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Michael Gordon

Publications and source records attributed to Michael Gordon.

At least 19 recordsLinked to original sources
PubMed2005

Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.

Adult↗
PubMed2005

Epidermal growth factor receptor gene polymorphisms predict pelvic recurrence in patients with rectal cancer treated with chemoradiation.

An association between epidermal growth factor receptor (EGFR) signaling pathway and response of cancer cells to ionizing radiation has been reported. Recently, a polymorphic variant in the EGFR gene that leads to an arginine-to-lysine substitution in the extracellular domain at codon 497 within subdomain IV of EGFR has been identified. The variant EGFR (HER-1 497K) may lead to attenuation in ligand binding, growth stimulation, tyrosine kinase activation, and induction of proto-oncogenes myc, fos, and jun. A (CA)(n) repeat polymorphism in intron 1 of the EGFR gene that alters EGFR expression in vitro and in vivo has also been described. In the current pilot study, we assessed both polymorphisms in 59 patients with locally advanced rectal cancer treated with adjuvant or neoadjuvant chemoradiation therapy using PCR-RFLP and a 5'-end [gamma-(33)P]ATP-labeled PCR protocol. We tested whether either polymorphism alone or in combination can be associated with local recurrence in the setting of chemoradiation treatment. We found that patients with HER-1 497 Arg/Arg genotype or lower number of CA repeats (both alleles <20) tended to have a higher risk of local recurrence (P = 0.24 and 0.31, respectively). Combined analysis showed the highest risk for local recurrence was seen in patients who possessed both a HER-1 497 Arg allele and <20 CA repeats (P = 0.05, log-rank test). Our data suggest that the HER-1 R497K and EGFR intron 1 (CA)(n) repeat polymorphisms may be potential indicators of radiosensitivity in patients with rectal cancer treated with chemoradiation.

Adult↗
PubMed2005

Gene polymorphisms of epidermal growth factor receptor and its downstream effector, interleukin-8, predict oxaliplatin efficacy in patients with advanced colorectal cancer.

BACKGROUND: Researchers have recently reported an association between the epidermal growth factor receptor (EGFR) pathway and platinum-chemotherapy sensitivity in cancer patients. The (CA)(n) repeat polymorphism in intron 1 of the EGFR gene has been identified and found to alter EGFR expression in vitro as well as in vivo. A higher number of these CA repeats is associated with lower EGFR levels, whereas a low number of repeats is associated with higher EGFR levels. A second key polymorphism within the EGFR pathway (HER1 R497K) is a single nucleotide change (G-A) in codon 497 of the EGFR gene, which leads to an arginine-lysine substitution in the extracellular domain of subdomain IV. Furthermore, interleukin-8 (IL-8), recently identified as an EGFR downstream effector, plays a vital role in tumor angiogenesis and progression. Three other polymorphisms, each related to the IL-8 gene, have also been identified as playing a pivotal role in the EGFR pathway: T-251A in the promoter region of the IL-8 gene, G+2607C in exon 2 of the IL-8 receptor CXCR1 gene, and C+785T in exon 11 of the IL-8 receptor CXCR2 gene. PATIENTS AND METHODS: In this study, we employed a 5'-end 33P-gATP-labeled polymerase chain reaction (PCR) protocol as well as the PCR-restriction fragment length polymorphism method in order to determine the genotypes for the previously mentioned polymorphisms in 105 patients with metastatic colorectal cancer. Tests were conducted to establish whether these polymorphisms could predict clinical outcome to 5-flourouracil/oxaliplatin chemotherapy. RESULTS: Among all patients assessed, those possessing < 20 EGFR CA repeats were more likely to show disease progression than were patients with >or= 20 CA repeats (P = 0.019; log-rank test). Also, patients with the CXCR1 GC genotype were found to have an increased relative risk of time to tumor progression that was 1.55 (95% CI, 0.8-3.0) times that of patients with the homozygous GG genotype (P = 0.17; log-rank test). CONCLUSION: Overall, our data suggest that gene polymorphisms active in the EGFR pathway may be associated with the sensitivity of colorectal cancer patients to platinum-based chemotherapy.

