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Biomedical subjects

E Greenwald

Publications and source records attributed to E Greenwald.

At least 19 recordsLinked to original sources
PubMed1996

Loss of retinoic acid receptors in mouse skin and skin tumors is associated with activation of the ras(Ha) oncogene and high risk for premalignant progression.

Retinoic acid receptor transcripts (RARalpha and RARgamma) are decreased in benign mouse epidermal tumors relative to normal skin and are almost absent in carcinomas. In this report, the expression of RARalpha and RARgamma proteins was analyzed by immunoblotting in benign skin tumors induced by two different promotion protocols designed to yield tumors at low or high risk for malignant conversion. RARalpha was slightly reduced in papillomas promoted with 12-O-tetradecanoylphorbol-13-acetate (low risk) and markedly decreased or absent in papillomas promoted by mezerein (high risk). However, mezerein also caused substantial reduction of RARalpha in nontumorous skin. RARgamma was not detected in tumors from either protocol and was greatly reduced in skin treated by either promoter. Both RARalpha and RARgamma proteins were decreased in keratinocytes overexpressing an oncogenic v-ras(Ha) gene, and RARalpha was underexpressed in a benign keratinocyte cell line carrying a mutated c-ras(Ha) gene. Introduction of a recombinant RARalpha expression vector into benign keratinocyte tumor cells reduced the S-phase population and inhibited [3H]thymidine incorporation in response to retinoic acid. Furthermore, transactivation of B-RARE-tk-LUC by retinoic acid was markedly decreased in keratinocytes transduced with the v-ras(Ha) oncogene (v-ras(Ha)-keratinocytes). Blocking protein kinase C function in v-ras(Ha)-keratinocytes with bryostatin restored RARalpha protein to near normal levels, reflecting the involvement of protein kinase C in RARalpha regulation. Both RARalpha and RARgamma are down-regulated in cultured keratinocytes by 12-O-tetradecanoylphorbol-13-acetate, further implicating PKC in the regulation of retinoid receptors. Our data suggest that modulation of RARs could contribute to the neoplastic phenotype in mouse skin carcinogenesis and may be involved in the differential promoting activity of mezerein and 12-O-tetradecanoylphorbol-13-acetate, particularly for selecting tumors at high risk for malignant conversion.

Animals↗
PubMed1996

Retinoic acid down-regulation of fibronectin and retinoic acid receptor alpha proteins in NIH-3T3 cells. Blocks of this response by ras transformation.

All-trans-retinoic acid (RA) markedly reduced the level of intracellular fibronectin (FN) in a time- and concentration-dependent fashion in NIH-3T3 cells, but not in NIH-3T3 cells transformed by an activated Ha-ras oncogene. Pulse/chase experiments indicated that RA affects FN biosynthesis rather than its turnover rate. Steady state levels of FN transcripts did not change after treatment of the cells with RA for various times or concentrations, suggesting that RA acts at the translational level. Similar effects were observed in other fibroblasts. In NIH-3T3 cells, RA had distinct effects on different receptors; it down-modulated retinoic acid receptor (RAR) a protein and transcript levels, it up-regulated RAR beta transcripts, and it had no effect on RAR gamma. Transformation of NIH-3T3 cells with an activated Ha-ras oncogene down-modulated RAR expression and abolished responsiveness to RA. We identified the retinoid signal transduction pathways responsible for the effects of RA on FN and RAR alpha proteins by the use of the retinoid X receptor-selective compound, SR11237, by stable over-expression of a truncated form of the RAR alpha gene, RAR alpha 403 with strong RAR dominant negative activity, and by overexpression of RAR alpha. We conclude that: 1) RA-dependent FN down-modulation is mediated by RARs, 2) retinoid X receptors mediate the observed reduction of RAR alpha by RA, and 3) the block of RA responsiveness in Ha-ras cells cannot be overcome by overexpression of RAR alpha. These studies have defined fibronectin and RAR alpha as targets of RA in fibroblast cells and have shown that oncogenic transformation renders the cells resistant to RA action.

3T3 Cells↗
PubMed1992

A retrospective study of long-term methods of coping with having been sexually abused during childhood.

Methods of coping with childhood sexual abuse were retrospectively studied in a community sample of 54 adult women who had been sexually abused in childhood. From the time the abuse ended until the present, "denial" and "emotional suppression" were the coping methods most commonly employed of the nine methods measured. One purpose of this study was to determine if the methods used to cope with the aftermath of being sexually abused during childhood were associated with current psychological adjustment beyond what could be predicted by the characteristics of the abusive experience per se. A partial correlation analysis and a multiple regression analysis suggested that avoidant/emotion suppressing coping strategies although frequently used and rated by subjects as helpful, were in fact associated with poorer adult psychological adjustment.

