- Email: [email protected]
030 Osteopontin inhibits cytotoxicity by human natural killer cell
European Journal o f Obstetrics & Gynecology and Reproductive Biology 123 (2005) S 1 ~ 6 6
$32
infiltrating endometriosis originating from peritoneal lesions. Moreover different series aimed at evaluating the existence of an asymmetric distribution of retroperitoneal endometriosis showed inconsistent results. The purpose of this study was to evaluate the existence of a left right asymmetry in the distribution of endometriosis involving the uterosacral ligaments. Materials a n d M e t h o d s : Intraoperative details of patients undergoing laparoscopic treatment for endometriosis involving the uterosacral ligaments between January 2003 and March 2005 at our institution were retrieved from the Endoscopic Unit database. Only cases with histologically proven deep infiltrating endometriosis were included. Results: A total of 33 patients underwent laparoscopic resection of endometriosis infiltrating the uterosacral ligaments during the study period. The median (range) age was 30 years ( 2 0 4 3 ) . Median operative time was 80 minutes (15 300). In 6 (18.18%) cases both uterosacral ligaments were involved. In the group with unilateral deep endometriosis infiltrating the uterosacral ligament (N=27, 81.8%), the observed proportion of endometriosis on the left side (18/27, 66.7%) was significantly higher than the expected proportion of 50% (P = 0.03). In patients with left uterosacral ligament involvement, concomitant left endometriomas and left ureteral involvement were found in 7 (7/18, 38.9%) and 8 cases (8/18, 44.4%), respectively. C o n c l u s i o n : Our findings support the existence of a left prevalence of endometriotic involvement of the uterosacral ligament. Further studies are needed to assess whether the same theories advocated to explain the l e f t right asymmetry of peritoneal implants are also suitable for the retroperitoneal disease.
•
Laparoscopic ureterolysis for the treatment of ureteral endometriosis: our experience
Scarperi 2, xZ Raspaolo 2, F. Ghezzi 1 . I Unioersity of Insubria, Varese, Italy," 2University of Verona, E B e r e t t a 1 , A . C r o m i 1 , M . Serati 1 , A . S a c c o 1 , S.
~
Effects of VA-2914 on organotypic culture of endometrium
S.R. Ravet, C. Munaut, E Frankenne, A. NOB1, J.M. Foidart. University of
Liege, Liege, Belgium VA-2914 is a synthetic selective progesterone receptor modulator (SPRM) with potential for use in fertility control, treatment of fibroids and endometriosis, cervical ripening for induction of labor, and treatment of breast cancer and gliomas. In vivo and in vitro studies have shown the antiprogestative activity of VA-2914 associated with low antiglucocorticoids potency. The aim of our work is to study the effects of VA-2914 on endometrium by using organotypic culture system. This culture system offers several advantages which include ease of preparation; it' s a physiological method, the explants are immobilized on a membrane and not submerged in culture medium; and the culture conditions are similar to in vivo conditions. Our present investigation focused on the expression of matrix metalloproteinases (MMPs). Those enzymes have been previously shown to be hormonally regulated in the endometrium using the organotypic culture system. Endometrial biopsies were performed at different time of cycle in patients having regular ovulatory cycles, no endometrial pathology and without hormonal treatment. The explants were cultured for 2 days in medium supplemented with different concentrations of VA-2914 ( 10-7 to 10-t 5 M) associated or not with estradiol (E2) and progesterone (P4). The analysis by zymography of the expression of MMPs in conditionned media show a trend of VA-2914 to inhibit the activation of MMP-2 and -9, regardless of the concentrations (from 10-7 to 10-tSM), whereas E2 alone enhanced this activation. When P4 was associated with E2, a clear inhibition of the activation of MMP-2 and -9 was observed. By contrast, VA-2914 could not modify the effects of E2 which stimulates secretion and activation of MMP-2 and -9. RNA was extracted from fresh and cultured tissues. The mRNA level of MMP-2, -9 and P/LAB analysed by RT-PCR were mainly modulated after culture as compared to the fresh tissue. No effect of VA-2914 was observed with or not hormonal supplement. In conclusion, the ability of VA-2914 to inhibit the activation of MMP-2 and -9 indicated that this molecule could be interesting in the treatment of dysfunctional uterine bleeding.
