Biomedical subjects

Janet Rader

Publications and source records attributed to Janet Rader.

8 recordsLinked to original sources

PubMed2006

Human papillomaviruses target the double-stranded RNA protein kinase pathway.

The double-stranded RNA protein kinase (PKR) pathway plays a vital role in the innate immune response to viral infection. Activation of PKR following virus entry can lead to a shutdown in translation, thereby inhibiting viral protein synthesis and replication. Little is currently known about whether human papillomaviruses (HPVs) modulate PKR expression and activity. In this study, normal human foreskin keratinocytes (NHKs) transfected stably with the HPV 31 or 16 genomes and cell lines expressing the HPV 16 E6 and E7 oncoproteins were used to examine effects on the PKR pathway. HPV gene products were found to modulate PKR phosphorylation, activity and localization. The levels of total PKR protein were reduced modestly in cells that maintained HPV 16 or 31 episomes through a reduction in PKR transcription. However, levels of phosphorylated PKR were decreased 4-fold through a post-transcriptional mechanism mediated by E6 and E7 that was independent of the transcriptional downregulation mediated by HPV. In response to infection by vesicular stomatitis virus, phosphorylation of eIF2alpha was blocked in cells expressing HPV oncoproteins, but not in NHKs. Finally, it was observed that the cellular localization of PKR was altered by HPV gene products in HPV raft cultures, as well as HPV-positive patient biopsies. This effect was mediated by the HPV E6 oncoprotein and leads to the co-localization of PKR with P-bodies. These studies demonstrate that high-risk HPVs target the PKR pathway by multiple mechanisms.

Animals↗

PubMed2005

Lack of benefit of concurrent chemotherapy in patients with cervical cancer and negative lymph nodes by FDG-PET.

PURPOSE: To compare the outcome of patients with cervical cancer and negative lymph nodes by fluorodeoxyglucose-positron emission tomography (FDG-PET) treated with irradiation (RT) and concurrent chemotherapy or RT alone. METHODS AND MATERIALS: This was a prospective data registry of 65 patients with cervical cancer and negative lymph nodes by whole-body FDG-PET. The tumor stage was IB2 in 11, IIB in 37, and IIIB in 17 patients. RT alone was administered to 15 and RT with concurrent weekly cisplatin to 50 patients. RESULTS: The 5-year overall survival estimate was 85% with RT and 81% with RT and concurrent chemotherapy (p = 0.91). The corresponding 5-year cause-specific survival estimates were 78% and 74% (p = 0.98). The differences in the sites of recurrence (pelvis vs. distant metastasis) were not statistically significant between the two groups (p = 0.77). A Cox proportional hazards model of survival outcome did not identify chemotherapy, overall treatment time, or radiation dose as statistically significant prognostic factors. Severe complications included one rectovaginal fistula, one rectal stricture requiring colostomy (both in the concurrent chemotherapy group), and one death from chemotherapy-related complications. CONCLUSION: Irradiation with concurrent cisplatin was not advantageous compared with RT alone in patients with negative lymph nodes on FDG-PET.

Adenocarcinoma↗

PubMed2004

Lymph node control in cervical cancer.

PURPOSE: The aim was to evaluate pretreatment lymph node size, irradiation dose, and failure patterns. METHODS: Pretreatment PET and CT were performed in 208 patients. Lymph nodes were scored as either positive or negative by PET and lymph node size was measured by CT. Lymph node irradiation dose and sites of failure were recorded. RESULTS: The mean pelvic lymph node doses were: PET negative nodes, < or =1 cm, 66.8 Gy, and 0/76 failures; PET positive nodes, < or =1 cm, 66.8 Gy, and 3/89 failures; 1.1-< or =2 cm, 66.9 Gy, and 0/21 failures; 2.1-< or =3 cm, 69.4 Gy, and 2/15 failures; and 3.1 to < or =4 cm, 74.1 Gy, and 0/5 failures. The mean paraaortic lymph node dose was 43.3 Gy and there were no paraaortic failures for 24 patients with PET positive < or =1 cm nodes, 0/5 failures for 1.1 to < or =2 cm, and 0/4 failures for 2.1 to < or =3 cm. The most common site of failure was distant metastases. CONCLUSIONS: The irradiation doses given in this study were adequate to control most lymph node metastases. Positive lymph nodes of any size at diagnosis were the most significant predictor for developing distant metastases.

Adult↗

PubMed2004

Posttherapy [18F] fluorodeoxyglucose positron emission tomography in carcinoma of the cervix: response and outcome.

PURPOSE: The aim of this study was to evaluate response to therapy using posttherapy molecular imaging with [(18)F] fluorodeoxyglucose (FDG), and to compare the response with patient outcome. PATIENTS AND METHODS: This was a retrospective medical record review of 152 patients with carcinoma of the cervix. All patients underwent a pre- and posttreatment whole-body positron emission tomography (PET) imaging scan with FDG. Patients were treated with external irradiation and intracavitary brachytherapy, and most received concurrent weekly cisplatin. Posttherapy whole-body FDG-PET was performed 1 to 12 months (mean, 3 months) after completion of treatment. RESULTS: The posttherapy PET did not show any abnormal FDG uptake in 114 patients, and their 5-year cause-specific survival estimate was 80%. There was persistent (in the irradiated region) abnormal FDG uptake in the cervix or lymph nodes in 20 patients. Their 5-year cause-specific survival estimate was 32%. New anatomic sites (in unirradiated regions) of abnormal FDG uptake were present in 18 patients, and none were alive at 5 years. A Cox proportional hazards model of survival outcome indicated that any abnormal posttherapy FDG uptake (persistent or new) was the most significant prognostic factor for developing metastatic disease and death from cervical cancer when compared with pretreatment- and treatment-related prognostic factors (P <.0001). CONCLUSION: Posttherapy abnormal FDG uptake (persistent or new) as detected by whole-body PET measures tumor response and might be predictive of tumor recurrence and death from cervical cancer. Prospective validation of these results is warranted.