Adaptation, Psychological↗
PubMed1991

Psychiatric complications during flooding therapy for posttraumatic stress disorder.

The authors use six case vignettes to illustrate underrecognized complications occurring during flooding therapy for posttraumatic stress disorder (PTSD), including exacerbation of depression, relapse of alcoholism, and precipitation of panic disorder. A common denominator to the majority of these cases appears to be the mobilization of negative posttrauma appraisal, accompanied by shame, guilt, and anger. The authors suggest that flooding may not be helpful for these negative emotions in the manner that it is for anxiety. Suggestions for preventing and treating complications of flooding therapy for PTSD include employing more cognitive forms of therapy in cases at risk; supporting abstinence from alcohol and other substances; providing adjunctive pharmacologic treatment as indicated, e.g., tricyclics for depression or panic; and providing long-term follow-up.

Acute Disease↗
PubMed1990

Childhood sexual abuse: long-term effects on psychological and sexual functioning in a nonclinical and nonstudent sample of adult women.

The purpose of this study was to explore how the experience of childhood sexual abuse is related to long-term psychological and sexual functioning in a nonclinical and nonstudent community sample of women. Questionnaires were distributed to 1,500 nurses and returned anonymously. Fifty-four women who had been sexually abused as children (age 15 or younger) responded. These subjects were then matched with 54 nonabused control subjects. Although there was no difference on a measure of self-esteem, the abused group reported more symptoms of distress on the Global Severity Index and on seven out of nine subscales of the Derogatis Brief Symptom Inventory. They also reported more disturbance on a scale which examined psychological symptoms that have been commonly reported in the literature to be particularly associated with sexual abuse. These differences between the abused and nonabused groups were evident even after controlling for differences in subjects' perceptions of parental emotional support. Unlike the results for psychological adjustment, however, the abused subjects did not differ from the control subjects on self-reported levels of sexual satisfaction or sexual dysfunction.

Adaptation, Psychological↗
PubMed1989

The relation between sexual activity among children during preadolescence and/or early adolescence and sexual behavior and sexual adjustment in young adulthood.

This study examined whether current sexual behavior and sexual adjustment in a sample of 433 college students differed as a function of having engaged in sexual activity with other children during preadolescence (prior to age 13) and/or early adolescence (ages 13-15). Four groups were compared: subjects who only had an early adolescent sexual experience; subjects who had both preadolescent and early adolescent experiences; subjects who had no sexual experience with another child during either preadolescence or early adolescence. There were no significant differences between these groups on measures of incidence of premarital intercourse, age at first intercourse, number of different intercourse partners, sexual satisfaction, sexual arousal, or sexual dysfunctions. It was concluded that in general the simple occurrence or nonoccurrence of sexual activity among children during these developmental periods has little impact, either positive or negative, on later sexual adjustment during young adulthood. Some expections, depending on the specific types of childhood sexual activity involved, were noted.

Adaptation, Psychological↗
PubMed1989

Long-term effects of sexual experiences with siblings and nonsiblings during childhood.

Long-term differences in young adults' sexual behavior and adjustment following preadolescent sibling and nonsibling peer childhood sexual experiences were investigated. Questionnaire data were collected from 526 undergraduate college students. Of this sample, 25 (5%) reported having had only a sibling sexual encounter, 61 (12%) reported having had both a sibling and a nonsibling childhood sexual experience, 236 (45%) reported having had only a nonsibling sexual experience, and 204 (39%) reported no sexual experience with another child prior to age 13. No differences were found between the sibling, nonsibling, and no-experience groups on a variety of adult sexual behavior and sexual adjustment measures, including incidence of premarital intercourse, age at first intercourse, number of intercourse partners, sexual satisfaction, sexual arousal, and sexual dysfunctions. It was concluded that adult sexual adjustment is not negatively or positively influenced by typical early childhood sexual experiences among similar-aged siblings.

Adaptation, Psychological↗
PubMed1984

"Second-effort" surgical resection for bulky ovarian cancer.

Eighteen women with bulky ovarian cancer at the start of chemotherapy were brought to second laparotomy after 6 months of combination chemotherapy in an effort to resect previously unresectable tumor masses. Only one of 18 had significant resection of bulk tumor such that no gross tumor was remaining, although 8 of 15 had the residual uterus removed and 6 of 10 had resection of residual ovary or ovaries. Failure to resect tumor was due to absence of any gross tumor (33%), presence of myriad small seedlings not amenable to resection (22%), or massive residual tumor (18%). Partial resection was accomplished in 22%, but all relapsed promptly in spite of continued aggressive therapy with drugs and whole abdominal irradiation. It is concluded that 6-month "second-effort" surgical resection is unlikely to benefit many women with bulky ovarian cancer, and that surgical resection must be attempted early in the course of the disease if it is to be effective.

