Biomedical subjects

S Waggoner

Publications and source records attributed to S Waggoner.

28 records · Page 2Linked to original sources

PubMed1998

Viral ribonucleoprotein complex formation and nucleolar-cytoplasmic relocalization of nucleolin in poliovirus-infected cells.

The poliovirus 3' noncoding region (3'NCR) is involved in the efficient synthesis of viral negative-stranded RNA molecules. A strong interaction between a 105-kDa host protein and the wild-type 3'NCR, but not with a replication-defective mutant 3'NCR, was detected. This 105-kDa protein was identified as nucleolin which predominantly resides in the nucleolus and has been proposed to function in the folding of rRNA precursor molecules. A functional role for nucleolin in viral genome amplification was examined in a cell-free extract which has been shown to support the assembly of infectious virus from virion RNA. At early times of viral gene expression, extracts depleted of nucleolin produced less infectious virus than extracts depleted of fibrillarin, another resident of the nucleolus, indicating a functional role of nucleolin in the early stages of the viral life cycle in this in vitro system. Immunofluorescence analysis of uninfected and infected cells showed a nucleocytoplasmic relocalization of nucleolin, but not of fibrillarin, in poliovirus-infected cells. Relocalization of nucleolin was not simply a consequence of virally induced inhibition of translation or transcription, because inhibitors of translation or transcription did not induce nucleolar-cytoplasmic relocalization of nucleolin. These findings suggest a novel virus-induced mechanism by which certain nucleolar proteins are selectively redistributed in infected cells.

Amino Acid Sequence↗

PubMed1997

Late rectal sequelae following definitive radiation therapy for carcinoma of the uterine cervix: a dosimetric analysis.

PURPOSE: This study attempted to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients treated with radiation therapy (RT) for cervical carcinoma. METHODS AND MATERIALS: A total of 183 patients with cervical carcinoma (67 Stage I, 93 Stage II, and 23 Stage III) treated with definitive RT with a minimum of 2 years follow-up were evaluated. Treatment consisted of external beam pelvic RT (EBRT) followed by intracavitary RT (ICRT) consisting of one or two insertions. Complications were scored and analyzed as a function of 25 patient and treatment factors. Conventional total rectal doses were obtained by adding together the EBRT and ICRT rectal doses. To account for differences in dose rate between the ICRT and EBRT, and variations in EBRT fractionation schemes, biologically equivalent rectal doses (BED) were calculated using a linear quadratic model. In addition, the influence of the varying proportions of EBRT and ICRT rectal doses were evaluated. RESULTS: Twenty-eight patients (15.3%) developed late rectal sequelae (13 Grade 1, 3 Grade 2, and 12 Grade 3). Diabetes (p = 0.03), Point A dose (p = 0.04), and conventional EBRT dose (p = 0.03) were the most significant factors on multivariate analysis. Logistic regression analysis demonstrated a low risk (<10%) of late rectal sequelae below conventional and biological rectal doses of 75 Gy and 135 BED, respectively. The percentage of rectal dose delivered by the EBRT significantly influenced the dose-response relationship. A defined threshold percentage above which rectal sequelae were more common was identified over the range of doses evaluated. This threshold was 87% at a total rectal dose of 60 Gy and decreased to 60% at 80 Gy. CONCLUSION: Diabetes, Point A, and EBRT doses are the most significant factors associated with the risk of late rectal sequelae in patients treated with RT for cervical carcinoma. The percentage of rectal dose delivered by the EBRT significantly affects the conventional and biological dose-response relationship. This suggests that the volume of rectum irradiated is an important and independent parameter in the development of late rectal sequelae.

Adult↗

PubMed1996

Monosomy 22 in two ovarian granulosa cell tumors.

Cytogenetic studies of ovarian sex cord stromal cell tumors, although limited in number, have found trisomy 12 to be a recurring abnormality, especially in fibromas and granulosa cell tumors (GCTs). However, recent fluorescence in situ hybridization (FISH) studies have failed to confirm a high prevalence of trisomy 12 in GCTs. We describe the karyotypic findings in one adult and one juvenile GCT. Only the juvenile GCT had an extra, abnormal chromosome 12, but both the adult and juvenile GCT had monosomy 22. In light of these findings and the data in the literature, we suggest that monosomy 22 may be important in the genesis of these relatively rare tumors.

Adult↗

PubMed1995

Acute myelomonocytic leukemia with abnormal eosinophils presenting as an ovarian mass: a report of two cases and a review of the literature.

