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J E Cunningham

Publications and source records attributed to J E Cunningham.

At least 19 recordsLinked to original sources
PubMed2005

Associations of short-term weight changes and weight cycling with incidence of essential hypertension in the EPIC-Potsdam Study.

The aim of this study was to examine the relationships of short-term weight gain, weight loss, and weight cycling on the odds of developing hypertension. Normotensive middle-aged German men and women (n=12,362) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study were assigned to categories of 2-year short-term weight changes that were self-reported to have occurred prior to recruitment into the study (gain only, loss only, weight cycling, stable). After 2 years of follow-up after recruitment, 180 cases of incident essential hypertension were identified. In logistic regression models, odds ratios were estimated for the associations between short-term weight changes and risk of developing hypertension. Obesity status (BMI>or=30 or BMI<30 kg/m2) modified the associations between short-term weight change and incidence of diagnosed hypertension. Among obese individuals, short-term weight gain occurring during the 2 years prior to recruitment (OR=2.79, 95% CI 1.19-6.56), weight loss (OR=6.74, 95% CI 2.58-17.6) and weight cycling (OR=4.29, 95% CI 1.55-11.9) were strongly positively associated with incident hypertension, adjusted for age and gender, compared to obese individuals with short-term stable weight. No significant associations between short-term weight changes and risk of diagnosed hypertension were detected among non-obese individuals. Short-term weight changes appeared to present strong risk factors for developing hypertension among obese individuals. The effect seen for weight cycling supports the hypothesis that weight cycling increases the risk of hypertension. The finding for short-term weight loss may be explained by subsequent weight regain and needs further investigation.

Adult↗
PubMed2001

A case-control study of unilateral and bilateral breast carcinoma patients.

BACKGROUND: Women with unilateral breast carcinoma are at increased risk for developing contralateral disease. The clinical significance of bilateral breast carcinoma has not been fully defined, and the subset of patients who may benefit from medical or surgical risk-reduction intervention has not yet been characterized. The purpose of this study was to evaluate risk factors and outcomes for bilateral breast carcinoma. METHODS: A subject group of 70 bilateral breast carcinoma patients (62% metachronous) was matched by age and survival interval with a control group of 70 unilateral breast carcinoma patients. Median follow-up was 103 months. RESULTS: Eighty-two percent of the unilateral patients and 80% of the bilateral patients had Stage I or II disease at diagnosis. Median age at presentation was 53 years. In the bilateral group, the contralateral cancer was diagnosed at the same or earlier stage than the first cancer in 87% of cases. Bilateral patients were significantly more likely to have multicentric disease and to have a positive family history for breast carcinoma compared with the unilateral group. There were no significant differences regarding history of exogenous hormone exposure, lobular histology, hormone-receptor status, or HER-2/neu expression. Five-year disease-free survival was 94% for the unilateral breast carcinoma patients and 91% for the bilateral breast carcinoma patients (P = 0.16). CONCLUSIONS: Survival for patients with bilateral breast carcinoma is similar to that of patients with unilateral disease; however, prophylactic risk-reduction intervention for the contralateral breast should be considered in patients who have multicentric unilateral disease or a positive family history for breast carcinoma.

Adult↗
PubMed2001

The macrobiotic diet in cancer.

Macrobiotics is one of the most popular alternative or complementary comprehensive lifestyle approaches to cancer. The centerpiece of macrobiotics is a predominantly vegetarian, whole-foods diet that has gained popularity because of remarkable case reports of individuals who attributed recoveries from cancers with poor prognoses to macrobiotics and the substantial evidence that the many dietary factors recommended by macrobiotics are associated with decreased cancer risk. Women consuming macrobiotic diets have modestly lower circulating estrogen levels, suggesting a lower risk of breast cancer. This may be due in part to the high phytoestrogen content of the macrobiotic diet. As with most aspects of diet in cancer therapy, there has been limited research evaluating the effectiveness of the macrobiotic diet in alleviating suffering or prolonging survival of cancer patients. The few studies have compared the experience of cancer patients who tried macrobiotics with expected survival rates or assembled series of cases that may justify more rigorous research. On the basis of available evidence and its similarity to dietary recommendations for chronic disease prevention, the macrobiotic diet probably carries a reduced cancer risk. However, at present, the empirical scientific basis for or against recommendations for use of macrobiotics for cancer therapy is limited. Any such recommendations are likely to reflect biases of the recommender. Because of its popularity and the compelling evidence that dietary factors are important in cancer etiology and survival, further research to clarify whether the macrobiotic diet or similar dietary patterns are effective in cancer prevention and treatment is warranted.

