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Biomedical subjects

A Berchuck

Publications and source records attributed to A Berchuck.

At least 181 records · Page 10Linked to original sources
PubMed1989

Transforming growth factor-beta inhibits prostaglandin production in amnion and A431 cells.

We studied the effect of transforming growth factor-beta (TGF-beta) on prostaglandin E2 (PGE2) production and mitogenesis in human amnion cells and compared the response in amnion cells with that in A431 cells. Both amnion cells and A431 cells respond to epidermal growth factor (EGF) with increased production of PGE2 whereas EGF promotes mitogenesis in amnion cells but not in A431 cells. In amnion cells, TGF-beta was not mitogenic, and did not alter the mitogenic response of cells to EGF. Treatment of amnion cells with TGF-beta did, however, cause a decrease in PGE2 production relative to untreated cells, although EGF stimulated PGE2 production was not attenuated. In A431 cells, TGF-beta acted to decrease PGE2 production relative to untreated cells and to attenuate the stimulation of PGE2 production effected by EGF. The inhibitory action of TGF-beta on PG production in amnion and A431 cells is contrary to the stimulation of PG production in mouse calvaria reported by others and is suggestive that the effect of TGF-beta on prostaglandin production, like its effect on growth, varies between different cell types. Inhibition of PG production by treatment of amnion or A431 cells with mefenamic acid did not alter thymidine incorporation into DNA in response to EGF; similarly, the addition of PGE2 or PGF2 alpha to culture media of amnion or A431 cells had no effect on mitogenesis (in the absence or presence of EGF). Based on these findings, we conclude that PG production and EGF action on proliferation (stimulation in amnion cells; inhibition in A431 cells) are dissociated.

Amnion↗
PubMed1989

Pelvic exenteration: factors associated with major surgical morbidity.

Sixty-nine women underwent pelvic exenteration at Duke University Medical Center from 1970 through 1987. The operative mortality rate was 7.2% with a trend toward a reduction during the course of the study. One or more serious gastrointestinal or genitourinary surgical complication occurred in 26 (38%) patients and 20 (29%) required reoperation for these complications. There was a trend (P less than 0.1) toward an increase in surgical complications among patients who received prior radiation therapy and those requiring urinary diversion, with a decrease among those who underwent gracilis flap pelvic reconstruction. Patients with sigmoid or ileal conduits had a significantly higher incidence of severe surgical complications than those with transverse colon conduits or posterior exenteration alone (P less than 0.05). Those in whom an ileal conduit was constructed without gracilis flap pelvic reconstruction had significantly more surgical morbidity compared to those who underwent pelvic reconstruction or received a transverse colon conduit (P less than 0.05). Multiple changes in technique since 1978 including (1) the routine use of surgical staplers for bowel resection and anastomosis, (2) the introduction of the transverse colon conduit, and (3) the use of gracilis flap for pelvic reconstruction have combined to produce a significant (P less than 0.05) decrease in life-threatening surgical complications.

Adult↗
PubMed1989

Reactivity of epidermal growth factor receptor monoclonal antibodies with human uterine tissues.

Two monoclonal antibodies (29.1 and 528), which were raised against the epidermal growth factor receptor, were used to evaluate expression of epidermal growth factor receptor in frozen uterine tissue with immunohistochemical techniques. Monoclonal antibody 29.1 stained only vascular endothelium and glandular epithelium in patients who were blood type A. This staining pattern is consistent with the previously reported blood type A specificity of this antibody. Monoclonal antibody 528, which recognizes a peptide determinant is thought to be specific for the epidermal growth factor receptor, stained both endometrial glands and endometrial stromal cells heavily. Faint staining was also seen in myometrium in most cases. This marked difference in expression of epidermal growth factor receptor between endometrium and myometrium contrasts with results of prior biochemical studies in which tissue homogenates were used. No variation in intensity of staining was seen between proliferative and secretory endometrium with the use of either antibody.

ABO Blood-Group System↗
PubMed1989

Short gracilis myocutaneous flaps for vulvovaginal reconstruction after radical pelvic surgery.