Female↗

PubMed2004

Spindle cell ossifying amyloidotic tumor of the fallopian tube.

We report a unique tumor of the fallopian tube that was an incidental finding in a 60-year-old woman. The tumor was characterized by nests of spindle cells embedded in a partially ossified, hyalinized stroma, that also contained amyloid and basement membrane-like material. The histologic appearance of the tumor cells suggested an epithelial nature, but no immunohistochemical or ultrastructural evidence of such was found. The circumscription of the tumor and its lack of mitotic activity and cytologic atypia suggest a benign nature, but the histogenesis and appropriate classification of the tumor remain unclear.

Amyloid↗

PubMed2003

A randomized phase II evaluation of bryostatin-1 (NSC #339555) in persistent or recurrent squamous cell carcinoma of the cervix: A Gynecologic Oncology Group Study.

OBJECTIVES: The Gynecologic Oncology Group performed a randomized phase II study to determine the antitumor activity and toxicity of two different schedules of administration of bryostatin-1 in patients with persistent or recurrent squamous cell carcinoma of the cervix. METHODS: Eligible patients were randomized to receive either bryostatin-1 25 mug/m(2) as a 1-h infusion weekly for 3 weeks followed by a 1-week rest (Regimen I) or bryostatin-1 120 mug/m(2) as a 72-h continuous infusion every 2 weeks (Regimen II). RESULTS: A total of 70 patients were enrolled on this study. There were 32 eligible patients on Regimen I and 33 eligible patients on Regimen II; all but 4 had had prior chemotherapy. There were two partial responses (one on each treatment arm) among the 65 eligible patients (response rates = 3.1 and 3.0%, respectively). Ten patients on each regimen had stable disease. The most common adverse event was myalgia; 8 of 32 patients (25%) on Regimen I and 16 of 33 patients (48%) on Regimen II had any grade of myalgia. There was no significant myelosuppression on either treatment arm. CONCLUSIONS: Both of these schedules and doses of bryostatin-1 are inactive as single agents in the second-line treatment of squamous cell carcinoma of the cervix.

Adult↗

PubMed2002

MSI in endometrial carcinoma: absence of MLH1 promoter methylation is associated with increased familial risk for cancers.

Loss of DNA mismatch repair occurs in a variety of malignancies and is associated with genome-wide instability of microsatellite repeats, a molecular phenotype referred to as microsatellite instability (MSI). MSI is a consistent feature of colorectal and endometrial tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC). Sporadic colorectal and endometrial cancers that exhibit MSI frequently have methylation of the MLH1 promoter. We undertook a detailed family and medical history study to compare family cancer risk for women with MSI-positive and -negative endometrial cancers. The MLH1 promoter methylation status was determined for all cancers. Family histories were developed for 80 probands (40 with MSI-positive and 40 with MSI-negative tumors). The numbers of reported cancers in first- and second-degree relatives of the 2 groups were similar. There was a modest increase in familial cancer clustering for MSI-positive probands. When MSI-positive tumors were subclassified according to MLH1 promoter methylation, a clear association between methylation status and familial cancer risk was evident. Women with MSI-positive endometrial cancers in which the MLH1 promoter was unmethylated had a 7-fold relative risk (RR) of demonstrating familial clustering of cancers [RR 7.07 (95% confidence interval 2.29-21.81)]. The women with MSI-positive, MLH1-unmethylated tumors were significantly younger than the rest of the study population (56.1 years vs. 65.4, p < or = 0.01). Age of onset and tumor MSI not associated with MLH1 promoter methylation may point to women with a genetic susceptibility to malignancies.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Evaluation of the family history collection process and the accuracy of cancer reporting among a series of women with endometrial cancer.

UNLABELLED: Family history data are critical in the study of hereditary cancer syndromes and the identification of cancer modifier genes. PURPOSE: The purpose of this study was to analyze the process for collecting and verifying reported cancer family histories and identify reporting inaccuracies among a series of women with endometrial cancer. EXPERIMENTAL DESIGN: Detailed family histories were obtained from 80 women enrolled in a research study. Medical records were collected to verify cancer reporting. RESULTS: Participants reported 289 cancers among themselves and 2925 first-, second-, and third-degree relatives. There was a significant relationship between the number of telephone contacts made with each participant and the fraction of records retrieved from hospitals (chi(2) = 23.68, d.f. = 7, P = 0.001). Medical records were retrieved for 102 of 289 (35%) reported cancers and 10 additional cancers, not initially reported by participants. Medical records were more likely to be retrieved if the relative with cancer was living, closely related to the study participant, and the cancer type was known. The success in retrieving medical records declined with increasing record age (chi(2) = 35.07, d.f. = 5, P < 0.001). Thirty-two of the 112 (28.6%) verified cancers were identified to be inaccurately reported, with a significantly higher number of inaccurate reports among second- and third-degree relatives than first-degree relatives (P = 0.02). Two participants, who did not accurately report their cancer family history, had an increase in their family-based risk assessment after medical record collection. CONCLUSIONS: Additional studies to improve record collection efficiency and identify cancer reporting accuracy are needed among general research populations.

Adult↗