- Email: [email protected]
Gene therapy of epithelial ovarian cancer using adenoviral vectors
ONCOLOGY, DYSPLASIA, AND CYTOPATHOLOGY with Krukenberg tumors. Reports should include age, site of GI primary, time from diagnosis of primary to ovarian metastasis, and overall survival as well as survival from the time of diagnosis and treatment of the Krukenberg. We wish to alert the clinician that persistent GI symptoms always warrant investigation. Pelvic inflammatory disease, pregnancy, and postpartum endometritis may mask the GI symptoms. Delays in diagnosis should be avoided. During surgery, the gynecologic surgeon must do a complete upper abdominal exploration, and the general surgeon must do a complete pelvic evaluation. Since Krukenberg tumors are rare, a national registry should be started to gather information on these patients; this might lead to better diagnosis and treatment.
an average of 16 days to 74 days. Trials with multiple injection in a novel immune-competent mouse model of ovarian cancer are underway in our laboratory.
Gene therapy of epithelial ovarian cancer using adenoviral vectors
Objective: Screening for cervical cancer has been one of the major successes in American health care. The reasons for screening failure have not been well described. We have encountered 24 patients in the past year on our gynecologic oncology service who have presented with grossly visible stage IB or higher cervical cancers. A questionnaire was developed to determine why these patients presented with invasive cervical cancer, a theoretically preventable disease.
Ayman Al-Hendy, MD, PhD Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Ovarian cancer is the fourth most common cause of death in women. Gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir (GCV) treatment has been successfully applied in the treatment of different cancers in experimental animals and in humans. In a recent report, we have demonstrated that the HSV-tk/ GCV system can be used efficiently to kill human epithelial ovarian cancer cells (Gynecol Obstet Invest 1997;43:268 – 75). In this work, we wanted to test the ability of the HSV-tk/GCV to treat ovarian cancer in an animal model. The immune-deficient nude mice model was employed, and mice were injected intraperitoneally with the human epithelial ovarian cancer cell line OVCAR3, 108 cell/ mouse. The mice were divided into three different groups, groups 1 and 2 were treated by intraperitoneal injection of adenovirus carrying the HSV-tk gene (ad-tk) on day 3 after cell implantation. Group 1 received 2 3 108 pfu/mouse; group 2 received 20 3 108 pfu/mouse. Group 3 did not receive any viral injection and served as our negative control. All mice received GCV 10 mg/kg IP bid for 6 days. All mice were hosted in the same facilities and had access to food and water ad libitum. Mice in group 3 started to show clinical manifestations of disease by day 10, and all mice were dead by day 21 (16 6 1.5). At this point mice in groups 1 and 2 appeared perfectly healthy. Autopsy done on group 3 mice demonstrated multiple cancer implants in the abdominal cavity plus hemorrhagic ascitis. In contrast, autopsy on sample mice from groups 1 and 2 at the same time point failed to demonstrate any macroscopic or microscopic cancer. On further follow-up, mice in groups 1 and 2 started to show cancer-related signs, eg, weight loss, movement difficulty, poor reflex response, and finally death. Survival varied between 50 and 101 days with a mean of 66 6 17 days for group 1 and 74 6 13 days for group 2. Autopsy done on treated mice demonstrated multiple cancer implants and ascitis. In conclusion, a single injection of ad-tk/GCV was able to improve survival in an ovarian cancer mouse model from 158
Factors leading to delay in diagnosis of invasive cervical cancer Melissa Dworkin, MD, Maureen Killackey, MD, Jacqueline C. Johnson, MD St. Luke’s-Roosevelt Hospital Center, New York, New York
Methods: All patients seen at our hospital center with grossly visible cervical cancer were offered entry into this prospective study, approved by the IRB. After informed consent was obtained, a questionnaire was administered to the patients by a physician. The questions involved sexual and gynecologic history, symptom review, social history, and personal concerns involving gynecologic exams. Twenty-four patients were approached for the study and 20 were enrolled. Four patients were unable to participate secondary to medical or social conditions that did not allow them to complete the questionnaire. Results: Of the 20 patients enrolled in this study, 14 of 20 (70%) presented with bleeding irregularities. Upon further questioning, 19 of 20 (95%) reported a history of abnormal bleeding. Only 3 of 20 (15%) patients reported a history of an abnormal Papanicolaou smear, and 7 of 20 (35%) reported not having had a Papanicolaou in the past 5 years. Two patients had never had a Papanicolaou smear. Seventeen of 20 (85%) of all patients in the study had medical insurance at the time of diagnosis, and only 2 patients reported lack of insurance as the reason they had not been seen by a gynecologist in the past 2 years. The majority of the study patients, 17 of 20 (85%) had contact with medical personnel in the 2 years prior to diagnosis. Sixteen of the 20 patients had been seen by a physician, 5 of 20 had surgery or other invasive procedures, and 6 of 20 had been seen in an emergency department. Only 5 of 20 patients knew that a Papanicolaou smear is a screening test for cervical cancer. Five of the 20 thought it to be a test for infections, and 10 of 20 did not know the purpose of a Papanicolaou smear. The main reason women gave for not having had a Papanicolaou smear in the past 2 years was that they felt healthy and had no symptoms (12/20). Conclusion: The majority of patients in our study (17/20) reported contact with a physician within 2 years of diagnosis of their invasive cervical cancer. It appears that failure to screen and lack of understanding regarding Papanicolaou smear screening, rather than lack of access to medical care, is a major cause for delay in diagnosis of cervical cancer. Prim Care Update Ob/Gyns
an average of 16 days to 74 days. Trials with multiple injection in a novel immune-competent mouse model of ovarian cancer are underway in our laboratory.