Diet, Macrobiotic↗
PubMed2000

Breast buddies.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed1998

Alterations of p53, cyclin D1, Rb, and H-ras in human oral carcinomas related to tobacco use.

BACKGROUND: Epidemiologic studies have indicated that environmental and personal habits, particularly tobacco use and alcohol abuse, are major etiologic factors in the induction and progression of head and neck squamous cell carcinomas (HNSCC). Molecular studies have focused on HNSCC related to smoking but not those associated with smokeless tobacco. METHODS: The authors studied immunohistochemical evidence of alterations of p53, cyclin D1, and Rb in 34 human oral carcinomas related to tobacco use. They also examined p53 and H-ras using single strand conformation polymorphism (SSCP) and sequencing analysis. RESULTS: Overexpression of cyclin D1 was found in 41% of cases, and accumulation of p53 was found in 59%. Only 9% of the samples did not show Rb staining. In SSCP and sequencing analysis, 17 cases showed mutations in the conserved region of the p53 gene. No mutations were detected in codons 12, 13, or 61 of the H-ras gene. CONCLUSIONS: Overexpression of cyclin D1 and p53 mutations are common alterations in HNSCC. In contrast, the loss of Rb function seems to occur infrequently, and mutations in the H-ras gene apparently do not play a role in this cancer. HNSCC associated with smokeless tobacco contained the same alterations as those related to smoking.

Adult↗
PubMed1996

Mutations of the p16 gene in gliomas.

In the present study we investigated the frequency of p16 gene exon 2 mutations in 35 malignant gliomas, using either direct sequencing of the PCR products or cloning into the pCRII vector and sequencing of the cloned PCR products. No mutations were detected during direct sequencing of the PCR products. However, after sequencing of individual clones, we found multiple mutations in 5 tumors involving codons 73(GCC to ACC, Ala to Thr), 76 (GCC to GTC, Ala to Val), 85(GCT to ACT, Ala to Thr), 98(CAC to TAC, His to Tyr), 102 (GCG to GTG, Ala to Val), 106 (GTG to ATG, Val to Met), 107 (CGC to TGC, Arg to Cys), 127 (GCA to GTA, Ala to Val), 128 (CGG to TGG, Arg to Trp) and 136 (GGC to GAC, Gly to Asp). Mutations were found only in glioblastomas and were either C to T or G to A transitions. Each mutation was detected in a small percentage of tumor cells (1.3-22%) using individual colony sequencing and southern hybridization with mutant oligonucleotides, consistent with the heterogenous cell population of glioblastomas. The presence of p16 gene mutations only in glioblastomas suggests that they are late events in glioma development.

Adult↗
PubMed1995

Peripheral hyperalgesia in experimental neuropathy: mediation by alpha 2-adrenoreceptors on post-ganglionic sympathetic terminals.