Adult↗
PubMed2004

A Phase I trial of a potent P-glycoprotein inhibitor, zosuquidar trihydrochloride (LY335979), administered intravenously in combination with doxorubicin in patients with advanced malignancy.

PURPOSE: Our intention was to (a) to investigate the safety and tolerability of a potent P-glycoprotein modulator, zosuquidar trihydrochloride (LY335979), when administered i.v. alone or in combination with doxorubicin, (b) to determine the pharmacokinetics of zosuquidar and correlate exposure to inhibition of P-glycoprotein function in a surrogate assay, and (c) to compare the pharmacokinetics of doxorubicin in the presence and absence of zosuquidar. PATIENTS AND METHODS: Patients with advanced malignancies who provided written informed consent received zosuquidar and doxorubicin administered separately during the first cycle of therapy and then concurrently in subsequent cycles. Zosuquidar was given i.v. over 48 h in a cohort-dose escalation manner until the occurrence of dose-limiting toxicity or protocol specified maximum exposure. Doxorubicin doses of 45, 60, 75 mg/m(2) were administered during the course of the trial. RESULTS: Dose escalation proceeded through 9 cohorts with a total of 40 patients. The maximal doses administered were 640 mg/m(2) of zosuquidar and 75 mg/m(2) of doxorubicin. No dose-limiting toxicity of zosuquidar was observed. Pharmacokinetic analysis revealed that, in the presence of zosuquidar at doses that exceeded 500 mg, there was a modest decrease in clearance (17-22%) and modest increase in area under the curve (15-25%) of doxorubicin. This change was associated with an enhanced leukopenia and thrombocytopenia but was without demonstrable clinical significance. The higher doses of zosuquidar were associated with maximal P-glycoprotein inhibition in natural killer cells. CONCLUSION: Zosuquidar can be safely coadministered with doxorubicin using a 48 h i.v. dosing schedule.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Low colony counts of asymptomatic group B streptococcus bacteriuria: a survey of practice patterns.

The purpose of this study was to survey expert opinion on the management of low colony counts (< 100,000 colony forming units/mL) of asymptomatic group B streptococcus (GBS) bacteriuria discovered in the first trimester. A survey was sent to the 241 senior obstetricians affiliated with each of the Obstetrics and Gynecology training programs in the United States on July 10, 2002. Surveys received by the deadline (September 1, 2002) were included in the dataset. Eighty-five completed surveys were returned for a response rate of 35%. Seventy-seven percent reported treating low colony counts of asymptomatic GBS bacteriuria in the first trimester at the time of diagnosis, whereas 23% stated they did not treat prior to labor (margin of error 7.5% with 95% confidence). Nine percent stated that their institution had a written protocol for the treatment of low colony counts of asymptomatic GBS bacteriuria. Two physicians indicated that they screened for asymptomatic GBS bacteriuria at 28 weeks. Currently, no generally accepted protocol for the management of low colony counts of asymptomatic GBS bacteriuria exists. This survey indicates that most of the responding senior obstetricians at United States training programs treat low colony counts of asymptomatic GBS bacteriuria in the first trimester.

Bacteriuria↗
PubMed2004

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Aged↗
PubMed2003

Ethical issues in end-of-life geriatric care: the approach of three monotheistic religions-Judaism, Catholicism, and Islam.

Ethical dilemmas pervade modern geriatric medicine. What is considered right or wrong will differ depending on, among other things, the patient's religion. The three Abrahamic monotheistic religions, Judaism, Christianity (its Catholic variant), and Islam all have carefully considered positions on medical ethics. Although much is held in common, there are significant differences. The authors present three clinical cases, each of which presents ethical dilemmas typical of geriatric care, especially at the end of life. On the basis of these scenarios, the normative ethical position of each religion is compared and contrasted. It is hoped that this approach will offer the geriatrician a useful approach to treating patients in an increasingly multicultural society.

