Introduction Lymphadenectomy is a common procedure in gynecologic oncology. Nonetheless, it is as... more Introduction Lymphadenectomy is a common procedure in gynecologic oncology. Nonetheless, it is associated to important number of side effects. During the last decade there have been enormous efforts to develop different SLN techniques to reduce complications without affecting survival. Objective Evaluate the experience of SLN technique in a university setting. Methods Retrospective review of 58 cervical and endometrial cancers evaluated with SLN. Results Forty-one of the patients presented with uterine cervical cancer and 17 endometrial cancer. The method used for detection of the SLN was patent blue dye only in 42 patients (72%), technetium 99 in 2 (3.5%), both techniques was used in 10 (17%) and ICG in 4 (%) cases. 40 (69%) patients had laparoscopy. At least one pelvic SLN was detected in 53 (91.4%) 7 patients. Bilateral detection was achieved in 39 (67.2%). Most of the SLN were identified next to external iliac vessels and the obturator fossa. In 97% of the 92 samples identified ...
AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 4366 Ovarian cancer constitutes one of the m... more AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 4366 Ovarian cancer constitutes one of the main causes of death from gynecological cancers worldwide. In spite of an excellent initial response with the use of aggressive cytoreductive surgery plus adjuvant chemotherapy the overall survival is poor. Thus, finding of new modalities of treatments remains a major challenge when dealing with advanced stages of this disease. During last years evidence has been published supporting pleitropic effects of statins beyond their better known effect, this is, the cardioprotective effect due to beneficial changes in lipid metabolism and in the inflammatory response involved in atheroma plaque formation. Statins, HMG-CoA reductase inhibitors, would induce cell death in some epithelial cancers (i.e. breast cancer) but the explanatory mechanisms are not well characterized. Objectives: We investigated if statins induce apoptosis in ovarian cancer cell lines and what are the mechanisms explaining t...
AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 1920 Ovarian cancer constitutes the main c... more AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 1920 Ovarian cancer constitutes the main cause of death from gynecologic cancers. Despite using extensive cytoreductive surgery followed by intensive chemotherapy there is poor survival at advanced stages. Thus, finding new strategies of treatment constitutes a great challenge. We already demonstrated that TRAIL, a member of TNF family, induces apoptosis in ovarian cancer cells. In addition, we have found that 2-methoxyestradiol (2ME), an estrogen metabolite, kills cancer but not normal ovarian cells. Objectives: We investigated if TRAIL induces apoptosis in primary cultured ovarian cancer cells and if 2ME enhances TRAIL mediated apoptosis in this type of cancer. Furthermore, we investigated the mechanisms behind any interaction between them. Methods: Cell viability was studied by the MTS assay. Apoptosis was confirmed through DNA laddering, FACS, in vitro caspase activity assay, and W-B of different proteins involved in the apo...
Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, al... more Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, allowing metastasis and cancer progression. Here, we studied whether simvastatin, a lipophilic statin, could impair the metastatic potential of CICs in high-grade serous ovarian cancer (HGS-ovC), the most lethal among the gynecologic malignancies. qPCR, immunoblotting, and immunohistochemistry were used to assess simvastatin effects on proteins involved in stemness and epithelial-mesenchymal cell plasticity (EMT). Its effects on tumor growth and metastasis were evaluated using different models (e.g., spheroid formation and migration assays, matrigel invasion assays, 3D-mesomimetic models, and cancer xenografts). We explored also the clinical benefit of statins by comparing survival outcomes among statin users versus non-users. Herein, we demonstrated that simvastatin modifies the stemness and EMT marker expression patterns (both in mRNA and protein levels), and severely impairs the spheroi...
The Journal of Clinical Endocrinology Metabolism, Jul 2, 2013
MEG3 is an imprinted gene encoding a novel noncoding RNA that suppresses tumor cell growth. Altho... more MEG3 is an imprinted gene encoding a novel noncoding RNA that suppresses tumor cell growth. Although highly expressed in the normal human pituitary, it is unknown which of the normal pituitary cell types and pituitary tumors express MEG3. Our objectives were 1) to investigate cell-type- and tumor-type-specific expression of MEG3 in the human pituitary and 2) to investigate whether methylation in the intergenic differentially methylated region (IG-DMR) at the DLK1/MEG3 locus is involved in the loss of MEG3 expression in tumors. RT-PCR, quantitative RT-PCR, Northern blot, and a combination of in situ hybridization and immunofluorescence were used to determine the cell-type- and tumor-type-specific MEG3 expression. Bisulfite treatment and PCR sequencing of genomic DNA were used to measure the CpG methylation status in the normal and tumor tissues. Five normal human pituitaries and 17 clinically nonfunctioning, 11 GH-secreting, seven prolactin-secreting, and six ACTH-secreting pituitary adenomas were used. All normal human pituitary cell types express MEG3. However, loss of MEG3 expression occurs only in nonfunctioning pituitary adenomas of a gonadotroph origin. All other pituitary tumor phenotypes examined express MEG3. Hypermethylation of the IG-DMR at the DLK1/MEG3 locus is present in nonfunctioning pituitary adenomas. MEG3 is the first human gene identified expressed in multiple normal human pituitary cell types with loss of expression specifically restricted to clinically nonfunctioning pituitary adenomas. The IG-DMR hypermethylation may be an additional mechanism for MEG3 gene silencing in such tumors.