Verona, Italy Objective: Ureteral endometriosis is relatively uncommon, accounting for less than 0.5% of all endometriotic lesions. This rare entity may result in major morbidity, due to silent ureteral obstruction and secondary compromise of renal function. An early diagnosis based on a high index of suspicion and a timely surgical excision of ureteral endometriosis are critical to avoid renal failure. Nevertheless, the treatment of choice of ureteral endometriosis is controversial. It has been suggested that laparoscopic ureterolysis represents an effective treatment option in most patients, even in cases with moderate or severe pyelic dilatation. However, in other series a significant proportion of women required reconstructive surgery after that conservative attempts to relieve obstruction have failed. We report our experience in patients undergoing laparoscopic conservative approach for the management of ureteral endometriosis. Materials and Methods: The study group consisted of patients with preoperative diagnosis of moderate or severe hydronephrosis undergoing laparoscopic treatment of endometrosis between November 2003 and January 2005. All women with clinical suspicion of deep infiltrating endometriosis underwent preoperative renal ultrasound. In the presence of an abnormality detected on ultrasound or in patients complaining urological symptomps intravenous pyelography (IVP) was performed. In all cases ureteral endometriosis was managed with laparoscopic ureterolysis. Follow-up evaluations were scheduled at 1, 3, 6, 12 postoperative months. All patients underwent postoperative IVP at the 3-months follow-up assessment. Results: Sixteen patients underwent conservative laparoscopic treatment of ureteral endometriosis during the study period. The median (range) age of the patients was 32.5 years (26 43). Bilateral involvement of ureters was found in 1 (6.25%) case. In women with unilateral lesions the left ureter was more frequently affected than the right one (12 (80%) vs 3 (20%), P =0.004). Ureteral involvement was associated with utero-sacral ligaments endometriosis in 93.7% (15/16) of cases. In two patients a JJ ureteral stent was temporarily inserted in a retrograde manner before surgery to facilitate the ureteral dissection. The median (range) operative time was 132 minutes (45 300). No inadvertent ureteral injury or resection occurred during the procedure. In all cases ureteral endometriotic lesions were histologically confirmed. The median (range) follow-up time was 9 months (3 12 months). Fifteen patients (93.7%) were clinically and objectively (patent ureter on IVP) cured. Only one patient required the performance of a laparotomic ureteroneocystostomy, due to recurrent ureteral dilatation 3 months after laparoscopy. C o n c l u s i o n : Our findings suggest that a conservative laparoscopic approach is an effective treatment option in most patients with ureteral endometriosis exhibiting moderate to severe hydronephrosis.
~
Osteopontin inhibits cytotoxicity by human natural killer cell
Z.H.Q.E Zhou, L.J.H. Long, L.J.H. Leng. Peking Union Medical College
Hospital, Peking, China Osteopontin (OPN), a secreted acidic phosphoglycoprotein found in increased in amounts in respose to certain infections and malignant transformation. In this studay we examined the action of OPN on natural killer (N~) cells cytotoxicity. A human OPN eDNA was cloned into the pTriEx- 1 Vector and the encoded protein purified from an induced culture of Tuner(DE3)pLacI carrying the plasmid. Using the recombinant OPN, we raised murine monoclonal antibody (E7-E9-B7-G7). It was found that recombinant OPN (from R&D Inc.) could inhibit the cytotoxicity of the NK cells using LDH releasing test. The cytotoxicity was decreased with dose-dependent of the consentrations of OPN under 500 ng/ml but it was increased in the concentration of OPN above 500 ng/ml. When OPN was prior to incubate with the monoclonal antibody (E7-E9-B7-G7), the inhibition effect of OPN could be deleted, but it had no affection on the increasing cytotoxicity of OPN at above 500ng/ml. It was still increased. The monoclonal antibody (E7-E9-B7-G7) could restore somehow the inhibition of the cytotoxicity of NK cells when incubation with the mixture of the monoclonal antibody with the peritoneal fluid of patients with endometriosis. Our experiments demonstraded that OPN be one of the inhibitors and activators of the cytotoxicity of natural killer and one of the inhibitors of the activity of NK cell in patients with endometriosis.