Aged↗
PubMed2002

Ethical challenges in end-of-life therapies in the elderly.

With the increasing numbers of elderly in the population of all western countries and the increasing life expectancy at birth, many seniors spend the last period of their life with various afflictions that may require the need for long-term institutional care. During the last period of life, many seniors and their families face decisions that challenge ethical principles and may cause conflict among family members as well as healthcare professionals. The commonly used ethical principles of autonomy, beneficence, nonmaleficence and justice, although forming a useful foundation for the evaluation of decision-making dilemmas, alone cannot resolve many clinically challenging situations. Healthcare professionals must clearly understand the clinical state of the patient for whom a difficult decision is being contemplated. Levels of function, clinical symptoms, the expected trajectory of change and possible treatment options have to be balanced against the person's values and wishes, either self-expressed directly or through an advance directive, or communicated by surrogate decision makers. At times, physicians face difficult treatment dilemmas when patients or families request treatments that are not legally sanctioned, such as when physician-assisted suicide is requested by a suffering patient. At other times conflicts occur when patients or surrogates wish to continue with therapies that are no longer considered necessary or suitable by the physician. At the societal level, sometimes an expensive drug that is deemed necessary by the physicians is not covered by a government-sponsored or private health plan. The issue of distributive justice must be considered in a situation such as when long-term facilities or acute hospitals treating frail, cognitively impaired elders consider withholding or withdrawing various treatments because of poor clinical outcomes coupled with excessive costs. The often controversial issue of nutrition and hydration in the end-of-life period frequently causes treatment conflicts and dilemmas among surrogates and staff, as does the highly charged issue of cardiopulmonary resuscitation in this frail and very vulnerable population. The real challenge for healthcare providers in the field of geriatric long-term care is to balance compassionate and appropriate care with respect for the choices and wishes of patients and their families. This should be accomplished while at the same time safeguarding the professional standards and ethical integrity of healthcare providers responsible for this care.

Aged↗
PubMedDate not supplied

Families dealing with stroke desire information about self-care needs.

As hospital lengths of stay have decreased, healthcare professionals have less opportunity to fully educate stroke patients and their families regarding self-care before the patient is discharged home. Consequently, families often need continuing education provided to them in outpatient settings. The purpose of this study was to identify the self-care needs about which people dealing with stroke most frequently want information. Twenty-four people responded to a survey that listed 48 self-care needs structured within Orem's universal self-care requisites (USCRs). The top five self-care needs about which information was desired were: preventing falls; maintaining adequate nutrition; staying active; managing stress; and dealing with emotional and mood changes. These needs correlated with several of Orem's USCRs. By keeping these needs in mind, healthcare professionals can develop better educational materials and provide more pertinent information to stroke patients and their families during homecare or office visits, support group meetings, or via the Internet.

Aged↗
PubMedDate not supplied

Report from the society for biological therapy and vascular biology faculty of the NCI workshop on angiogenesis monitoring.

The field of tumor angiogenesis has seen explosive growth over the last 5 years. Preclinical as well as early clinical evaluation of novel compounds is progressing at a rapid pace. To gain a perspective on the field and to take stock of advances in the understanding of molecular mechanisms underlying the process of tumor angiogenesis as well as ways of monitoring the activity of agents, the Society for Biologic Therapy and the National Cancer Institute's Vascular Biology Faculty convened a Workshop on Angiogenesis Monitoring in November 2002. The Workshop was composed of invited speakers and participants from academia, industry, and government. It was divided into 3 sessions, each chaired by leaders in the field. The first focused on advances in the understanding of the cellular and molecular mechanisms of angiogenesis in tumors. The second examined preclinical assay systems that are useful in vascular biology. The third addressed the translation to the clinic and monitoring of antiangiogenic activity of agents in patients and novel trial designs. What follows is a summary of the discussions and findings of each session.

Animals↗