Rats in which the sciatic nerve is partially transected develop hyperalgesia which is relieved by sympathectomy. We carried out experiments using this model of experimental peripheral neuropathy to examine the peripheral mechanisms underlying sympathetically maintained pain. Subcutaneous injection of noradrenaline (NA) into the affected paw exacerbated the hyperalgesia but had no effect in control animals. Injection of the non-specific alpha-adrenergic blocker phentolamine and the alpha 2-adrenergic blocker yohimbine significantly relieved the hyperalgesia, while injection of the alpha 1-adrenergic blocker prazosin had no effect. Peripheral injection of the alpha 2-adrenergic agonist clonidine had no significant effect, while injection of the alpha 1-adrenergic agonist phenylephrine produced slight exacerbation of mechanical hyperalgesia. Hyperalgesia was eliminated by peripheral injection of indomethacin into the affected paw. Following a chemical sympathectomy, hyperalgesia was eliminated and injection of NA into the hyperalgesic paw had no effect on pain thresholds. We concluded that NA exacerbates hyperalgesia in this experimental model by acting on alpha 2-adrenoreceptors which are located on post-ganglionic sympathetic terminals. Our results are consistent with the proposal (Levine et al. 1986) that activation of these adrenoreceptors brings about an increased release of prostaglandins which sensitises nociceptors.

Adrenergic alpha-Agonists↗
PubMed1995

Prognostic significance of p53 immunoreactivity in patients with glioma.

Abnormal p53 as revealed by immunostaining has been shown to be a predictor of poor outcome in a variety of malignant tumors. This study examines the relationship of p53 immunostaining and survival in 182 adult patients with gliomas. Tumor tissues obtained from patients with glioma within 4 months of initial diagnosis were investigated by immunohistochemical analysis for detection of p53 protein abnormalities using the monoclonal antibody PAb 1801. There were 122 patients with glioblastoma multiforme, 48 patients with anaplastic glioma, and 12 patients with low-grade glioma. Among these patients, 73 of those with glioblastoma multiforme, 35 with anaplastic glioma, and 6 with low-grade glioma had positive p53 immunoreactivity. Kaplan-Meier survival plots (log rank test) showed that the patients with anaplastic astrocytoma or low-grade glioma and p53-positive tumors had longer survival times compared to the patients with p53-negative tumors. No differences in survival were detected among the glioblastoma patients. Cox proportional hazards regression analysis, adjusted for age at diagnosis, showed that the p53 positivity was a significant predictor of longer survival (relative risk = 0.56; 95% confidence intervals = 0.35, 0.90; P = 0. 015) in anaplastic astrocytoma patients, but not in glioblastoma patients (relative risk = 1.03; 95% confidence intervals = 0.82, 1. 29; P = 0.80). These results suggest that anaplastic glioma patients with p53 protein alterations may have a better response to chemoradiation, possibly because the malignant cells cannot arrest in G1 to correct lethal damage induced by chemotherapy or radiotherapy.

Adult↗
PubMed1994

Germline p53 gene mutations in subsets of glioma patients.

BACKGROUND: Heritable germline mutations of the p53 gene have been described in patients with Li-Fraumeni syndrome, occasionally in nonfamilial malignancies such as multifocal osteosarcoma, in a small subgroup of young patients with two or more primary malignancies, and in patients with sporadic breast carcinoma. We recently reported that multifocal gliomas are frequently associated with other primary malignancies, and we hypothesized that genetic alterations may account for this phenomenon. PURPOSE: We examined the frequency of germline p53 gene mutations in patients with glioma and either multifocality of lesions, history of an additional primary (different) malignancy, or a family history of cancer. METHODS: Lymphocytes from 51 glioma patients were analyzed for germline p53 gene mutations using RNA-polymerase chain reaction analysis, single-strand conformation polymorphism, and gene sequencing techniques. RESULTS: Germline p53 gene mutations were detected in six of 19 patients with multifocal glioma, including two with family history of cancer, one with another primary malignancy, and two with all three risk factors; one of four patients with unifocal glioma, another primary malignancy, and a family history of cancer; and two of 15 patients with unifocal glioma and a family history of cancer but no second malignancies. No mutations were detected in the patient with unifocal glioma and another malignancy or in the 12 control patients with unifocal glioma and no second malignancies or family history of cancer. Patients having mutations were younger than other patients in the same group. CONCLUSIONS: Germline p53 mutations are frequent in patients with multifocal glioma, glioma and another primary malignancy, and glioma associated with a family history of cancer, particularly if these factors are combined. IMPLICATIONS: Relatives at high risk can be identified for genetic counseling, early cancer detection, and possible enrollment in chemoprevention trials.