Adult↗
PubMed1983

Cis-platin based combination chemotherapy for advanced ovarian cancer. High overall response rate with curative potential only in women with small tumor burdens.

Thirty-eight women with advanced ovarian cancer were given monthly cycles of intravenous cyclophosphamide, Adriamycin (doxorubicin) and cis-platin, and oral hexamethylmelamine. Of 26 with tumor which would be evaluated for response, 42% had complete remission and 50% partial remission. Median time to disease progression from entry for all 38 patients was 13 months, and median survival 23.5 months. The bulk of tumor at the time chemotherapy was begun was the only significant prognostic factor for time to disease progression and survival. Of the seven women surviving free of disease a median of three years later, five had no mass greater than 2 centimeters in diameter at entry. Toxicity was predominantly myelosuppression and vomiting, with mild peripheral neuropathy in 27% and no significant renal or cardiac toxicity. The response rate of 92% is much higher than that previously reported with melphalan, and the survival considerably longer. The toxicity is acceptable, given the substantial improvement in results.

Adult↗
PubMed1982

Efficacy study of intensive cis-platin therapy in advanced non-small cell bronchogenic carcinoma.

Thirty patients with advanced non-small cell bronchogenic carcinoma were treated with cis-platin, 75 mg/M2 weekly for three weeks, then every three weeks. Eighteen were ambulatory, 22 had distant metastases, 14 had prior irradiation, and none had prior chemotherapy. Ten patients (33%) had objective remissions lasting a median of three months. Responders lived a median of five months, compared to three months for nonresponders. Transient mild azotemia was noted in twelve patients. Cis-platin has definite but modest activity in non-small cell bronchogenic carcinoma.

Adenocarcinoma↗
PubMed1981

Effective chemotherapy for esophageal cancer with methotrexate, bleomycin, and cis-diamminedichloroplatinum II.

Ten patients with squamous cancer of the esophagus were treated with an outpatient regimen combining cis-diamminedichloroplatinum (II), methotrexate and bleomycin. Nine of these had metastatic disease or recurrence after radiotherapy. Objective responses were noted in 50%, regardless of performance status or metastatic site. None of three patients with prior radiation therapy responded, however. Median duration of response was six months. Responders survived a median of eight months versus five months for nonresponders. Three patients had severe hematologic toxicity. A single patient with massive disease confined to the esophagus had an excellent response to six weeks of chemotherapy before radical irradiation. He is disease-free after two years but is paraplegic from radiation myelitis. This chemotherapy program is an effective palliative therapy for metastatic esophageal cancer. Its safety and efficacy as part of the initial treatment of local disease should be further investigated.

Aged↗
PubMed1980

Effective outpatient combination chemotherapy for advanced cancer of the head and neck.

Forty-six patients with advanced cancer of the head and neck, 42 of whom had failed conventional radiotherapy or surgical excision, or both, were treated on an outpatient basis with a regimen consisting of bleomycin, methotrexate and cis-diamminedichloroplatinum II. Objective responses were noted in 29 patients, with eight having apparent complete remissions. The median duration of partial response was only five months, but the median duration of complete remission was 11 months. Median survival time for nonresponders was four months, for partial responders, six months, and for complete responders, 20 months. Toxicity was acceptable. This regimen can be safely and conveniently used prior to radical excision or irradiation. The results in patients who failed to respond to prior therapy appear substantially superior to those achieved with methotrexate alone.

Adult↗
PubMed1980

Combination chemotherapy of advanced ovarian cancer with hexamethylmelamine, cis-Platinum, and doxorubicin after failure of prior therapy.

Forty-nine women received a combination of cis-platinum and hexamethylmelamine (36 also received doxorubicin) for advanced ovarian cancer progressing after therapy that included an alkylating agent or extended field radiation. Twenty-six (53%) had an objective remission that lasted a median of 6 months from start of treatment. Response rate was independent of age, extent of prior therapy, and performance status. A long interval from initial diagnosis to entry, response to therapy, and ambulatory performance predicted improved survival from entry. No patient is surviving free of disease. Myelosuppression and vomiting were moderately severe but tolerable. Azotemia and peripheral neuropathy were infrequent and milk. These drugs have major activity in this poor-risk group and should be studied as part of initial therapy when enhanced efficacy and reduced toxicity are to be expected.

Adult↗