The short gracilis myocutaneous flap derives its blood supply from terminal branches of the obturator artery, and the vascular pedicle derived from the medial femoral circumflex artery is sacrificed. Twenty-one short gracilis myocutaneous flaps were used for vulvovaginal reconstructions in 11 patients undergoing radical pelvic surgery: bilateral flaps in nine patients for neovaginal construction after pelvic exenterations, bilateral flaps in one patient for vulvovaginal reconstruction after radical vulvovaginectomy, and a unilateral flap in one patient for vulvovaginal reconstruction after radical vulvectomy with partial vaginectomy. Major complications consisted of bilateral flap necrosis occurring in one patient who had received preoperative irradiation to the vulva and groin combined with chemotherapy. Minor degrees of necrosis (less than 5%) and/or separation of vaginal suture lines occurred in five patients without marked loss of the flaps. Vaginal caliber and depth are excellent in ten patients (91%) after follow-up of 1-22 months. The short gracilis flap is an excellent alternative to the more bulky gracilis flap, which derives its blood supply from perforating branches of the femoral artery. Based on our experience, the short gracilis flap provides adequately vascularized tissue for vulvovaginal reconstruction in patients after radical pelvic surgery, but should not be used in patients who have received extensive groin irradiation.

Adult↗
PubMed1988

Epidermal growth factor, vanadate, and 12-O-tetradecanoylphorbol-13-acetate inhibit growth and stimulate prostaglandin E2 production in A431 cells.

The cell line designated as A431 is characterized by an extraordinary capacity for binding of epidermal growth factor (EGF); but paradoxically, these cells also are characterized by failure of replication in response to treatment with EGF and other mitogens. In this study, we took advantage of this unique response of A431 cells to EGF and other mitogenic agents. Specifically, we investigated the dependency of mitogen-stimulated prostaglandin production on mitogenesis. The effects of treatment of A431 cells with epidermal growth factor and two other mitogenic agents, viz., sodium orthovanadate and 12-O-tetradecanoylphorbol-13-acetate (TPA), on DNA synthesis and prostaglandin production were evaluated. The rate of prostaglandin production in A431 cells that were treated with each of these agents increased in a manner that was dependent upon the duration of treatment and the concentration of the agent tested. Thus, by use of A431 cells, we find that the effects of 'mitogenic' agents on cell replication and prostaglandin production are clearly dissociable.

Cell Line↗
PubMed1988

Treatment of uterine leiomyosarcoma.

We reviewed 46 cases treated at the Gynecology Service of Memorial Sloan-Kettering Cancer Center from 1970-1984 to evaluate the impact of modern multimodal therapy on survival of patients with uterine leiomyosarcoma. Eighteen patients had their primary treatment at Memorial Hospital, whereas the remaining 28 patients were referred either after primary surgery (ten) or after the development of recurrent disease (18). Thirty-four patients initially had disease confined to the uterus. Twelve of these patients received various adjuvant treatment regimens after hysterectomy, and 83.3% developed recurrent disease; 68.2% of 22 patients who received no adjuvant therapy developed recurrent disease. Twelve patients who presented with extrauterine disease all died within two years of initial treatment. Thirty-seven patients were treated for persistent or recurrent disease after primary treatment. No objective responses to radiation therapy were seen in these patients. Doxorubicin used alone or in combination produced a 16.7% response rate (average duration four months), whereas there were no responses to chemotherapeutic regimens not containing doxorubicin. The disease-free survival rate for all patients in this study was 22%; those patients who presented with stage I and II disease had a 29% survival rate.

Adult↗
PubMed1985

Cervical adenoid cystic carcinoma associated with ascites.

Two new cases of cervical adenoid cystic carcinoma are reported. The addition of these two cases brings the total number of reported cases in the literature to 88 making this the most common gynecologic site of occurrence for this unusual tumor. Ascites developed in both of these cases after primary radiation therapy. The significance of this unique association is discussed.

Aged↗
PubMed1984

Cervicovaginal fistula formation: a new complication of Shirodkar cerclage.

In this article, cervicovaginal fistula formation is reported for the first time as a complication of failure to remove a cervical cerclage during labor. Along with the available literature, the case presented here suggests the value of timely removal of a cerclage in the face of strong uterine contractions. Should cervical laceration/rupture occur, immediate repair should be attempted. If chronic cervicovaginal fistula occurs, preterm delivery through the defect and frank uterine rupture are risks with succeeding pregnancies.