Adult↗
PubMed1994

Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.

PURPOSE: The purpose of this phase I trial was to determine the toxicity and maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) in cancer patients. PATIENTS AND METHODS: Following tracer doses of iodine-131-labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days. RESULTS: The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed. CONCLUSION: Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.

Adolescent↗
PubMed1992

Production of citric and oxalic acids and solubilization of calcium phosphate by Penicillium bilaii.

An isolate of Penicillium bilaii previously reported to solubilize mineral phosphates and enhance plant uptake of phosphate was studied. Using agar media with calcium phosphate and the pH indicator alizarin red S, the influence of the medium composition on phosphate solubility and medium acidification was recorded. The major acidic metabolites produced by P. bilaii in a sucrose nitrate liquid medium were found to be oxalic acid and citric acid. Citric acid production was promoted under nitrogen-limited conditions, while oxalic acid production was promoted under carbon-limited conditions. Citric acid was produced in both growth and stationary phases, but oxalic acid production occurred only in stationary phase. When submerged cultures which normally produce acid were induced to sporulate, the culture medium shifted toward alkaline rather than acid reaction with growth.

Agar↗
PubMed1991

Clinical pharmacology, metabolism, and tissue distribution of 90Y-labeled monoclonal antibody B72.3 after intraperitoneal administration.

B72.3 is a murine monoclonal antibody that recognizes a high-molecular-weight tumor-associated glycoprotein (TAG-72). Nine patients with TAG-72-positive ovarian carcinoma or papillary serous carcinoma of the peritoneum received an intraperitoneal infusion of 2, 4, or 10 mg B72.3 labeled with 0.5-1.2 (mean, 0.8) mCi 90Y. All patients had laparotomy, with multiple tissue and tumor samples removed 3-7 days later. The concentration of the total 90Y label in peritoneal fluid cleared with an extrapolated half-life of 68.6 +/- 4.5 hours. A low-molecular-weight 90Y-labeled species of metabolite was identified by high-performance liquid chromatography. The concentration of this low-molecular-weight species initially increased in the peritoneal fluid, with a half-life of 0.9 hour, and was rapidly cleared from the peritoneal cavity, with a half-life of 23.1 hours. Both the 90Y-labeled metabolite and the 90Y-labeled B72.3 were absorbed into the plasma, with half-lives of 16 +/- 2.2 hours and 25 +/- 5 hours, respectively. The clearance half-lives for these agents in plasma were 25 +/- 3 hours for the metabolite and 42 +/- 17 hours for B72.3. Approximately 8%-11% of the total injected 90Y label appeared in urine over 72 hours. Most of the label (about 70%) was present as the 90Y-labeled metabolite, but about 30% of the 90Y label in urine appeared identical to the authentic 90Y-labeled B72.3 standard when assayed by chromatography. Tissue distribution studies showed that normal tumor tissue and omentum contained the highest content of 90Y (about 0.017% of the injected dose per gram), followed in descending order by liver, normal lymph nodes, peritoneum, bone, and fascia. The lowest concentrations of 90Y were found in rectus abdominis muscle, bone marrow, and fat. There was substantial heterogeneity in the uptake of the 90Y label into tumor sites among patients and among different sites within the same patient. No correlation could be demonstrated between the TAG-72 content and the amount of 90Y label found in tumor sites. Preliminary radiation dosimetry estimates suggest that the tumor sites received about 82.8 cGy for each millicurie of 90Y administered. Thus, if an adequate total radiation dose can be achieved, 90Y-labeled B72.3 should be therapeutically useful for treating diffuse intraperitoneal disease.

Adult↗
PubMed1990

Bronchial micronuclei as a marker of an early stage of carcinogenesis in the human tracheobronchial epithelium.

In the bronchial epithelium, smoking initiates a multistep process that first appears histologically as premalignant squamous metaplasia/dysplasia, a biological predecessor of squamous-cell lung cancer. Reflecting chromosomal damage from a carcinogenic insult, micronuclei may reveal earlier events in the carcinogenic sequence. We prospectively evaluated and correlated micronucleus count, histology (index of metaplasia) and smoking exposure in 35 consecutive subjects (9 active smokers, 10 previous smokers and 16 never-smokers) undergoing diagnostic bronchoscopy. Samples for micronuclei and histological evaluation were taken from the main carinal mucosa in each subject for site-specific comparisons. The median and mean micronucleus counts per 1,000 cells were significantly higher in active smokers than in non-smokers (subjects who had never smoked and previous smokers): median counts were 3.7 vs. 1.4, p = 0.03; mean counts were 4.7 vs. 1.9, p = 0.01. There was no significant difference, however, in micronucleus counts between subjects who had never smoked and previous smokers. Bronchial metaplasia and smoking history were not associated. Our findings suggest that micronuclei are a readily quantitated, early intermediate-endpoint marker for detecting tobacco-initiated tracheobronchial carcinogenesis.

Adult↗
PubMed1989

Activation of tumoricidal properties in monocytes from cancer patients following intravenous administration of liposomes containing muramyl tripeptide phosphatidylethanolamine.

This study examined the antitumor properties of blood monocytes isolated from patients undergoing a phase I trial with liposomes containing muramyl tripeptide phosphatidylethanolamine (L-MTP-PE). Peripheral blood monocytes were isolated from 28 patients receiving twice weekly i.v. injections of escalating doses of L-MTP-PE. Monocytes were harvested before therapy and at various times during the 9-week treatment period. Activation of monocyte-mediated tumorilytic activity was found in 24 of the 28 patients at some time during treatment. Whereas the maximum tolerated dose of L-MTP-PE was 4-6 mg/m2, the optimal biological dose in terms of macrophage activation was 0.5-2.0 mg/m2. The spontaneous secretion of interleukin 1 from monocytes isolated pre- and postinfusion was monitored in two patients. In both patients interleukin 1 secretion correlated with the cytotoxic activity of the monocytes. We conclude that the systemic administration of L-MTP-PE can render the blood monocytes of cancer patients tumor cytotoxic. Since L-MTP-PE is an immunomodulator devoid of direct antiproliferative effects on tumor cells, the data suggest that future clinical trials be conducted using the optimal biological dose rather than the maximum tolerated dose.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Phase I trial of liposomal muramyl tripeptide phosphatidylethanolamine in cancer patients.

Twenty-eight evaluable patients with metastatic cancer refractory to standard therapy received escalating doses of muramyl tripeptide phosphatidylethanolamine (MTP-PE) (.05 to 12 mg/m2) in phosphatidylserine (PC):phosphatidylcholine (PS) liposomes (lipid:MTP-PE) ratio 250:1). Liposomal MTP-PE (L-MTP-PE) was infused over 1 hour twice weekly; doses were escalated within individual patients every 3 weeks as tolerated for a total treatment duration of 9 weeks. Routine clinical laboratory parameters, acute phase reactants and various immunologic tests were monitored at various time points during treatment. Toxicity was moderate (less than or equal to grade II) in 24 patients with chief side effects being chills (80% of patients), fever (70%), malaise (60%), and nausea (55%). In four patients L-MTP-PE treatment was deescalated due to severe malaise and recurrent fever higher than 38.8 degrees C. The maximum-tolerated dose (MTD) was 6 mg/m2. Significant (P less than .05) increases in WBC count, absolute granulocyte count, ceruloplasmin, beta 2-microglobulin, c-reactive protein, monocyte tumoricidal activity, and serum IL-1 beta were found. Significant decreases in serum cholesterol were also observed. Clearance of intravenously (iv)-infused technetium-99 (99mTc)-labeled liposomes containing MTP-PE in four patients was biphasic; gamma camera scans revealed uptake of radiolabel in liver, spleen, lung, nasopharynx, thyroid gland, and tumor (two patients). No objective tumor regression was seen. In view of its definite immunobiologic activity and lack of major toxicity, additional phase II and adjuvant trials of L-MTP-PE are warranted.

Acetylmuramyl-Alanyl-Isoglutamine↗