1-~'] Diagnostic accuracy of laparoscopy for endometriosis: evaluation of visual diagnosis and histological findings: a step towards 'see & treat management' S. Manzoor, E Odejinmi. Whipps Cross Hospital, London, UnitedKingdom Biopsy specimen of peritoneal lesions suggestive of endometriosis provides histological confirmation in 3.1 100% cases depending on lesion type and location. However the biopsy specimen of normal appearing peritoneum provides histological confirmation of endometriosis in 0 13% of cases. The exact nature and character of endometriotic lesion macro and microscopically is still debatable. A clear understanding of this concept would revolutionise the laparoscopic treatment for endometriosis. Introduction:
$32
infiltrating endometriosis originating from peritoneal lesions. Moreover different series aimed at evaluating the existence of an asymmetric distribution of retroperitoneal endometriosis showed inconsistent results. The purpose of this study was to evaluate the existence of a left right asymmetry in the distribution of endometriosis involving the uterosacral ligaments. Materials a n d M e t h o d s : Intraoperative details of patients undergoing laparoscopic treatment for endometriosis involving the uterosacral ligaments between January 2003 and March 2005 at our institution were retrieved from the Endoscopic Unit database. Only cases with histologically proven deep infiltrating endometriosis were included. Results: A total of 33 patients underwent laparoscopic resection of endometriosis infiltrating the uterosacral ligaments during the study period. The median (range) age was 30 years ( 2 0 4 3 ) . Median operative time was 80 minutes (15 300). In 6 (18.18%) cases both uterosacral ligaments were involved. In the group with unilateral deep endometriosis infiltrating the uterosacral ligament (N=27, 81.8%), the observed proportion of endometriosis on the left side (18/27, 66.7%) was significantly higher than the expected proportion of 50% (P = 0.03). In patients with left uterosacral ligament involvement, concomitant left endometriomas and left ureteral involvement were found in 7 (7/18, 38.9%) and 8 cases (8/18, 44.4%), respectively. C o n c l u s i o n : Our findings support the existence of a left prevalence of endometriotic involvement of the uterosacral ligament. Further studies are needed to assess whether the same theories advocated to explain the l e f t right asymmetry of peritoneal implants are also suitable for the retroperitoneal disease.
•
Laparoscopic ureterolysis for the treatment of ureteral endometriosis: our experience
Scarperi 2, xZ Raspaolo 2, F. Ghezzi 1 . I Unioersity of Insubria, Varese, Italy," 2University of Verona, E B e r e t t a 1 , A . C r o m i 1 , M . Serati 1 , A . S a c c o 1 , S.
~
Effects of VA-2914 on organotypic culture of endometrium
S.R. Ravet, C. Munaut, E Frankenne, A. NOB1, J.M. Foidart. University of
Liege, Liege, Belgium VA-2914 is a synthetic selective progesterone receptor modulator (SPRM) with potential for use in fertility control, treatment of fibroids and endometriosis, cervical ripening for induction of labor, and treatment of breast cancer and gliomas. In vivo and in vitro studies have shown the antiprogestative activity of VA-2914 associated with low antiglucocorticoids potency. The aim of our work is to study the effects of VA-2914 on endometrium by using organotypic culture system. This culture system offers several advantages which include ease of preparation; it' s a physiological method, the explants are immobilized on a membrane and not submerged in culture medium; and the culture conditions are similar to in vivo conditions. Our present investigation focused on the expression of matrix metalloproteinases (MMPs). Those enzymes have been previously shown to be hormonally regulated in the endometrium using the organotypic culture system. Endometrial biopsies were performed at different time of cycle in patients having regular ovulatory cycles, no endometrial pathology and without hormonal treatment. The explants were cultured for 2 days in medium supplemented with different concentrations of VA-2914 ( 10-7 to 10-t 5 M) associated or not with estradiol (E2) and progesterone (P4). The analysis by zymography of the expression of MMPs in conditionned media show a trend of VA-2914 to inhibit the activation of MMP-2 and -9, regardless of the concentrations (from 10-7 to 10-tSM), whereas E2 alone enhanced this activation. When P4 was associated with E2, a clear inhibition of the activation of MMP-2 and -9 was observed. By contrast, VA-2914 could not modify the effects of E2 which stimulates secretion and activation of MMP-2 and -9. RNA was extracted from fresh and cultured tissues. The mRNA level of MMP-2, -9 and P/LAB analysed by RT-PCR were mainly modulated after culture as compared to the fresh tissue. No effect of VA-2914 was observed with or not hormonal supplement. In conclusion, the ability of VA-2914 to inhibit the activation of MMP-2 and -9 indicated that this molecule could be interesting in the treatment of dysfunctional uterine bleeding.