Adult↗
PubMedDate not supplied

Aberrant splicing of the TSG101 tumor suppressor gene in human breast and ovarian cancers.

OBJECTIVE: To determine whether large deletions or other alterations in the putative tumor suppressor gene TSG101 play a role in the molecular pathogenesis of breast and ovarian cancers. METHODS: Expression of TSG101 transcripts was examined in breast and ovarian cancers using the reverse transcriptase-polymerase chain reaction (RT-PCR), and selected transcripts were sequenced. Southern blot analysis was performed to determine whether there were genomic deletions in the TSG101 gene, and Northern blot analysis was used to examine the relative abundance of various transcripts. RESULTS: All the cancerous and normal breast tissue examined expressed full length 1145 base pair (bp) TSG101 transcripts. Additional truncated transcripts were seen using the RT-PCR in 57 (64%) of 89 primary breast cancers, 1 (20%) of 5 breast cancer cell lines, 3 (50%) of 6 normal breast tissues, 16 (64%) of 25 primary ovarian cancers and 1 (33%) of 3 ovarian cancer cell lines. Only the primary breast (21%) and ovarian (24%) cancers had three or more truncated transcripts. None of the normal tissues or cell lines examined had more than two aberrant transcripts. DNA sequencing revealed that the most commonly expressed truncated transcript arises because of loss of 902 bp between codons 153 and 1055. Only full length TSG101 transcripts were seen on Northern blot analysis of breast cancer cell lines, however. There was no evidence of genomic deletions in the TSG101 gene on Southern blot analysis. CONCLUSION: Truncated TSG101 transcripts that probably represent splice variants are present in some breast and ovarian cancers, but there is no evidence to suggest that loss of this putative tumor suppressor gene plays a role in the molecular pathogenesis of these cancers.

Base Sequence↗
PubMedDate not supplied

Rectus abdominis myocutaneous flaps for neovaginal reconstruction after radical pelvic surgery.

The objective of this article is to compare the flap-specific complications associated with vertical (VRAM) and transverse (TRAM) rectus abdominis myocutaneous flap vaginal reconstructions performed during radical pelvic procedures. A retrospective chart review was performed to identify all patients who underwent VRAM and TRAM neovaginal reconstructions performed on the Gynecologic Oncology Service at Duke University Medical Center. Flap-specific complications were compared between the two techniques. From 1988 to 2003, 14 VRAM and 18 TRAM flap neovaginal reconstructions were performed on 32 women during the course of 22 (68%) total pelvic exenterations, 8 (25%) partial exenterations, and 2 (6%) radical vulvovaginectomies. Twenty-eight (88%) patients had been previously treated with radiation therapy or concurrent chemoradiation. Associated procedures included continent urinary conduit in 21 (66%), rectosigmoid reanastomosis in 8 (25%), and intraoperative or postoperative sidewall radiation therapy in 7 (22%) of patients. Overall median survival was 14 months (range: 2-week postoperative death to 65 months), with two (6%) acute postoperative mortalities. Fifteen flap-specific complications occurred in 12 (38%) patients, with no significant differences in flap type. Abdominal wound complications included four (12%) superficial wound separations, while one (3%) patient had a fascial dehiscence associated with complex fistulas that contributed to her death, but no patient developed incisional hernia. One patient each developed > 50% flap loss after TRAM and < 50% flap loss after VRAM flap, respectively. Four (12%) patients developed vaginal stricture or stenosis, two (6%) required percutaneous drainage of pelvic abscess or hematoma, and two (6%) developed rectovaginal fistula. Univariate analysis revealed a trend for increasing flap loss with body mass index > 35 (P = 0.056, Fisher exact two-tailed test), but there were no significant associations with other patient characteristics or flap-specific complications. Thirteen (62%) of 21 patients who survived >12 months reported coitus. Both VRAM and TRAM are reliable techniques for neovaginal reconstructions after radical pelvic surgery and have a similar distribution of flap-specific complications involving the donor and recipient sites.

Adult↗
PubMedDate not supplied

Use of trastuzumab in the treatment of metastatic endometrial cancer.

Systemic therapy of metastatic endometrial cancer is relatively ineffective. Response rates to chemotherapy and hormonal therapy in published studies range from 11% to 57%, but most responses are partial and of limited duration. In this case, we present a 76-year-old woman with stage IIIA endometrial adenocarcinoma who was initially treated with surgery and pelvic radiation. She developed multiple pulmonary metastases. She was treated with weekly paclitaxel chemotherapy. Immunostaining revealed that the primary endometrial cancer overexpressed HER-2/neu. Trastuzumab was added to the regimen, and a dramatic partial response was achieved. After a second pulmonary relapse following discontinuation of prior therapy, she was again successfully treated with trastuzumab in combination with paclitaxel and then docetaxel. Therefore, trastuzumab may be a useful adjuvant to taxane-based chemotherapy in some patients with metastatic endometrial cancers that overexpress HER-2/neu.

Adenocarcinoma↗
PubMedDate not supplied

High expression of insulin-like growth factor binding protein-2 messenger RNA in epithelial ovarian cancers produces elevated preoperative serum levels.

The molecular etiology of epithelial ovarian cancer remains unclear. Using microarray expression analysis, we recently reported that expression of the insulin-like growth factor binding protein-2 (IGFBP-2) gene is elevated in advanced epithelial ovarian cancers. The aim of this study was to further delineate the role of IGFBP-2 in the pathoetiology of epithelial ovarian cancer and determine if elevated ovarian cancer IGFBP-2 gene expression is reflected in serum. Relative IGFBP-2 expression was measured using quantitative real-time polymerase chain reaction in 113 epithelial ovarian cancers and 6 normal ovarian surface epithelial samples. Preoperative serum IGFBP-2 levels were measured by radioimmunoassay in 84 women (42 ovarian cancers, 26 benign gynecological conditions, and 10 healthy female controls). Ovarian cancers demonstrated 38-fold higher mean IGFBP-2 expression than normal ovarian epithelium (P < 0.01). Serum IGFBP-2 levels were elevated in women with early- and advanced-stage ovarian cancer compared to controls and patients with benign gynecological conditions (P = 0.05 and P < 0.01, respectively). Epithelial ovarian cancers express high levels of IGFBP-2 relative to normal ovarian epithelium, and this is associated with elevated serum IGFBP-2 levels compared to both normal controls and patients with benign gynecological disease. Our findings provide further support that the insulin-like growth factor pathway plays a significant role in epithelial ovarian cancer pathogenesis. Further, IGFBP-2 may represent an additional serum biomarker with utility in detection and monitoring of epithelial ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Identification of genes associated with ovarian cancer metastasis using microarray expression analysis.

Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.

Bayes Theorem↗
PubMedDate not supplied

Pathogenesis of ovarian cancers.

OBJECTIVE: To review our current understanding of the molecular genetic events involved in the development of epithelial ovarian cancers. METHODS: Molecular biologic techniques have been used to examine the role of growth-stimulatory genes (oncogenes) and -inhibitory genes (tumor suppressors) in ovarian cancer. RESULTS: A number of different peptide growth factors and their receptors are expressed by normal and malignant ovarian epithelial cells. However, the role, if any, of growth factors in ovarian carcinogenesis or maintenance of the transformed phenotype remains unknown. Amplification and overexpression of the HER-2/neu and c-myc oncogenes occur in a significant fraction of epithelial ovarian cancers (20-30%). Overexpression of HER-2/neu has correlated with poor survival in some studies, whereas c-myc amplification is more common in serous cancers. Mutation of the K-ras oncogene frequently occurs in borderline ovarian tumors, but is less common in invasive epithelial ovarian cancers. Mutation of the p53 tumor suppressor gene occurs in approximately half of advanced (stage III/IV) ovarian cancers and in 15% of early (stage IA/IB) cases. Most recently, preliminary studies have focused on the role of other tumor suppressor genes, cyclins, WAF1, and DNA mismatch repair genes. CONCLUSIONS: An understanding of the molecular events involved in the pathogenesis of epithelial ovarian cancer is beginning to evolve. Improvements in early diagnosis, treatment, and prevention of this deadly disease are dependent on further progress in this area.

Carcinoma↗
PubMedDate not supplied

Relationship between expression of coactivators and corepressors of hormone receptors and resistance of ovarian cancers to growth regulation by steroid hormones.

OBJECTIVE: To determine whether aberrant expression of hormone receptor corepressors or coactivators or defects in estrogen receptor-mediated transcription might underlie resistance of ovarian cancers to hormonal therapy. METHODS: Northern analysis, Western analysis, and polymerase chain reaction were used to examine expression of estrogen receptor (ER), progesterone receptor (PR), the nuclear receptor corepressors N-CoR and SMRT, and the steroid receptor coactivator BRG-1 in ovarian cancer cell lines and primary cancers. The effect of BRG-1 transfection on ER-mediated transcription was examined. We also determined the effect of estrogen and the pure estrogen antagonist ICI 182,780 on cell cycle profile and expression of ER. Finally, we examined the ability of estrogen to upregulate expression of known estrogen-responsive genes. RESULTS: Among primary ovarian cancers, 18 of 52 (35%) expressed N-CoR, and 37 of 52 (71%) expressed SMRT, but there was no correlation between expression of corepressors and hormone receptor status. All of the primary ovarian cancers and cell lines expressed BRG-1. Estrogen stimulation of two cell lines expressing ER (SKOV3, OVCA 432) elicited low levels of ER-mediated transcription that was not enhanced by BRG-1 transfection. ICI 182,780 did not induce cell cycle arrest in these cell lines, but there was evidence of downregulation of ER, indicating a ligand-receptor interaction. However, estrogen did not elicit increased transcription of estrogen-responsive genes (PR, myc, fos, pS2). CONCLUSION: Inappropriate expression of the nuclear corepressors N-CoR and SMRT or the coactivator BRG-1 does not underlie the resistance of ovarian cancers to hormonal therapy. Further studies are needed to elucidate the mechanisms underlying the inability of ovarian cancers to undergo ER-mediated transcription if we hope to understand their resistance to hormonal therapy.

Blotting, Northern↗
PubMedDate not supplied

Effect of epidermal growth factor on ornithine decarboxylase activity in A431 cells.

Epidermal growth factor (EGF) stimulates mitogenesis in a number of cell lines; but in A431 cells, EGF causes inhibition of replication. To investigate the possibility that an alteration in the polyamine biosynthetic pathway could be associated with this unusual response of A431 cells to EGF, we evaluated the effect of EGF on ornithine decarboxylase activity. We also evaluated the action of inhibitors of ornithine decarboxylase (difluoromethyl ornithine and retinoic acid) on A431 cell replication. We found a significant stimulatory effect of EGF on ornithine decarboxylase activity and a significant inhibition of cell replication by ornithine decarboxylase inhibitors. These findings are suggestive that the paradoxical response of A431 cells to EGF stimulation is not due to an aberrant response in polyamine formation. Specifically, we found that A431 cells respond, like other cell types, to a growth factor (viz., EGF) with an increase in ODC activity. Moreover, in A431 cells ornithine decarboxylase activity is required for replication.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Early ovarian cancer: a review of its genetic and biologic factors, detection, and treatment.

Early-stage ovarian carcinoma requires comprehensive surgical staging; reexploration for patients who had suboptimal initial surgery would indicate an apparent early ovarian carcinoma. After proper surgery, patients can be subdivided into a high- or low-risk group, and treatment options then can be discussed with the patient. Patients in the low-risk category can be followed up expectantly without any form of adjuvant therapy. Patients in the high-risk category, however, should be encouraged to participate in randomized clinical trials, because it is unclear at the current time which combination of chemotherapy and how many treatments should be used. A platinum-based paclitaxel regimen probably should be used, although the relative merits of carboplatin and cisplatin and the appropriate schedule for taxol (1 hour vs. 3 hours vs. 24 hours vs. 96 hours) are yet unknown. It is hoped that clinicians will continue to encourage patients to participate in randomized clinical trials so that optimal therapy for early ovarian cancer can be established.

Biomarkers, Tumor↗