We report a 76-year-old woman with a virilization syndrome characterized by progressive androgeni... more We report a 76-year-old woman with a virilization syndrome characterized by progressive androgenic alopecia, clitoris enlargement and hirsutism predominating in the face. Plasma testosterone was 711 ng/dl. Magnetic resonance imaging showed slightly enlarged ovaries with a cyst in the left. A bilateral oophorectomy was performed, demonstrating the presence of a Leydig cell hilar tumor in the right ovary. The patient had a good postoperative evolution with reduction of androgen levels and reversion of alopecia.
Pituitary adenomas sometimes progress after surgery and can be locally invasive. Ki-67 and p53 ex... more Pituitary adenomas sometimes progress after surgery and can be locally invasive. Ki-67 and p53 expression are referred to as indicators of aggressive behavior in the World Health Organization Classification of Endocrine Tumors. The real value of these markers including an appropriate threshold for Ki-67 labeling index correlating with tumor progression is controversial. We identified 24 consecutive pituitary adenomas from patients who required surgery for recurrence within 5 years of their first procedure and 31 consecutive adenomas with no evidence of postsurgical progression within 5 years of first surgery. Case selection was based upon availability of complete clinical information, blocks, and slides for study. Immunohistochemistry for Ki-67 revealed that the tumors without progression had a proliferation index of 0.41% +/- 0.01% (mean +/- SEM) (n = 31) (range, 0.08%-1.2%) and the first biopsy from those tumors which progressed had a mean proliferation index of 1.45% +/- 0.09% (m...
Introduction Lymphadenectomy is a common procedure in gynecologic oncology. Nonetheless, it is as... more Introduction Lymphadenectomy is a common procedure in gynecologic oncology. Nonetheless, it is associated to important number of side effects. During the last decade there have been enormous efforts to develop different SLN techniques to reduce complications without affecting survival. Objective Evaluate the experience of SLN technique in a university setting. Methods Retrospective review of 58 cervical and endometrial cancers evaluated with SLN. Results Forty-one of the patients presented with uterine cervical cancer and 17 endometrial cancer. The method used for detection of the SLN was patent blue dye only in 42 patients (72%), technetium 99 in 2 (3.5%), both techniques was used in 10 (17%) and ICG in 4 (%) cases. 40 (69%) patients had laparoscopy. At least one pelvic SLN was detected in 53 (91.4%) 7 patients. Bilateral detection was achieved in 39 (67.2%). Most of the SLN were identified next to external iliac vessels and the obturator fossa. In 97% of the 92 samples identified ...
AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 4366 Ovarian cancer constitutes one of the m... more AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 4366 Ovarian cancer constitutes one of the main causes of death from gynecological cancers worldwide. In spite of an excellent initial response with the use of aggressive cytoreductive surgery plus adjuvant chemotherapy the overall survival is poor. Thus, finding of new modalities of treatments remains a major challenge when dealing with advanced stages of this disease. During last years evidence has been published supporting pleitropic effects of statins beyond their better known effect, this is, the cardioprotective effect due to beneficial changes in lipid metabolism and in the inflammatory response involved in atheroma plaque formation. Statins, HMG-CoA reductase inhibitors, would induce cell death in some epithelial cancers (i.e. breast cancer) but the explanatory mechanisms are not well characterized. Objectives: We investigated if statins induce apoptosis in ovarian cancer cell lines and what are the mechanisms explaining t...
AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 1920 Ovarian cancer constitutes the main c... more AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA 1920 Ovarian cancer constitutes the main cause of death from gynecologic cancers. Despite using extensive cytoreductive surgery followed by intensive chemotherapy there is poor survival at advanced stages. Thus, finding new strategies of treatment constitutes a great challenge. We already demonstrated that TRAIL, a member of TNF family, induces apoptosis in ovarian cancer cells. In addition, we have found that 2-methoxyestradiol (2ME), an estrogen metabolite, kills cancer but not normal ovarian cells. Objectives: We investigated if TRAIL induces apoptosis in primary cultured ovarian cancer cells and if 2ME enhances TRAIL mediated apoptosis in this type of cancer. Furthermore, we investigated the mechanisms behind any interaction between them. Methods: Cell viability was studied by the MTS assay. Apoptosis was confirmed through DNA laddering, FACS, in vitro caspase activity assay, and W-B of different proteins involved in the apo...
Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, al... more Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, allowing metastasis and cancer progression. Here, we studied whether simvastatin, a lipophilic statin, could impair the metastatic potential of CICs in high-grade serous ovarian cancer (HGS-ovC), the most lethal among the gynecologic malignancies. qPCR, immunoblotting, and immunohistochemistry were used to assess simvastatin effects on proteins involved in stemness and epithelial-mesenchymal cell plasticity (EMT). Its effects on tumor growth and metastasis were evaluated using different models (e.g., spheroid formation and migration assays, matrigel invasion assays, 3D-mesomimetic models, and cancer xenografts). We explored also the clinical benefit of statins by comparing survival outcomes among statin users versus non-users. Herein, we demonstrated that simvastatin modifies the stemness and EMT marker expression patterns (both in mRNA and protein levels), and severely impairs the spheroi...
The Journal of Clinical Endocrinology Metabolism, Jul 2, 2013
MEG3 is an imprinted gene encoding a novel noncoding RNA that suppresses tumor cell growth. Altho... more MEG3 is an imprinted gene encoding a novel noncoding RNA that suppresses tumor cell growth. Although highly expressed in the normal human pituitary, it is unknown which of the normal pituitary cell types and pituitary tumors express MEG3. Our objectives were 1) to investigate cell-type- and tumor-type-specific expression of MEG3 in the human pituitary and 2) to investigate whether methylation in the intergenic differentially methylated region (IG-DMR) at the DLK1/MEG3 locus is involved in the loss of MEG3 expression in tumors. RT-PCR, quantitative RT-PCR, Northern blot, and a combination of in situ hybridization and immunofluorescence were used to determine the cell-type- and tumor-type-specific MEG3 expression. Bisulfite treatment and PCR sequencing of genomic DNA were used to measure the CpG methylation status in the normal and tumor tissues. Five normal human pituitaries and 17 clinically nonfunctioning, 11 GH-secreting, seven prolactin-secreting, and six ACTH-secreting pituitary adenomas were used. All normal human pituitary cell types express MEG3. However, loss of MEG3 expression occurs only in nonfunctioning pituitary adenomas of a gonadotroph origin. All other pituitary tumor phenotypes examined express MEG3. Hypermethylation of the IG-DMR at the DLK1/MEG3 locus is present in nonfunctioning pituitary adenomas. MEG3 is the first human gene identified expressed in multiple normal human pituitary cell types with loss of expression specifically restricted to clinically nonfunctioning pituitary adenomas. The IG-DMR hypermethylation may be an additional mechanism for MEG3 gene silencing in such tumors.
We report a 76-year-old woman with a virilization syndrome characterized by progressive androgeni... more We report a 76-year-old woman with a virilization syndrome characterized by progressive androgenic alopecia, clitoris enlargement and hirsutism predominating in the face. Plasma testosterone was 711 ng/dl. Magnetic resonance imaging showed slightly enlarged ovaries with a cyst in the left. A bilateral oophorectomy was performed, demonstrating the presence of a Leydig cell hilar tumor in the right ovary. The patient had a good postoperative evolution with reduction of androgen levels and reversion of alopecia.
Pituitary adenomas sometimes progress after surgery and can be locally invasive. Ki-67 and p53 ex... more Pituitary adenomas sometimes progress after surgery and can be locally invasive. Ki-67 and p53 expression are referred to as indicators of aggressive behavior in the World Health Organization Classification of Endocrine Tumors. The real value of these markers including an appropriate threshold for Ki-67 labeling index correlating with tumor progression is controversial. We identified 24 consecutive pituitary adenomas from patients who required surgery for recurrence within 5 years of their first procedure and 31 consecutive adenomas with no evidence of postsurgical progression within 5 years of first surgery. Case selection was based upon availability of complete clinical information, blocks, and slides for study. Immunohistochemistry for Ki-67 revealed that the tumors without progression had a proliferation index of 0.41% +/- 0.01% (mean +/- SEM) (n = 31) (range, 0.08%-1.2%) and the first biopsy from those tumors which progressed had a mean proliferation index of 1.45% +/- 0.09% (m...
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