Gene therapy of epithelial ovarian cancer using adenoviral vectors
Objective: Screening for cervical cancer has been one of the major successes in American health care. The reasons for screening failure have not been well described. We have encountered 24 patients in the past year on our gynecologic oncology service who have presented with grossly visible stage IB or higher cervical cancers. A questionnaire was developed to determine why these patients presented with invasive cervical cancer, a theoretically preventable disease.
Ayman Al-Hendy, MD, PhD Department of Obstetrics and Gynecology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada Ovarian cancer is the fourth most common cause of death in women. Gene therapy using the herpes simplex virus thymidine kinase (HSV-tk) gene followed by ganciclovir (GCV) treatment has been successfully applied in the treatment of different cancers in experimental animals and in humans. In a recent report, we have demonstrated that the HSV-tk/ GCV system can be used efficiently to kill human epithelial ovarian cancer cells (Gynecol Obstet Invest 1997;43:268 – 75). In this work, we wanted to test the ability of the HSV-tk/GCV to treat ovarian cancer in an animal model. The immune-deficient nude mice model was employed, and mice were injected intraperitoneally with the human epithelial ovarian cancer cell line OVCAR3, 108 cell/ mouse. The mice were divided into three different groups, groups 1 and 2 were treated by intraperitoneal injection of adenovirus carrying the HSV-tk gene (ad-tk) on day 3 after cell implantation. Group 1 received 2 3 108 pfu/mouse; group 2 received 20 3 108 pfu/mouse. Group 3 did not receive any viral injection and served as our negative control. All mice received GCV 10 mg/kg IP bid for 6 days. All mice were hosted in the same facilities and had access to food and water ad libitum. Mice in group 3 started to show clinical manifestations of disease by day 10, and all mice were dead by day 21 (16 6 1.5). At this point mice in groups 1 and 2 appeared perfectly healthy. Autopsy done on group 3 mice demonstrated multiple cancer implants in the abdominal cavity plus hemorrhagic ascitis. In contrast, autopsy on sample mice from groups 1 and 2 at the same time point failed to demonstrate any macroscopic or microscopic cancer. On further follow-up, mice in groups 1 and 2 started to show cancer-related signs, eg, weight loss, movement difficulty, poor reflex response, and finally death. Survival varied between 50 and 101 days with a mean of 66 6 17 days for group 1 and 74 6 13 days for group 2. Autopsy done on treated mice demonstrated multiple cancer implants and ascitis. In conclusion, a single injection of ad-tk/GCV was able to improve survival in an ovarian cancer mouse model from 158
Factors leading to delay in diagnosis of invasive cervical cancer Melissa Dworkin, MD, Maureen Killackey, MD, Jacqueline C. Johnson, MD St. Luke’s-Roosevelt Hospital Center, New York, New York
Methods: All patients seen at our hospital center with grossly visible cervical cancer were offered entry into this prospective study, approved by the IRB. After informed consent was obtained, a questionnaire was administered to the patients by a physician. The questions involved sexual and gynecologic history, symptom review, social history, and personal concerns involving gynecologic exams. Twenty-four patients were approached for the study and 20 were enrolled. Four patients were unable to participate secondary to medical or social conditions that did not allow them to complete the questionnaire. Results: Of the 20 patients enrolled in this study, 14 of 20 (70%) presented with bleeding irregularities. Upon further questioning, 19 of 20 (95%) reported a history of abnormal bleeding. Only 3 of 20 (15%) patients reported a history of an abnormal Papanicolaou smear, and 7 of 20 (35%) reported not having had a Papanicolaou in the past 5 years. Two patients had never had a Papanicolaou smear. Seventeen of 20 (85%) of all patients in the study had medical insurance at the time of diagnosis, and only 2 patients reported lack of insurance as the reason they had not been seen by a gynecologist in the past 2 years. The majority of the study patients, 17 of 20 (85%) had contact with medical personnel in the 2 years prior to diagnosis. Sixteen of the 20 patients had been seen by a physician, 5 of 20 had surgery or other invasive procedures, and 6 of 20 had been seen in an emergency department. Only 5 of 20 patients knew that a Papanicolaou smear is a screening test for cervical cancer. Five of the 20 thought it to be a test for infections, and 10 of 20 did not know the purpose of a Papanicolaou smear. The main reason women gave for not having had a Papanicolaou smear in the past 2 years was that they felt healthy and had no symptoms (12/20). Conclusion: The majority of patients in our study (17/20) reported contact with a physician within 2 years of diagnosis of their invasive cervical cancer. It appears that failure to screen and lack of understanding regarding Papanicolaou smear screening, rather than lack of access to medical care, is a major cause for delay in diagnosis of cervical cancer. Prim Care Update Ob/Gyns