surgery when indicated, was evaluated in patients with advanced stage squamous cell carcinoma of the head and neck. Thirty patients with stage III (n = 5) or IV (n = 25) disease received intravenous cisplatin 100 mg/m2 by 6-hour continuous infusion on days 1, 21, and 42 of HEBI. Radiation fractions of 110 cGy were given twice daily, separated by 4 to 6 hours, beginning within 12 hours after cisplatin delivery.

Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy.

Two simple translocations in a primary squamous cell carcinoma of the head and neck.

A 59-year-old white man was diagnosed with primary squamous cell carcinoma at the base of the tongue (clinical stage T4N3aM0). Cytogenetic analysis of the metaphase spreads obtained from primary cultures of the tumor tissue revealed a clonal abnormality with a 46,XY,t(2;6) (p23;q21),t(18;19)(q21;q13) karyotype.

Gender and identity issues in the analytic process.

The influence of gender--of analyst and analysand--in the unfolding of the analytic process is being addressed. A brief discussion of the reasons why such influence was either dismissed or denied in the analytic literature until recently, is followed by an overview of possible analyst-analysand interactions in the four gender-related dyads. Finally two specific developments, not uncommon in the transference of female patients in analysis with female analysts (and their countertransference implications) are presented.

Studies of the affective state in bereaved children.

The process of bereavement in children ranges from the absence of grief to symptoms of anxiety and conduct disturbances. Some psychoanalytic opinion holds that the absence of grief, associated with lack of cognitive maturity, leads to the development of psychopathology later in life. Other writers describe a mourning response, taking the form of ambivalence, anxiety, and care giving, which may protect against subsequent depression.

Diffuse large-cell lymphoma of B-cell origin and deficient T-cell function in a patient with rheumatoid arthritis.

An increased incidence of non-Hodgkin's lymphoma has been described in patients with rheumatoid arthritis. Mechanisms related to abnormal immune regulation have been postulated, but no patients with rheumatoid arthritis and lymphoma have been previously well characterized immunologically. We describe here a patient with long-standing rheumatoid arthritis in whom a B-cell diffuse large-cell lymphoma developed.

GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.

We evaluated, in a multi-center trial, the safety and efficacy of GR 38032F (GR-C507/75), a novel and selective serotonin antagonist, in preventing acute emesis in chemotherapy-naive patients receiving treatment with regimens containing high-dose cisplatin (greater than or equal to 100 mg/m2). Eighty-five patients were randomized to receive GR 38032F, 0.18 mg/kg, either every six or every eight hours for three doses, beginning 30 minutes before cisplatin.

Database and search techniques for two-dimensional gel protein data: a comparison of paradigms for exploratory data analysis and prospects for biological modeling.

Two-dimensional (2-D) polyacrylamide gel electrophoresis can detect thousands of polypeptides, separating them by apparent molecular weight (Mr) and isoelectric point (pI). Thus it provides a more realistic and global view of cellular genetic expression than any other technique. This technique has been useful for finding sets of key proteins of biological significance.

Narcissism and the personal myth.

Kris (1956) described the concept of the personal myth as an autobiographical story built around a family romance fantasy seen specifically in obsessive characters and serving a defensive function. In this paper the concept of the personal myth was expanded to include similar defensive constellations originating from within the grandiose self, built around omnipotent and omniscient fantasies and occurring in character formations with pregenital, narcissistic pathology. The case of a known author and poet, Nikos Kazantzakis, was used to illustrate the thesis of the paper.

On transference: developmental and clinical considerations.

Following a short historical overview of the evolution of the concept of transference, the factors involved in this process are examined. The developmental or dynamic aspects of transference, that is, its illusory character defined by the "potential space" within which transference develops, and the importance of the holding environment at the early stages of therapy for an optimal development of transference are discussed. To understand resistances, Merton Gill's distinction of resistances to the awareness of the transference, and resistances to the resolution of the transference are particularly relevant.

Pregnancy, developmental crisis and object relations: psychoanalytic considerations.

The psychoanalytic literature until recently was focused on the task of understanding and conceptualizing motherhood as 'not secondary' (to the girl's wish for the penis) but the central organizer of the woman's sexual drive. Pregnancy was viewed as a developmental crisis but little had been written on the internal shifts and realignments in the mental organization of the woman during pregnancy. Material from the analyses of three women during their first pregnancy is discussed and some theoretical conclusions are offered.

Psychopathology in the offspring of parents with bipolar affective disorders.

Thirty-nine children from intact families with a manic-depressive parent were evaluated by a semi-structured clinical interview and a number of rating scales for the presence or absence of psychopathology. This sample represents a larger one than in an earlier study, which showed minimal offspring psychopathology compared with reports of other investigators. The current study also examines the inter-relationships between the presence or absence of offspring psychopathology with both genetic loading and a number of psychosocial variables including measures of parental marital adjustment, severity and chronicity of proband parent illness and early exposure of children to parental illness.

Lymphocyte blastogenesis. Post-transcriptional controls of protein synthesis.

To better understand the regulation of macromolecular synthesis in the response of lymphocytes to a mitogen, we have used two-dimensional electrophoresis to search for specificity in the early increase seen in protein synthesis in human lymphocytes treated with phytohemagglutinin and examined the role of new RNA synthesis in this response. Our results confirm a major increase in overall protein synthesis after 4 h of phytohemagglutinin treatment. A further disproportionate increase in the synthetic rates of certain polypeptides was observed using two-dimensional polyacrylamide gel electrophoresis.

The female analyst and the erotized transference.

The concept of erotized transference is discussed from Freud's original writings on the subject to those of recent contributors. It is noted that there exists an almost complete absence of reports in the literature of male patients developing an erotized transference to their female analysts. The question of how significant the gender of the analyst is in the unfolding of the transference and its vicissitudes is raised.