Acute myelomonocytic leukemia is a neoplastic blood disease that can occur as an extramedullary tumor called a granulocytic sarcoma. Granulocytic sarcoma can be the presenting feature of acute leukemia and can occur as an abdominal or pelvic mass. Two cases of granulocytic sarcomas presenting as ovarian masses in patients with acute myelomonocytic leukemia with a characteristic inversion of chromosome 16 are described and the current literature regarding treatment and prognosis is reviewed.

Adolescent↗

PubMed1993

Clinical assessment of 111In-CYT-103 immunoscintigraphy in ovarian cancer.

The ability of 111In-CYT-103 immunoscintigraphy to aid in the diagnosis of patients with primary or recurrent/residual ovarian cancer was evaluated in a multicenter trial. The 111In-labeled immunoconjugate of the monoclonal antibody B72.3 was prepared using a site-specific conjugation method. A total of 103 patients received a 1 mg infusion of 111In-CYT-103 and subsequently underwent surgery or biopsy. The infusion of 111In-CYT-103 was well tolerated; only 1 patient experienced a modest elevation in blood pressure that was likely related to the infusion. 111In-CYT-103 immunoscintigraphy correctly identified surgically confirmed tumor in 68% of patients with ovarian adenocarcinoma. The sensitivity of 111In-CYT-103 immunoscintigraphy was positively influenced both by the size of the tumor lesion and the tumor TAG-72 antigen expression. The overall sensitivity of 111In-CYT-103 immunoscintigraphy was greater than that of CT imaging (44%). Antibody imaging detected occult disease in 20 of 71 patients with surgically documented ovarian adenocarcinoma; 6 patients being evaluated after initial surgery and chemotherapy had an otherwise negative presurgical workup and a normal CA 125 serum level. The results of this trial also indicate that 111In-CYT-103 immunoscintigraphy can contribute to the medical and surgical management of some patients with ovarian cancer. The results of this trial indicate that 111In-CYT-103 immunoscintigraphy should be a valuable addition to the presurgical evaluation of patients with suspected persistent or recurrent ovarian cancer.

Adenocarcinoma↗

PubMed1991

Manometric characterization of rectal dysfunction following radical hysterectomy.

Bladder dysfunction thought to be due to partial denervation has been described following radical hysterectomy. Some patients experience acute and chronic rectal dysfunction characterized by difficulty with defecation and loss of defecatory urge. To define this abnormality, anorectal pressure profiles were examined in 15 patients with Stage I carcinoma of the cervix before and after radical hysterectomy. Profiles were done using standard anorectal manometry with a water-infused system. In all patients preoperative manometric profiles were normal; postoperative studies were abnormal in all patients. Features seen include altered relaxation of the internal sphincter, increased distension needed to trigger relaxation, and decreased rectal sensation; external sphincters and resting internal sphincters were unchanged. Postoperatively, 12 patients reported problems with rectal function. A physiologic defect is definable in patients undergoing radical hysterectomy; this suggests disruption of the spinal reflex arcs controlling rectal emptying. These physiologic abnormalities correlate with the clinical symptomatology experienced by some patients. Continuing definition and evaluation of management options in this situation should be useful in developing effective therapy for rectal dysfunction following radical hysterectomy.

Defecation↗

PubMed1991

Reverse hysterocolposigmoidectomy (RHCS) for resection of panpelvic tumors.

Lateral retroperitoneal approaches to abdominopelvic masses are commonly employed; the reverse hysterocolposigmoidectomy (RCHS) in addition utilizes transabdominal entry of the vaginal and rectovaginal spaces to provide medial access to the uterosacral and cardinal ligaments as well expose a tumor-free segment of the rectosigmoid for en bloc resection of panpelvic tumors. Thirty-one patients underwent reverse hysterocolpectomy for extensive, symptomatic pelvic malignancies. All patients had complete resection of pelvic tumor, and there were no perioperative deaths. Sigmoid resection was required in 25 patients with 22 primary reanastomosis and 3 end colostomies performed. In 6 patients, vaginal entry facilitated tumor resection while sparing the rectosigmoid. Average operative blood loss was 2677 cc. Early postoperative morbidity (1-30 days) occurred in 13 patients; febrile morbidity (6 patients) was the common complication. Late morbidity (1-6 months) was seen in 10 patients, including 1 fatal pulmonary embolism at 5 months. Subsequent therapy was tolerated well. Mean survival/follow-up is 15.7 months (range, 1 to 49 months). Seventeen patients are alive, seven patients without evidence of disease (average 13.4 months), and ten patients are alive with disease (average follow-up, 28.3 months). Thirteen patients are dead of disease or complication (average survival, 13.7 months). We conclude that RHCS facilitates resection of extensive pelvic tumors with acceptable morbidity.

Adult↗

PubMed1990

Human cervical and foreskin epithelial cells immortalized by human papillomavirus DNAs exhibit dysplastic differentiation in vivo.

Human papillomavirus (HPV) DNAs are detected in approximately 90% of anogenital carcinomas. To assess directly the effect of HPV on squamous differentiation, normal human cervical and foreskin epithelial cells and cells immortalized by recombinant HPV DNAs were transplanted beneath a skin-muscle flap in athymic mice. Xenografts containing normal cells formed well-differentiated stratified squamous epithelia 2 to 3 weeks after transplantation, but cell lines immortalized by four HPV types (HPV16, HPV18, HPV31, and HPV33) detected in anogenital cancer exhibited dysplastic morphology and molecular alterations in gene expression characteristic of intraepithelial neoplasia. Morphological alterations were accompanied by delayed commitment to terminal differentiation, alterations in the pattern of involucrin expression, and reductions in levels of involucrin and keratin 1 RNAs. HPV18-immortalized cells developed dysplastic changes more rapidly than cells immortalized by HPV16 DNA. These results show that human genital epithelial cells immortalized by HPV DNAs detected in genital cancers undergo dysplastic differentiation in vivo.

Animals↗

PubMed1990

Rapid dysplastic transformation of human genital cells by human papillomavirus type 18.

This study delineates differences in biologic activity between human papillomavirus (HPV) types 16 and 18. Human cervical and foreskin epithelial cells were cultured and transfected with recombinant HPV-16 and -18 DNA, resulting in immortalized cell lines. Normal epithelial cells as well as HPV-16 and -18 immortalized cells of both early passages (less than 40 population doublings) and late passages (greater than 180 population doublings) were transplanted in athymic mice. Normal squamous cells formed well-stratified epithelium, while HPV immortalized cells developed either normal-appearing epithelium or typical dysplastic changes. Dysplastic changes were seen in none of the 13 grafts with early-passage HPV-16 cell lines, while 9 of 14 grafts with early-passage HPV-18 cell lines developed dysplasias (P less than 0.0004). These results support previous clinical observations suggesting that HPV-18 may be associated with a more aggressive and rapidly progressive form of cervical neoplasia.

Cell Transformation, Viral↗

PubMedDate not supplied

Comparative response of normal and of human papillomavirus-16 immortalized human epithelial cervical cells to benzo[a]pyrene.

Laboratory evidence suggests synergism of human papillomavirus (HPV) infection with cigarette smoking behaviors in enhancing the risk of cervical cancer. In this preliminary investigation, we tested the hypothesis that HPV infection may alter the metabolic activation of tobacco smoke carcinogens, such as benzo[a]pyrene (B[a]P), thereby playing a role in the etiology of cervical cancer. We examined in vitro the metabolism and DNA adduct formation of [3H]B[a]P in normal and HPV-16 immortalized human epithelial cervical cells in culture, and investigated the effect of [3H]B[a]P on growth of these cells. Cultures of normal human cervical cells and of HPV-16 immortalized cervical epithelial cells were exposed to 0.2 microM [3H]B[a]P for 24 and 48 h. [3H]B[a]P inhibited growth of both normal and HPV-16 immortalized cervical cells. However, the growth inhibition of normal cells was more profound than that of HPV-16 immortalized cells. Comparison of the metabolism of [3H]B[a]P in these cells indicated that they both metabolize [3H]B[a]P predominantly to [3H]trans-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene ([3H]B[a]P-9, 10-diol), [3H]r-7,t-8, 9,c-10-tetrahydroxy-7,8,9, 10-tetrahydrobenzo[a]pyrene ([3H]trans-anti-B[a]P-tetraol), and unknown polar products. Enzymatic hydrolysis of water-soluble metabolites indicated that the levels of glucuronide and sulfate conjugates in these cells are negligible. Similarly, both cell lines form similar [3H]B[a]P-DNA adducts. However, the level of the (+)[3H] anti-B[a]P diol epoxide (BPDE)-deoxyguanosine adduct in HPV-16 immortalized cells after 24 and 48 h exposures was 3.8 and 3. 1 pmol/mg DNA, respectively, which is 2.2-fold and 2.6-fold greater than the level of this adduct in normal cells. Under the conditions and within the time frame employed in these assays, both the cell growth and DNA damage induced by [3H]B[a]P appear to be higher in HPV-16 immortalized cells than those detected in normal cells. The results, although preliminary, suggest that HPV-16 immortalized cervical cells are more susceptible to DNA damage by BaP which, in part, may enhance their transformation to malignant cells.

Benzopyrenes↗