Verona, Italy Objective: Ureteral endometriosis is relatively uncommon, accounting for less than 0.5% of all endometriotic lesions. This rare entity may result in major morbidity, due to silent ureteral obstruction and secondary compromise of renal function. An early diagnosis based on a high index of suspicion and a timely surgical excision of ureteral endometriosis are critical to avoid renal failure. Nevertheless, the treatment of choice of ureteral endometriosis is controversial. It has been suggested that laparoscopic ureterolysis represents an effective treatment option in most patients, even in cases with moderate or severe pyelic dilatation. However, in other series a significant proportion of women required reconstructive surgery after that conservative attempts to relieve obstruction have failed. We report our experience in patients undergoing laparoscopic conservative approach for the management of ureteral endometriosis. Materials and Methods: The study group consisted of patients with preoperative diagnosis of moderate or severe hydronephrosis undergoing laparoscopic treatment of endometrosis between November 2003 and January 2005. All women with clinical suspicion of deep infiltrating endometriosis underwent preoperative renal ultrasound. In the presence of an abnormality detected on ultrasound or in patients complaining urological symptomps intravenous pyelography (IVP) was performed. In all cases ureteral endometriosis was managed with laparoscopic ureterolysis. Follow-up evaluations were scheduled at 1, 3, 6, 12 postoperative months. All patients underwent postoperative IVP at the 3-months follow-up assessment. Results: Sixteen patients underwent conservative laparoscopic treatment of ureteral endometriosis during the study period. The median (range) age of the patients was 32.5 years (26 43). Bilateral involvement of ureters was found in 1 (6.25%) case. In women with unilateral lesions the left ureter was more frequently affected than the right one (12 (80%) vs 3 (20%), P =0.004). Ureteral involvement was associated with utero-sacral ligaments endometriosis in 93.7% (15/16) of cases. In two patients a JJ ureteral stent was temporarily inserted in a retrograde manner before surgery to facilitate the ureteral dissection. The median (range) operative time was 132 minutes (45 300). No inadvertent ureteral injury or resection occurred during the procedure. In all cases ureteral endometriotic lesions were histologically confirmed. The median (range) follow-up time was 9 months (3 12 months). Fifteen patients (93.7%) were clinically and objectively (patent ureter on IVP) cured. Only one patient required the performance of a laparotomic ureteroneocystostomy, due to recurrent ureteral dilatation 3 months after laparoscopy. C o n c l u s i o n : Our findings suggest that a conservative laparoscopic approach is an effective treatment option in most patients with ureteral endometriosis exhibiting moderate to severe hydronephrosis.
~
Osteopontin inhibits cytotoxicity by human natural killer cell
Z.H.Q.E Zhou, L.J.H. Long, L.J.H. Leng. Peking Union Medical College
Hospital, Peking, China Osteopontin (OPN), a secreted acidic phosphoglycoprotein found in increased in amounts in respose to certain infections and malignant transformation. In this studay we examined the action of OPN on natural killer (N~) cells cytotoxicity. A human OPN eDNA was cloned into the pTriEx- 1 Vector and the encoded protein purified from an induced culture of Tuner(DE3)pLacI carrying the plasmid. Using the recombinant OPN, we raised murine monoclonal antibody (E7-E9-B7-G7). It was found that recombinant OPN (from R&D Inc.) could inhibit the cytotoxicity of the NK cells using LDH releasing test. The cytotoxicity was decreased with dose-dependent of the consentrations of OPN under 500 ng/ml but it was increased in the concentration of OPN above 500 ng/ml. When OPN was prior to incubate with the monoclonal antibody (E7-E9-B7-G7), the inhibition effect of OPN could be deleted, but it had no affection on the increasing cytotoxicity of OPN at above 500ng/ml. It was still increased. The monoclonal antibody (E7-E9-B7-G7) could restore somehow the inhibition of the cytotoxicity of NK cells when incubation with the mixture of the monoclonal antibody with the peritoneal fluid of patients with endometriosis. Our experiments demonstraded that OPN be one of the inhibitors and activators of the cytotoxicity of natural killer and one of the inhibitors of the activity of NK cell in patients with endometriosis.
1-~'] Diagnostic accuracy of laparoscopy for endometriosis: evaluation of visual diagnosis and histological findings: a step towards 'see & treat management' S. Manzoor, E Odejinmi. Whipps Cross Hospital, London, UnitedKingdom Biopsy specimen of peritoneal lesions suggestive of endometriosis provides histological confirmation in 3.1 100% cases depending on lesion type and location. However the biopsy specimen of normal appearing peritoneum provides histological confirmation of endometriosis in 0 13% of cases. The exact nature and character of endometriotic lesion macro and microscopically is still debatable. A clear understanding of this concept would revolutionise the laparoscopic treatment for endometriosis. Introduction: